WorldWideScience

Sample records for biological therapy

  1. Biological therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Sivamani Raja

    2010-01-01

    Full Text Available The treatment of psoriasis has undergone a revolution with the advent of biologic therapies, including infliximab, etanercept, adalimumab, efalizumab, and alefacept. These medications are designed to target specific components of the immune system and are a major technological advancement over traditional immunosuppressive medications. These usually being well tolerated are being found useful in a growing number of immune-mediated diseases, psoriasis being just one example. The newest biologic, ustekinumab, is directed against the p40 subunit of the IL-12 and IL-23 cytokines. It has provided a new avenue of therapy for an array of T-cell-mediated diseases. Biologics are generally safe; however, there has been concern over the risk of lymphoma with use of these agents. All anti-TNF-α agents have been associated with a variety of serious and "routine" opportunistic infections.

  2. Biologic therapies for juvenile arthritis

    OpenAIRE

    Wilkinson, N; Jackson, G.; Gardner-Medwin, J.

    2003-01-01

    A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or bl...

  3. [Biological therapy for osteoporosis].

    Science.gov (United States)

    Nakamura, Shinya; Tanaka, Sakae

    2014-06-01

    Osteoporosis is a disorder of bone formation and resorption balance. Advances in our knowledge of the molecular mechanisms of bone formation and resorption led to promising therapeutic targets for osteoporosis. In the novel biological drugs, denosumab, a monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) has been clinically applied by positive effect on bone mineral density, negative effect on bone resorption, preventive effect on fragility fractures and safety. Odanacatib, a cathepsin K inhibitor is drawing attention as an antiresorptive drug which has lower bone resorption potency than bisphosphoneate. On the other hand, BHQ-880, an anti-Dickkopf-1 (Dkk-1) antibody and romosozumab (AMG-785) , an anti-sclerostin antibody which activate Wnt/β-catenin signaling pathway are drawing attention as bone formation accelerators with no bone resorption acceleration. Clinical studies of these drugs are now ongoing and their clinical applications are expected. PMID:24870844

  4. Biologic therapy of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Damjanov Nemanja

    2009-01-01

    Full Text Available Rheumatoid arthritis (RA and juvenile idiopathic/rheumatoid arthritis (JIA are chronic, inflammatory, systemic, auto-immune diseases characterized by chronic arthritis leading to progressive joint erosions. The individual functional and social impact of rheumatoid arthritis is of great importance. Disability and joint damage occur rapidly and early in the course of the disease. The remarkably improved outcomes have been achieved initiating biologic therapy with close monitoring of disease progression. Biologic agents are drugs, usually proteins, which can influence chronic immune dysregulation resulting in chronic arthritis. According to the mechanism of action these drugs include: 1 anti-TNF drugs (etanercept, infiximab, adalimumab; 2 IL-1 blocking drugs (anakinra; 3 IL-6 blocking drugs (tocilizumab; 4 agents blocking selective co-stimulation modulation (abatacept; 5 CD 20 blocking drugs (rituximab. Biologics targeting TNF-alpha with methotrexate have revolutionized the treatment of RA, producing significant improvement in clinical, radiographic, and functional outcomes not seen previously. The new concept of rheumatoid arthritis treatment defines early diagnosis, early aggressive therapy with optimal doses of disease modifying antirheumatic drugs (DMARDs and, if no improvement has been achieved during six months, early introduction of biologic drugs. The three-year experience of biologic therapy in Serbia has shown a positive effect on disease outcome.

  5. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  6. Fungal Infections and New Biologic Therapies.

    Science.gov (United States)

    Vallabhaneni, Snigdha; Chiller, Tom M

    2016-05-01

    The development of biologic therapies targeting proinflammatory mediators has led to significant advances in the treatment of immune-mediated inflammatory diseases (IMIDs). Blocking undesired inflammatory effects also has the potential to disrupt the body's immune response and increase the risk for infections, including fungal infections. This review summarizes the published data on the frequency and risk for fungal infections among patients treated with biologics, with a focus on the newer therapies approved for use with IMIDs in the last 10 years. The use of biologics is associated with a small but important risk of fungal infections. Pneumocystis jirovecii pneumonia, histoplasmosis, and candidiasis are some of the most common fungal infections associated with biologics. Providers should be vigilant for fungal infection among patients taking biologics, be aware that biologic agents may alter the typical presentation of fungal infections, and take timely steps to diagnose and treat fungal infection to reduce resultant morbidity and mortality. PMID:27032792

  7. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  8. Biologic therapies: what and when?

    OpenAIRE

    Johnston, Sarah L

    2007-01-01

    Over the past two decades, major advances have been made in the understanding of the immune system and disease pathogenesis. This has coincided with the development of biologic therapies—monoclonal antibodies and fusion proteins. The decision of when to use such treatment in the clinic is not always straightforward. In addition to immune biology, the focus of this review will be on the application of these treatments to immune‐mediated diseases and the molecular targets involved in pathogenes...

  9. Cardiovascular toxicities of biological therapies

    DEFF Research Database (Denmark)

    Ryberg, Marianne

    2013-01-01

    effects. One serious adverse effect is the risk of cardiovascular dysfunction. Some targeted therapies, eg, treatment with monoclonal antibodies or angiogenesis inhibitors, have shown an increased risk of cardiac events. Their influence on the cardiovascular system, however, seems to be transient, but...

  10. Biological Therapy in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Mariana Postal

    2012-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations. Despite new and improved therapy having positively impacted the prognosis of SLE, a subgroup of patients do not respond to conventional therapy. Moreover, the risk of fatal outcomes and the damaging side effects of immunosuppressive therapies in SLE call for an improvement in the current therapeutic management. New therapeutic approaches are focused on B-cell targets, T-cell downregulation and costimulatory blockade, cytokine inhibition, and the modulation of complement. Several biological agents have been developed, but this encouraging news is associated with several disappointments in trials and provide a timely moment to reflect on biologic therapy in SLE.

  11. Step Therapy And Biologics: No Easy Answers

    OpenAIRE

    HAGLAND, MARK

    2006-01-01

    For what diseases is it best to try traditional drug therapies first, and are there any instances in which going straight to the biologic is reasonable? Doctors and patients want the latest and greatest, but payers want better safety and efficacy data.

  12. Biological Considerations When Comparing Proton Therapy. With Photon Therapy

    NARCIS (Netherlands)

    Paganetti, Harald; van Luijk, Peter

    2013-01-01

    Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of photons, leading to a different biological

  13. Optimizing biological therapy in Crohn's disease.

    Science.gov (United States)

    Gecse, Krisztina Barbara; Végh, Zsuzsanna; Lakatos, Péter László

    2016-01-01

    Anti-TNF therapy has revolutionized the treatment of inflammatory bowel diseases, including both Crohn's disease and ulcerative colitis. However, a significant proportion of patients does not respond to anti-TNF agents or lose response over time. Recently, therapeutic drug monitoring has gained a major role in identifying the mechanism and management of loss of response. The aim of this review article is to summarize the predictors of efficacy and outcomes, the different mechanisms of anti-TNF/biological failure in Crohn's disease and identify strategies to optimize biological treatment. PMID:26471077

  14. Biological Therapy-Induced Systemic Vasculitis.

    Science.gov (United States)

    Gutiérrez-González, Luis Arturo

    2016-07-01

    The use of biologics has been associated with the paradoxical development of biologics-induced autoimmune diseases. The purpose of this review was to describe the key immunopathogenic mechanisms involved in the development of these conditions, and to discuss the clinical and laboratory characteristics usually described in the medical literature, reviewing case reports as well as records on national biologic therapies (BIOGEAS, RABBIT, BSRBR-RA, BIOBADAVEN). More than 200 cases have so far been reported, all of them diagnosed on the basis of the histopathology or meeting the ACR/Chapel Hill criteria. Over 75 % of the cases were females with a mean age of 48 ± 5 years. More than 50 % had rheumatoid arthritis. Most of the biologics-associated vasculitis developed in 90 ± 31 days. Complete resolution in almost 75 % of the cases was observed upon treatment discontinuation; however, steroid therapy was indicated for all patients and one death was recorded. The use of cyclophosphamide, rituximab or plasma exchange was reserved for the most severe cases. PMID:27165496

  15. Biologic therapy for inflammatory bowel disease.

    Science.gov (United States)

    Ardizzone, Sandro; Bianchi Porro, Gabriele

    2005-01-01

    Despite all of the advances in our understanding of the pathophysiology of inflammatory bowel disease (IBD), we still do not know its cause. Some of the most recently available data are discussed in this review; however, this field is changing rapidly and it is increasingly becoming accepted that immunogenetics play an important role in the predisposition, modulation and perpetuation of IBD. The role of intestinal milieu, and enteric flora in particular, appears to be of greater significance than previously thought. This complex interplay of genetic, microbial and environmental factors culminates in a sustained activation of the mucosal immune and non-immune response, probably facilitated by defects in the intestinal epithelial barrier and mucosal immune system, resulting in active inflammation and tissue destruction. Under normal situations, the intestinal mucosa is in a state of 'controlled' inflammation regulated by a delicate balance of proinflammatory (tumour necrosis factor [TNF]-alpha, interferon [IFN]-gamma, interleukin [IL]-1, IL-6, IL-12) and anti-inflammatory cytokines (IL-4, IL-10, IL-11). The mucosal immune system is the central effector of intestinal inflammation and injury, with cytokines playing a central role in modulating inflammation. Cytokines may, therefore, be a logical target for IBD therapy using specific cytokine inhibitors. Biotechnology agents targeted against TNF, leukocyte adhesion, T-helper cell (T(h))-1 polarisation, T-cell activation or nuclear factor (NF)-kappaB, and other miscellaneous therapies are being evaluated as potential therapies for IBD. In this context, infliximab is currently the only biologic agent approved for the treatment of inflammatory and fistulising Crohn's disease. Other anti-TNF biologic agents have emerged, including CDP 571, certolizumab pegol (CDP 870), etanercept, onercept and adalimumab. However, ongoing research continues to generate new biologic agents targeted at specific pathogenic mechanisms involved

  16. Gastric cancer and trastuzumab: first biologic therapy in gastric cancer

    OpenAIRE

    Gunturu, Krishna S; Woo, Yanghee; Beaubier, Nike; Remotti, Helen E.; Saif, M. Wasif

    2013-01-01

    Gastric cancer remains difficult to cure and has a poor overall prognosis. Chemotherapy and multimodality therapy has shown some benefit in the treatment of gastric cancer. Current therapies for gastric cancer have their limitations; thus, we are in need of newer treatment options including targeted therapies. Here, we review the biologic therapy with trastuzumab in human epidermal growth factor receptor 2 (HER2)+ gastric cancer.

  17. The future of osteoarthritis therapeutics: emerging biological therapy.

    Science.gov (United States)

    Mobasheri, A

    2013-12-01

    Biological therapy is a thriving area of research and development, and is well established for chronic forms of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, there is no clinically validated biological therapy for osteoarthritis (OA). Chronic forms of OA are increasingly viewed as an inflammatory disease. OA was largely regarded as a "wear and tear disease". However, the disease is now believed to involve "low grade" inflammation and the growth of blood vessels and nerves from the subchondral bone into articular cartilage. This realization has focused research effort on the development and evaluation of biological therapy that targets proinflammatory mediators, angiogenic factors and cytokines in articular cartilage, subchondral bone and synovium in chronic forms of OA. This review article provides an overview of emerging biological therapy for OA, and discusses recent molecular targets implicated in angiogenesis and neurogenesis and progress with antibody-based therapy, calcitonin, and kartogenin, the small molecule stimulator of chondrogenesis. PMID:24170255

  18. Biologic therapy in inflammatory bowel disease

    DEFF Research Database (Denmark)

    Theede, Klaus; Dahlerup, Jens Frederik; Fallingborg, Jan;

    2013-01-01

    depends on the primary response to induction therapy. Effect of maintenance therapy should be evaluated clinically and paraclinically at least every 26-52 weeks, and maybe supplemented by endoscopy or MRI scan. Decision of treatment discontinuation is based on disease manifestation, treatment response and...... paraclinical parameters. In fistulising Crohn's disease, treatment with infliximab or adalimumab can be initiated in simple fistula with rectal inflammation or complex fistula when the initial treatment has insufficient effect. Further treatment strategy depends on the primary response to induction therapy...... not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with...

  19. The Future of Osteoarthritis Therapeutics: Emerging Biological Therapy

    OpenAIRE

    Mobasheri, A.

    2013-01-01

    Biological therapy is a thriving area of research and development, and is well established for chronic forms of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). However, there is no clinically validated biological therapy for osteoarthritis (OA). Chronic forms of OA are increasingly viewed as an inflammatory disease. OA was largely regarded as a “wear and tear disease”. However, the disease is now believed to involve “low grade” inflammation and the growth of blood vessels and nerve...

  20. Biologics in dermatologic therapy - An update

    Directory of Open Access Journals (Sweden)

    Coondoo Arijit

    2009-01-01

    Full Text Available Biologics are protein molecules which are used in various diseases to target the specific points in the immunopathogenesis of the diseases. The molecules are produced by recombinant DNA technology. The molecules bind to the specific targets without interfering wtih rest of the pathogenetic pathways. Therefore the so called ′immunosuppressives′ have, although, a broader broader spectrum of action on immune system, their side-effects are also equally more. The biologics, because of their spefic action on the immune system, have very little side effects. The biologics which have revolutionized the treatment of various dermatologic diseases have been discussed here.

  1. Biofield therapies: biophysical basis and biological regulations?

    Science.gov (United States)

    Movaffaghi, Zahra; Farsi, Mohammad

    2009-02-01

    Complementary and alternative medicine (CAM) is increasingly popular in biomedical health care. One area of alternative medicine, biofield therapies, claims to manipulate individuals 'energy field' in order to enhance healing and wellbeing. This article reviews some recent studies addressing the characterization of endogenous energy fields and the way they affect the physiologic processes. PMID:19161953

  2. BGRT: Biologically guided radiation therapy - The future is fast approaching!

    International Nuclear Information System (INIS)

    Rapid advances in functional and biological imaging, predictive assays, and our understanding of the molecular and cellular responses underpinning treatment outcomes herald the coming of the long-sought goal of implementing patient-specific biologically guided radiation therapy (BGRT) in the clinic. Biological imaging and predictive assays have the potential to provide patient-specific, three-dimensional information to characterize the radiation response characteristics of tumor and normal structures. Within the next decade, it will be possible to combine such information with advanced delivery technologies to design and deliver biologically conformed, individualized therapies in the clinic. The full implementation of BGRT in the clinic will require new technologies and additional research. However, even the partial implementation of BGRT treatment planning may have the potential to substantially impact clinical outcomes

  3. Updates in biological therapies for knee injuries: tendons

    OpenAIRE

    Demange, Marco Kawamura; de Almeida, Adriano Marques; Rodeo, Scott A.

    2014-01-01

    Tendons are subjected to tendinopathies caused by inflammation, degeneration, and weakening of the tendon, due to overuse and trauma, which may eventually lead to tendon rupture. Recently, there has been increasing interest in biological approaches to augment tissue healing. Tendon healing occurs through a dynamic process with inflammation, cellular proliferation, and tissue remodeling. In this review article, we discuss the more frequently proposed biological therapies for tendon injuries as...

  4. THE THYROID GLAND STATUS IN PATIENTS WITH ANKYLOSING SPONDYLITIS DURING STANDARD THERAPY AND BIOLOGICAL THERAPY

    OpenAIRE

    G. R. Akhunova; F V Valeeva; I. G. Salikhov

    2014-01-01

    Aim. To evaluate the condition of the thyroid gland in patients with ankylosing spondylitis (AS) during standard therapy and biologicaltherapy (infliximab).Subjects and methods. Twenty-six patients with AS were examined; some of them received biological therapy with infliximab, while the others took non-steroidal anti-inflammatory drugs. The structuralunctional state of thyroid gland was evaluated in all patients. The effect of therapy was evaluated by the ASAS criteria. The efficiency of the...

  5. Salivary Gland Cancers: Biology and Systemic Therapy.

    Science.gov (United States)

    Goyal, Gaurav; Mehdi, Syed A; Ganti, Apar Kishor

    2015-10-01

    Salivary gland tumors are a relatively rare and heterogeneous group of tumors with variable pathologic and phenotypic characteristics. The lack of clinical outcomes data and randomized controlled trials pertaining to them makes it difficult to formulate definitive treatment protocols that could help with making decisions regarding choice of therapy. Most studies involving systemic chemotherapy have not shown promising patient outcome results. With recent advances in molecular technology, however, it is now possible to identify specific genetic alterations and biomarkers as possible targets for therapeutic purposes. For example, in mucoepidermoid carcinomas, one of the most common types of malignant salivary gland tumors, a commonly seen genetic translocation [t(11;19)(q21;p13), which involves the CRTC1 and MAML2 genes] has been found to be associated with improved survival, making it a possible prognostic marker. Also, this translocation gives rise to a fusion protein that appears to render tumors highly sensitive to epidermal growth factor receptor (EGFR) inhibition. However, the results of phase II trials of EGFR inhibitors-as well as other targeted agents--in salivary gland tumors have been disappointing: there has been some disease stabilization but no objective responses. There remains a need for well-designed prospective clinical studies to improve management of these tumors. PMID:26470903

  6. Biological therapies for rheumatoid arthritis: progress to date.

    Science.gov (United States)

    Malviya, Gaurav; Salemi, Simonetta; Laganà, Bruno; Diamanti, Andrea Picchianti; D'Amelio, Raffaele; Signore, Alberto

    2013-08-01

    Biologic drugs for the management of rheumatoid arthritis (RA) have revolutionized the therapeutic armamentarium with the development of several novel monoclonal antibodies, which include murine, chimeric, humanized, fully human antibodies and fusion proteins. These biologics bind to their targets with high affinity and specificity. Since 1998, nine different biologics have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of RA, and several others are in different stages of clinical trials. This field is in continuous evolution and new biologics are tested every year. Therefore a precise analysis is required in order to have a detailed and updated state of the art of this field. In this review, our main aim is to analyse all available biological therapies that are FDA and EMA approved for the treatment of RA and also those that are in clinical trials for the management of RA patients. PMID:23558378

  7. Soluble cytokine receptors in biological therapy.

    Science.gov (United States)

    Fernandez-Botran, Rafael; Crespo, Fabian A; Sun, Xichun

    2002-08-01

    Due to their fundamental involvement in the pathogenesis of many diseases, cytokines constitute key targets for biotherapeutic approaches. The discovery that soluble forms of cytokine receptors are involved in the endogenous regulation of cytokine activity has prompted substantial interest in their potential application as immunotherapeutic agents. As such, soluble cytokine receptors have many advantages, including specificity, low immunogenicity and high affinity. Potential disadvantages, such as low avidity and short in vivo half-lifes, have been addressed by the use of genetically-designed receptors, hybrid proteins or chemical modifications. The ability of many soluble cytokine receptors to inhibit the binding and biological activity of their ligands makes them very specific cytokine antagonists. Several pharmaceutical companies have generated a number of therapeutic agents based on soluble cytokine receptors and many of them are undergoing clinical trials. The most advanced in terms of clinical development is etanercept (Enbrel, Immunex), a fusion protein between soluble TNF receptor Type II and the Fc region of human IgG1. This TNF-alpha; antagonist was the first soluble cytokine receptor to receive approval for use in humans. In general, most agents based on soluble cytokine receptors have been safe, well-tolerated and have shown only minor side effects in the majority of patients. Soluble cytokine receptors constitute a new generation of therapeutic agents with tremendous potential for applications in a wide variety of human diseases. Two current areas of research are the identification of their most promising applications and characterisation of their long-term effects. PMID:12171504

  8.  Biological therapies in systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Dorota Suszek

    2012-08-01

    Full Text Available  The prevention of chronic organic damage and complete inhibition of inflammatory activity of the disease are the main goals in the treatment of systemic lupus erythematosus (SLE. Current therapies of SLE are not effective enough and they may cause various serious side effects. Biological therapies, affecting important pathogenetic disturbances in the immunological system of SLE patients, give hope for the development of a new treatment for SLE. Currently the most advanced clinical trials are being conducted with anti-lymphocyte B drugs, such as rituximab, belimumab and epratuzumab. Belimumab as the first biological agent was registered for treatment of the active, seropositive form of SLE. The advances in immunology and rheumatology nowadays raise the hope of finding effective and safe treatment for SLE. In our article we present an overview of data concerning perspectives of biological treatment in SLE.

  9. Biological basis of heavy ion beams for cancer therapy

    International Nuclear Information System (INIS)

    Fast neutron therapy has started firstly and proton therapy has commenced secondly, fast neutron shows better biological effects compared to conventional radiations but its dose distribution is not good, and proton demonstrates excellent dose distribution but its biological effects are almost the same as that of conventional radiations. On the other hand, negative pi-mesons and heavy ions indicate high radiobiological effect and excellent dose distribution, therefore these particle radiations is considered to be more attractive for radiotherapeutic radiations to enhance cure rate of cancers. The biological strong points of these particles are as follows : 1) cells exposed to these particle radiations shows less recovery after irradiation compared to conventional radiations, 2) these radiations show high biological effects (high value of relative biological effectiveness = RBE) when the same dose is given, 3) big effects on hypoxic cells which exsist in tumor, i.e. the value of oxygen enhancement ratio (OER) is low, 4) the differences in radiosensitivity by stages of cell cycle are not so great (data was not shown in present paper), 5) biological effects at prepeak plateau region in depth dose curve formed by these particle radiations is less than that at peak region (therefore, if beam is modulated to cover tumor at spraed out broad peak, tumors is given more biological effect compared to normal tissues which is to be exposed to radiations at prepaeak region). Clinical trial using heavy ions are being performed at Lawrence Berkeley Laboratory which is only one facility to be able to try clinical trial. The results of clinical trials at Lawrence Berkeley Laboratory suggest to be very prospective to enhance tumor cure rate, however it is too early to estimate the effect of heavy ion therapy. (J.P.N.)

  10. Cardiovascular safety of biologic therapies for the treatment of RA.

    Science.gov (United States)

    Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

    2012-01-01

    Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies. PMID:22083220

  11. EUD-based biological optimization for carbon ion therapy

    International Nuclear Information System (INIS)

    Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

  12. EUD-based biological optimization for carbon ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748 (Germany)

    2015-11-15

    Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

  13. Osteosarcoma Genetics and Epigenetics: Emerging Biology and Candidate Therapies

    Science.gov (United States)

    Morrow, James J.; Khanna, Chand

    2016-01-01

    Osteosarcoma is the most common primary malignancy of bone, typically presenting in the first or second decade of life. Unfortunately, clinical outcomes for osteosarcoma patients have not substantially improved in over 30 years. This stagnation in therapeutic advances is perhaps explained by the genetic, epigenetic, and biological complexities of this rare tumor. In this review we provide a general background on the biology of osteosarcoma and the clinical status quo. We go on to enumerate the genetic and epigenetic defects identified in osteosarcoma. Finally, we discuss ongoing large-scale studies in the field and potential new therapies that are currently under investigation. PMID:26349415

  14. Biological imaging in radiation therapy: role of positron emission tomography

    International Nuclear Information System (INIS)

    In radiation therapy (RT), staging, treatment planning, monitoring and evaluation of response are traditionally based on computed tomography (CT) and magnetic resonance imaging (MRI). These radiological investigations have the significant advantage to show the anatomy with a high resolution, being also called anatomical imaging. In recent years, so called biological imaging methods which visualize metabolic pathways have been developed. These methods offer complementary imaging of various aspects of tumour biology. To date, the most prominent biological imaging system in use is positron emission tomography (PET), whose diagnostic properties have clinically been evaluated for years. The aim of this review is to discuss the valences and implications of PET in RT. We will focus our evaluation on the following topics: the role of biological imaging for tumour tissue detection/delineation of the gross tumour volume (GTV) and for the visualization of heterogeneous tumour biology. We will discuss the role of fluorodeoxyglucose-PET in lung and head and neck cancer and the impact of amino acids (AA)-PET in target volume delineation of brain gliomas. Furthermore, we summarize the data of the literature about tumour hypoxia and proliferation visualized by PET. We conclude that, regarding treatment planning in radiotherapy, PET offers advantages in terms of tumour delineation and the description of biological processes. However, to define the real impact of biological imaging on clinical outcome after radiotherapy, further experimental, clinical and cost/benefit analyses are required. (topical review)

  15. Tumor biology and cancer therapy – an evolving relationship

    OpenAIRE

    Lother Ulrike; Krndija Denis; Ahn Johann; Seufferlein Thomas; Adler Guido; von Wichert Götz

    2009-01-01

    Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pa...

  16. Immune reconstitution inflammatory syndrome associated with biologic therapy.

    Science.gov (United States)

    Gupta, Malika; Jafri, Kashif; Sharim, Rebecca; Silverman, Susanna; Sindher, Sayantani B; Shahane, Anupama; Kwan, Mildred

    2015-02-01

    The use of biologics in the treatment of autoimmune disease, cancer, and other immune conditions has revolutionized medical care in these areas. However, there are drawbacks to the use of these medications including increased susceptibility to opportunistic infections. One unforeseen risk once opportunistic infection has occurred with biologic use is the onset of immune reconstitution inflammatory syndrome (IRIS) upon drug withdrawal. Although originally described in human immunodeficiency virus (HIV) patients receiving highly active antiretroviral therapy, it has become clear that IRIS may occur when recovery of immune function follows opportunistic infection in the setting of previous immune compromise/suppression. In this review, we draw attention to this potential pitfall on the use of biologic drugs. PMID:25504263

  17. Recent advances in biological therapy for inflammatory bowel disease.

    Science.gov (United States)

    Kurtovic, Jelica; Segal, Isidor

    2004-01-01

    Immune system is a major determinant of pathophysiology of inflammatory bowel disease (IBD), and cytokines are well known mediators of immune system. Recently, informations on pro-inflammatory cytokines and their role in IBD have led to development of potential therapeutic approach to manipulate these cytokines and there by inhibiting inflammation in IBD. These therapeutic approaches include inhibitors of the tumour necrosis factor (TNF)-alpha lymphocyte trafficking, type 1 T helper (Th1) cell polarization and nuclear factor type beta; immunoregulatory cytokines and various growth factors. Studies on these therapies have documented variable results and the outcomes of many clinical trials are awaited. However, these potential therapies, if become real may revolutionise approach in patients with IBD. Analysis of the inflammed mucosa from patients with Crohn disease (CD) and ulcerative colitis (UC) have shown increased expression of certain proinflammatory cytokines such as interleukin-1 (IL-1), interleukin 6 (IL-6) and TNF-alpha. The latter is important in the recruitment of neutrophils into inflammed tissue, a process which results from three physiological steps: (i) rolling, (ii) adhesion, and (iii) transendothelial migration. Understanding of the biology of chronic inflammation has expanded the therapies available for IBD and particularly CD. At present, the biological therapies that are being used in clinical practice or investigated for the treatment of IBD are predominantly proteins, usually delivered intravenously or subcutaneously. The therapies used include: 1. TNF-alpha inhibitors: infliximab, CDP 571, etanercept, onercept, CNI- 1493 and thalidomide. 2. Inhibitors of lymphocyte trafficking: natalizumab, LPD-02 and ICAM-1. 3. Inhibitors of Th1 polarization: monoclonal antibodies for IL-12, interferon (IFN)-gamma and anti IFN-gamma. 4. Immunoregulatory cytokines: IL-10 and IL-11. 5. Inhibitors of nuclear factor kappa (beta NF-kbeta.) 6. Growth factors

  18. [Combination biological therapy for fistular Crohn's disease: clinical demonstration].

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Konoplyannikov, A G; Ruchkina, I N; Lischchinskaya, A A

    2014-01-01

    Perianal fistulas are the most common and frequently encountered types of fistulas in Crohn's disease (CD). They are incurable, may worsen quality of life in a patient and increase the risk of total bowel resection. Despite the significant impact of biological (anticytokine) therapy for fistular CD, treatment in this category of patients remains a difficult task with the high risk of recurrent CD. Mesenchymal stromal cells (MSCs) having immunomodulatory properties and a great regenerative potential are currently also used to treat fistulas in CD and perianal fistulas of another etiology. The given clinical case demonstrates that complete fistula healing could be achieved only after a few local administrations of MSCs in combination with infliximab and azathioprine. World and our experiences indicate that there is a need for randomized controlled trials with a sufficient number of patients to prove the efficacy of MSCs in the combination therapy of fistulas in CD. PMID:24772517

  19. 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.

  20. Genetically engineered biological agents in therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-10-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.

  1. Genetically engineered biological agents in therapy for systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-01-01

    Full Text Available Systemic lupus erythematosus (SLE is a prototype for chronic autoimmune disease. Its prevalence is 20 to 70 cases per 100,000 women and varies by race and ethnicity. Despite considerable progress in traditional therapy, many problems associated with the management of these patients need to be immediately solved: thus, 50-80% are found to have activity signs and/or frequent exacerbations and about 30% of the patients have to stop work; Class IV lupus nephritis increases the risk of terminalrenal failure. In the past 20 years great progress has been made in studying the pathogenesis of SLE: biological targets to affect drugs have been sought and fundamentally new therapeutic goals defined. Belimumab is the first genetically biological agent specially designed to treat SLE, which is rightly regarded as one of the most important achievements of rheumatology in the past 50 years.

  2. Local therapy, systemic benefit: challenging the paradigm of biological predeterminism.

    Science.gov (United States)

    Kurtz, J M

    2006-04-01

    This paper briefly reviews the historical evolution of paradigms that have been purported to characterise the clinical behaviour of breast cancer, with the intention of guiding treatment approaches. Results from randomised clinical trials and the explosion of knowledge in the area of cancer biology have discredited the monolithic paradigms that had dominated thinking about breast cancer in the past. Contemporary notions of breast cancer biology recognise that, although some cancers disseminate well before becoming clinically detectable, acquisition of a metastatic phenotype can occur at any point (or not at all) in the local evolution of the tumour. As a consequence, both systemic and timely local--regional therapies can be expected to influence disease dissemination and patient survival. This is consistent with results observed in clinical trials, overviews of which indicate that prevention of four local recurrences will, on the average, prevent one death from breast cancer. Optimisation of local-regional treatment is an important goal in breast cancer management. PMID:16605046

  3. Negative Pressure Wound Therapy. Therapy Settings and Biological Effects in Peripheral Wounds

    OpenAIRE

    Borgquist, Ola

    2013-01-01

    Negative pressure wound therapy (NPWT) promotes wound healing through several mechanisms, e.g., altered periwound blood flow, mechanical deformation of the wound edge tissue, and drainage of excess fluid and debris. The general aim of this thesis was to study the impact of different levels of negative pressure, different wound filling materials (foam or gauze), and different ways of applying the negative pressure (continuously, intermittently or variably) on the biological effects of NPWT in ...

  4. Potential of biological images for radiation therapy of cancer

    International Nuclear Information System (INIS)

    Full text: Recent technical advances in 3D conformal and intensity modulated radiotherapy (3DCRT and IMRT) based, on patient-specific CT and MRI images, have the potential of delivering exquisitely conformal dose distributions to the target volume while avoiding critical structures. Emerging clinical results in terms of reducing treatment-related morbidity and increasing local control appear promising. Recent developments in imaging have suggested that biological images may further positively impact cancer diagnosis, characterization and therapy. While in the past radiological images are largely anatomical, the new types of images can provide metabolic, biochemical, physiological, functional and molecular (genotypic and phenotypic) information. For radiation therapy, images that give information about factors (e.g. tumor hypoxia, Tpot) that influence radiosensitivity and treatment outcome can be regarded as radiobiological images. The ability of IMRT to 'paint' (in 2D) or 'sculpt' (in 3D) the dose, and produce exquisitely conformal dose distributions begs the '64 million dollar question' as to how to paint or sculpt, and whether biological imaging may provide the pertinent information. Can this new approach provide 'radiobiological phenotypes' non-invasively, and incrementally improve upon the predictive assays of radiobiological characteristics such as proliferative activity (Tpot - the potential doubling time), radiosensitivity (SF2 - the surviving fraction at a dose of 2 Gy), energy status (relative to sublethal damage repair), pH (a possible surrogate of hypoxia), tumor hypoxia, etc. as prognosticator(s) of radiation treatment outcome. Important for IMRT, the spatial (geometrical) distribution of the radiobiological phenotypes provide the basis for dose distribution design to conform to both the physical (geometrical) and the biological attributes. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

  5. Low Level Laser Therapy: laser radiation absorption in biological tissues

    Science.gov (United States)

    Di Giacomo, Paola; Orlando, Stefano; Dell'Ariccia, Marco; Brandimarte, Bruno

    2013-07-01

    In this paper we report the results of an experimental study in which we have measured the transmitted laser radiation through dead biological tissues of various animals (chicken, adult and young bovine, pig) in order to evaluate the maximum thickness through which the power density could still produce a reparative cellular effect. In our experiments we have utilized a pulsed laser IRL1 ISO model (based on an infrared diode GaAs, λ=904 nm) produced by BIOMEDICA s.r.l. commonly used in Low Level Laser Therapy. Some of the laser characteristics have been accurately studied and reported in this paper. The transmission results suggest that even with tissue thicknesses of several centimeters the power density is still sufficient to produce a cell reparative effect.

  6. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    Directory of Open Access Journals (Sweden)

    A Patel

    2009-02-01

    Full Text Available Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the effects of inflammatory reactions on stem cells and extrapolate on information pertaining to cancer biology. The discussion focuses on integrins and cytokines, and identifies the transcription factor, nuclear factor-kappa B (NFκB as central to the inflammatory response. Since stem cell therapy has been proposed for type II diabetes mellitus, metabolic syndrome, pulmonary edema, these disorders are used as examples to discuss the roles of inflammatory mediators. We propose prospects for future research on targeting the NFκB signaling pathway. Finally, we explore the bridge between inflammation and stem cells, including neural stem cells and adult stem cells from the bone marrow. The implications of mesenchymal stem cells in regenerative medicine as pertaining to inflammation are vast based on their anti-inflammatory and immunosuppressive effects. Such features of stem cells offer great potential for therapy in graft-versus-host disease, conditions with a significant inflammatory component, and tissue regeneration.Keywords: mesenchymal stem cells, cancer, cytokines

  7. Biological basis of combination therapy with radiation and bleomycin

    International Nuclear Information System (INIS)

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C2W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C2W cells were irradiated, incubated at 370C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

  8. Biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy

    International Nuclear Information System (INIS)

    Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) photon and kilovoltage (kV) photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage photons caused the highest enhancement due to the high interaction probability between GNPs and kV photons. The cell survival fraction can be significantly reduced for both proton and MV photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus. (paper)

  9. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  10. Biologic therapy and tuberculosis: our experience and review of literature

    Directory of Open Access Journals (Sweden)

    Fabroni C

    2013-07-01

    Full Text Available Caterina Fabroni,1 Angelo Massimiliano D’Erme,2 Torello Lotti3 1Department of Dermatology, Misericordia e Dolce Hospital, Prato, Italy; 2Division of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy; 3Guglielmo Marconi University, Rome, Italy Abstract: Psoriasis is an inflammatory dermatologic disease that can often involve not only the skin and mucosal surfaces but also the bones and joints. It affects approximately 3% of the world’s population, and has a chronic-relapsing course. The management of psoriasis is often difficult and, particularly in the case of moderate to severe forms, the use of systemic therapies is mandatory. The introduction of biologic drugs has greatly improved our ability to treat psoriasis. However, it is necessary to underline that antitumor necrosis factor-α treatments may reactivate latent tuberculosis infection and cause particularly disseminated or extrapulmonary disease. Physicians should carry out proper screening of patients before starting treatment with antitumor necrosis factor-α, in order to identify individuals with latent tuberculosis infection. We report our experience in this field and review the various existing tests to screen for tuberculosis. Keywords: infliximab, adalimumab, tuberculosis, psoriasis

  11. Drug-Encoded Biomarkers for Monitoring Biological Therapies.

    Science.gov (United States)

    Tsoneva, Desislava; Stritzker, Jochen; Bedenk, Kristina; Zhang, Qian; Frentzen, Alexa; Cappello, Joseph; Fischer, Utz; Szalay, Aladar A

    2015-01-01

    Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers. PMID:26348361

  12. Biological Therapies for Rheumatoid Arthritis : Progress to Date

    NARCIS (Netherlands)

    Malviya, Gaurav; Salemi, Simonetta; Lagana, Bruno; Diamanti, Andrea Picchianti; D'Amelio, Raffaele; Signore, Alberto

    2013-01-01

    Biologic drugs for the management of rheumatoid arthritis (RA) have revolutionized the therapeutic armamentarium with the development of several novel monoclonal antibodies, which include murine, chimeric, humanized, fully human antibodies and fusion proteins. These biologics bind to their targets w

  13. Biologic therapy improves psoriasis by decreasing the activity of monocytes and neutrophils.

    Science.gov (United States)

    Yamanaka, Keiichi; Umezawa, Yoshinori; Yamagiwa, Akisa; Saeki, Hidehisa; Kondo, Makoto; Gabazza, Esteban C; Nakagawa, Hidemi; Mizutani, Hitoshi

    2014-08-01

    Therapy with monoclonal antibodies to tumor necrosis factor (TNF)-α and the interleukin (IL)-12/23 p40 subunit has significantly improved the clinical outcome of patients with psoriasis. These antibodies inhibit the effects of the target cytokines and thus the major concern during their use is the induction of excessive immunosuppression. Recent studies evaluating the long-term efficacy and safety of biologic therapy in psoriasis have shown no significant appearance of serious adverse effects including infections and malignancies. However, the immunological consequence and the mechanism by which the blockade of a single cytokine by biologics can successfully control the activity of psoriasis remain unclear. In the current study, we investigated the effect of biologic therapy on cytokine production of various lymphocytes and on the activity of monocytes and neutrophils in psoriatic patients. Neutrophils, monocytes and T cells were purified from heparinized peripheral venous blood by Ficoll density gradient centrifugation, and γ-interferon, TNF-α and IL-17 production from lymphocytes was measured by flow cytometer. The activation maker of neutrophils and the activated subsets of monocytes were also analyzed. Biologic therapy induced no significant changes in the cytokine production by lymphocytes from the skin and gut-homing T cells. However, neutrophil activity and the ratio of activated monocyte population increased in severely psoriatic patients were normalized in psoriatic patients receiving biologic therapy. The present study showed that biologic therapy ameliorates clinical symptoms and controls the immune response in patients with psoriasis. PMID:25099154

  14. Biological Effectiveness and Application of Heavy Ions in Radiation Therapy Described by a Physical and Biological Model

    DEFF Research Database (Denmark)

    Olsen, Kjeld J.; Hansen, Johnny W.

    A description is given of the physical basis for applying track structure theory in the determination of the effectiveness of heavy-ion irradiation of single- and multi-hit target systems. It will be shown that for applying the theory to biological systems the effectiveness of heavy-ion irradiation......-LET radiation applied simultaneously in therapy....

  15. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

    Full Text Available Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control meets the standard management of patients in biological therapy. Results. The study shows that in the case of the resistance progressing when applying preparations of biological therapy, methotrexate is useful at a dose of 15-20mg/week for up to 6 months. The combined use of biologic therapy and methotrexate in the treatment of patients with psoriasis vulgaris, "escape effect" contributes to the marked regression of clinical symptoms and allows to control the process long enough, which is confirmed by the dynamics of the index PASI, BRS and DLQI. The combined method is highly safe, as evidenced by the lack of inhibition of hematopoiesis, the normal level of hepatic transaminases and serum creatinine, which greatly improves patient compliance in this type of therapy. Conclusion. The article presents the data of the combined application of biological medication therapy (ustekinumab and methotrexate for the treatment of patients with the common form of psoriasis vulgaris. In the case of the development of resistance of biological therapy recommended the appointment of methotrexate. The combined use of methotrexate and biologic therapy in the treatment of patients with psoriasis vulgaris contributes to marked regression of clinical symptoms and allows to control the process for a long time.

  16. Medical and biological requirements for boron neutron capture therapy

    International Nuclear Information System (INIS)

    In conventional radiation therapy, tumor doses applied to most solid tumors are limited by the tolerance of normal tissues. The promise of Boron Neutron Capture Therapy lies in its potential to deposit high doses of radiation very specifically to tumor tissue. Theoretically ratios of tumor to normal tissue doses can be achieved significantly higher than conventional radiotherapeutic techniques would allow. Effective dose distributions obtainable are a complex function of the neutron beam characteristics and the macro and micro distributions of boron in tumor and normal tissues. Effective RBE doses are calculated in tumors and normal tissue for thermal, epithermal and 2 keV neutrons

  17. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    OpenAIRE

    Sinuhe eHahn

    2015-01-01

    It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells...

  18. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    OpenAIRE

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem c...

  19. Tutorial in oral antithrombotic therapy: Biology and dental implications

    OpenAIRE

    Fakhri, Hamid Reza; Janket, Sok Ja; Jackson, Elizabeth A.; Baird, Alison E; Dinnocenzo, Richard; Meurman, Jukka H

    2013-01-01

    Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants. Method: We searched Medline using search terms “antithrombotic”, “antihemostasis” ...

  20. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    OpenAIRE

    Patel, Shyam A; Heinrich, Andrew C; Bobby Y. Reddy; Rameshwar, Pranela

    2009-01-01

    Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide array of biological processes. Recently, there has been an upsurge of interest in the interactions between mediators of inflammation and other cells such as stem cells and cancer cells. Since tissue injuries are associated with the release of inflammatory mediators, it would be difficult to address this subject without considering the implications of their systemic effects. In this review, we discuss the ef...

  1. Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy

    OpenAIRE

    de Bolle, Leen; Naesens, Lieve; De Clercq, Erik

    2005-01-01

    Human herpesvirus 6 (HHV-6) is a betaherpesvirus that is closely related to human cytomegalovirus. It was discovered in 1986, and HHV-6 literature has expanded considerably in the past 10 years. We here present an up-to-date and complete overview of the recent developments concerning HHV-6 biological features, clinical associations, and therapeutic approaches. HHV-6 gene expression regulation and gene products have been systematically characterized, and the multiple interactions between HHV-6...

  2. Macroscopic Biological Characteristics of Individualized Therapy in Chinese Mongolian Osteopathy

    Science.gov (United States)

    Namula, Zhao; Mei, Wang; Li, Xue-en

    Objective: Chinese Mongolian osteopathy has been passed down from ancient times and includes unique practices and favorable efficacy. In this study, we investigate the macroscopic biological characteristics of individualized Chinese Mongolian osteopathy, in order to provide new principle and methods for the treatment of bone fracture. Method: With a view to provide a vital link between nature and humans, the four stages of Chinese Mongolian osteopathy focus on the unity of the mind and body, the limbs and body organs, the body and its functions, and humans and nature. Results: We discuss the merits of individualized osteopathy in terms of the underlying concepts, and evaluate the approaches and principles of traditional medicine, as well as biomechanics. Conclusions: Individualized Mongolian osteopathy targets macroscopic biological components including dynamic reduction, natural fixation, and functional healing. Chinese Mongolian osteopathy is a natural, ecological and non-invasive osteopathy that values the link between nature and humans, including the unity of mind and body. The biological components not only serve as a foundation for Chinese Mongolian osteopathy but are also important for the future development of modern osteopathy, focusing on individualization, actualization and integration.

  3. Biological therapies for psoriasis: Adherence and outcome analysis from a clinical perspective.

    Science.gov (United States)

    Ross, Christopher; Marshman, Gillian; Grillo, Marianne; Stanford, Tyman

    2016-05-01

    We evaluated and compared patients' long-term adherence to biological therapies in a real-life clinical setting. Secondary aims included weight changes on biological therapy and reporting adverse effects. This prospective case-note review included 58 patients, undergoing 84 treatment series including etanercept (21), adalimumab (24), infliximab (14) and ustekinumab (25). Patients' adherence was greatest with ustekinumab (being 6.7-fold less likely to withdraw from treatment than etanercept, P = 0.014), while the difference in treatment adherence of adalimumab and infliximab compared to etanercept was not statistically significant. Adalimumab and infliximab were associated with an increase in weight, while ustekinumab was associated with weight loss compared with etanercept (not statistically significant). Long-term patient adherence to biologic therapy in patients with psoriasis is greatest with ustekinumab. PMID:25754697

  4. Preeclampsia – will Orphan Drug Status facilitate innovative biological therapies?

    Directory of Open Access Journals (Sweden)

    Sinuhe eHahn

    2015-02-01

    Full Text Available It is generally accepted that development of novel therapies to treat pregnancy-relates disorders, such as preeclampsia, is hampered to the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder, exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia be accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture which relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in angiogenic growth factors, complement activation, reduced levels of placenta protein 13 or excessive neutrophil activation evident in preeclampsia.

  5. Preeclampsia – Will Orphan Drug Status Facilitate Innovative Biological Therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

  6. Preeclampsia - will orphan drug status facilitate innovative biological therapies?

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

    It is generally accepted that the development of novel therapies to treat pregnancy-related disorders, such as preeclampsia, is hampered by the paucity of research funding. Hence, it is with great interest to become aware of at least three novel therapeutic approaches for the treatment of this disorder: exploiting either the anticoagulant activity of antithrombin, the free radical scavenging activity of alpha-1-microglobulin, or the regenerative capacity of placenta-derived mesenchymal stem cells. As these projects are being carried out by small biotech enterprises, the question arises of how they are able to fund such undertakings. A novel strategy adopted by two of these companies is that they successfully petitioned US and EU agencies in order that preeclampsia is accepted in the register of rare or orphan diseases. This provides a number of benefits including market exclusivity, assistance with clinical trials, and dedicated funding schemes. Other strategies to supplement meager research funds, especially to test novel approaches, could be crowdfunding, a venture that relies on intimate interaction with advocacy groups. In other words, preeclampsia meets Facebook. Perhaps similar strategies can be adopted to examine novel therapies targeting either the imbalance in pro- or anti-angiogenic growth factors, complement activation, reduced levels of placenta protein 13, or excessive neutrophil activation evident in preeclampsia. PMID:25767802

  7. Biologic therapy with anti-TNFa in rheumathoid atrhritis

    Directory of Open Access Journals (Sweden)

    G. Ferraccioli

    2011-09-01

    Full Text Available Objective: To evaluate the efficacy, the tolerability, and treatment survival of the association of anti-TNFa (Infliximab, Etanercept, Adalimumab plus Methotrexate vs Methotrexate as monotherapy in patients with reumathoid arthritis (RA. Methods: Review of published controlled randomized clinical studies on the association of anti-TNFa plus Methotrexate vs Methotrexate alone in patients with rheumathoid arthritis (RA. Results in terms of remission and progression of radiologic damage, and clinical response expressed in terms of ACR 50 or ACR 70 were reviewed in the different studies. Results: In patients with RA the association of anti-TNFa plus Methotrexate led to a greater remission of radiologic damage and marked improvement of clinical response expressed as ACR 50 or ACR 70 compared to therapy with Methotrexate only. Conclusions: In the absence of controlled studies, review of the published studies showed that in RA patients the association of anti-TNFa plus Methotrexate is extremely more efficacious than therapy with Methotrexate only. Choice of the drug depends on the activity of the disease, the necessity of a fast response, the presence of side effects, the schedule of treatment and consequently the direct and indirect costs of the drug, and the easiness on supply and distribution.

  8. Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

    OpenAIRE

    Alexey Verkhovtsev; Eugene Surdutovich; Solov’yov, Andrey V.

    2016-01-01

    Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects rela...

  9. Mesenchymal stem cells: cell biology and potential use in therapy

    DEFF Research Database (Denmark)

    Kassem, Moustapha; Kristiansen, Malthe; Abdallah, Basem M

    2004-01-01

    Mesenchymal stem cells are clonogenic, non-haematopoietic stem cells present in the bone marrow and are able to differentiate into multiple mesoderm-type cell lineages e.g. osteoblasts, chondrocytes, endothelial-cells and also non-mesoderm-type lineages e.g. neuronal-like cells. Several methods...... are currently available for isolation of the mesenchymal stem cells based on their physical and immunological characteristics. Because of the ease of their isolation and their extensive differentiation potential, mesenchymal stem cells are among the first stem cell types to be introduced in the clinic. Recent...... studies have demonstrated that the life span of mesenchymal stem cells in vitro can be extended by increasing the levels of telomerase expression in the cells and thus allowing culture of large number of cells needed for therapy. In addition, it has been shown that it is possible to culture the cells...

  10. Microbeam radiation therapy. Physical and biological aspects of a new cancer therapy and development of a treatment planning system

    International Nuclear Information System (INIS)

    Microbeam Radiation Therapy (MRT) is a novel treatment strategy against cancer. Highly brilliant synchrotron radiation is collimated to parallel, a few micrometre wide, planar beams and used to irradiate malignant tissues with high doses. The applied peak doses are considerably higher than in conventional radiotherapy, but valley doses between the beams remain underneath the established tissue tolerance. Previous research has shown that these beam geometries spare normal tissue, while being effective in tumour ablation. In this work physical and biological aspects of the therapy were investigated. A therapy planning system was developed for the first clinical treatments at the European Synchrotron Radiation Facility in Grenoble (France) and a dosimetry method based on radiochromic films was created to validate planned doses with measurements on a micrometre scale. Finally, experiments were carried out on a cellular level in order to correlate the physically planned doses with the biological damage caused in the tissue. The differences between Monte Carlo dose and dosimetry are less than 10% in the valley and 5% in the peak regions. Developed alternative faster dose calculation methods deviate from the computational intensive MC simulations by less than 15% and are able to determine the dose within a few minutes. The experiments in cell biology revealed an significant influence of intercellular signalling on the survival of cells close to radiation boundaries. These observations may not only be important for MRT but also for conventional radiotherapy.

  11. Microbeam radiation therapy. Physical and biological aspects of a new cancer therapy and development of a treatment planning system

    Energy Technology Data Exchange (ETDEWEB)

    Bartzsch, Stefan

    2014-11-05

    Microbeam Radiation Therapy (MRT) is a novel treatment strategy against cancer. Highly brilliant synchrotron radiation is collimated to parallel, a few micrometre wide, planar beams and used to irradiate malignant tissues with high doses. The applied peak doses are considerably higher than in conventional radiotherapy, but valley doses between the beams remain underneath the established tissue tolerance. Previous research has shown that these beam geometries spare normal tissue, while being effective in tumour ablation. In this work physical and biological aspects of the therapy were investigated. A therapy planning system was developed for the first clinical treatments at the European Synchrotron Radiation Facility in Grenoble (France) and a dosimetry method based on radiochromic films was created to validate planned doses with measurements on a micrometre scale. Finally, experiments were carried out on a cellular level in order to correlate the physically planned doses with the biological damage caused in the tissue. The differences between Monte Carlo dose and dosimetry are less than 10% in the valley and 5% in the peak regions. Developed alternative faster dose calculation methods deviate from the computational intensive MC simulations by less than 15% and are able to determine the dose within a few minutes. The experiments in cell biology revealed an significant influence of intercellular signalling on the survival of cells close to radiation boundaries. These observations may not only be important for MRT but also for conventional radiotherapy.

  12. State of the art biological therapies in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one ofthe most lethal malignancies with a five-year survivalrate of approximately 5%. Several target agents havebeen tested in PDAC, but almost all have failed todemonstrate efficacy in late phase clinical trials, despitethe better understanding of PDAC molecular biologygenerated by large cancer sequencing initiatives in thepast decade. Eroltinib (a small-molecule tyrosine-kinaseinhibitor of epidermal growth factor receptor) plusgemcitabine is the only schedule with a biological agentapproved for advanced pancreatic cancer, but it hasresulted in a very modest survival benefit in unselectedpatients. In our work, we report a summary of the mainclinical trials (closed and ongoing) that refer to biologicaltherapy evaluation in pancreatic cancer treatment.

  13. Paediatric high and low grade glioma: the impact of tumour biology on current and future therapy.

    Science.gov (United States)

    Hargrave, Darren

    2009-08-01

    Gliomas are the most common type of paediatric brain tumour and range from benign low grade gliomas which can be resected/observed to aggressive brainstem gliomas with dismal survival rates. Current therapies rely on neurosurgery, radiotherapy, chemotherapy or combination of these conventional modalities and although histopathology helps to direct therapy, molecular pathology has so far not played a major role in the management of paediatric glioma. However, increasing knowledge of glioma biology is starting to impact on drug development towards targeted therapies. Pilocytic astrocytoma, the most common childhood low grade brain tumour, has recently been shown to harbour an activated BRAF/MAPK/ERK pathway in the majority of cases; this represents an attractive target for new agents. The molecular biology of adult malignant glioma is now well described and targeted therapies against VEGFR are already playing a role in the management of glioblastoma. It is likely that high grade gliomas in children and adults share common aberrant molecular pathways but the frequency and mechanisms involved probably will exhibit key differences and on-going comprehensive molecular analyses of paediatric high grade glioma are essential to determine which targets are important in children. However, selection for specific targeted therapy is unlikely to be based on, or restricted by, age but will require individual case by case testing for target presence in order to direct and maximise the efficacy of molecular therapy. Brainstem glioma remains a tumour with a dismal prognosis but relatively little is known about the underlying biology and progress will require a concerted effort to collect tissue by biopsy and autopsy to allow appropriate analysis to identify and validate targets. A new era of molecular based therapies offers the promise of major benefits in the management of paediatric glioma but translating this promise into reality will require further understanding of the biology

  14. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O2 and H2O2) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  15. Ribonucleotide reductase and cancer: biological mechanisms and targeted therapies.

    Science.gov (United States)

    Aye, Y; Li, M; Long, M J C; Weiss, R S

    2015-04-16

    Accurate DNA replication and repair is essential for proper development, growth and tumor-free survival in all multicellular organisms. A key requirement for the maintenance of genomic integrity is the availability of adequate and balanced pools of deoxyribonucleoside triphosphates (dNTPs), the building blocks of DNA. Notably, dNTP pool alterations lead to genomic instability and have been linked to multiple human diseases, including mitochondrial disorders, susceptibility to viral infection and cancer. In this review, we discuss how a key regulator of dNTP biosynthesis in mammals, the enzyme ribonucleotide reductase (RNR), impacts cancer susceptibility and serves as a target for anti-cancer therapies. Because RNR-regulated dNTP production can influence DNA replication fidelity while also supporting genome-protecting DNA repair, RNR has complex and stage-specific roles in carcinogenesis. Nevertheless, cancer cells are dependent on RNR for de novo dNTP biosynthesis. Therefore, elevated RNR expression is a characteristic of many cancers, and an array of mechanistically distinct RNR inhibitors serve as effective agents for cancer treatment. The dNTP metabolism machinery, including RNR, has been exploited for therapeutic benefit for decades and remains an important target for cancer drug development. PMID:24909171

  16. Update on Biologic Therapies for Systemic Lupus Erythematosus.

    Science.gov (United States)

    Borba, Helena Hiemisch Lobo; Funke, Andreas; Wiens, Astrid; Utiyama, Shirley Ramos da Rosa; Perlin, Cássio Marques; Pontarolo, Roberto

    2016-07-01

    Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible. PMID:27299782

  17. Natural Killer Cells: Biology and Clinical Use in Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    William H. D. Hallett; William J. Murphy

    2004-01-01

    Natural killer (NK) cells have the ability to mediate both bone marrow rejection and promote engraftment, as well as the ability to elicit potent anti-tumor effects. However the clinical results for these processes are still elusive. Greater understanding of NK cell biology, from activating and inhibitory receptor functions to the role of NK cells in allogeneic transplantation, needs to be appreciated in order to draw out the clinical potential of NK cells. Mechanisms of bone marrow cell (BMC) rejection are known to be dependant on inhibitory receptors specific for major histocompatibility complex (MHC) molecules and on activating receptors that have many potential ligands. The modulation of activating and inhibitory receptors may hold the key to clinical success involving NK cells. Pre-clinical studies in mice have shown that different combinations of activating and inhibitory receptors on NK cells can reduce graft-versus-host disease (GVHD), promote engraftment, and provide superior graft-versus-tumor (GVT) responses. Recent clinical data have shown that the use of KIR-ligand incompatibility produces tremendous graft-versus-leukemia effect in patients with acute myeloid leukemia at high risk of relapse. This review will attempt to be a synthesis of current knowledge concerning NK cells, their involvement in BMT, and their use as an immunotherapy for cancer and other hematologic malignancies. Cellular & Molecular Immunology. 2004;1(1):12-21.

  18. Tutorial in oral antithrombotic therapy: Biology and dental implications

    Science.gov (United States)

    Fakhri, Hamid R.; Janket, Sok J.; Baird, Alison E.; Dinnocenzo, Richard; Meurman, Jukka H.

    2013-01-01

    Objectives: Recent developments of new direct oral anticoagulants that target specific clotting factors necessitate understanding of coagulation biology. The objective of this tutorial is to offer dental professionals a review of coagulation mechanisms and the pharmacodynamics of the conventional and new oral anticoagulants. Also, we summarized the dental implications of the conventional and new anticoagulants. Method: We searched Medline using search terms “antithrombotic”, “antihemostasis” or “anticoagulation” and combined them with the search results of “dental”, “oral surgery” or “periodontal”. We restricted the results to “human” and “English”. Results: The early coagulation cascade, the new cell-based coagulation model, the pharmacokinetics and pharmacodynamics of conventional antithrombotics, and new oral anticoagulants were reviewed. The new direct factor Xa inhibitors and the direct thrombin inhibitor (s), called direct oral anticoagulants (DOAs) have rapid onset of action, fast elimination on cessation, and fewer drug-drug or drug-food interactions than warfarin. However, the lack of antidotes raises concerns that some dental procedures may trigger serious hemorrhagic events. Additionally, careful perioperative withdrawal and resumption protocols for the DOAs are reviewed, because DOAs’ blood levels are dependent on renal function. Also, various reversal strategies in the event of excessive bleedings are summarized. Perioperative management of dental patients taking new DOAs and conventional oral anticoagulants are also discussed. However, the perioperative strategies for DOAs are yet to be validated in randomized trials. Key words:Coagulation cascade, cell-based coagulation model, factor Xa inhibitors, direct thrombin inhibitors, prothrombin complex concentrates. PMID:23524440

  19. Waldenström macroglobulinemia: biology, genetics, and therapy

    Directory of Open Access Journals (Sweden)

    Paludo J

    2016-07-01

    Full Text Available Jonas Paludo,1,2 Stephen M Ansell,1 1Division of Hematology, 2Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Waldenström macroglobulinemia (WM is a distinct clinicopathologic entity characterized by the presence of a lymphoplasmacytic lymphoma, a non-Hodgkin lymphoma, and IgM monoclonal gammopathy. WM is an indolent, uncommon malignancy mostly affecting the elderly. Patient outcomes have modestly improved since the introduction of rituximab to conventional cytotoxic chemotherapy more than 20 years ago. However, the pivotal discovery of the somatic MYD88 L265P mutation, harbored by most patients with WM, and the somatic CXCR4 WHIM mutations, similar to germline CXCR4 mutations seen in the warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis (WHIM syndrome, present in approximately one-third of patients with WM, has fundamentally changed our understanding of this disease and expanded the potential therapeutic targets. Within this new paradigm, ibrutinib emerged as a promising new drug. Ibrutinib targets Bruton’s tyrosine kinase, a downstream protein in the B-cell receptor pathway that is overactivated by the MYD88 L265P mutation. A seminal Phase II trial of ibrutinib in previously treated WM patients showed impressive response rates and confirmed the effects of MYD88 L265P and CXCR4 WHIM mutations in response to therapy. Ibrutinib is the first and only US Food and Drug Administration–approved drug specifically for the treatment of WM. However, before ibrutinib can be established as the standard of care for WM, long-term data regarding efficacy and safety are required. Further research to address ibrutinib resistance and cost-effectiveness is also imperative before ibrutinib can gain widespread acceptance. This review will cover the present pathophysiologic understanding of WM in light of the recent MYD88 and CXCR4 discovery, as well as current and emergent treatment regimens with focus on ibrutinib

  20. Risk of infection with biologic antirheumatic therapies in patients with rheumatoid arthritis.

    Science.gov (United States)

    Lahiri, Manjari; Dixon, William G

    2015-04-01

    There are currently 10 licensed biologic therapies for the treatment of rheumatoid arthritis in 2014. In this article, we review the risk of serious infection (SI) for biologic therapies. This risk has been closely studied over the last 15 years within randomised controlled trials, long-term extension studies and observational drug registers, especially for the first three antitumour necrosis factor (TNF) drugs, namely infliximab, etanercept and adalimumab. The risk of SI with the newer biologics rituximab, tocilizumab, abatacept and tofacitinib is also reviewed, although further data from long-term observational studies are awaited. Beyond all-site SI, we review the risk of tuberculosis, other opportunistic infections and herpes zoster, and the effect of screening on TB rates. Lastly, we review emerging opportunities for stratifying the risk. Patients can be risk-stratified based on both modifiable and non-modifiable patient characteristics such as age, co-morbidity, glucocorticoid use, functional status and recent previous SI. PMID:26362745

  1. Superheroes in autoimmune warfare: biologic therapies in current South African practice.

    Science.gov (United States)

    Tarr, G; Hodkinson, B; Reuter, H

    2014-11-01

    Biologic drugs targeting immune cells or cytokines underlying systemic inflammation have dramatically improved outcomes in patients with rheumatological and autoimmune diseases. Nine biologic drugs are currently available in South Africa (SA)--all showing good efficacy and safety profiles. Their high cost and potential adverse events preclude them from being used as first-line agents. They are therefore indicated for severe disease refractory to standard therapies, and their use must be initiated by a specialist. The most important adverse effect of this class of drugs is infection and, in SA, tuberculosis is of particular concern. As new targets in the immune system are identified, new biologics will be developed. The current challenges are to optimise standard care for all patients with autoimmune diseases, and to offer the appropriate biologic to patients with refractory disease. PMID:25909121

  2. Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review

    International Nuclear Information System (INIS)

    The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

  3. Biological therapy in inflammatory bowel diseases: access in Central and Eastern Europe.

    Science.gov (United States)

    Rencz, Fanni; Péntek, Márta; Bortlik, Martin; Zagorowicz, Edyta; Hlavaty, Tibor; Śliwczyński, Andrzej; Diculescu, Mihai M; Kupcinskas, Limas; Gecse, Krisztina B; Gulácsi, László; Lakatos, Peter L

    2015-02-14

    Biological drugs opened up new horizons in the management of inflammatory bowel diseases (IBD). This study focuses on access to biological therapy in IBD patients across 9 selected Central and Eastern European (CEE) countries, namely Bulgaria, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania and Slovakia. Literature data on the epidemiology and disease burden of IBD in CEE countries was systematically reviewed. Moreover, we provide an estimation on prevalence of IBD as well as biological treatment rates. In all countries with the exception of Romania, lower biological treatment rates were observed in ulcerative colitis (UC) compared to Crohn's disease despite the higher prevalence of UC. Great heterogeneity (up to 96-fold) was found in access to biologicals across the CEE countries. Poland, Bulgaria, Romania and the Baltic States are lagging behind Hungary, Slovakia and the Czech Republic in their access to biologicals. Variations of reimbursement policy may be one of the factors explaining the differences to a certain extent in Bulgaria, Latvia, Lithuania, and Poland, but association with other possible determinants (differences in prevalence and incidence, price of biologicals, total expenditure on health, geographical access, and cost-effectiveness results) was not proven. We assume, nevertheless, that health deterioration linked to IBD might be valued differently against other systemic inflammatory conditions in distinct countries and which may contribute to the immense diversity in the utilization of biological drugs for IBD. In conclusion, access to biologicals varies widely among CEE countries and this difference cannot be explained by epidemiological factors, drug prices or total health expenditure. Changes in reimbursement policy could contribute to better access to biologicals in some countries. PMID:25684937

  4. Screening prior to biological therapy in Crohn's disease : Adherence to guidelines and prevalence of infections. Results from a multicentre retrospective study

    NARCIS (Netherlands)

    van der Have, Mike; Belderbos, Tim D. G.; Fidder, Herma H.; Leenders, Max; Dijkstra, Gerard; Peters, Charlotte P.; Eshuis, Emma J.; Ponsioen, Cyriel Y.; Siersema, Peter D.; van Oijen, Martijn G. H.; Oldenburg, Bas

    2014-01-01

    Background: Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. Aims: To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. Meth

  5. Biological effects of a disposable, canisterless negative pressure wound therapy system.

    OpenAIRE

    Malmsjö, Malin; Huddleston, Elizabeth; Martin, Robin

    2014-01-01

    Objective: Recent developments of negative pressure wound therapy (NPWT) systems have focused on making pumps smaller, lighter, and more portable. The recently introduced PICO system manages wound fluid through a highly breathable film within the dressing, thereby negating the need for a canister, which allows greater mobility and patient concordance. The aim of this study is to compare the biological effects of this system compared to a traditional NPWT system. Methods: Laboratory tests were...

  6. Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the adult and pediatric experiences

    OpenAIRE

    STOLL, MATTHEW L.; Gotte, Alisa C

    2008-01-01

    Matthew L Stoll, Alisa C GotteDepartment of Pediatrics, Division of Rheumatology, UT Southwestern Medical Center, Dallas, TX, USAAbstract: Biologics have advanced the therapy of adult and pediatric arthritis. They have been linked to rare serious adverse outcomes, but the actual risk of these events is controversial in adults, and largely unknown in pediatrics. Because of the paucity of safety and efficacy data in children, pediatric rheumatologists often rely on the adult literature. Herein,...

  7. Mind-body therapies and control of inflammatory biology: A descriptive review.

    Science.gov (United States)

    Bower, Julienne E; Irwin, Michael R

    2016-01-01

    The use of mind-body therapies, including Tai Chi, Qigong, yoga, and meditation, has grown steadily in recent years. These approaches have been shown to be effective in reducing symptoms and improving quality of life, and research has begun to examine the impact of these therapies on biological processes, including inflammation. A review of 26 randomized controlled trials was conducted to describe the effects of mind-body therapies (MBTs) on circulating, cellular, and genomic markers of inflammation. This qualitative evaluation showed mixed effects of MBTs on circulating inflammatory markers, including CRP and IL-6, and on measures of stimulated cytokine production. More consistent findings were seen for genomic markers, with trials showing decreased expression of inflammation-related genes and reduced signaling through the proinflammatory transcription factor NF-κB. Potential mechanisms for these effects are discussed, including alterations in neuroendocrine, neural, and psychological and behavioral processes. PMID:26116436

  8. EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects

    Energy Technology Data Exchange (ETDEWEB)

    Perez, Rolando, E-mail: rolando@cim.sld.cu; Moreno, Ernesto; Garrido, Greta; Crombet, Tania [Center of Molecular Immunology, P.O. Box 16040, Havana 11600 (Cuba)

    2011-04-18

    Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

  9. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    Energy Technology Data Exchange (ETDEWEB)

    Min, Jung Joon; Nguyen, Vu H. [Chonnam National University Medical School, Gwangju (Korea, Republic of); Gambhir, Sanjiv S. [Stanford University, California(United States)

    2010-04-15

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  10. Molecular Imaging of Biological Gene Delivery Vehicles for Targeted Cancer Therapy: Beyond Viral Vectors

    International Nuclear Information System (INIS)

    Cancer persists as one of the most devastating diseases in the world. Problems including metastasis and tumor resistance to chemotherapy and radiotherapy have seriously limited the therapeutic effects of present clinical treatments. To overcome these limitations, cancer gene therapy has been developed over the last two decades for a broad spectrum of applications, from gene replacement and knockdown to vaccination, each with different requirements for gene delivery. So far, a number of genes and delivery vectors have been investigated, and significant progress has been made with several gene therapy modalities in clinical trials. Viral vectors and synthetic liposomes have emerged as the vehicles of choice for many applications. However, both have limitations and risks that restrict gene therapy applications, including the complexity of production, limited packaging capacity, and unfavorable immunological features. While continuing to improve these vectors, it is important to investigate other options, particularly nonarrival biological agents such as bacteria, bacteriophages, and bacteria-like particles. Recently, many molecular imaging techniques for safe, repeated, and high-resolution in vivo imaging of gene expression have been employed to assess vector-mediated gene expression in living subjects. In this review, molecular imaging techniques for monitoring biological gene delivery vehicles are described, and the specific use of these methods at different steps is illustrated. Linking molecular imaging to gene therapy will eventually help to develop novel gene delivery vehicles for preclinical study and support the development of future human applications.

  11. TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

    Energy Technology Data Exchange (ETDEWEB)

    Orton, C [Wayne State University, Grosse Pointe, MI (United States); Borras, C [Radiological Physics and Health Services, Washington, DC (United States); Carlson, D [Yale University School of Medicine, New Haven, CT (United States)

    2014-06-15

    Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

  12. TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

    International Nuclear Information System (INIS)

    Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protection will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how

  13. Current Status of Biological Therapies for the Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Tang, Tianyi; Eldabaje, Robert; Yang, Lixi

    2016-07-01

    Compared to early-stage melanoma when surgical excision is possible, metastatic disease continues to offer a much grimmer prognosis as traditional chemotherapy treatment regimens offer relatively little survival benefit. This has led to changes in treatment approaches over the preceding two decades as contemporary methods for the treatment of advanced or metastatic melanoma now involve a number of biological modalities, which include immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. Clinically available immunotherapeutic agents include interleukin 2 (IL-2), as well as drugs targeting the important immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v-Raf murine sarcoma viral oncogene homolog B (BRAF), receptor tyrosine kinases, MEK inhibitors and potential future therapeutic targets, such as the CDK4/CDK6, PTEN and GNAQ/GNA11 genes. Additionally, an increasing understanding of the role of epigenetic alterations in the development and progression of melanoma now offers a new potential drug target. Several of these agents have shown promising results; however, in many investigations, combinations of different therapeutic approaches, each with different mechanisms of action, have yielded improved outcomes as treatment regimens continue to be further optimized by active research and patient disease sub-group analyses. This review summarizes the novel biological agents and new treatments, directly contributing to the significant improvement of biological therapies and markedly advancing knowledge of clinical application of newly approved and developed therapies in treatment of patients with metastatic melanoma. PMID:27354579

  14. Person-centred care in rheumatology nursing in patients undergoing biological therapy : An explorative and interventional study

    OpenAIRE

    Larsson, Ingrid

    2013-01-01

    Aim: The overall aim was to explore and evaluate rheumatology nursing from a person-centred care perspective in patients undergoing biological therapy. Methods: This thesis focuses on patients with chronic inflammatory arthritis (CIA) who were undergoing biological therapy at a rheumatology clinic in Sweden. Papers I and II had an explorative descriptive design with a phenomenographic approach. The 40 participants were interviewed about their dependence on or independence of a nurse for the a...

  15. Effect of biologic therapy on radiological progression in rheumatoid arthritis: what does it add to methotrexate?

    Directory of Open Access Journals (Sweden)

    Jones G

    2012-07-01

    Full Text Available Graeme Jones, Erica Darian-Smith, Michael Kwok, Tania WinzenbergMenzies Research Institute, University of Tasmania, Tasmania, AustraliaAbstract: There have been substantial advances in the treatment of rheumatoid arthritis in recent years. Traditional disease-modifying antirheumatic drugs (DMARDs have been shown to have small effects on the progression of radiographic damage. This quantitative overview summarizes the evidence for biologic DMARDS and radiographic damage either alone or in combination with methotrexate. Two outcomes were used (standardized mean difference and odds of progression. A total of 21 trials were identified of which 18 had useable data. For biologic monotherapy, tocilizumab, adalimumab, and etanercept were significantly better than methotrexate, with tocilizumab ranking first in both outcomes while golimumab was ineffective in both outcomes. For a biologic in combination with methotrexate compared with methotrexate alone, most therapies studied (etanercept, adalimumab, infliximab, certolizumab, tocilizumab, and rituximab were effective at slowing X-ray progression using either outcome, with infliximab ranking first in both outcomes. The exceptions to this were golimumab (no effect on standardized mean difference and abatacept (no effect on odds of progression. This effect was additional to methotrexate; thus, the overall benefit is moderate to large in magnitude, which is clearly of major clinical significance for sufferers of rheumatoid arthritis and supports the use of biologic DMARDs in those with a poor disease prognosis.Keywords: rheumatoid, trials, meta-analysis, radiographs, biologic, disease-modifying antirheumatic drugs, DMARDs

  16. [Rituximab (MabThera)--a new biological medicine in rheumatoid arthritis therapy].

    Science.gov (United States)

    Nemec, P

    2007-11-01

    Rheumatoid arthritis (RA) is a serious, chronic, inflammatory disorder that damages the joints. The chronic destructive process causes pain to patients with RA and leads to the development of permanent disability. At present, great emphasis is placed on timely and effective therapy for RA, which is able to halt or slow the development of the disorder. At present we do not have any means of curing RA, the main objective for treatment is to induce remission of the disorder and prevent structural damage to the joints and the development of permanent disability. The relatively frequent failure of disease modifying medications (DMARDs) lead to efforts to find new resources for the treatment of RA. So called biological medicines were recently introduced into therapeutic use. These were mainly TNFalpha blockers. Experience has shown that approximately a third of patients with RA do not respond even to treatment with such medicines. Rituximab (MabThera), a monoclonal antibody against CD20 positive B-lymphocytes, is a new biological medicine approved for RA therapy. It represents a new hope for patients with active RA, for whom earlier therapy with TNFa blockers has failed. PMID:18277630

  17. Multiscale approach predictions for biological outcomes in ion-beam cancer therapy

    Science.gov (United States)

    Verkhovtsev, Alexey; Surdutovich, Eugene; Solov’Yov, Andrey V.

    2016-06-01

    Ion-beam therapy provides advances in cancer treatment, offering the possibility of excellent dose localization and thus maximising cell-killing within the tumour. The full potential of such therapy can only be realised if the fundamental mechanisms leading to lethal cell damage under ion irradiation are well understood. The key question is whether it is possible to quantitatively predict macroscopic biological effects caused by ion radiation on the basis of physical and chemical effects related to the ion-medium interactions on a nanometre scale. We demonstrate that the phenomenon-based MultiScale Approach to the assessment of radiation damage with ions gives a positive answer to this question. We apply this approach to numerous experiments where survival curves were obtained for different cell lines and conditions. Contrary to other, in essence empirical methods for evaluation of macroscopic effects of ionising radiation, the MultiScale Approach predicts the biodamage based on the physical effects related to ionisation of the medium, transport of secondary particles, chemical interactions, thermo-mechanical pathways of biodamage, and heuristic biological criteria for cell survival. We anticipate this method to give great impetus to the practical improvement of ion-beam cancer therapy and the development of more efficient treatment protocols.

  18. Effectiveness of Biologic and Conventional Systemic Therapies in Adults with Chronic Plaque Psoriasis in Daily Practice: A Systematic Review.

    Science.gov (United States)

    Zweegers, Jeffrey; Otero, Marisol E; van den Reek, Juul M P A; van Lümig, Paula P; Driessen, Rieke J; Kievit, Wietske; Seyger, Marieke M B; van de Kerkhof, Peter C M; de Jong, Elke M G J

    2016-04-12

    The efficacy of biologic or conventional systemic therapies for psoriasis has been shown in randomized controlled trials. Effectiveness, however, has been studied in daily practice cohorts, and no aggregation of effectiveness data is available. This systematic review searched PubMed and EMBASE and summarized the real-world evidence on effectiveness of biologics (adalimumab, etanercept, infliximab and ustekinumab) and conventional systemic therapies (acitretin, cyclosporine, fumarates and methotrexate) for the treatment of plaque psoriasis in adults. Thirty-two studies were included. Few data were available on infliximab, ustekinumab and conventional systemics. Results show that biologics and conventional systemics were effective in real-life treatment of psoriasis, with large ranges in the percentage of patients reaching 75% improvement in psoriasis area and severity index score compared with baseline, especially for etanercept and adalimumab treatment. Combination therapies of biologics with conventional systemics, and dose adjustments of biologics were frequently applied strategies and may explain the large range in improvements between cohorts. PMID:26537336

  19. Effects of physical therapy for the management of patients with ankylosing spondylitis in the biological era.

    Science.gov (United States)

    Giannotti, Erika; Trainito, Sabina; Arioli, Giovanni; Rucco, Vincenzo; Masiero, Stefano

    2014-09-01

    Exercise is considered a fundamental tool for the management of ankylosing spondylitis (AS), in combination with pharmacological therapy that with the advent of biological therapy has improved dramatically the control of signs and symptoms of this challenging disease. Current evidence shows that a specific exercise protocol has not been validated yet. The purpose of this review is to update the most recent evidence (July 2010-November 2013) about physiotherapy in AS, analyzing the possible role and synergistic interactions between exercise and biological drugs. From 117 studies initially considered, only 15 were included in the review. The results support a multimodal approach, including educational sessions, conducted in a group setting, supervised by a physiotherapist and followed by a maintaining home-based regimen. Spa exercise and McKenzie, Heckscher, and Pilates methods seem promising in AS rehabilitation, but their effectiveness should be further investigated in future randomized controlled trials (RCTs). When performed in accordance with the American College of Sports Medicine guidelines, cardiovascular training has been proven safe and effective and should be included in AS rehabilitation protocols. Exercise training plays an important role in the biological era, being now applicable to stabilized patients, leading ultimately to a better management of AS by physiatrists and rheumatologists throughout the world. On the basis of the current evidence, further research should aim to determine which exercise protocols should be recommended. PMID:24797772

  20. Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

    International Nuclear Information System (INIS)

    The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

  1. Use of Biologic Agents in Combination with Other Therapies for the Treatment of Psoriasis

    OpenAIRE

    Cather, Jennifer C.; Crowley, Jeffrey J.

    2014-01-01

    Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient’s quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF...

  2. Biological Tests for Boron Neutron Capture Therapy Research at the TRIGA Mark II Reactor in Pavia

    Energy Technology Data Exchange (ETDEWEB)

    Protti, N.; Ballarini, F.; Bortolussi, S.; De Bari, A.; Stella, S.; Altieri, S. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Nuclear Physics National Institute (INFN), Pavia (Italy); Bruschi, P. [Department of Nuclear and Theoretical Physics, University of Pavia, Pavia (Italy); Bakeine, J.G.; Cansolino, L.; Clerici, A.M. [Laboratory of Experimental Surgery, Department of Surgery, University of Pavia, Pavia (Italy)

    2011-07-01

    The thermal column of the TRIGA Mark II reactor of the Pavia University is used as an irradiation facility to perform biological tests and irradiations of living systems for Boron Neutron Capture Therapy (BNCT) research. The suitability of the facility has been ensured by studying the neutron flux and the photon background in the irradiation chamber inside the thermal column. This characterization has been realized both by flux and dose measurements as well as by Monte Carlo simulations. The routine irradiations concern in vitro cells cultures and different tumor animal models to test the efficacy of the BNCT treatment. Some results about these experiments will be described. (author)

  3. The combined application of biological therapy and methotrexate in case of escape phenomenon progressing

    OpenAIRE

    Ponich E.S.; Kruglova L.S.; Babushkin A.M.

    2015-01-01

    Aim: the study of the efficacy of methotrexate in patients with the "escape effect" during the ustekinumab therapy. Materials and Methods. The results of methotrexate at a dose of 15-20mg/week in treatment of 4 patients receiving biologic and developed "escape effect". Ustekinumab is used as a hypodermic injection at a dose of 45 mg for a body weight of a patient no more than 100 kg, and 90 mg of body weight over 100 kg, at the zero week, the 4th week and then every 12 weeks. Patients control...

  4. In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

    DEFF Research Database (Denmark)

    Waugh, C. M.; Morrissey, D.; Jones, E.;

    2015-01-01

    Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session...... of ESWT was administered to the mid-portion of the Achilles tendon in thirteen healthy individuals (aged 25.7 ± 7.0 years) and patellar or Achilles tendon of six patients with tendinopathies (aged 39.0 ± 14.9 years). Dialysate samples from the surrounding peri-tendon were collected before and...... in tendinopathy by promoting the inflammatory and catabolic processes that are associated with removing damaged matrix constituents. The non-response of some individuals may help to explain why ESWT does not improve symptoms in all patients and provides a potential focus for future research....

  5. Surgery and radiation therapy of triple-negative breast cancers: From biology to clinics.

    Science.gov (United States)

    Bernier, Jacques; Poortmans, Philip M P

    2016-08-01

    Triple negative breast cancer refers to tumours lacking the expression of the three most used tumour markers, namely oestrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). These cancers are known to carry a more dismal prognosis than the other molecular subtypes. Whether a more aggressive local-regional treatment is warranted or not in patients with triple-negative breast cancer is still a matter of debate. Indeed there remain a number of grey zones with respect to the optimization of the extent and the timing of surgery and radiation therapy (RT) in this patient population, also in consideration of the significant heterogeneity in biological behaviour and response to treatment identified for these tumours. The objective of this review is to provide an insight into the biological and clinical behaviour of triple-negative breast cancers and revisit the most recent advances in their management, focussing on local-regional treatments. PMID:27318170

  6. Pulmonary complications of biological therapies in children and adults with rheumatic diseases.

    Science.gov (United States)

    Nisar, Muhammad K; Ostör, Andrew J K

    2013-12-01

    The management of rheumatic conditions, including those occurring in children, has improved dramatically over the last decade following the introduction of biologic disease-modifying anti-rheumatic drugs (bDMARDS) into the therapeutic arsenal. The benefits have been realised in multiple aspects of disease including signs and symptoms, bone and cartilage destruction, disability and quality of life. Overall, bDMARDS have an acceptable safety profile in the short to medium term in adults and children, however, that following longer term use remains unclear. As these drugs target key signalling molecules and cells of the immune system, adverse events are not unanticipated. In this review we will discuss pulmonary complications of biologic therapies used in the management of rheumatic diseases in both children and adults. PMID:23462434

  7. Optimal management of prostate cancer with lethal biology - state-of-the-art local therapy

    Directory of Open Access Journals (Sweden)

    Brian F Chapin

    2015-01-01

    Full Text Available Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. [1] ,[2] ,[3] ,[4] ,[5] However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient′s death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT. Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes [6] while others showing an advantage of surgery over RT. [7] ,[8] ,[9] ,[10] ,[11] Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. [12], [13], [14] Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. [11] While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [2] ,[3] ,[15

  8. Optimal management of prostate cancer with lethal biology--state-of-the-art local therapy.

    Science.gov (United States)

    Chapin, Brian F

    2015-01-01

    Defining prostate cancer with lethal biology based upon clinical criteria is challenging. Locally advanced/High-Grade prostate cancer can be downstaged or even downgraded with cure in up to 60% of patients with primary therapy. However, what is known is that high-grade prostate cancers have a greater potential for recurrence and progression to metastatic disease, which can ultimately result in a patient's death. Patients with clinical features of "high-risk" prostate cancer (cT2c, PSA >20, ≥ Gl 8 on biopsy) are more likely to harbor more aggressive pathologic findings. The optimal management of high-risk prostate cancer is not known as there are not prospective studies comparing surgery to radiation therapy (RT). Retrospective and population-based studies are subject to many biases and attempts to compare surgery and radiation have demonstrated mixed results. Some show equivalent survival outcomes while others showing an advantage of surgery over RT. Local therapy for high-risk disease does appear to be beneficial. Improved outcomes realized with local therapy have been clearly demonstrated by several prospective studies evaluating androgen deprivation therapy (ADT) alone versus ADT plus RT. The combination of local with systemic treatment showed improved disease-specific and overall survival outcomes. Unfortunately, primary ADT for N0M0 prostate cancer is still inappropriately applied in general practice. While the surgical literature is largely retrospective, it too demonstrates that surgery in the setting of high-risk prostate cancer is effective in providing durable disease-specific and overall survivals. [ PMID:26178396

  9. Advanced pancreatic cancer: flourishing novel approaches in the era of biological therapy.

    Science.gov (United States)

    Chiu, Joanne W; Wong, Hilda; Leung, Roland; Pang, Roberta; Cheung, Tan-To; Fan, Sheung-Tat; Poon, Ronnie; Yau, Thomas

    2014-09-01

    The progress in the development of systemic treatment for advanced pancreatic cancer (APC) has been slow. The mainstream treatment remains using chemotherapy including gemcitabine, FOLFIRINOX, and nab-paclitaxel. Erlotinib is the only approved biological therapy with marginal benefit. Studies of agents targeting epidermal growth factor receptor, angiogenesis, and RAS signaling have not been satisfying, and the usefulness of targeted therapy in APC is uncertain. Understanding in molecular processes and tumor biology has opened the door for new treatment strategies such as targeting insulin-like growth factor 1 receptor, transforming growth factor β, phosphoinositide 3-kinase/AKT/mammalian target of rapamycin pathway, and Notch pathway. New directions also include the upcoming immunotherapy and many novel agents that act on the microenvironment. The practice of personalized medicine using predictive biomarkers and pharmacogenomics signatures may also enhance the effectiveness of existing treatment. Future treatment approaches may involve comprehensive genomic assessment of tumor and integrated combinations of multiple agents to overcome treatment resistance. PMID:25117068

  10. Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the adult and pediatric experiences

    Directory of Open Access Journals (Sweden)

    Matthew L Stoll

    2008-06-01

    Full Text Available Matthew L Stoll, Alisa C GotteDepartment of Pediatrics, Division of Rheumatology, UT Southwestern Medical Center, Dallas, TX, USAAbstract: Biologics have advanced the therapy of adult and pediatric arthritis. They have been linked to rare serious adverse outcomes, but the actual risk of these events is controversial in adults, and largely unknown in pediatrics. Because of the paucity of safety and efficacy data in children, pediatric rheumatologists often rely on the adult literature. Herein, we reviewed the adult and pediatric literature on five classes of medicines: Tumor necrosis factor (TNF inhibitors, anakinra, rituximab, abatacept, and tocilizumab. For efficacy, we reviewed randomized controlled studies in adults, but did include lesser qualities of evidence for pediatrics. For safety, we utilized prospective and retrospective studies, rarely including reports from other inflammatory conditions. The review included studies on rheumatoid arthritis and spondyloarthritis, as well as juvenile idiopathic arthritis. Overall, we found that the TNF inhibitors have generally been found safe and effective in adult and pediatric use, although risks of infections and other adverse events are discussed. Anakinra, rituximab, abatacept, and tocilizumab have also shown positive results in adult trials, but there is minimal pediatric data published with the exception of small studies involving the subgroup of children with systemic onset juvenile idiopathic arthritis, in whom anakinra and tocilizumab may be effective therapies.Keywords: juvenile idiopathic arthritis, biologics, rheumatoid arthritis

  11. A biological aspect on radium therapy, and approach to new radiotherapy by several sessions a day

    International Nuclear Information System (INIS)

    Through radiobiological study of treatment with radium, it was revealed that radium therapy has two such important features as (1) short overall treatment time and (2) low-dose rate irradiation and that it showed a higher therapeutic ratio than that of conventional high-dose rate fractionated irradiation. After searching for a high-dose rate irradiation method with these advantages of radium treatment, results were obtained which suggested the possibility of new radio-therapy with several sessions a day. In the new method, a small dose was applied several times a day. Then, the time-dose relationship of the new therapy was investigated, and an attempt was made to calculate the dose fractionation that seemed practical. The results obtained were in good agreement with those of Svoboda's recent clinical experience. However, since these results were based on many biological hypotheses, clinical application of them at present is risky. Prior to clinical application, it will be necessary to conduced a number of animal experiments. (auth.)

  12. Matching Biological Mesh and Negative Pressure Wound Therapy in Reconstructing an Open Abdomen Defect

    Directory of Open Access Journals (Sweden)

    Fabio Caviggioli

    2014-01-01

    Full Text Available Reconstruction of open abdominal defects is a clinical problem which general and plastic surgeons have to address in cooperation. We report the case of a 66-year-old man who presented an abdominal dehiscence after multiple laparotomies for a sigmoid-rectal adenocarcinoma that infiltrated into the abdominal wall, subsequently complicated by peritonitis and enteric fistula. A cutaneous dehiscence and an incontinent abdominal wall resulted after the last surgery. The abdominal wall was reconstructed using a biological porcine cross-linked mesh Permacol (Covidien Inc., Norwalk, CT. Negative Pressure Wound Therapy (NPWT, instead, was used on the mesh in order to reduce wound dimensions, promote granulation tissue formation, and obtain secondary closure of cutaneous dehiscence which was finally achieved with a split-thickness skin graft. Biological mesh behaved like a scaffold for the granulation tissue that was stimulated by the negative pressure. The biological mesh was rapidly integrated in the abdominal wall restoring abdominal wall continence, while the small dehiscence, still present in the central area, was subsequently covered with a split-thickness skin graft. The combination of these different procedures led us to solve this complicated case obtaining complete wound closure after less than 2 months.

  13. [Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloarthritides].

    Science.gov (United States)

    Mota, Licia Maria Henrique da; Cruz, Bóris Afonso; Brenol, Claiton Viegas; Pollak, Daniel Feldman; Pinheiro, Geraldo da Rocha Castelar; Laurindo, Ieda Maria Magalhães; Pereira, Ivânio Alves; Carvalho, Jozélio Freire de; Bertolo, Manoel Barros; Pinheiro, Marcelo de Medeiros; Freitas, Max Victor Carioca; Silva, Nilzio Antônio da; Louzada-Júnior, Paulo; Sampaio-Barros, Percival Degrava; Giorgi, Rina Dalva Neubarth; Lima, Rodrigo Aires Corrêa; Andrade, Luis Eduardo Coelho

    2015-01-01

    The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia/SBR) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis (RA) and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment. PMID:26054442

  14. Long-term subcutaneous recombinant interleukin-2 as maintenance therapy: biological effects and clinical implications.

    Science.gov (United States)

    Guida, M; Abbate, I; Casamassima, A; Musci, M D; Latorre, A; Lorusso, V; Correale, M; De Lena, M

    1995-01-01

    Several trials have evaluated the therapeutic efficacy of rIL-2 combined with more traditional treatments such as chemotherapy and radiotherapy, but the use of IL-2 as adjuvant therapy for minimal residual disease or to maintain clinical response obtained with other standard treatments has yet to be investigated. The aim of the present trial was to study the biological effects of maintenance long-term treatment (6 months) with subcutaneous low-dose IL-2 in 16 patients with different neoplasms previously treated with chemo-immuno therapeutic regimens or with surgery (7 metastatic renal cancers, 5 locally advanced renal cancers previously subjected to radical nephrectomy, 2 metastatic breast cancers, 1 small cell lung cancer, and 1 metastatic melanoma). Clinical tolerability, feasibility and therapeutic implications are also discussed. The IL-2 schedule was as follows: 4.5 million IU/day, 3 times weekly for 6 months. A total of 14 patients completed therapy without requiring dose modifications and are free of progression after a median duration of 8+ months (range: 7+ to 34+) while two patients progressed during therapy (one inflammatory breast cancer and one renal cancer). Important and persistent hemato-immunostimulating effects in both soluble (IL-2, sIL-2R, IL-6) and cellular (lymphocyte subsets, monocytes, eosinophils) parameters were noted during the entire treatment. The IL-2 related toxicity was quite low. Moreover, this long-term IL-2 therapy could control neoplastic growth and thus prolong clinical response obtained with standard treatments. Prospective randomized studies regarding the clinical efficacy have been initiated. PMID:8547958

  15. Investigating the robustness of ion beam therapy treatment plans to uncertainties in biological treatment parameters

    CERN Document Server

    Boehlen, T T; Dosanjh, M; Ferrari, A; Fossati, P; Haberer, T; Mairani, A; Patera, V

    2012-01-01

    Uncertainties in determining clinically used relative biological effectiveness (RBE) values for ion beam therapy carry the risk of absolute and relative misestimations of RBE-weighted doses for clinical scenarios. This study assesses the consequences of hypothetical misestimations of input parameters to the RBE modelling for carbon ion treatment plans by a variational approach. The impact of the variations on resulting cell survival and RBE values is evaluated as a function of the remaining ion range. In addition, the sensitivity to misestimations in RBE modelling is compared for single fields and two opposed fields using differing optimization criteria. It is demonstrated for single treatment fields that moderate variations (up to +/-50\\%) of representative nominal input parameters for four tumours result mainly in a misestimation of the RBE-weighted dose in the planning target volume (PTV) by a constant factor and only smaller RBE-weighted dose gradients. Ensuring a more uniform radiation quality in the PTV...

  16. Biological models in vivo for boron neutronic capture studies as tumors therapy

    International Nuclear Information System (INIS)

    The use of experimental models for Boron Neutronic Capture studies as Tumors Therapy have as two main objectives: 1) To contribute to the basic knowledge of the biological mechanisms involved to increase the method therapeutical advantage, and 2) To explore the possible application of this therapeutic method to other pathologies. In this frame it was studied the carcinogenesis model of hamster cheek pouch, a type of human buccal cancer. Biodistribution studies of boron compound were performed in tumor, blood and in different precancerous and normal tissues as well as BNCT studies. Results validated this method for BNCT studies and show the capacity of the oral mucosa tumors of selectively concentrate the boron compound, showing a deleterious clear effect on the tumor after 24 hours with BNCT treatment. (author)

  17. Guidance for the management of patients with latent tuberculosis infection requiring biologic therapy in rheumatology and dermatology clinical practice.

    Science.gov (United States)

    Cantini, Fabrizio; Nannini, Carlotta; Niccoli, Laura; Iannone, Florenzo; Delogu, Giovanni; Garlaschi, Giacomo; Sanduzzi, Alessandro; Matucci, Andrea; Prignano, Francesca; Conversano, Michele; Goletti, Delia

    2015-06-01

    Since the introduction of biologics for the treatment of rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and psoriasis (Pso) an increased risk of tuberculosis (TB) reactivation in patients with latent tuberculosis infection (LTBI) has been recorded for anti-TNF agents, while a low or absent risk is associated with the non-anti-TNF targeted biologics. To reduce this risk several recommendation sets have been published over time, but in most of them the host-related risk, and the predisposing role to TB reactivation exerted by corticosteroids and by the traditional disease-modifying anti-rheumatic drugs has not been adequately addressed. Moreover, the management of the underlying disease, and the timing of biologic restarting in patients with TB occurrence have been rarely indicated. A multidisciplinary expert panel, the Italian multidisciplinary task force for screening of tuberculosis before and during biologic therapy (SAFEBIO), was constituted, and through a review of the literature, an evidence-based guidance for LTBI detection, identification of the individualized level of risk of TB reactivation, and practical management of patients with TB occurrence was formulated. The literature review confirmed a higher TB risk associated with monoclonal anti-TNF agents, a low risk for soluble receptor etanercept, and a low or absent risk for non-anti-TNF targeted biologics. Considering the TB reactivation risk associated with host demographic and clinical features, and previous or current non-biologic therapies, a low, intermediate, or high TB reactivation risk in the single patient was identified, thus driving the safest biologic choice. Moreover, based on the underlying disease activity measurement and the different TB risk associated with non-biologic and biologic therapies, practical indications for the treatment of RA, PsA, AS, and Pso in patients with TB occurrence, as well as the safest timing of biologic restarting, were provided

  18. Biological therapies for the treatment of juvenile idiopathic arthritis: Lessons from the adult and pediatric experiences.

    Science.gov (United States)

    Stoll, Matthew L; Gotte, Alisa C

    2008-06-01

    Biologics have advanced the therapy of adult and pediatric arthritis. They have been linked to rare serious adverse outcomes, but the actual risk of these events is controversial in adults, and largely unknown in pediatrics. Because of the paucity of safety and efficacy data in children, pediatric rheumatologists often rely on the adult literature. Herein, we reviewed the adult and pediatric literature on five classes of medicines: Tumor necrosis factor (TNF) inhibitors, anakinra, rituximab, abatacept, and tocilizumab. For efficacy, we reviewed randomized controlled studies in adults, but did include lesser qualities of evidence for pediatrics. For safety, we utilized prospective and retrospective studies, rarely including reports from other inflammatory conditions. The review included studies on rheumatoid arthritis and spondyloarthritis, as well as juvenile idiopathic arthritis. Overall, we found that the TNF inhibitors have generally been found safe and effective in adult and pediatric use, although risks of infections and other adverse events are discussed. Anakinra, rituximab, abatacept, and tocilizumab have also shown positive results in adult trials, but there is minimal pediatric data published with the exception of small studies involving the subgroup of children with systemic onset juvenile idiopathic arthritis, in whom anakinra and tocilizumab may be effective therapies. PMID:19707357

  19. Tailored treatment options for patients with psoriatic arthritis and psoriasis: review of established and new biologic and small molecule therapies.

    Science.gov (United States)

    Elyoussfi, Sarah; Thomas, Benjamin J; Ciurtin, Coziana

    2016-05-01

    The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I-IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are

  20. A CLINICAL STUDY ON THE INCIDENCE AND MANAGEMENT OF BIOLOGICAL COMPLICATIONS IN IMPLANT THERAPY

    Directory of Open Access Journals (Sweden)

    Nicolae VASILE

    2015-09-01

    Full Text Available The scope of the study was to evidence the methods recommended for avoiding, managing and implementing an efficient treatment capable of reducing the biological complications accompanying implant therapies. Materials and method. The study evaluates the patients with prosthesis charged implants - or during their osseointegration period - inserted in the Clinic of The Emergency Military Hospital of Sibiu, over a 5 year period (2009-2014. Retrospective investigation was based on the evaluation of the treatment files and on the imagistic and clinical analyses of the 125 patients to whom 385 implants had been inserted. Results and discussion. The study demonstrates that, when implants are the support of an overdenture, surrounded by either limited keratinized gingiva or mobile tissues, the presence of the bacterial plaque is considerable, the peri-implant pocket exceeds 5 mm, and sensitivity and bleeding are produced on contact with the probe. In susceptible patients, or in those with pathological periodontal antecedents, the re-infection potential has been always higher. The clinical study confirms that, invariably, peri-implantitis is associated with the existence of the bacterial plaque and also with the presence of a peri-implant pocket exceeding 4 mm (8.9%, with partial exposure of the covering screw (4.5% and fixed restaurations without self-cleaning spaces (2%. Conclusions. Out of the post-surgery biological complications, peri-implantitis is the most frequent one, causing a – sometimes total – loss of the alveolar bone around the osseointegrated implant.

  1. Promising biological therapies for ulcerative colitis: A review of the literature

    Institute of Scientific and Technical Information of China (English)

    Hirotada; Akiho; Azusa; Yokoyama; Shuichi; Abe; Yuichi; Nakazono; Masatoshi; Murakami; Yoshihiro; Otsuka; Kyoko; Fukawa; Mitsuru; Esaki; Yusuke; Niina; Haruei; Ogino

    2015-01-01

    Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.

  2. In vivo biological response to extracorporeal shockwave therapy in human tendinopathy

    Directory of Open Access Journals (Sweden)

    CM Waugh

    2015-05-01

    Full Text Available Extracorporeal shock wave therapy (ESWT is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session of ESWT was administered to the mid-portion of the Achilles tendon in thirteen healthy individuals (aged 25.7 ± 7.0 years and patellar or Achilles tendon of six patients with tendinopathies (aged 39.0 ± 14.9 years. Dialysate samples from the surrounding peri-tendon were collected before and immediately after ESWT. Interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, vascular endothelial growth factor and interferon-γ were quantified using a cytometric bead array while gelatinase activity (MMP-2 and -9 was examined using zymography. There were no statistical differences between the biological tissue response to ESWT in healthy and pathological tendons. IL-1β, IL-2, IL-6 and IL-8 were the cytokines predominantly detected in the tendon dialysate. IL-1β and IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were elevated immediately after ESWT and remained significantly elevated for four hours post-ESWT (p < 0.001. Pro-forms of MMP-2 and -9 also increased after ESWT (p < 0.003, whereas there were no significant changes in active MMP forms. In addition, the biological response to ESWT treatment could be differentiated between possible responders and non-responders based on a minimum 5-fold increase in any inflammatory marker or MMP from pre- to post-ESWT. Our findings provide novel evidence of the biological mechanisms underpinning ESWT in humans in vivo. They suggest that the mechanical stimulus provided by ESWT might aid tendon remodelling in tendinopathy by promoting the inflammatory and catabolic processes that are associated with removing damaged matrix constituents. The non-response of some individuals may

  3. Biological drugs targeting the immune response in the therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Saveria Pastore

    2008-08-01

    Full Text Available Saveria Pastore1, Emanuela Gubinelli2, Luca Leoni2, Desanka Raskovic2, Liudmila Korkina11Laboratory of Tissue Engineering and Cutaneous Physiopathology; 2Second Dermatology Unit, Istituto Dermopatico dell’Immacolata, IRCCS, Roma, ItalyAbstract: Chronic plaque psoriasis affects more than 2% of world population, has a chronic recurrent behavior, gives a heavy burden to the patients’ quality of life, and hence remains a huge medical and social problem. The clinical results of conventional therapies of psoriasis are not satisfactory. According to the current knowledge of the molecular and cellular basis of psoriasis, it is defined as an immune-mediated chronic inflammatory and hyperproliferative skin disease. A new generation of biological drugs, targeting molecules and cells involved into perturbed pro-inflammatory immune response in the psoriatic skin and joints, has been recently designed and applied clinically. These biological agents are bioengineered proteins such as chimeric and humanized antibodies and fusion proteins. In particular, they comprise the antitumor necrosis factor-α agents etanercept, infliximab, and adalimumab, with clinical efficacy in both moderate-severe psoriasis and psoriatic arthritis, and the anti-CD11a efalizumab with selective therapeutic action exclusively in the skin. Here, we overview recent findings on the molecular pathways relevant to the inflammatory response in psoriasis and present our clinical experience with the drugs currently employed in the dermatologic manifestations, namely etanercept, infliximab, and efalizumab. The growing body of clinical data on the efficacy and safety of antipsoriasis biological drugs is reviewed as well. Particular focus is given to long-term safety concerns and feasibility of combined therapeutic protocols to ameliorate clinical results.Keywords: psoriasis, immune-mediated inflammation, etanercept, infliximab, efalizumab

  4. Plasma cell myeloma--new biological insights and advances in therapy.

    Science.gov (United States)

    Barlogie, B; Epstein, J; Selvanayagam, P; Alexanian, R

    1989-03-01

    Plasma cell myeloma is a more complex neoplasm than suggested by the relative uniformity of its dominant plasma cells, which represent the terminal stage of normal B-cell differentiation. Phenotypic, molecular, and cellular genetic data favor the presence of a myeloma stem cell early in hematopoietic development so that, as in chronic myelogenous leukemia (CML), a far distance exists between the primordial malignant cell that was the target of malignant transformation and the dominant clinical phenotype. Traces of pre-B, myeloid, and T cells are coexpressed with the mature B-cell phenotype, an occurrence unknown in normal B-cell differentiation. Analogous to CML, disease progression is marked by disease dedifferentiation, occasionally with cessation of myeloma protein production and development instead of extramedullary lymphomalike features with high LDH or myelodysplasia/acute myelogenous leukemia (AML) syndromes. The prognostic importance of serum LDH levels even in newly diagnosed myeloma suggests the early presence of tumor cells with "LDH phenotype," which, as a result of drug resistance and proliferative advantage, expand preferentially during disease progression. Further characterization of these cells may provide important clues about the ontogeny of multiple myeloma. Myeloma cells express many receptors for different biological signals that might be exploitable for therapy with immunotoxins or radioisotopes. Plasma cells and their precursors also produce a variety of cytokines, some of which have putatively autostimulatory functions (eg, IL-1, IL-5, IL-6) and/or are related to disease manifestations (eg, IL-1 and TNF-beta as OAF). The wealth of cellular expression by plasma cells provides clues for understanding the mechanisms of gene activation and the nature of abnormal growth and differentiation. The accuracy of prognostically relevant staging systems has been refined with the use of new quantitative parameters that reflect tumor mass (ie, serum B2M

  5. The iSBTc/SITC primer on tumor immunology and biological therapy of cancer: a summary of the 2010 program

    Directory of Open Access Journals (Sweden)

    Urba Walter J

    2011-01-01

    Full Text Available Abstract The Society for Immunotherapy of Cancer, SITC (formerly the International Society for Biological Therapy of Cancer, iSBTc, aims to improve cancer patient outcomes by advancing the science, development and application of biological therapy and immunotherapy. The society and its educational programs have become premier destinations for interaction and innovation in the cancer biologics community. For over a decade, the society has offered the Primer on Tumor Immunology and Biological Therapy of Cancer™ in conjunction with its Annual Scientific Meeting. This report summarizes the 2010 Primer that took place October 1, 2010 in Washington, D.C. as part of the educational offerings associated with the society's 25th anniversary. The target audience was basic and clinical investigators from academia, industry and regulatory agencies, and included clinicians, post-doctoral fellows, students, and allied health professionals. Attendees were provided a review of basic immunology and educated on the current status and most recent advances in tumor immunology and clinical/translational caner immunology. Ten prominent investigators presented on the following topics: innate immunity and inflammation; an overview of adaptive immunity; dendritic cells; tumor microenvironment; regulatory immune cells; immune monitoring; cytokines in cancer immunotherapy; immune modulating antibodies; cancer vaccines; and adoptive T cell therapy. Presentation slides, a Primer webinar and additional program information are available online on the society's website.

  6. Implication of stem cells in the biology and therapy of head and neck cancer [

    Directory of Open Access Journals (Sweden)

    Wollenberg, Barbara

    2012-04-01

    tumours is expected. Those occur in tumours and they have typical stem cell characteristics like self-regeneration and the potential of differentiation and are potentially responsible for tumour growth. With their ability of self-regeneration they would have the ability to form a complete tumour out of every single cell. That tumour would histologically look like the tumour those cells initially originated from. Of particular interest regarding those currently still elusive cancer stem cells is their resistance towards current therapies like radiotherapy or chemotherapy. Those insights now get a completely new meaning in tumour biology: Does a cancer stem cell exist, which is able to initiate and keep up tumour growth despite all possible therapeutic interventions? This presentation will outline the current views regarding cancer stem cells in non HPV associated HNSCC and it will highlight problems, which are currently researched on. The objective must be to understand the biology of those cells in a way that make an extended range of therapeutics possible. A therapy, which specifically targets cancer stem cells, could improve the chances of recovery.

  7. Biological effective doses in 300 patients undergoing therapy with 177Lu-octreotate

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: fractionated therapy with 177Lu-octreotate has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. The main aim of this study was to calculate the biological effective dose (BED) to the kidneys using an individualized dosimetry protocol, and to assess differences in the number of possible treatment cycles based on BED compared to those based on absorbed dose. Methods: a total of 148 female and 152 male patients with neuroendocrine tumors with high somatostatin receptor expression (grade 3 or 4) were included. After infusion of 7.4 GBq of 177Lu-octreotate SPECT/CT images over the abdomen were acquired at 24, 96 and 168 h after infusion. Absorbed dose to kidneys was calculated based on pharmacokinetic data obtained from SPECT/CT. From this the effective half-life of 177Lu-octreotate in the kidneys was estimated, and BED was calculated using the equation described by Barone et al. (1). Results and discussion: for a single treatment cycle of 7.4 GBq, median (1:st-3:rd quartiles) BED was 5.0 Gy (3.9-6.1) in the right kidney and 4.7 Gy (3.7-5.8) in the left kidney. For the same treatment cycle, BED was 9.0% (7.1-11.3) and 8.7% (7.0-10.9) higher than absorbed dose in right and left kidneys, respectively. In patients with high absorbed doses, BED could be more than 20% higher than absorbed dose. Assuming an absorbed dose limit of 23 Gy and a BED limit of 45 Gy to the kidneys, the possible number of treatment cycles was 5.4 (4.5-6.8) based on absorbed dose while using BED increased the number of possible cycles to 9.8 (8.1-12.5). Conclusions: although biological effective dose to the kidneys is higher than absorbed dose, use of BED to estimate the number of possible treatment cycles in 177Lu-octreotate therapy may allow for more treatment cycles than the use of absorbed dose. Refs: 1) Barone, R. et al. Patient-specific dosimetry in predicting renal toxicity with (90)Y

  8. How do patients with inflammatory bowel disease want their biological therapy administered?

    Directory of Open Access Journals (Sweden)

    Lindsay Hannah

    2010-01-01

    Full Text Available Abstract Background Infliximab is usually administered by two monthly intravenous (iv infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn's Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration. The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD patients for two currently available anti-TNF agents and the reasons for their choices. Methods An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous were available, which drug route of administration would they choose. Results One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response. The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent preferred infliximab and 19 patients (24 percent preferred adalimumab (p = 0.07. Twenty-six patients (33 percent did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv was: "I do not like the idea of self-injecting," (67 percent. For those patients who preferred adalimumab (sc the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent. Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab six patients stated that they would prefer infliximab if given

  9. Stereotactic body radiation therapy for abdominal oligometastases: a biological and clinical review

    International Nuclear Information System (INIS)

    Advances in imaging and biological targeting have led to the development of stereotactic body radiation therapy (SBRT) as an alternative treatment of extracranial oligometastases. New radiobiological concepts, such as ceramide-induced endothelial apoptosis after hypofractionated high-dose SBRT, and the identification of patients with oligometastatic disease by microRNA expression may yet lead to further developments. Key factors in SBRT are delivery of a high dose per fraction, proper patient positioning, target localisation, and management of breathing–related motion. Our review addresses the radiation doses and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland oligometastases and treatment outcomes. Reported local control (LC) rates for liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 -100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are rare. SBRT of adrenal gland oligometastases shows promising results in the case of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe and effective treatment option for abdominal oligometastases

  10. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials

    International Nuclear Information System (INIS)

    Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

  11. Openness to and preference for attributes of biologic therapy prior to initiation among patients with rheumatoid arthritis: patient and rheumatologist perspectives and implications for decision making

    Science.gov (United States)

    Bolge, Susan C; Goren, Amir; Brown, Duncan; Ginsberg, Seth; Allen, Isabel

    2016-01-01

    Purpose Despite American College of Rheumatology recommendations, appropriate and timely initiation of biologic therapies does not always occur. This study examined openness to and preference for attributes of biologic therapies among patients with rheumatoid arthritis (RA), differences in patients’ and rheumatologists’ perceptions, and discussions around biologic therapy initiation. Patients and methods A self-administered online survey was completed by 243 adult patients with RA in the US who were taking disease-modifying antirheumatic drugs (DMARDs) and had never taken, but had discussed biologic therapy with a rheumatologist. Patients were recruited from a consumer panel (n=142) and patient advocacy organization (n=101). A separate survey was completed by 103 rheumatologists who treated at least 25 patients with RA per month with biologic therapy. Descriptive and bivariate analyses were conducted separately for patients and rheumatologists. Attributes of biologic therapy included route of administration (intravenous infusion or subcutaneous injection), frequency of injections/infusions, and duration of infusion. Results Over half of patients (53.1%) were open to both intravenous infusion and subcutaneous injection, whereas rheumatologists reported 40.7% of patients would be open to both. Only 26.3% of patients strongly preferred subcutaneous injection, whereas rheumatologists reported 35.2%. Discrepancies were even more pronounced among specific patient types (eg, older vs younger patients and Medicare recipients). Among patients, 23% reported initiating discussion about biologics and 54% reported their rheumatologist initiated the discussion. A majority of rheumatologists reported discussing in detail several key aspects of biologics, whereas a minority of patients reported the same. Conclusion Preferences differed among patients with RA from rheumatologists’ perceptions of these preferences for biologic therapy, including greater openness to intravenous

  12. Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    Science.gov (United States)

    Warren, Richard B; Smith, Catherine H; Yiu, Zenas Z N; Ashcroft, Darren M; Barker, Jonathan N W N; Burden, A David; Lunt, Mark; McElhone, Kathleen; Ormerod, Anthony D; Owen, Caroline M; Reynolds, Nick J; Griffiths, Christopher E M

    2015-11-01

    Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients. PMID:26053050

  13. How do patients with inflammatory bowel disease want their biological therapy administered?

    LENUS (Irish Health Repository)

    Allen, Patrick B

    2010-01-01

    BACKGROUND: Infliximab is usually administered by two monthly intravenous (iv) infusions, therefore requiring visits to hospital. Adalimumab is administered by self subcutaneous (sc) injections every other week. Both of these anti-TNF drugs appear to be equally efficacious in the treatment of Crohn\\'s Disease and therefore the decision regarding which drug to choose will depend to some extent on patient choice, which may be based on the mode of administration.The aims of this study were to compare preferences in Inflammatory Bowel Disease (IBD) patients for two currently available anti-TNF agents and the reasons for their choices. METHODS: An anonymous questionnaire was distributed to IBD patients who had attended the Gastroenterology service (Ulster Hospital, Dundonald, Belfast, N. Ireland. UK) between January 2007 and December 2007. The patients were asked in a hypothetical situation if the following administering methods of anti-TNF drugs (intravenous or subcutaneous) were available, which drug route of administration would they choose. RESULTS: One hundred and twenty-five patients fulfilled the inclusion criteria and were issued questionnaires, of these 78 questionnaires were returned (62 percent response). The mean age of respondent was 44 years. Of the total number of respondents, 33 patients (42 percent) preferred infliximab and 19 patients (24 percent) preferred adalimumab (p = 0.07). Twenty-six patients (33 percent) did not indicate a preference for either biological therapy and were not included in the final analysis. The commonest reason cited for those who chose infliximab (iv) was: "I do not like the idea of self-injecting," (67 percent). For those patients who preferred adalimumab (sc) the commonest reason cited was: "I prefer the convenience of injecting at home," (79 percent). Of those patients who had previously been treated with an anti-TNF therapy (n = 10, all infliximab) six patients stated that they would prefer infliximab if given the choice

  14. Relationship between biologic tissue heterogeneity and absorbed dose distribution in therapy of oncologic patients with cyclotron U-120 fast neutrons

    International Nuclear Information System (INIS)

    Effect of biological tissue heterogeneity on the absorbed dose distribution of U-120 cyclotron fast neutron beam was studied by estimation and experimental method. It was found that adipose and bone tissues significantly changes the pattern of neutron absorbed dose distribution in patient body. Absorbed dose in adipose layer increase by 20% as compared to the dose in soft biological tissue. Approximation method for estimation of the absorbed dose distribution of fast neutrons in heterogeneities was proposed which could be applied in the dosimetric planning of U-120 cyclotron neutron therapy of neoplasms

  15. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  16. Treatment of cancer of the pancreas by intraoperative electron beam therapy: physical and biological aspects

    Energy Technology Data Exchange (ETDEWEB)

    Bagne, F.R.; Dobelbower, R.R. Jr.; Milligan, A.J.; Bronn, D.G.

    1989-01-01

    Radiation therapy has had a significant and an expanded role in the management of cancer of the pancreas during the last decade. In particular, for locally advanced disease, radiation therapy has improved the median survival of patients to 1 year. Intraoperative electron beam therapy has been applied to unresectable and resectable pancreatic cancer in an attempt to enhance local control of disease and to improve patient survival. This paper presents a survey of the role of radiation therapy in treatment of cancer of the pancreas, provides information on the radiobiological aspects of this treatment modality and details the physical and dosimetric characteristics of intraoperative radiation therapy with electrons. Presented are the design specifics of an applicator system, central axis beam data, applicator parameters, dose distribution data, shielding, treatment planning and means of verification. Emphasis is placed on the collaboration and cooperation necessary for all members of the intraoperative radiation therapy team including surgeons, radiation therapists, medical physicists, anesthesiologists, technologists, and nurses.29 references.

  17. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  18. The biological effects of deuterium depletion. A possible new tool in cancer therapy

    International Nuclear Information System (INIS)

    It is known that the deuterium/hydrogen mass ratio is the largest of stable isotopes of the same element, causing differences in the physical and chemical behaviour between the two hydrogen isotopes. The possible role of naturally occurring deuterium - whose concentration is over 16 mmol/l in surface water, 12-14 mmol/l in living organisms - in biological systems was first investigated in the early 90s. The results revealed that deuterium depleted water (DDW): i) inhibits cell proliferation of different cell lines in vitro (MDA and MCF-7: human breast, PC-3: human prostate, M14: human melanoma, HT-29: human colon, L929: mouse fibroblast, A4: murine haemopoietic); ii) as drinking water causes partial or complete tumour regression in xenotransplanted mice (MDA, MCF-7, PC-3); iii) can induce complete or partial tumour regression in dogs and cats with different tumours; iv) induced apoptosis in vitro and vivo; v) has a significant influence on the e-mye, Ha-ras and p53 genes by reducing their expression; vi) shows efficacy in Phase II double blind clinical trial with human prostate cancer. It is generally accepted that the earliest event in the response of mammalian cells to mitogens is the elevation of pHi, which may be the proliferative trigger. It is also known that the binding site for protons to be transported by plasma membrane H4-ATPasc of yeast does not accept deuterons with the same case as H4 or perhaps not at all. It is therefore reasonable to assume that when the cell eliminates the H4 to govern the pHi by activating the Na+/H4 antiport system the D/H ratio increases in the intracellular space. We suggest that the cell cycle regulating system is somehow able to recognize the change in the D/H ratio and when this ratio reaches a certain threshold this will trigger the molecular mechanism which causes the cell to enter the S phase. The decrease of D concentration caused by DDW can interfere with the signal transduction pathways thus leading to tumour

  19. Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

    International Nuclear Information System (INIS)

    Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

  20. A colorimetric determination of boron in biological sample for boron neutron capture therapy (BNCT)

    International Nuclear Information System (INIS)

    The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of glyemas and gluoblastomas grade III and IV than other therapies. During the treatment the levels of Na210B12H11SH must be known in several compartiments of the organism and with this purpose the method of colorimetric determination of boron using curcumine was established. This method is simple, reprodutible and adequate sensitivity for this control. (author)

  1. A new-age for biologic therapies: Long-term drug free therapy with BiP?

    Directory of Open Access Journals (Sweden)

    Adrian Matthew Shields

    2012-02-01

    Full Text Available Heat shock proteins (HSPs and other members of the much broader stress protein family have been shown to play important roles in coordinating multiple phases of immunological reactions; from facilitating immunological recognition, to promoting and regulating immunological responses and finally augmenting the resolution of inflammation and return to immunological homeostasis. In this review, we consider the challenges facing the stress protein field as we enter 2012; in particular we consider the role that HSPs and stress proteins may play in the initiation and termination of immunological responses. Special attention is afforded to the resolution-associated molecular pattern, binding immunoglobulin protein (BiP, also known as GRP78. We review the evidence that resolution-promoting proteins such as BiP may herald a new generation of biologics for inflammatory disease and reflect on the challenges of achieving clinical remission in rheumatoid arthritis with novel therapeutics and correlating clinical remission with immunological parameters of resolution of inflammation.

  2. An Official American Thoracic Society Workshop Report 2015. Stem Cells and Cell Therapies in Lung Biology and Diseases.

    Science.gov (United States)

    Wagner, Darcy E; Cardoso, Wellington V; Gilpin, Sarah E; Majka, Susan; Ott, Harald; Randell, Scott H; Thébaud, Bernard; Waddell, Thomas; Weiss, Daniel J

    2016-08-01

    The University of Vermont College of Medicine, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, Cystic Fibrosis Foundation, European Respiratory Society, International Society for Cellular Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 27 to 30, 2015, at the University of Vermont. The conference objectives were to review the current understanding of the role of stem and progenitor cells in lung repair after injury and to review the current status of cell therapy and ex vivo bioengineering approaches for lung diseases. These are all rapidly expanding areas of study that both provide further insight into and challenge traditional views of mechanisms of lung repair after injury and pathogenesis of several lung diseases. The goals of the conference were to summarize the current state of the field, discuss and debate current controversies, and identify future research directions and opportunities for both basic and translational research in cell-based therapies for lung diseases. This 10th anniversary conference was a follow up to five previous biennial conferences held at the University of Vermont in 2005, 2007, 2009, 2011, and 2013. Each of those conferences, also sponsored by the National Institutes of Health, American Thoracic Society, and respiratory disease foundations, has been important in helping guide research and funding priorities. The major conference recommendations are summarized at the end of the report and highlight both the significant progress and major challenges in these rapidly progressing fields. PMID:27509163

  3. A short history of anti-rheumatic therapy - VII. Biological agents

    Directory of Open Access Journals (Sweden)

    B. Gatto

    2011-11-01

    Full Text Available The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

  4. The role of nuclear reactions in Monte Carlo calculations of absorbed and biological effective dose distributions in hadron therapy

    CERN Document Server

    Brons, S; Elsässer, T; Ferrari, A; Gadioli, E; Mairani, A; Parodi, K; Sala, P; Scholz, M; Sommerer, F

    2010-01-01

    Monte Carlo codes are rapidly spreading among hadron therapy community due to their sophisticated nuclear/electromagnetic models which allow an improved description of the complex mixed radiation field produced by nuclear reactions in therapeutic irradiation. In this contribution results obtained with the Monte Carlo code FLUKA are presented focusing on the production of secondary fragments in carbon ion interaction with water and on CT-based calculations of absorbed and biological effective dose for typical clinical situations. The results of the simulations are compared with the available experimental data and with the predictions of the GSI analytical treatment planning code TRiP.

  5. Atmospheric-pressure plasma-jet from micronozzle array and its biological effects on living cells for cancer therapy

    Science.gov (United States)

    Kim, Kangil; Choi, Jae Duk; Hong, Yong Cheol; Kim, Geunyoung; Noh, Eun Joo; Lee, Jong-Soo; Yang, Sang Sik

    2011-02-01

    We propose a plasma-jet device with a micrometer-sized nozzle array for use in a cancer therapy. Also, we show the biological effects of atmospheric-pressure plasma on living cells. Nitrogen-plasma activated a surrogate DNA damage signal transduction pathway, called the ataxia telangiectasia mutated (ATM)-checkpoint kinase 2 pathway, suggesting that the nitrogen-plasma generates DNA double-strand breaks. Phosphorylation of H2AX and p53 was detected in the plasma-treated cells, leading to apoptotic cell death. Thus, an effect for the nitrogen plasma in the control of apoptotic cell death provides insight into the how biological effects of the nitrogen-plasma can be applied to the control of cell survival, a finding with potential therapeutic implications.

  6. A Mechanism-Based Approach to Predict the Relative Biological Effectiveness of Protons and Carbon Ions in Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: The physical and potential biological advantages of proton and carbon ions have not been fully exploited in radiation therapy for the treatment of cancer. In this work, an approach to predict proton and carbon ion relative biological effectiveness (RBE) in a representative spread-out Bragg peak (SOBP) is derived using the repair-misrepair-fixation (RMF) model. Methods and Materials: Formulas linking dose-averaged linear-quadratic parameters to DSB induction and processing are derived from the RMF model. The Monte Carlo Damage Simulation (MCDS) software is used to quantify the effects of radiation quality on the induction of DNA double-strand breaks (DSB). Trends in parameters α and β for clinically relevant proton and carbon ion kinetic energies are determined. Results: Proton and carbon ion RBE are shown to increase as particle energy, dose, and tissue α/β ratios decrease. Entrance RBE is ∼1.0 and ∼1.3 for protons and carbon ions, respectively. For doses in the range of 0.5 to 10 Gy, proton RBE ranges from 1.02 (proximal edge) to 1.4 (distal edge). Over the same dose range, the RBE for carbon ions ranges from 1.5 on the proximal edge to 6.7 on the distal edge. Conclusions: The proposed approach is advantageous because the RBE for clinically relevant particle distributions is guided by well-established physical and biological (track structure) considerations. The use of an independently tested Monte Carlo model to predict the effects of radiation quality on DSB induction also minimizes the number of ad hoc biological parameters that must be determined to predict RBE. Large variations in predicted RBE across an SOBP may produce undesirable biological hot and cold spots. These results highlight the potential for the optimization of physical dose for a uniform biological effect.

  7. New and emerging biologic therapies for moderate-to-severe plaque psoriasis: mechanistic rationales and recent clinical data for IL-17 and IL-23 inhibitors

    OpenAIRE

    Gaspari, Anthony A.; Tyring, Stephen

    2015-01-01

    The development of effective and well-tolerated biologic therapies has advanced the management of psoriasis by enabling clinicians to treat underlying disease mechanisms. Biologics approved for the treatment of moderate-to-severe psoriasis include three tumor necrosis factor alpha inhibitors and an interleukin-12/interleukin-23 inhibitor. The establishment of the immunological basis of psoriasis has led to the development of biologic agents targeting specific downstream mediators in the psori...

  8. Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans

    OpenAIRE

    Liang, X.; Penagaricano, J.; Zheng, D.; Morrill, S.; Zhang, X; Corry, P.; Griffin, R. J.; Han, E. Y.; Hardee, M.; Ratanatharathom, V.

    2016-01-01

    Background The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. Methods Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dos...

  9. Modeling metastasis biology and therapy in real time in the mouse lung

    OpenAIRE

    Mendoza, Arnulfo; Hong, Sung-Hyeok; Osborne, Tanasa; Khan, Mohammed A.; Campbell, Kirk; Briggs, Joseph; Eleswarapu, Ananth; Buquo, Lauren; Ren, Ling; Hewitt, Stephen M; Dakir, El-H; Garfield, Susan; Walker, Renard; Merlino, Glenn; Green, Jeffrey E

    2010-01-01

    Pulmonary metastasis remains the leading ca use of death for cancer patients. Opportunities to improve treatment outcomes for patients require new methods to study and view the biology of metastatic progression. Here, we describe an ex vivo pulmonary metastasis assay (PuMA) in which the metastatic progression of GFP-expressing cancer cells, from a single cell to the formation of multicellular colonies, in the mouse lung microenvironment was assessed in real time for up to 21 days. The biologi...

  10. From Molecular Biology to Clinical Trials: Toward Personalized Colorectal Cancer Therapy.

    Science.gov (United States)

    Palma, Sabina; Zwenger, Ariel O; Croce, María V; Abba, Martín C; Lacunza, Ezequiel

    2016-06-01

    During the past years, molecular studies through high-throughput technologies have led to the confirmation of critical alterations in colorectal cancer (CRC) and the discovery of some new ones, including mutations, DNA methylations, and structural chromosomal changes. These genomic alterations might act in concert to dysregulate specific signaling pathways that normally exert their functions on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Targeted therapy against key components of altered signaling pathways has allowed an improvement in CRC treatment. However, a significant percentage of patients with CRC and metastatic CRC will not benefit from these targeted therapies and will be restricted to systemic chemotherapy. Mechanisms of resistance have been associated with specific gene alterations. To fully understand the nature and significance of the genetic and epigenetic defects in CRC that might favor a tumor evading a given therapy, much work remains. Therefore, a dynamic link between basic molecular research and preclinical studies, which ultimately constitute the prelude to standardized therapies, is very important to provide better and more effective treatments against CRC. We present an updated revision of the main molecular features of CRC and their associated therapies currently under study in clinical trials. Moreover, we performed an unsupervised classification of CRC clinical trials with the aim of obtaining an overview of the future perspectives of preclinical studies. PMID:26777471

  11. 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

  12. Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ

    International Nuclear Information System (INIS)

    Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations. Patients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months. Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Median age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery. Preoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women

  13. Clinical and regulatory perspectives on biosimilar therapies and intended copies of biologics in rheumatology.

    Science.gov (United States)

    Mysler, Eduardo; Pineda, Carlos; Horiuchi, Takahiko; Singh, Ena; Mahgoub, Ehab; Coindreau, Javier; Jacobs, Ira

    2016-05-01

    Biologics are vital to the management of patients with rheumatic and musculoskeletal diseases such as rheumatoid arthritis and other inflammatory and autoimmune conditions. Nevertheless, access to these highly effective treatments remains an unmet medical need for many people around the world. As patents expire for existing licensed biologic (originator) products, biosimilar products can be approved by regulatory authorities and enter clinical use. Biosimilars are highly similar copies of originator biologics approved through defined and stringent regulatory processes after having undergone rigorous analytical, non-clinical, and clinical evaluations. The introduction of high-quality, safe, and effective biosimilars has the potential to expand access to these important medicines. Biosimilars are proven to be similar to the originator biologic in terms of safety and efficacy and to have no clinically meaningful differences. In contrast, "intended copies" are copies of originator biologics that have not undergone rigorous comparative evaluations according to the World Health Organization recommendations, but are being commercialized in some countries. There is a lack of information about the efficacy and safety of intended copies compared with the originator. Furthermore, they may have clinically significant differences in formulation, dosages, efficacy, or safety. In this review, we explore the differences between biosimilars and intended copies and describe key concepts related to biosimilars. Familiarity with these topics may facilitate decision making about the appropriate use of biosimilars for patients with rheumatic and musculoskeletal diseases. PMID:26920148

  14. Biological therapies in the systemic management of psoriasis : International Consensus Conference

    NARCIS (Netherlands)

    Sterry, W.; Barker, J.; Boehncke, W.H.; Bos, J.D.; Chimenti, S.; Christophers, E.; Brassinne, M. de la; Ferrandiz, C.; Griffiths, C.E.; Katsambas, A.; Kragballe, K.; Lynde, C.; Menter, A.; Ortonne, J.P.; Papp, K.A.; Prinz, J.C.; Rzany, B.; Ronnevig, J.; Saurat, J.H.; Stahle, M.; Stengel, F.M.; Kerkhof, P.C.M. van de; Voorhees, J.

    2004-01-01

    Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management

  15. Low power laser therapy — an introduction and a review of some biological effects

    OpenAIRE

    Thiel, Haymo

    1986-01-01

    This report gives a brief introduction to the characteristics of therapeutic low power laser devices. Absorption, tissue penetration and physiological mechanisms of laser irradiation are discussed. The biological effects of low power laser light are reviewed in the areas of collagen metabolism, woundhealing, inflammation and pain control. Contraindications, precautions and side effects of low power laser irradiation are discussed.

  16. Concomitant fibromyalgia in rheumatoid arthritis is associated with the more frequent use of biological therapy

    DEFF Research Database (Denmark)

    Lage-Hansen, P R; Chrysidis, S; Lage-Hansen, M;

    2015-01-01

    OBJECTIVES: To compare the 28-joint Disease Activity Score (DAS28) and its components in patients with rheumatoid arthritis (RA) with and without concomitant fibromyalgia (FM), and to investigate the use of biological treatment in the two groups. METHOD: Questionnaires developed to diagnose FM were...

  17. Rheumatoid arthritis therapy with genetically engineered biological agents in the Republic of Karelia

    Directory of Open Access Journals (Sweden)

    Irina Mikhailovna Marusenko

    2013-01-01

    Full Text Available The paper considers whether a current treatment option for rheumatoid arthritis with genetically engineered biological agents that selectively block the activity of individual proinflammatory mediators and cell surface antigens involved in autoimmune inflammation may be performed in Karelia, which can achieve control of the disease, retard its progression, and improve prognosis.

  18. Rheumatoid arthritis therapy with genetically engineered biological agents in the Republic of Karelia

    Directory of Open Access Journals (Sweden)

    Irina Mikhailovna Marusenko

    2013-12-01

    Full Text Available The paper considers whether a current treatment option for rheumatoid arthritis with genetically engineered biological agents that selectively block the activity of individual proinflammatory mediators and cell surface antigens involved in autoimmune inflammation may be performed in Karelia, which can achieve control of the disease, retard its progression, and improve prognosis.

  19. Rheumatoid arthritis therapy with genetically engineered biological agents in the Republic of Karelia

    OpenAIRE

    Irina Mikhailovna Marusenko

    2013-01-01

    The paper considers whether a current treatment option for rheumatoid arthritis with genetically engineered biological agents that selectively block the activity of individual proinflammatory mediators and cell surface antigens involved in autoimmune inflammation may be performed in Karelia, which can achieve control of the disease, retard its progression, and improve prognosis.

  20. Rheumatoid arthritis and periodontitis: Biological links and the emergence of dual purpose therapies

    Directory of Open Access Journals (Sweden)

    Modi Depinder

    2009-01-01

    Full Text Available Rheumatoid arthritis and periodontitis are widely prevalent diseases and are characterized by tissue destruction due to chronic inflammation. Recently, there is growing evidence that the two diseases share many pathological features. This article reviews their clinical and biological links. However, there are only a limited number of studies in this area, which prevent us from offering clear evidence.

  1. Heavy charged particle radiobiology: using enhanced biological effectiveness and improved beam focusing to advance cancer therapy.

    Science.gov (United States)

    Allen, Christopher; Borak, Thomas B; Tsujii, Hirohiko; Nickoloff, Jac A

    2011-06-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. PMID:21376738

  2. A two decade contribution of molecular cell biology to the centennial of Alzheimer's disease: are we progressing toward therapy?

    Science.gov (United States)

    Dillen, Katleen; Annaert, Wim

    2006-01-01

    Alzheimer's disease (AD), described for the first time 100 years ago, is a neurodegenerative disease characterized by two neuropathological hallmarks: neurofibrillary tangles containing hyperphosphorylated tau and senile plaques. These lesions are likely initiated by an imbalance between production and clearance of amyloid beta, leading to increased oligomerization of these peptides, formation of amyloid plaques in the brain of the patient, and final dementia. Amyloid beta is generated from amyloid precursor protein (APP) by subsequent beta- and gamma-secretase cleavage, the latter being a multiprotein complex consisting of presenilin-1 or -2, nicastrin, APH-1, and PEN-2. Alternatively, APP can be cleaved by alpha- and gamma-secretase, precluding the production of Abeta. In this review, we discuss the major breakthroughs during the past two decades of molecular cell biology and the current genetic and cell biological state of the art on APP proteolysis, including structure-function relationships and subcellular localization. Finally, potential directions for cell biological research toward the development of AD therapies are briefly discussed. PMID:17148000

  3. MELOMICS: Contributions of computer science and biology to receptive music therapy

    OpenAIRE

    Vico Vela, Francisco José; Sánchez Quintana, Carlos Alberto; Albarracín Molina, David

    2014-01-01

    It is surprising the fact that while the personalized medicine model is more and more accepted, receptive music therapy is still applied collectively. Although, in some hospitals the subject (patient or health-medical staff) is allowed to select the genre or artist, with most published clinical studies reporting on concrete types of music (eg, relaxing or classical) that are applied to groups of patients. Customizing songs to patient characteristics would make the study much more complex: ...

  4. The biological effects of extracorporeal shock wave therapy (eswt) on tendon tissue

    OpenAIRE

    Notarnicola, Angela; Moretti, Biagio

    2012-01-01

    There is currently great interest in the use of Extracorporeal Shock Wave Therapy (ESWT) and in clarifying the mechanisms of action in tendon pathologies. The success rate ranges from 60% to 80% in epicondylitis, plantar fasciitis, cuff tendinitis, trocanteritis, Achilles tendinitis or jumper’s knee. In contrast to urological treatments (lithotripsy), where shockwaves are used to disintegrate renal stones, in musculoskeletal treatments (orthotripsy), shockwaves are not being used to disintegr...

  5. Biological therapy with TNF-inhibitors in pediatric rheumatology. Review of the litterature and personal experience

    OpenAIRE

    F. Fantini; Gattinara, M; Pontikaki, I; Gerloni, V

    2011-01-01

    The therapeutic approach to JIA is sometimes very troublesome and progression to erosive polyarthritis may occur in all JIA categories. Only Methotrexate has shown efficacy and safety in a large controlled trial. Nevertheless, in many cases, drug resistance or intolerance has led to try other therapeutic options, with still debatable results. Therefore, there has been space, in the last few years, for new therapies as the TNF-inhibitors. This therapeutic approach has shown a dramatic clinical...

  6. Heavy Charged Particle Radiobiology: Using Enhanced Biological Effectiveness and Improved Beam Focusing to Advance Cancer Therapy

    OpenAIRE

    Allen, Christopher; Borak, Thomas B.; Tsujii, Hirohiko; Jac A Nickoloff

    2011-01-01

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilitie...

  7. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Koritzinsky, Marianne, E-mail: mkoritzi@uhnresearch.ca

    2015-10-01

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers.

  8. [Molecular biological foundation of targeted therapy for metastatic renal cell carcinoma].

    Science.gov (United States)

    Chong, Lai; Xiaodong, Teng

    2016-05-25

    The incidence of renal cell carcinoma (RCC) is increasing. Radical cure by surgery can only be achieved in patients with early stage tumors. How to precisely use antineoplastic agents after surgery is an important problem to be solved. Most metastatic RCCs are pathologically identified as clear cell RCC (ccRCC), thus to develop agents targeting ccRCC is critical. Most clinically available targeted therapies are based on targeting some spots in specific pathways; or based on targeting new anti-tumor mechanisms, such as programmed death-1(PD-1), antibody-drug conjugates (ADC) and stem cells. There is still no targeted therapy having definite effect to most RCC patients. Only von Hippel-Lindau (VHL) pathway so far has been confirmed to be related to ccRCC development and progression; the inactivation of VHL gene causes many significant downstream gene changes. The key proteins involved in VHL pathway may be potential therapeutic targets for ccRCC. In this article, we review the current progress of targeted therapy for RCC, focus on the molecular characteristics of ccRCC, its relation to VHL pathway, the potential therapeutic targets and future clinical application for metastatic ccRCC. PMID:27045248

  9. Metformin: A Novel Biological Modifier of Tumor Response to Radiation Therapy

    International Nuclear Information System (INIS)

    Over the last decade, evidence has emerged to support a role for the antidiabetic drug metformin in the prevention and treatment of cancer. In particular, recent studies demonstrate that metformin enhances tumor response to radiation in experimental models, and retrospective analyses have shown that diabetic cancer patients treated with radiation therapy have improved outcomes if they take metformin to control their diabetes. Metformin may therefore be of utility for nondiabetic cancer patients treated with radiation therapy. The purpose of this review is to examine the data pertaining to an interaction between metformin and radiation, highlighting the essential steps needed to advance our current knowledge. There is also a focus on key biomarkers that should accompany prospective clinical trials in which metformin is being examined as a modifying agent with radiation therapy. Existing evidence supports that the mechanism underlying the ability of metformin to enhance radiation response is multifaceted, and includes direct radiosensitization as well as a reduction in tumor stem cell fraction, proliferation, and tumor hypoxia. Interestingly, metformin may enhance radiation response specifically in certain genetic backgrounds, such as in cells with loss of the tumor suppressors p53 and LKB1, giving rise to a therapeutic ratio and potential predictive biomarkers

  10. Impact of tissue specific parameters on the predition of the biological effectiveness for treatment planning in ion beam therapy

    International Nuclear Information System (INIS)

    Treatment planning in ion beam therapy requires a reliable estimation of the relative biological effectiveness (RBE) of the irradiated tissue. For the pilot project at GSI Helmholtzzentrum fuer Schwerionenforschung GmbH and at other European ion beam therapy centers RBE prediction is based on a biophysical model, the Local Effect Model (LEM). The model version in use, LEM I, is optimized to give a reliable estimation of RBE in the target volume for carbon ion irradiation. However, systematic deviations are observed for the entrance channel of carbon ions and in general for lighter ions. Thus, the LEM has been continuously developed to improve accuracy. The recent version LEM IV has proven to better describe in-vitro cell experiments. Thus, for the clinical application of LEM IV it is of interest to analyze potential differences compared to LEM I under treatment-like conditions. The systematic analysis presented in this work is aiming at the comparison of RBE-weighted doses resulting from different approaches and model versions for protons and carbon ions. This will facilitate the assessment of consequences for clinical application and the interpretation of clinical results from different institutions. In the course of this thesis it has been shown that the RBE-weighted doses predicted on the basis of LEM IV for typical situations representing chordoma treatments differ on average by less than 10 % to those based on LEM I and thus also allow a consistent interpretation of the clinical results. At Japanese ion beam therapy centers the RBE is estimated using their clinical experience from neutron therapy in combination with in-vitro measurements for carbon ions (HIMAC approach). The methods presented in this work allow direct comparison of the HIMAC approach and the LEM and thus of the clinical results obtained at Japanese and European ion beam therapy centers. Furthermore, the sensitivity of the RBE on the model parameters was evaluated. Among all parameters the

  11. Establishing a new marketplace for biologic therapy with biosimilar agents: importance of extrapolation of data

    OpenAIRE

    Bressler B; Dingermann T

    2015-01-01

    Brian Bressler,1 Theo Dingermann2 1St Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Institute of Pharmaceutical Biology, Frankfurt, Germany Abstract: Despite their enormous value for our health care system, biopharmaceuticals have become a serious threat to the system itself due to their high cost. Costs may be warranted if the medicine is new and innovative; however, it is no longer an innovation when its patent protection expires. As patents and exclusiviti...

  12. Biologic Mechanisms of Oral Cancer Pain and Implications for Clinical Therapy

    OpenAIRE

    Viet, C.T.; SCHMIDT, B.L.

    2012-01-01

    Cancer pain is an ever-present public health concern. With innovations in treatment, cancer patients are surviving longer, but uncontrollable pain creates a poor quality of life for these patients. Oral cancer is unique in that it causes intense pain at the primary site and significantly impairs speech, swallowing, and masticatory functions. We propose that oral cancer pain has underlying biologic mechanisms that are generated within the cancer microenvironment. A comprehensive understanding ...

  13. Choice of Biologic Therapy for Patients with Rheumatoid Arthritis: The Infection Perspective

    OpenAIRE

    De Keyser, Filip

    2011-01-01

    Biologicals revolutionized the treatment of Rheumatoid Arthritis (RA). The targeted suppression of key inflammatory pathways involved in joint inflammation and destruction allows better disease control, which, however, comes at the price of an elevated infection risk due to relative immunosuppression. The disease-related infection risk and the infection risk associated with the use of TNF-α inhibitors (infliximab, adalimumab, etanercept, golimumab and certolizumab pegol), rituximab, abatacept...

  14. Cyclin E Transgenic Mice: Discovery Tools for Lung Cancer Biology, Therapy, and Prevention

    OpenAIRE

    Freemantle, Sarah J.; Dmitrovsky, Ethan

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in the United States and many other countries. This fact underscores the need for clinically relevant models to increase our understanding of lung cancer biology and to help design and implement preventive and more-effective therapeutic interventions for lung cancer. New murine transgenic models of non-small cell lung cancer (NSCLC) have been engineered for this purpose. In one such model, overexpression of the cell-cycle regulator ...

  15. Biological Therapies for Cartilage Lesions in the Hip: A New Horizon.

    Science.gov (United States)

    Chahla, Jorge; LaPrade, Robert F; Mardones, Rodrigo; Huard, Johnny; Philippon, Marc J; Nho, Shane; Mei-Dan, Omer; Pascual-Garrido, Cecilia

    2016-07-01

    Treatment of hip cartilage disease is challenging, and there is no clear algorithm to address this entity. Biomarkers are arising as promising diagnostic tools because they could play a role in the early assessment of the prearthritic joint and as a prognostic factor before and after treatment. The potential effect of biomarkers may be used to categorize individuals at risk of evolving to severe osteoarthritis, to develop new measures for clinical progression of the disease, and to develop new treatment options for the prevention of osteoarthritis progression. A trend toward a less invasive biological treatment will usher in a new treatment era. With the growth of surgical skills in hip arthroscopy, cartilage restoration techniques are evolving in a fast and exponential manner. Biological and surgical treatments have been proposed to treat these pathologies. Biological treatments include platelet-rich plasma, stem cells or bone marrow aspirate concentration, hyaluronic acid, losartan, and fish oil. Surgical treatments include microfracture alone or augmented, direct repair, autologous chondrocyte implantation, matrix-induced chondrocyte implantation, autologous matrix-induced chondrogenesis, mosaicplasty, osteochondral allograft transplantation, and stem cells implanted in matrix (stem cells in membranes/expanded stem cells). This article reviews new evidence available on treatment options for chondral lesions and early osteoarthritis of the hip. [Orthopedics. 2016; 39(4):e715-e723.]. PMID:27359284

  16. Establishing a new marketplace for biologic therapy with biosimilar agents: importance of extrapolation of data

    Directory of Open Access Journals (Sweden)

    Bressler B

    2015-06-01

    Full Text Available Brian Bressler,1 Theo Dingermann2 1St Paul’s Hospital, University of British Columbia, Vancouver, BC, Canada; 2Institute of Pharmaceutical Biology, Frankfurt, Germany Abstract: Despite their enormous value for our health care system, biopharmaceuticals have become a serious threat to the system itself due to their high cost. Costs may be warranted if the medicine is new and innovative; however, it is no longer an innovation when its patent protection expires. As patents and exclusivities expire on biological drugs, biosimilar products defined as highly similar to reference biologics are being marketed. The goal of biosimilar development is to establish a high degree of biosimilarity, not to reestablish clinical efficacy and safety. Current sophisticated analytical methods allow the detection of even small changes in quality attributes and can therefore enable sensitive monitoring of the batch-to-batch consistency and variability of the manufacturing process. The European Medicines Agency (EMA, US Food and Drug Administration (FDA, and Health Canada have determined that a reduced number of nonclinical and clinical comparative studies can be sufficient for approval with clinical data from the most sensitive indication extrapolated to other indications. Extrapolation of data is a scientifically based principle, guided by specific criteria, and if approved by the EMA, FDA, and/or Health Canada is appropriate. Enablement of extrapolation of data is a core principle of biosimilar development, based on principles of comparability and necessary to fully realize cost savings for these drugs. Keywords: biosimilars, Inflectra, infliximab, pharmacoeconomics, Canada, Europe 

  17. Physical and biological pretreatment quality assurance of the head and neck cancer plan with the volumetric modulated arc therapy

    Science.gov (United States)

    Park, So-Hyun; Lee, Dong-Soo; Lee, Yun-Hee; Lee, Seu-Ran; Kim, Min-Ju; Suh, Tae-Suk

    2015-09-01

    The aim of this work is to demonstrate both the physical and the biological quality assurance (QA) aspects as pretreatment QA of the head and neck (H&N) cancer plan for the volumetric modulated arc therapy (VMAT). Ten H&N plans were studied. The COMPASS® dosimetry analysis system and the tumor control probability (TCP) and the normal tissue complication probability (NTCP) calculation free program were used as the respective measurement and calculation tools. The reliability of these tools was verified by a benchmark study in accordance with the TG-166 report. For the physical component of QA, the gamma passing rates and the false negative cases between the calculated and the measured data were evaluated. The biological component of QA was performed based on the equivalent uniform dose (EUD), TCP and NTCP values. The evaluation was performed for the planning target volumes (PTVs) and the organs at risks (OARs), including the eyes, the lens, the parotid glands, the esophagus, the spinal cord, and the brainstem. All cases had gamma passing rates above 95% at an acceptance tolerance level with the 3%/3 mm criteria. In addition, the false negative instances were presented for the PTVs and OARs. The gamma passing rates exhibited a weak correlation with false negative cases. For the biological QA, the physical dose errors affect the EUD and the TCP for the PTVs, but no linear correlation existed between them. The EUD and NTCP for the OARs were shown the random differences that could not be attributed to the dose errors from the physical QA. The differences in the EUD and NTCP between the calculated and the measured results were mainly demonstrated for the parotid glands. This study describes the importance and the necessity of improved QA to accompany both the physical and the biological aspects for accurate radiation treatment.

  18. Nano-Bio-Technology and Sensing Chips: New Systems for Detection in Personalized Therapies and Cell Biology

    Directory of Open Access Journals (Sweden)

    Sandro Carrara

    2010-01-01

    Full Text Available Further advances in molecular medicine and cell biology also require new electrochemical systems to detect disease biomarkers and therapeutic compounds. Microelectronic technology offers powerful circuits and systems to develop innovative and miniaturized biochips for sensing at the molecular level. However, microelectronic biochips proposed in the literature often do not show the right specificity, sensitivity, and reliability required by biomedical applications. Nanotechnology offers new materials and solutions to improve the surface properties of sensing probes. The aim of the present paper is to review the most recent progress in Nano-Bio-Technology in the area of the development of new electrochemical systems for molecular detection in personalized therapy and cell culture monitoring.

  19. Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies

    CERN Document Server

    Wambersie, A; Menzel, H G; Gahbauer, R; DeLuca, P M; Hendry, J H; Jones, D T L

    2011-01-01

    When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatment prescription. However, the clinical outcome does not only depend on absorbed dose but also on a number of other factors such as dose per fraction, overall treatment time and radiation quality radiation biology effectiveness (RBE). Therefore, weighting factors have to be applied when different types of treatments are to be compared or to be combined. This had led to the concept of `isoeffective absorbed dose', introduced by ICRU and International Atomic Energy Agency (IAEA). The isoeffective dose D(IsoE) is the dose of a treatment carried out under reference conditions producing the same clinical effects on the target volume as those of the actual treatment. It i...

  20. Biological dosimetry studies for boron neutron capture therapy at the RA-1 research reactor facility

    International Nuclear Information System (INIS)

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminescent dosimeters to characterize the BNCT facility developed at the RA-1 research reactor operated by the National Atomic Energy Commission in Buenos Aires. Biological dosimetry was performed employing the hamster cheek pouch oral cancer model previously validated for BNCT studies by our group. Results indicate that the RA-1 neutron source produces useful dose rates for BNCT studies but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications. (author)

  1. Use of biological based therapy in patients with cardiovascular diseases in a university-hospital in New York City

    Directory of Open Access Journals (Sweden)

    Rozenfeld Vitalina

    2005-03-01

    Full Text Available Abstract Background The use of complementary and alternative products including Biological Based Therapy (BBT has increased among patients with various medical illnesses and conditions. The studies assessing the prevalence of BBT use among patients with cardiovascular diseases are limited. Therefore, an evaluation of BBT in this patient population would be beneficial. This was a survey designed to determine the effects of demographics on the use of Biological Based Therapy (BBT in patients with cardiovascular diseases. The objective of this study was to determine the effect of the education level on the use of BBT in cardiovascular patients. This survey also assessed the perceptions of users regarding the safety/efficacy of BBT, types of BBT used and potential BBT-drug interactions. Method The survey instrument was designed to assess the findings. Patients were interviewed from February 2001 to December 2002. 198 inpatients with cardiovascular diseases (94 BBT users and 104 non-users in a university hospital were included in the study. Results Users had a significantly higher level of education than non-users (college graduate: 28 [30%] versus 12 [12%], p = 0.003. Top 10 BBT products used were vitamin E [41(43.6%], vitamin C [30(31.9%], multivitamins [24(25.5%], calcium [19(20.2%], vitamin B complex [17(18.1%], fish oil [12(12.8%], coenzyme Q10 [11(11.7%], glucosamine [10(10.6%], magnesium [8(8.5%] and vitamin D [6(6.4%]. Sixty percent of users' physicians knew of the BBT use. Compared to non-users, users believed BBT to be safer (p Conclusion Incidence of use of BBT in cardiovascular patients is high (47.5%, as is the risk of potential drug interaction. Health care providers need to monitor BBT use in patients with cardiovascular diseases.

  2. Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective

    International Nuclear Information System (INIS)

    The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small-cell lung cancers (NSCLCs). This presents an opportune target for new treatment strategies designed to selectively interfere with the cancer cell growth cycle. Recent investigations into the biology of the EGFR and its downstream signaling pathways have reminded us of the complexity of cancer cell communications from the cytoplasm to the nucleus. Multiple pathways are activated with stimulation of the autocrine and paracrine EGFR loop, from the ras-raf-MEK activation of ERK 1/2 to the P13K-Akt pathway, each playing an important role in cancer cell survival, invasion, and angiogenesis. Preclinical studies have demonstrated that molecules targeting the EGFR, either through extracellular blockade or intracellular interference with the EGFR-associated tyrosine kinase, reversibly or irreversibly, inhibit cancer cell growth. Potent antitumor effects have been observed in human tumor xenograft models. Preclinical studies have also demonstrated cooperative effects when anti-EGFR agents are combined with radiation or chemotherapy. Many of these agents have now entered into advanced human clinical trials with modest dose-related toxicity despite chronic administration. Encouraging response rates with single-agent targeted therapy have been reported in heavily pretreated patients with advanced NSCLC. In addition, agents targeting the angiogenic pathway, which plays a key role in the regulation of angiogenesis, may play an important role in enhancing the efficacy of anti-EGFR agents. This article will focus on the biology, rationale, and preclinical studies with targeted anti-EGFR and antiangiogenic therapies for the management of NSCLC

  3. Molecular markers and biological targeted therapies in metastatic colorectal cancer: expert opinion and recommendations derived from the 11th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2009.

    Science.gov (United States)

    Van Cutsem, E; Dicato, M; Arber, N; Berlin, J; Cervantes, A; Ciardiello, F; De Gramont, A; Diaz-Rubio, E; Ducreux, M; Geva, R; Glimelius, B; Glynne Jones, R; Grothey, A; Gruenberger, T; Haller, D; Haustermans, K; Labianca, R; Lenz, H J; Minsky, B; Nordlinger, B; Ohtsu, A; Pavlidis, N; Rougier, P; Schmiegel, W; Van de Velde, C; Schmoll, H J; Sobrero, A; Tabernero, J

    2010-06-01

    The article summarizes the expert discussion and recommendations on the use of molecular markers and of biological targeted therapies in metastatic colorectal cancer (mCRC), as well as a proposed treatment decision strategy for mCRC treatment. The meeting was conducted during the 11th ESMO/World Gastrointestinal Cancer Congress (WGICC) in Barcelona in June 2009. The manuscript describes the outcome of an expert discussion leading to an expert recommendation. The increasing knowledge on clinical and molecular markers and the availability of biological targeted therapies have major implications in the optimal management in mCRC. PMID:20534623

  4. BIOLOGICAL THERAPY AND INFECTIONS IN PATIENTS WITH RHEUMATOID ARTHRITIS: RELEVANCE AND PROSPECTS

    Directory of Open Access Journals (Sweden)

    B. S. Belov

    2014-01-01

    Full Text Available The past decades are marked by the obvious progress in rheumatology, which is related to the practical introduction of biological agents. At the same time the use of these drugs is associated with the increasing risk of infections of different nature and locations, including opportunistic ones (invasive mycoses, Pneumocystis pneumonia, etc., and with the greater risk of reactivation of latent infection, primary with that of tuberculosis. Beyond that point, there are cases of severe infections (pneumonia, sepsis, bacterial arthritis, skin and soft tissue lesions, etc., including those with a fatal outcome. This review analyzes mainly the past 3-year literature data on the rate and location of infections treated with biologics, which have been obtained in the placebo-controlled and direct comparative studies of patients with rheuma- toid arthritis. It characterizes the importance of different infections (tuberculosis, pneumonia, chronic viral hepati- tides, herpesvirus infections, etc. for treatment policy in the above patients. This underlines the need for wider immu- nization with different vaccines (chiefly against pneumococcus and influenza in patients with autoimmune inflam- matory rheumatic diseases. 

  5. Biologic therapies in the metastatic colorectal cancer treatment continuum--applying current evidence to clinical practice.

    Science.gov (United States)

    Peeters, Marc; Price, Timothy

    2012-08-01

    More therapeutic options are now available than ever before for patients with metastatic colorectal cancer (mCRC) and, as such, treatment decisions have become more complex. A multidisciplinary approach is, therefore, required to effectively manage these patients. In the past few years, many trials have reported on the value of combining biological agents, such as those targeting vascular endothelial growth factor A and epidermal growth factor receptors, with chemotherapy. However, despite the plethora of information now available, the optimal treatment strategy for patients with mCRC remains unclear. Indeed, the propensity of investigators to conduct clinical trials utilising a variety of chemotherapy backbones combined with the increased complexity of retrospectively incorporating analyses of genetic mutation status (e.g. KRAS and BRAF) have led to conflicting results for seemingly similar endpoints, particularly overall survival. As a result, guidelines that have been developed, whilst having some similarities, have distinct differences in terms of suggested therapeutic combinations. Therefore, here, we review and distil the currently available data reported from phase III trials of biologic agents in the first-, second- and third-line mCRC settings. PMID:21899955

  6. The FLUKA Monte Carlo code coupled with the local effect model for biological calculations in carbon ion therapy

    CERN Document Server

    Mairani, A; Kraemer, M; Sommerer, F; Parodi, K; Scholz, M; Cerutti, F; Ferrari, A; Fasso, A

    2010-01-01

    Clinical Monte Carlo (MC) calculations for carbon ion therapy have to provide absorbed and RBE-weighted dose. The latter is defined as the product of the dose and the relative biological effectiveness (RBE). At the GSI Helmholtzzentrum fur Schwerionenforschung as well as at the Heidelberg Ion Therapy Center (HIT), the RBE values are calculated according to the local effect model (LEM). In this paper, we describe the approach followed for coupling the FLUKA MC code with the LEM and its application to dose and RBE-weighted dose calculations for a superimposition of two opposed C-12 ion fields as applied in therapeutic irradiations. The obtained results are compared with the available experimental data of CHO (Chinese hamster ovary) cell survival and the outcomes of the GSI analytical treatment planning code TRiP98. Some discrepancies have been observed between the analytical and MC calculations of absorbed physical dose profiles, which can be explained by the differences between the laterally integrated depth-d...

  7. Method for estimating optimal spectral and energy parameters of laser irradiation in photodynamic therapy of biological tissue

    Science.gov (United States)

    Lisenko, S. A.; Kugeiko, M. M.

    2015-04-01

    We have solved the problem of layer-by-layer laser-light dosimetry in biological tissues and of selecting an individual therapeutic dose in laser therapy. A method is proposed for real-time monitoring of the radiation density in tissue layers in vivo, concentrations of its endogenous (natural) and exogenous (specially administered) chromophores, as well as in-depth distributions of the spectrum of light action on these chromophores. As the background information use is made of the spectrum of diffuse light reflected from a patient's tissue, measured by a fibre-optic spectrophotometer. The measured spectrum is quantitatively analysed by the method of approximating functions for fluxes of light multiply scattered in tissue and by a semi-analytical method for calculating the in-depth distribution of the light flux in a multi-layered medium. We have shown the possibility of employing the developed method for monitoring photosensitizer and oxyhaemoglobin concentrations in tissue, light power absorbed by chromophores in tissue layers at different depths and laser-induced changes in the tissue morphology (vascular volume content and ratios of various forms of haemoglobin) during photodynamic therapy.

  8. Stem cell therapy: a promising biological strategy for tendon-bone healing after anterior cruciate ligament reconstruction.

    Science.gov (United States)

    Hao, Zi-Chen; Wang, Shan-Zheng; Zhang, Xue-Jun; Lu, Jun

    2016-04-01

    Tendon-bone healing after anterior cruciate ligament (ACL) reconstruction is a complex process, impacting significantly on patients' prognosis. Natural tendon-bone healing usually results in fibrous scar tissue, which is of inferior quality compared to native attachment. In addition, the early formed fibrous attachment after surgery is often not reliable to support functional rehabilitation, which may lead to graft failure or unsatisfied function of the knee joint. Thus, strategies to promote tendon-bone healing are crucial for prompt and satisfactory functional recovery. Recently, a variety of biological approaches, including active substances, gene transfer, tissue engineering and stem cells, have been proposed and applied to enhance tendon-bone healing. Among these, stem cell therapy has been shown to have promising prospects and draws increasing attention. From commonly investigated bone marrow-derived mesenchymal stem cells (bMSCs) to emerging ACL-derived CD34+ stem cells, multiple stem cell types have been proven to be effective in accelerating tendon-bone healing. This review describes the current understanding of tendon-bone healing and summarizes the current status of related stem cell therapy. Future limitations and perspectives are also discussed. PMID:26929145

  9. Synthesis and biological evaluation of boronated polyglycerol dendrimers as potential agent for neutron capture therapy

    International Nuclear Information System (INIS)

    In this work, the polyglycerol dendrimer (PGLD) generation 5 was used to obtain a boronated macromolecule for boron neutron capture therapy. The PGLD dendrimer was synthesized by the ring opening polymerization of deprotonated glycidol using polyglycerol as core functionality in a step-growth processes denominated divergent synthesis. The PGLD dendritic structure was confirmed by gel permeation chromatography, nuclear magnetic resonance (1H-NMR, 13C-NMR) and matrix assisted laser desorption/ionization techniques. The synthesized dendrimer presented low dispersion in molecular weights (Mw/Mn = 1.05) and a degree of branching of 0.82, which characterize the polymer dendritic structure. Quantitative neutron capture radiography was used to investigate the boron-10 enrichment of the polyglycerol dendrimer. The in vitro cytotoxicity to Chinese hamster ovary cells of 10B-PGLD dendrimer indicate lower cytotoxicity, suggesting that the macromolecule is a biocompatible material. (author)

  10. Mitochondria in mesenchymal stem cell biology and cell therapy: From cellular differentiation to mitochondrial transfer.

    Science.gov (United States)

    Hsu, Yi-Chao; Wu, Yu-Ting; Yu, Ting-Hsien; Wei, Yau-Huei

    2016-04-01

    Mesenchymal stem cells (MSCs) are characterized to have the capacity of self-renewal and the potential to differentiate into mesoderm, ectoderm-like and endoderm-like cells. MSCs hold great promise for cell therapies due to their multipotency in vitro and therapeutic advantage of hypo-immunogenicity and lower tumorigenicity. Moreover, it has been shown that MSCs can serve as a vehicle to transfer mitochondria into cells after cell transplantation. Mitochondria produce most of the energy through oxidative phosphorylation in differentiated cells. It has been increasingly clear that the switch of energy supply from glycolysis to aerobic metabolism is essential for successful differentiation of MSCs. Post-translational modifications of proteins have been established to regulate mitochondrial function and metabolic shift during MSCs differentiation. In this article, we review and provide an integrated view on the roles of different protein kinases and sirtuins in the maintenance and differentiation of MSCs. Importantly, we provide evidence to suggest that alteration in the expression of Sirt3 and Sirt5 and relative changes in the acylation levels of mitochondrial proteins might be involved in the activation of mitochondrial function and adipogenic differentiation of adipose-derived MSCs. We summarize their roles in the regulation of mitochondrial biogenesis and metabolism, oxidative responses and differentiation of MSCs. On the other hand, we discuss recent advances in the study of mitochondrial dynamics and mitochondrial transfer as well as their roles in the differentiation and therapeutic application of MSCs to improve cell function in vitro and in animal models. Accumulating evidence has substantiated that the therapeutic potential of MSCs is conferred not only by cell replacement and paracrine effects but also by transferring mitochondria into injured tissues or cells to modulate the cellular metabolism in situ. Therefore, elucidation of the underlying mechanisms

  11. Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy.

    Science.gov (United States)

    Sell, Stewart; Nicolini, Andrea; Ferrari, Paola; Biava, Pier M

    2016-01-01

    Current medical literature acknowledges that embryonic micro-environment is able to suppress tumor development. Administering carcinogenic substances during organogenesis in fact leads to embryonic malformations, but not to offspring tumor growth. Once organogenesis has ended, administration of carcinogenic substances causes a rise in offspring tumor development. These data indicate that cancer can be considered a deviation in normal development, which can be regulated by factors of the embryonic microenvironment. Furthermore, it has been demonstrated that teratoma differentiates into normal tissues once it is implanted in the embryo. Recently, it has been shown that implanting a melanoma in Zebrafish embryo did not result in a tumor development; however, it did in the adult specimen. This demonstrates that cancer cells can differentiate into normal tissues when implanted in the embryo. In addition, it was demonstrated that other tumors can revert into a normal phenotype and/or differentiate into normal tissue when implanted in the embryo. These studies led some authors to define cancer as a problem of developmental biology and to predict the present concept of "cancer stem cells theory". In this review, we record the most important researches about the reprogramming and differentiation treatments of cancer cells to better clarify how the substances taken from developing embryo or other biological substances can induce differentiation of malignant cells. Lastly, a model of cancer has been proposed here, conceived by one of us, which is consistent with the reality, as demonstrated by a great number of researches. This model integrates the theory of the "maturation arrest" of cancer cells as conceived by B. Pierce with the theory which describes cancer as a process of deterministic chaos determined by genetic and/or epigenetic alterations in differentiated cells, which leads a normal cell to become cancerous. All the researches here described demonstrated that cancer

  12. WE-D-BRE-07: Variance-Based Sensitivity Analysis to Quantify the Impact of Biological Uncertainties in Particle Therapy

    International Nuclear Information System (INIS)

    Purpose: In particle therapy, treatment planning and evaluation are frequently based on biological models to estimate the relative biological effectiveness (RBE) or the equivalent dose in 2 Gy fractions (EQD2). In the context of the linear-quadratic model, these quantities depend on biological parameters (α, β) for ions as well as for the reference radiation and on the dose per fraction. The needed biological parameters as well as their dependency on ion species and ion energy typically are subject to large (relative) uncertainties of up to 20–40% or even more. Therefore it is necessary to estimate the resulting uncertainties in e.g. RBE or EQD2 caused by the uncertainties of the relevant input parameters. Methods: We use a variance-based sensitivity analysis (SA) approach, in which uncertainties in input parameters are modeled by random number distributions. The evaluated function is executed 104 to 106 times, each run with a different set of input parameters, randomly varied according to their assigned distribution. The sensitivity S is a variance-based ranking (from S = 0, no impact, to S = 1, only influential part) of the impact of input uncertainties. The SA approach is implemented for carbon ion treatment plans on 3D patient data, providing information about variations (and their origin) in RBE and EQD2. Results: The quantification enables 3D sensitivity maps, showing dependencies of RBE and EQD2 on different input uncertainties. The high number of runs allows displaying the interplay between different input uncertainties. The SA identifies input parameter combinations which result in extreme deviations of the result and the input parameter for which an uncertainty reduction is the most rewarding. Conclusion: The presented variance-based SA provides advantageous properties in terms of visualization and quantification of (biological) uncertainties and their impact. The method is very flexible, model independent, and enables a broad assessment of

  13. Hospital Admissions, Biological Therapy, and Surgery in Familial and Sporadic Cases of Inflammatory Bowel Disease

    DEFF Research Database (Denmark)

    Trier Moller, Frederik; Andersen, Vibeke; Andersson, Mikael;

    2015-01-01

    -related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial and......BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial...... and sporadic cases of IBD in a nationwide cohort study. METHODS: From national registries, covering a population of 8,295,773 individuals, we obtained information on date and year of diagnosis of IBD cases, gender, age, and family ties. Using Cox regression, we estimated hazard ratios for IBD...

  14. IMPACT OF BIOLOGICAL THERAPY ON BONE IN PATIENTS WITH RHEUMATOID ARTHRITIS

    Directory of Open Access Journals (Sweden)

    P. S. Dydykina

    2014-12-01

    Full Text Available The paper gives the data currently available in the literature on the impact of biological agents (BA on bone mineral density, metabolism, and remodeling in rheumatoid arthritis (RA. These agents, by virtue of their high efficacy, are widely used to treat patients with RA. Since localized and generalized bone resorption and destruction play a prominent role in its pathogenesis, an investigation of the effect of BA on bone may be of essential interest. Activated osteoclastogenesis occurs because of an interaction between the immune and bone systems under the influence of different proinflammatory cytokines. The inhibition of the latter has been ascertained to not only reduce joint inflammation, but also to prevent localized and generalized osteoporosis. This review discusses the results of these trials and the issues of further investigations.

  15. [Exosomes Derived from Mesenchymal Stem Cells--the Future Ideal Vector of Biological Therapy].

    Science.gov (United States)

    Zhang, Juan; Shi, Jing-Shu; Li, Jian

    2015-08-01

    MSC-exosomes are homogeneous menbrane vesicles with diameter 40-100 nm, derived from mesenchymal stem cells at physiological or pathology conditions. MSC-exosomes contain a great quantity and a wide variety of bioactive substances, such as proteins and miRNA. MSC-exosomes transfer bioactive substances to recipient cells to affect their functions through membrane fusion or endocytosis, which like the storage pools of signal vehicles for cell-to-cell comunication in vivo. MSC-exosomes can mimic the beneficial effect of MSC treatment, such as the promotion of tissue repair or the immune regulation. The biological property and functions of MSC-exosomes are reviwed in this article. PMID:26314469

  16. Thermal distribution in biological tissue at laser induced fluorescence and photodynamic therapy

    Science.gov (United States)

    Krasnikov, I. V.; Seteikin, A. Yu.; Drakaki, E.; Makropoulou, M.

    2012-03-01

    Laser induced fluorescence spectroscopy and photodynamic therapy (PDT) are techniques currently introduced in clinical applications for visualization and local destruction of malignant tumours as well as premalignant lesions. During the laser irradiation of tissues for the diagnostic and therapeutic purposes, the absorbed optical energy generates heat, although the power density of the treatment light for surface illumination is normally low enough not to cause any significantly increased tissue temperature. In this work we tried to evaluate the utility of Monte Carlo modeling for simulating the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed UV laser and a continuous wave visible laser beam. The analysis of the results showed that heat is not localized on the surface, but it is collected inside the tissue. By varying the boundary conditions on the surface and the type of the laser radiation (continuous or pulsed) we can reach higher than normal temperature inside the tissue without simultaneous formation of thermally damaged tissue (e.g. coagulation or necrosis zone).

  17. Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Bayoumi, Noha Anwer; Amin, Abeer M.; El-Kolaly, Mohamed T. [Egyptian Atomic Energy Authority, Cairo (Egypt). Hot Lab Center; Ismail, Nasser S.M.; Abouzid, Khaled A.M. [Ain-Shams Univ., Cairo (Egypt). Pharmaceutical Chemistry Dept.

    2015-07-01

    Cladribine, a purine analogue antimetabolite, was radioiodinated with {sup 125}I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified {sup 125}I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that {sup 125}I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of {sup 125}I-Cladribine mainly by kidneys. The uptake of {sup 125}I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4%ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of {sup 125}I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good-CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.

  18. Radioiodination and biological evaluation of Cladribine as potential agent for tumor imaging and therapy

    International Nuclear Information System (INIS)

    Cladribine, a purine analogue antimetabolite, was radioiodinated with 125I via direct electrophilic substitution reaction. The maximum radiochemical yield (92.5 ± 0.8%) was obtained when the reaction was done at ambient temperature for 30 min using 100 μg of Cladribine and 10 μg N-chlorosuccinamide (NCS) in 150 μL of 0.2 M phosphate buffer, pH 7. In vitro stability studies of HPLC purified 125I-Cladribine sample dissolved in 0.5 ml of 0.2 M phosphate buffer pH 7 at ambient temperature showed that 125I-Cladribine is stable up to 12 h post labeling. Biodistribution results revealed excretion of 125I-Cladribine mainly by kidneys. The uptake of 125I-Cladribine in the induced Ehrlich Ascites Carcinoma was 2.8 ± 0.4%ID/g at 1 h post injection with maximum tumor/muscle ratio of 5.5. The good uptake of 125I-Cladribine confirms the molecular docking studies results which indicate that iodinated Cladribine binds with polymerase enzyme with a good-CDOCKER energy. As a result, radioiodinated Cladribine may be used as a valuable agent for tumor diagnosis and therapy.

  19. Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

    Energy Technology Data Exchange (ETDEWEB)

    Sethi, Roshan V. [Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts (United States); Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Rapalino, Otto; Caruso, Paul [Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2014-03-01

    Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine the LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for

  20. The Molecular Biology of Soft-Tissue Sarcomas and Current Trends in Therapy

    Directory of Open Access Journals (Sweden)

    Jorge Quesada

    2012-01-01

    Full Text Available Basic research in sarcoma models has been fundamental in the discovery of scientific milestones leading to a better understanding of the molecular biology of cancer. Yet, clinical research in sarcoma has lagged behind other cancers because of the multiple clinical and pathological entities that characterize sarcomas and their rarity. Sarcomas encompass a very heterogeneous group of tumors with diverse pathological and clinical overlapping characteristics. Molecular testing has been fundamental in the identification and better definition of more specific entities among this vast array of malignancies. A group of sarcomas are distinguished by specific molecular aberrations such as somatic mutations, intergene deletions, gene amplifications, reciprocal translocations, and complex karyotypes. These and other discoveries have led to a better understanding of the growth signals and the molecular pathways involved in the development of these tumors. These findings are leading to treatment strategies currently under intense investigation. Disruption of the growth signals is being targeted with antagonistic antibodies, tyrosine kinase inhibitors, and inhibitors of several downstream molecules in diverse molecular pathways. Preliminary clinical trials, supported by solid basic research and strong preclinical evidence, promises a new era in the clinical management of these broad spectrum of malignant tumors.

  1. Tapering biologic and conventional DMARD therapy in rheumatoid arthritis: current evidence and future directions.

    Science.gov (United States)

    Schett, Georg; Emery, Paul; Tanaka, Yoshiya; Burmester, Gerd; Pisetsky, David S; Naredo, Esperanza; Fautrel, Bruno; van Vollenhoven, Ronald

    2016-08-01

    Improvements in the control of inflammation in rheumatoid arthritis (RA) by conventional synthetic and biologic disease-modifying antirheumatic drugs (DMARDs) have led to a substantial change in the clinical outcomes of patients during the last 30 years. Current treatment can lead to sustained remission in some patients raising questions about the optimal management strategies in this subgroup of patients. Today, tapering of DMARDs and even their discontinuation appears as an interesting concept for achieving a more tailored and dynamic treatment approach of RA, especially in patients, who achieved full disease control by DMARD treatment. In this review article, current developments of DMARD tapering are discussed. The article provides an overview of existing studies on this topic and addresses new strategies to reach drug-free remission. Furthermore, concepts for defining patients eligible for DMARD tapering are described and potential future strategies in using biomarkers in predicting the risk for disease relapse after initiation of DMARD tapering are addressed. These findings are finally considered in light of the vision to achieve cure as an ultimate goal in patients with RA achieving full control of inflammation. PMID:27261493

  2. Physical and tumor biological aspects and calculation model of dosage in boron neutron capture therapy (BNCT)

    Energy Technology Data Exchange (ETDEWEB)

    Rassow, J.; Poeller, F.; Meissner, P. (Essen Univ. (Gesamthochschule) (Germany). Abt. fuer Medizinische Strahlenphysik); Steinberg, F. (Essen Univ. (Gesamthochschule) (Germany). Inst. fuer Medizinische Strahlenbiologie)

    1993-01-01

    Fundamentally different aspects apply to dosage in boron neutron capture therapy (BNCT) compared to that in the case of normal radiotherapy with photons, electrons or heavy particles such as neutrons. The reason is that the latter only requires a knowledge of the stochastic distribution of the absorbed dose within cells, radiation quality and atomic composition of tissue in the regions of interest, whereas for the former the absolute concentration and microscopic distribution of [sup 10]B atoms in inter- and intracellular spaces of tumor and healthy cells is additionally of equal importance. The effects of radiation without [sup 10]B must always be superimposed on those of heavy particles resulting from neutron capture reactions on [sup 10]B atoms. Complex geometrical calculaations are necessary with respect to ranges of the heavy particles smaller than a cell diameter. Apart from the direct effects of radiation without [sup 10]B, the dosage therefore depends on thermal neutron fluence, [sup 10]B concentration, its extreme inhomogeneous macroscopic distribution in the tumor tissue, the cellular localization of the [sup 10]B atoms in the large intercellular space, the cell membrane, within cytoplasm or the cell nucleus, the geometrical probability of hitting the cell nucleus, and that such a hit finally results in a cell killing, and a Poisson statistical enhancement factor, which describes the dose-effect relation for cell survival. The calculations necessary are demonstrated in the case of a normal and a tumor cell type, each with representative cell diameter and nucleus size. It is evident that the microscopic distribution of [sup 10]B atoms is one of the most critical parameters which is still insufficiently known. (orig.).

  3. Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans

    International Nuclear Information System (INIS)

    The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D95%) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower TCP

  4. Reasons for discontinuation of subcutaneous biologic therapy in the treatment of rheumatoid arthritis: a patient perspective

    Directory of Open Access Journals (Sweden)

    Bolge SC

    2015-01-01

    Full Text Available Susan C Bolge,1 Amir Goren,2 Neeta Tandon1 1Health Economics and Outcomes Research, Janssen Scientific Affairs, LLC, Horsham, PA, USA; 2Health Outcomes Practice, Kantar Health, New York, NY, USA Objective: To examine reasons why rheumatoid arthritis patients discontinued subcutaneous (SQ anti-tumor necrosis factor (anti-TNF treatment in the past 12 months, so as to help inform successful, uninterrupted therapy.Methods: Data were collected in March and April 2011 using self-reported, internet-based questionnaires. Study inclusion criteria comprised: rheumatoid arthritis diagnosis; discontinuation of SQ anti-TNF medication (adalimumab, certolizumab, etanercept, or golimumab within the past 12 months; aged ≥18 years; United States residency; and consent to participate. Patients reported primary and other reasons for discontinuation of their most recently discontinued anti-TNF.Results: Questionnaires from 250 patients were analyzed; 72.8% were female, 80.8% were white, and median age was 51 years. Patients had discontinued etanercept (n=109, adalimumab (n=98, certolizumab (n=24, or golimumab (n=19 within the past 12 months. When prompted about their primary reason for discontinuation, lack of effectiveness (40.8% was cited most often, followed by injection experience (18.4%. Combining prompted primary and other reasons for discontinuation, 60.8% of patients reported lack of effectiveness, while 40.8% reported injection experience, which included: pain/burning/discomfort after injection (14.4%; pain/burning/discomfort during injection (13.2%; injection reactions such as redness/swelling after injection (12.4%; dislike of self-injection (11.6%; dislike of frequency of injection (10.4%; and fear of injection/needles (6.8%. Conclusion: From the patient perspective, there are unmet needs with regard to the effectiveness and injection experience associated with SQ anti-TNF medications, which may lead to discontinuation. Treatment options with a

  5. In Vivo Study of Biological Effects of Photodynamic Therapy on Cervical Cancer

    Science.gov (United States)

    Marquez-Lemus, V. A.; Noguez-Juarez, B. M.; Solano-Rodriguez, L.; Perez-Zapata, A. J.; Schneider-Ehrenberg, O. P.; Graue-wiechers, F.; Ramón-Gallegos, E.

    2005-01-01

    In 1999, Ramon et al examined the effects of δ-aminolevulinic acid (δ-ALA) on two cervical cancer cell lines (HeLa and CaLo) and normal cervical cells. The results reported additionally support the proposal that Photodynamic Therapy (PDT) could be an effective tool for treatment of cervical cancer (CeCa) by protoporphyrin IX (PpIX) accumulation. This cancer is in México considered a problem of public health. In this project PDT was applied in a CeCa mouse model by implantation of HeLa cells in nu/nu mice, exposing it to δ-ALA to a dose that induces the greater concentration of PpIX by intratumoral and oral route, as well as the power and the number of optimal irradiations at 630 nm with a diode laser; verifying which of the used doses does not produce significant damage to the organs by means of histopatologic techniques: liver, spleen, brain and kidney, the determination of reactive substances to tiobarbituric acid (TBAR'S) and measured the amount of residual δ-ALA, the size of the tumor at the beginning and at the end of the application of the PDT. Results. The cervical cancer mouse model is developed by implantation of 1,5 million HeLa cells, appearing at 15 days. The dose of δ-ALA that induces the greater concentration of PpIX in the tumor by intratumoral route was 40 mg of δ-ALA/kg body weight and for oral route it was 20 mg of δ-ALA/kg body weight, both routes did not present significant damage in the organs and according to the Analysis of Bifactorial Variance for the doses of δ-ALA and the organs no difference exists (p > 0.05). The power of the used laser was 150 J/cm2 and 250 J/cm2, both applied by intratumoral and oral route after the δ-ALA administration. The greater diminution in the size of the tumor (53%) was by the δ-ALA oral route administration to a power of 150 J/cm2 with 5 irradiations in intervals of 48 h.

  6. Review of the 25th annual scientific meeting of the International Society for Biological Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Jaffee Elizabeth M

    2011-05-01

    Full Text Available Abstract Led by key opinion leaders in the field, the 25th Annual Meeting of the International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC provided a scientific platform for ~500 attendees to exchange cutting-edge information on basic, clinical, and translational research in cancer immunology and immunotherapy. The meeting included keynote addresses on checkpoint blockade in cancer therapy and recent advances in therapeutic vaccination against cancer induced by Human Papilloma Virus 16. Participants from 29 countries interacted through oral presentations, panel discussions, and posters on topics that included dendritic cells and cancer, targeted therapeutics and immunotherapy, innate/adaptive immune interplay in cancer, clinical trial endpoints, vaccine combinations, countering negative regulation, immune cell trafficking to tumor microenvironment, and adoptive T cell transfer. In addition to the 50 oral presentations and >180 posters on these topics, a new SITC/iSBTc initiative to create evidence-based Cancer Immunotherapy Guidelines was announced. The SITC/iSBTc Biomarkers Taskforce announced the release of recommendations on immunotherapy biomarkers and a highly successful symposium on Immuno-Oncology Biomarkers that took place on the campus of the National Institutes of Health (NIH immediately prior to the Annual Meeting. At the Annual Meeting, the NIH took the opportunity to publicly announce the award of the U01 grant that will fund the Cancer Immunotherapy Trials Network (CITN. In summary, the Annual Meeting gathered clinicians and scientists from academia, industry, and regulatory agencies from around the globe to interact and exchange important scientific advances related to tumor immunobiology and cancer immunotherapy.

  7. Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry

    International Nuclear Information System (INIS)

    In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial

  8. A phenomenological relative biological effectiveness (RBE) model for proton therapy based on all published in vitro cell survival data

    International Nuclear Information System (INIS)

    Proton therapy treatments are currently planned and delivered using the assumption that the proton relative biological effectiveness (RBE) relative to photons is 1.1. This assumption ignores strong experimental evidence that suggests the RBE varies along the treatment field, i.e. with linear energy transfer (LET) and with tissue type. A recent review study collected over 70 experimental reports on proton RBE, providing a comprehensive dataset for predicting RBE for cell survival. Using this dataset we developed a model to predict proton RBE based on dose, dose average LET (LETd) and the ratio of the linear-quadratic model parameters for the reference radiation (α/β)x, as the tissue specific parameter.The proposed RBE model is based on the linear quadratic model and was derived from a nonlinear regression fit to 287 experimental data points. The proposed model predicts that the RBE increases with increasing LETd and decreases with increasing (α/β)x. This agrees with previous theoretical predictions on the relationship between RBE, LETd and (α/β)x. The model additionally predicts a decrease in RBE with increasing dose and shows a relationship between both α and β with LETd. Our proposed phenomenological RBE model is derived using the most comprehensive collection of proton RBE experimental data to date. Previously published phenomenological models, based on a limited data set, may have to be revised. (paper)

  9. Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)

    Energy Technology Data Exchange (ETDEWEB)

    Nagesha, D K; Tada, D B; Stambaugh, C K K; Gultepe, E; Jost, E; Levy, C O; Sridhar, S [Electronic Materials Research Institute and Department of Physics, Northeastern University, Boston, MA 02115 (United States); Cormack, R; Makrigiorgos, G M, E-mail: s.sridhar@neu.ed [Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States)

    2010-10-21

    Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

  10. Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)

    Science.gov (United States)

    Nagesha, D. K.; Tada, D. B.; Stambaugh, C. K. K.; Gultepe, E.; Jost, E.; Levy, C. O.; Cormack, R.; Makrigiorgos, G. M.; Sridhar, S.

    2010-10-01

    Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

  11. Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT)

    International Nuclear Information System (INIS)

    Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(d,l-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer.

  12. Biological behavior of 188Re-biotin chelate for multistep therapy with the avidin-biotin system

    International Nuclear Information System (INIS)

    The purpose of this study was to test the three-step targeting of tumors in mice using biotinylated antibody, streptavidin and radiolabeled biotin for radioimmunotherapy (RAIT). Three-step pretargetting can potentially decreases harmful radiation to normal tissues in radioimmunotherapy. 188Re from 188W-188Re generator, is recently introduced in therapeutic nuclear medicine and made it possible to use whenever needed. We studied biotin-chelates MGB for use in the avidin/biotin pretargetting system. Chelates that hold radiometals with high stability under physiological conditions are essential to avoid excessive radiation damage to non-target cells. We synthesized MAG2GABA-Biocytin (MGB), labeled with 188Re and evaluated biological behavior of 188Re-MGB. biotinyl MAG2GABA bind the therapeutic radiometal 188Re with excellent in vitro stability and have the required physiological properties for pretargetted therapy. In normal mice, 188Re-MGB was excreted via hepatobiliary pathway, %ID/g of GI tract was 52.1 at 120min. In Raji cells tumor bearing nude mice, liver and colon were higher than those of normal mouse. Tumor uptake at 120min was 0.05%ID/g. 188Re-MGB may have a role in pretargetted radioimmunotherapy

  13. Skin Delivery and in Vitro Biological Evaluation of Trans-Resveratrol-Loaded Solid Lipid Nanoparticles for Skin Disorder Therapies

    Directory of Open Access Journals (Sweden)

    Roberta B. Rigon

    2016-01-01

    Full Text Available The aim of this study was to evaluate the skin delivery and in vitro biological activity of trans-resveratrol (RES-loaded solid lipid nanoparticles (SLNs. The SLNs were composed of stearic acid, poloxamer 407, soy phosphatidylcholine (SPC, an aqueous phase and 0.1% RES. The particle size, polydispersity index (PdI and zeta potential were analyzed by dynamic light scattering (DLS. The SLNs were analyzed by scanning electron microscopy (SEM-FEG and differential scanning calorimetry (DSC. In vitro RES-SLN skin permeation/retention assays were conducted, and their tyrosinase inhibitory activity was evaluated. An MTT reduction assay was performed on HaCat keratinocytes to determine in vitro cytotoxicity. The formulations had average diameter lower than 200 nm, the addition of SPC promoted increases in PdI in the RES-SLNs, but decreases PdI in the RES-free SLNs and the formulations exhibited zeta potentials smaller than −3 mV. The DSC analysis of the SLNs showed no endothermic peak attributable to RES. Microscopic analysis suggests that the materials formed had nanometric size distribution. Up to 45% of the RES permeated through the skin after 24 h. The RES-loaded SLNs were more effective than kojic acid at inhibiting tyrosinase and proved to be non-toxic in HaCat keratinocytes. The results suggest that the investigated RES-loaded SLNs have potential use in skin disorder therapies.

  14. WE-E-17A-07: Patient-Specific Mathematical Neuro-Oncology: Biologically-Informed Radiation Therapy and Imaging Physics

    Energy Technology Data Exchange (ETDEWEB)

    Swanson, K; Corwin, D [Northwestern University, Chicago, IL (United States); Rockne, R

    2014-06-15

    Purpose: To demonstrate a method of generating patient-specific, biologically-guided radiation therapy (RT) plans and to quantify and predict response to RT in glioblastoma. We investigate the biological correlates and imaging physics driving T2-MRI based response to radiation therapy using an MRI simulator. Methods: We have integrated a patient-specific biomathematical model of glioblastoma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated RT optimization to construct individualized, biologically-guided plans. Patient-individualized simulations of the standard-of-care and optimized plans are compared in terms of several biological metrics quantified on MRI. An extension of the PI model is used to investigate the role of angiogenesis and its correlates in glioma response to therapy with the Proliferation-Invasion-Hypoxia- Necrosis-Angiogenesis model (PIHNA). The PIHNA model is used with a brain tissue phantom to predict tumor-induced vasogenic edema, tumor and tissue density that is used in a multi-compartmental MRI signal equation for generation of simulated T2- weighted MRIs. Results: Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized RT plans would have a significant impact on delaying tumor progression, with Days Gained increases from 21% to 105%. For the T2- MRI simulations, initial validation tests compared average simulated T2 values for white matter, tumor, and peripheral edema to values cited in the literature. Simulated results closely match the characteristic T2 value for each tissue. Conclusion: Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for RT generated biologically-guided doses that decreased normal tissue dose and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma. Simulated T2-MRI

  15. WE-E-17A-07: Patient-Specific Mathematical Neuro-Oncology: Biologically-Informed Radiation Therapy and Imaging Physics

    International Nuclear Information System (INIS)

    Purpose: To demonstrate a method of generating patient-specific, biologically-guided radiation therapy (RT) plans and to quantify and predict response to RT in glioblastoma. We investigate the biological correlates and imaging physics driving T2-MRI based response to radiation therapy using an MRI simulator. Methods: We have integrated a patient-specific biomathematical model of glioblastoma proliferation, invasion and radiotherapy with a multiobjective evolutionary algorithm for intensity-modulated RT optimization to construct individualized, biologically-guided plans. Patient-individualized simulations of the standard-of-care and optimized plans are compared in terms of several biological metrics quantified on MRI. An extension of the PI model is used to investigate the role of angiogenesis and its correlates in glioma response to therapy with the Proliferation-Invasion-Hypoxia- Necrosis-Angiogenesis model (PIHNA). The PIHNA model is used with a brain tissue phantom to predict tumor-induced vasogenic edema, tumor and tissue density that is used in a multi-compartmental MRI signal equation for generation of simulated T2- weighted MRIs. Results: Applying a novel metric of treatment response (Days Gained) to the patient-individualized simulation results predicted that the optimized RT plans would have a significant impact on delaying tumor progression, with Days Gained increases from 21% to 105%. For the T2- MRI simulations, initial validation tests compared average simulated T2 values for white matter, tumor, and peripheral edema to values cited in the literature. Simulated results closely match the characteristic T2 value for each tissue. Conclusion: Patient-individualized simulations using the combination of a biomathematical model with an optimization algorithm for RT generated biologically-guided doses that decreased normal tissue dose and increased therapeutic ratio with the potential to improve survival outcomes for treatment of glioblastoma. Simulated T2-MRI

  16. Biological Therapies for Cancer

    Science.gov (United States)

    ... Finally, lower white blood cell counts leave chemotherapy patients vulnerable to infections . Several growth factors that promote the growth of ... Flu-like symptoms Severe allergic reaction Urinary side effects Pain or burning sensation during urination Increased urgency or frequency of ...

  17. Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

    Science.gov (United States)

    Lee, J S; Lee, S M; Jeong, S W; Sung, Y G; Lee, J H; Kim, K W

    2016-07-01

    Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. PMID:27149303

  18. Different Risk of Tuberculosis and Efficacy of Isoniazid Prophylaxis in Rheumatoid Arthritis Patients with Biologic Therapy: A Nationwide Retrospective Cohort Study in Taiwan

    Science.gov (United States)

    Chen, Yi-Ming; Chang, Chia-Li; Chen, Hsin-Hua; Chen, Der-Yuan

    2016-01-01

    Increasing evidence indicates an increased risk of tuberculosis (TB) for rheumatoid arthritis (RA) patients receiving biologic therapy, and the effectiveness of isoniazid prophylaxis (INHP) in TB prevention. We aimed to examine 1) the incidence rate (IR) and risk factors for TB among RA patients receiving different therapies; 2) INHP effectiveness for TB prevention; 3) mortality rates after TB diagnosis in patients receiving different therapies. This retrospective study was conducted using a nationwide database: 168,720 non-RA subjects and a total of 42,180 RA patients including 36,162 csDMARDs-exposed, 3,577 etanercept-exposed, 1,678 adalimumab-exposed and 763 rituximab-exposed patients. TB risk was 2.7-fold higher in RA cohort compared with non-RA group, with an adjusted hazard ratio (aHR) of 2.58. Advanced age, male, the use of corticosteroids≧5mg/day, and the presence of diabetes mellitus (DM), chronic obstructive pulmonary disease and chronic kidney disease were risk factors for developing TB. Using csDMARDs-exposed group as reference, aHR of TB was the highest with adalimumab treatment (1.52), followed by etanercept (1.16), and the lowest with rituximab (0.08). INHP could effectively reduce TB risk in biologics-exposed patients. Mortality rates after TB diagnosis were higher in RA patients, particularly the elderly and those with DM, with lower rates in adalimumab-exposed patients compared with csDMARDs-exposed patients. In conclusion, TB risk was increased in patients receiving TNF-α inhibitors, but the risk associated with rituximab therapy was relatively low. With the effectiveness of INHP shown in the prevention of biologics-associated TB, stricter implementation of INHP should be beneficial. The mortality from biologics–associated TB may be efficiently reduced through increased awareness. PMID:27064275

  19. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-alpha, Oncostatin M and response to biologic therapies.

    LENUS (Irish Health Repository)

    Moran, Ellen M

    2009-01-01

    INTRODUCTION: The aim of this study was to examine IL-17A in patients, following anti-TNF-alpha therapy and the effect of IL-17A on matrix turnover and cartilage degradation. METHODS: IL-17A expression was examined by ELISA and immunohistology in the rheumatoid arthritis (RA) joints. RA whole synovial tissue explant (RA ST), primary synovial fibroblasts (RASFC), human cartilage and chondrocyte cultures were stimulated with IL-17A +\\/- TNF-alpha and Oncostatin M (OSM). Matrix metalloproteinase (MMP) and tissue inhibitor (TIMP-1) were assessed by ELISA and zymography. Cartilage proteoglycan release was assessed histologically by Safranin-O staining. Clinical parameters, IL-17A, MMP\\/TIMP were assessed in patients pre\\/post biologic therapy. RESULTS: IL-17A levels were higher in RA vs osteoarthritis (OA)\\/normal joints (P < 0.05). IL-17A up-regulated MMP-1, -2, -9, and -13 in RA ST, RASFC, cartilage and chondrocyte cultures (P < 0.05). In combination with TNF-alpha and OSM, IL-17A shifted the MMP:TIMP-1 ratio in favor of matrix degradation (all P < 0.05). Cartilage proteoglycan depletion in response to IL-17A was mild; however, in combination with TNF-alpha or OSM showed almost complete proteoglycan depletion. Serum IL-17A was detected in 28% of patients commencing biologic therapy. IL-17A negative patients demonstrated reductions post therapy in serum MMP1\\/TIMP4, MMP3\\/TIMP1 and MMP3\\/TIMP4 ratios and an increase in CS846 (all P < 0.05). No significant changes were observed in IL-17A positive patients. CONCLUSIONS: IL-17A is produced locally in the inflamed RA joint. IL-17A promotes matrix turnover and cartilage destruction, especially in the presence of other cytokines, mimicking the joint environment. IL-17A levels are modulated in vivo, following anti-TNF therapy, and may reflect changes in matrix turnover.

  20. RESULTS OF A CROSS-SECTIONAL EPIDEMIOLOGICAL STUDY DETERMINING THE NEEDS FOR GENETIC ENGINEERINGBIOLOGICALS FOR THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS IN REAL CLINICAL PRACTICE IN RUSSIA(IRACL)COMMUNICATION 2. DETERMINATION OF NEEDS FOR GENETIC ENGINEERING BIOLOGICALS

    OpenAIRE

    Shandor Fedorovich Erdes; O M Folomeyeva; E A Telnykh; E A Galushko

    2010-01-01

    Genetic engineering biologicals (GEBs) show promises in treating rheumatoid arthritis (RA), their efficacy and tolerability have been studied and indications and contraindications defined. However, the extensive application of GEBs is limited due to their high cost. In Russia, GEB therapy is paid by the government. To plan and optimize expenditures, it is necessary to have standardized indications and to know the number of patients who need biological therapy. Objective: To define...

  1. Targeted biological therapies for Graves' disease and thyroid-associated ophthalmopathy. Focus on B-cell depletion with Rituximab

    DEFF Research Database (Denmark)

    Hegedüs, Laszlo; Douglas, Raymond S; Nielsen, Claus H; Smith, Terry J

    2011-01-01

    Based on experience from the treatment of other autoimmune diseases and because of the limitations imposed by existing therapeutic options for Graves' disease (GD) and thyroid-associated ophthalmopathy (TAO), rituximab (RTX) was recently proposed as a novel therapy option. Here, we summarize the...... respond favourably to conventional therapy. It is the first in what is likely to be a series of new and emerging treatments specifically targeting relevant components of the immune system. Further studies will hopefully lead to improved and better tailored, individualized therapy for GD and especially TAO....

  2. Off-Label Biologic Regimens in Psoriasis: A Systematic Review of Efficacy and Safety of Dose Escalation, Reduction, and Interrupted Biologic Therapy

    OpenAIRE

    Elizabeth A. Brezinski; Armstrong, April W.

    2012-01-01

    OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment) with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SE...

  3. Biological effects of radiation

    International Nuclear Information System (INIS)

    This fourth chapter presents: cell structure and metabolism; radiation interaction with biological tissues; steps of the production of biological effect of radiation; radiosensitivity of tissues; classification of biological effects; reversibility, transmissivity and influence factors; pre-natal biological effects; biological effects in therapy and syndrome of acute irradiation

  4. Toward an Integration of Psychologic, Social, and Biologic Factors in Depression: Effects on Outcome and Course of Cognitive Therapy.

    Science.gov (United States)

    Simons, Anne D.; And Others

    1995-01-01

    Integrates key variables from three major domains (cognition, stress, and psychobiology) that are typically studied separately. Dysfunctional attitudes, negative life events, or sleep electroencephalogram were assessed in 53 outpatients before treatment with cognitive therapy. Results are discussed in terms of the promise of integrative research.…

  5. Convex reformulation of biologically-based multi-criteria intensity-modulated radiation therapy optimization including fractionation effects.

    NARCIS (Netherlands)

    Hoffmann, A.L.; Hertog, D. den; Siem, A.Y.; Kaanders, J.H.A.M.; Huizenga, H.

    2008-01-01

    Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan

  6. Recommendations for the use of biologic therapy in rheumatoid arthritis: update from the Italian Society for Rheumatology II. Safety.

    Science.gov (United States)

    Favalli, Ennio G; Caporali, Roberto; Sinigaglia, Luigi; Pipitone, Nicolo'; Miniati, Irene; Montecucco, Carlomaurizio; Matucci-Cerinic, Marco

    2011-01-01

    Given the availability of novel biologic agents for the treatment of rheumatoid arthritis (RA), various national scientific societies have developed specific recommendations in order to assist rheumatologists in prescribing these drugs. The Italian Society for Rheumatology (Società Italiana di Reumatologia, SIR) decided to update its recommendations, and, to this end, a systematic literature review was performed and the evidence derived from it was discussed and summarized as expert opinions. Levels of evidence and strength of recommendations were reported. The recommendations reported refer to the safety of biologic agents and are intended to help prescribing rheumatologists to optimise the use of biologic agents in patients with RA seen in everyday practice; they are not to be considered as a regulatory rule. PMID:21906424

  7. Preliminary biological evaluation of acridinic compounds for a targeted combined chemo and internal radionuclide therapy for melanoma

    International Nuclear Information System (INIS)

    The increasing incidence of melanoma and a lack of effective therapy on the disseminated form induces the development of selective tissue-targeted therapies. The aim of the present work was a targeting approach combining a bimodality therapy with the same compound exhibiting both chemo and internal radionuclide therapeutic properties. Benzamides are known to present a specific affinity for melanoma tissue. Former studies have shown that with aromatic and hetero-aromatic analogues of N-(2-diethylaminoethyl)- 4-iodo benzamide (B.Z.A.), the affinity for melanoma was maintained. In this context, new compounds have been designed and synthesized conjugating a cytotoxic hetero-aromatic moiety, an amino-alkyl amidic side chain for melanoma targeting and a radioiodine for internal radionuclide therapy. Acridinic derivatives known as cytotoxic DNA-intercalating agents have been chosen for this study. The cytotoxic activity of fifteen new compounds has been tested in vitro on a panel of cell lines and the I.C.50 values were determined. The three first selected compounds have been further evaluated: in vivo, on B 16 F0 melanoma bearing C 57 B.L.6 mice to determine the pharmacological kinetic and namely the tumoral affinity. Two compounds exhibited a high, specific and long lasting concentration in melanoma tumor giving them a kinetic profile favourable for an application to radionuclide therapy; in vitro, using the 'colony forming' test on melanoma cells, for a first approach of association of chemo toxicity and radiotoxicity. Assessed on the ability of cells to form colonies, the inhibition observed with the association for a same molecule of chemo toxic and radio toxic doses was quite exactly the sum of the two separate effects, a result providing a first validation of the radio chemotherapy concept; in vitro, by a preliminary determination of molecular mechanisms. Compared to parent compounds, results confirmed a maintain of DNA-intercalating properties. These first results

  8. In vitro Cytokine Synthesis by Lymphocytes in Children in Juvenile Idiopathic Arthritis Remission Against the Background of Genetically Engineered Biologic Drug Therapy

    Directory of Open Access Journals (Sweden)

    R.S. Zakirov

    2016-06-01

    Full Text Available The aim of the investigation to assess the capacity of lymphocytes for spontaneous and stimulated cytokine production in vitro in children in remission with juvenile rheumatoid arthritis treated with genetically engineered biological agents combined with immunosuppressants. Materials and Methods. We examined 18 children (8 girls and 10 boys aging from 2 to 12 years with various types of juvenile idiopathic arthritis treated with genetically engineered biological agents combined with immunosuppressants, no glucocorticoids were administered. The mean duration of genetically engineered biological agent therapy was 3.8 years. When included in the study all patients were recorded to have the disease remission according to Wallace criteria. Twelve age-matched children without chronic diseases and medical therapy were included in the control group. We assessed spontaneous and phytohemagglutinin (PHA-induced cytokine synthesis (IL-2, IL-4, IL-6, IL-8, IL-10, G-CSF, IFN-γ, TNF-α, as well as their synthesis stimulation index. Cytokine concentration was determined in whole blood cultures using multiplex test systems (Bio-Plex Pro Human Cytokine for Bio-Plex 200 (Bio-Plex Manager, version 5.0 (Bio-Rad, USA. Results. We compared the activity of spontaneous and stimulated cytokine synthesis in children with juvenile idiopathic arthritis and controls to find a significant decrease in the spontaneous synthesis of IL-4, IL-6, IL-8, G-CSF, IFN-γ, TNF-α, and no significant differences in spontaneous production of IL-2 and IL-10. The analysis of PHA-stimulated cultures in children with arthritis showed the higher production of IL-2, IL-4, IL-6, the decreased IL-10 production, and no significant differences in the production of IL-8, G-CSF, IFN-γ, TNF-α. The calculated stimulation indices of G-CSF, IL-8, and TNF-α were similar in both groups of children, while those of IL-2, IL-4, IL-6, IFN-γ appeared to be significantly higher, and the indices for IL-10

  9. Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since implementation in Japan: long-term results from a multicenter observational cohort study.

    Science.gov (United States)

    Kojima, Toshihisa; Takahashi, Nobunori; Funahashi, Koji; Asai, Shuji; Terabe, Kenya; Kaneko, Atsushi; Hirano, Yuji; Hayashi, Masatoshi; Miyake, Hiroyuki; Oguchi, Takeshi; Takagi, Hideki; Kanayama, Yasuhide; Yabe, Yuichiro; Watanabe, Tsuyoshi; Fujibayashi, Takayoshi; Shioura, Tomone; Ito, Takayasu; Yoshioka, Yutaka; Ishikawa, Hisato; Asai, Nobuyuki; Takemoto, Toki; Kojima, Masayo; Ishiguro, Naoki

    2016-04-01

    This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan. PMID:26846135

  10. Antiradiation UV Vaccine: UV Radiation, Biological effects, lesions and medical management - immune-therapy and immune-protection.

    Science.gov (United States)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key Words: Ultraviolet radiation,Standard Erythema Dose(SED), Minimal Erythema Dose(MED), Sun Burns, Solar Dermatitis, Sun Burned Disease, DNA Damage,Cell Damage, Antiradiation UV Vaccine, Immune-Prophylaxis of Sun Burned Diseases, Immune-Prophylaxis of Sun Burns, Immune-Therapy of Sun-Burned Disease and Sun Burns,Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Toxic Epidermal Necrolysis(TEN). Introduction: High doses of UV generated by solar source and artificial sources create an exposure of mammals and other species which can lead to ultraviolet(UV)radiation- associated disease (including erythema, epilation, keratitis, etc.). UV radiation belongs to the non-ionizing part of the electromagnetic spectrum and ranges between 100 nm and 400 nm with 100 nm having been chosen arbitrarily as the boundary between non-ionizing and ionizing radiation, however EMR is a spectrum and UV can produce molecular ionization. UV radiation is conventionally categorized into 3 areas: UV-A (>315-400 nm),UV-B (>280-315 nm)and UV-C (>100-280 nm) [IARC,Working Group Reports,2005] An important consequence of stratospheric ozone depletion is the increased transmission of solar ultraviolet (UV)radiation to the Earth's lower atmosphere and surface. Stratospheric ozone levels have been falling, in certain areas, for the past several decades, so current surface ultraviolet-B (UV-B) radiation levels are thought to be close to their modern day maximum. [S.Madronich et al.1998] Overexposure of ultraviolet radiation a major cause of skin cancer including basal cell carcinoma (BCC), squamous cell carcinoma (SCC) { collectively referred to as “non-melanoma" skin cancer (NMSC) and melanoma as well, with skin cancers being the most common cancer in North America. [Armstrong et al. 1993, Gallagher et al. 2005] Methods and Experimental Design: Our experiments and testing of a novel UV “Antiradiation Vaccine” have employed a wide variety of laboratory animals which include : Chinchilla

  11. Screening for Latent Tuberculosis in the Patient With Moderate to Severe Psoriasis Who Is a Candidate for Systemic and/or Biologic Therapy.

    Science.gov (United States)

    Martínez-López, A; Rodriguez-Granger, J; Ruiz-Villaverde, R

    2016-04-01

    Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening. PMID:26651325

  12. Clinically applicable Monte Carlo-based biological dose optimization for the treatment of head and neck cancers with spot-scanning proton therapy

    CERN Document Server

    Tseung, H Wan Chan; Kreofsky, C R; Ma, D; Beltran, C

    2016-01-01

    Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods: Recently, a fast and accurate Graphics Processor Unit (GPU)-based MC simulation of proton transport was developed and used as the dose calculation engine in a GPU-accelerated IMPT optimizer. Besides dose, the dose-averaged linear energy transfer (LETd) can be simultaneously scored, which makes biological dose (BD) optimization possible. To convert from LETd to BD, a linear relation was assumed. Using this novel optimizer, inverse biological planning was applied to 4 patients: 2 small and 1 large thyroid tumor targets, and 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional IMRT and IMPT plans were created for each case in Eclipse (Varian, Inc). The same critical structure PD constraints were use...

  13. Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis.

    OpenAIRE

    Paula FS; Delgado Alves J

    2014-01-01

    Therapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid ...

  14. The Future of Cell Therapy and Tissue Engineering in Cardiovascular Disease: The New Era of Biological Therapeutics

    OpenAIRE

    Heydarkhan-Hagvall, Sepideh; Nsair, Ali; Beygui, Ramin E.; Shemin, Richard J

    2010-01-01

    The use of living cells as a therapeutic option presents several challenges including identification of a suitable source, development of adequate derivation, maintenance and differentiation methods, and very importantly proof of safety and efficacy. One of the major issues for cardiovascular tissue engineering is determining the ideal cell type for use in regenerative therapies.Many clinical trials have used bone marrow derived mononuclear cells (BM-MNC) (Schächinger V 2006). These clinical ...

  15. Preliminary biological evaluation of acridinic compounds for a targeted combined chemo and internal radionuclide therapy for melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Gardette, M.; Papon, J.; Desbois, N.; Labarre, P.; Maisonial, A.; Maublant, J.; Madelmont, J.C.; Moins, N.; Chezal, J.M. [Centre Jean Perrin, Inserm-Universite d' Auvergne, 63 - Clermont Ferrand (France)

    2008-02-15

    The increasing incidence of melanoma and a lack of effective therapy on the disseminated form induces the development of selective tissue-targeted therapies. The aim of the present work was a targeting approach combining a bimodality therapy with the same compound exhibiting both chemo and internal radionuclide therapeutic properties. Benzamides are known to present a specific affinity for melanoma tissue. Former studies have shown that with aromatic and hetero-aromatic analogues of N-(2-diethylaminoethyl)- 4-iodo benzamide (B.Z.A.), the affinity for melanoma was maintained. In this context, new compounds have been designed and synthesized conjugating a cytotoxic hetero-aromatic moiety, an amino-alkyl amidic side chain for melanoma targeting and a radioiodine for internal radionuclide therapy. Acridinic derivatives known as cytotoxic DNA-intercalating agents have been chosen for this study. The cytotoxic activity of fifteen new compounds has been tested in vitro on a panel of cell lines and the I.C.50 values were determined. The three first selected compounds have been further evaluated: in vivo, on B 16 F0 melanoma bearing C 57 B.L.6 mice to determine the pharmacological kinetic and namely the tumoral affinity. Two compounds exhibited a high, specific and long lasting concentration in melanoma tumor giving them a kinetic profile favourable for an application to radionuclide therapy; in vitro, using the 'colony forming' test on melanoma cells, for a first approach of association of chemo toxicity and radiotoxicity. Assessed on the ability of cells to form colonies, the inhibition observed with the association for a same molecule of chemo toxic and radio toxic doses was quite exactly the sum of the two separate effects, a result providing a first validation of the radio chemotherapy concept; in vitro, by a preliminary determination of molecular mechanisms. Compared to parent compounds, results confirmed a maintain of DNA-intercalating properties. These

  16. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  17. Synthesis and Biological Evaluation of New Imidazolium and Piperazinium Salts of Pyropheophorbide-a for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Young Key Shim

    2008-08-01

    Full Text Available We have designed imidazolium and piperazinium salts of pyropheophorbide-a in order to develop effective photosensitizers which have good solubility in polar and non polar media and to reveal the possible influences of the piperazine and imidazole moieties on the biological activities of pyropheophorbide-a. The phototoxicity of those pyropheophorbide-a salts against A549 cells was studied in vitro and compared with that of pyropheophorbide-a. The result showed that complexing piperazine and imidazole into pyropheophorbide-a decreases its dark toxicity without greatly decreasing phototoxicity and, enhances its phototoxicity without greatly increasing dark toxicity, respectively. This work not only describes novel amphiphilic salt complexes of pyropheophobide-a which retain the biological activities of the parent compound pyropheophorbide-a and could be effective candidate for PDT, but also reveals the possibility of developing effective photosensitizers by complexing imidazole and piperazine into other hydrophobic photosensitizers.

  18. Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy

    Science.gov (United States)

    Oktaria, Sianne; Corde, Stéphanie; Lerch, Michael L. F.; Konstantinov, Konstantin; Rosenfeld, Anatoly B.; Tehei, Moeava

    2015-10-01

    Despite the use of multimodal treatments incorporating surgery, chemotherapy and radiotherapy, local control of gliomas remains a major challenge. The potential of a new treatment approach called indirect radio-chemo-beta therapy using the synergy created by combining methotrexate (MTX) with bromodeoxyuridine (BrUdR) under optimum energy x-ray irradiation is assessed. 9L rat gliosarcoma cells pre-treated with 0.01 μM MTX and/or 10 μM BrUdR were irradiated in vitro with 50 kVp, 125 kVp, 250 kVp, 6 MV and 10 MV x-rays. The cytotoxicity was assessed using clonogenic survival as the radiobiological endpoint. The photon energy with maximum effect was determined using radiation sensitization enhancement factors at 10% clonogenic survival (SER10%). The cell cycle distribution was investigated using flow cytometric analysis with propidium iodide staining. Incorporation of BrUdR in the DNA was detected by the fluorescence of labelled anti-BrUdR antibodies. The radiation sensitization enhancement exhibits energy dependence with a maximum of 2.3 at 125 kVp for the combined drug treated cells. At this energy, the shape of the clonogenic survival curve of the pharmacological agents treated cells changes substantially. This change is interpreted as an increased lethality of the local radiation environment and is attributed to supplemented inhibition of DNA repair. Radiation induced chemo-beta therapy was demonstrated in vitro by the targeted activation of combined pharmacological agents with optimized energy tuning of x-ray beams on 9 L cells. Our results show that this is a highly effective form of chemo-radiation therapy.

  19. Indirect radio-chemo-beta therapy: a targeted approach to increase biological efficiency of x-rays based on energy

    International Nuclear Information System (INIS)

    Despite the use of multimodal treatments incorporating surgery, chemotherapy and radiotherapy, local control of gliomas remains a major challenge. The potential of a new treatment approach called indirect radio-chemo-beta therapy using the synergy created by combining methotrexate (MTX) with bromodeoxyuridine (BrUdR) under optimum energy x-ray irradiation is assessed. 9L rat gliosarcoma cells pre-treated with 0.01 μM MTX and/or 10 μM BrUdR were irradiated in vitro with 50 kVp, 125 kVp, 250 kVp, 6 MV and 10 MV x-rays. The cytotoxicity was assessed using clonogenic survival as the radiobiological endpoint. The photon energy with maximum effect was determined using radiation sensitization enhancement factors at 10% clonogenic survival (SER10%). The cell cycle distribution was investigated using flow cytometric analysis with propidium iodide staining. Incorporation of BrUdR in the DNA was detected by the fluorescence of labelled anti-BrUdR antibodies. The radiation sensitization enhancement exhibits energy dependence with a maximum of 2.3 at 125 kVp for the combined drug treated cells. At this energy, the shape of the clonogenic survival curve of the pharmacological agents treated cells changes substantially. This change is interpreted as an increased lethality of the local radiation environment and is attributed to supplemented inhibition of DNA repair. Radiation induced chemo-beta therapy was demonstrated in vitro by the targeted activation of combined pharmacological agents with optimized energy tuning of x-ray beams on 9 L cells. Our results show that this is a highly effective form of chemo-radiation therapy. (paper)

  20. Advances in molecular biology of lung disease: aiming for precision therapy in non-small cell lung cancer.

    Science.gov (United States)

    Rooney, Claire; Sethi, Tariq

    2015-10-01

    Lung cancer is the principal cause of cancer-related mortality in the developed world, accounting for almost one-quarter of all cancer deaths. Traditional treatment algorithms have largely relied on histologic subtype and have comprised pragmatic chemotherapy regimens with limited efficacy. However, because our understanding of the molecular basis of disease in non-small cell lung cancer (NSCLC) has improved exponentially, it has become apparent that NSCLC can be radically subdivided, or molecularly characterized, based on recurrent driver mutations occurring in specific oncogenes. We know that the presence of such mutations leads to constitutive activation of aberrant signaling proteins that initiate, progress, and sustain tumorigenesis. This persistence of the malignant phenotype is referred to as "oncogene addiction." On this basis, a paradigm shift in treatment approach has occurred. Rational, targeted therapies have been developed, the first being tyrosine kinase inhibitors (TKIs), which entered the clinical arena > 10 years ago. These were tremendously successful, significantly affecting the natural history of NSCLC and improving patient outcomes. However, the benefits of these drugs are somewhat limited by the emergence of adaptive resistance mechanisms, and efforts to tackle this phenomenon are ongoing. A better understanding of all types of oncogene-driven NSCLC and the occurrence of TKI resistance will help us to further develop second- and third-generation small molecule inhibitors and will expand our range of precision therapies for this disease. PMID:26182407

  1. The modification of radiation therapy by RP-170, hypoxic cell sensitizer, and OK-432, biological response modifier (BRM)

    International Nuclear Information System (INIS)

    Combination therapy with radiation, RP-170 and OK-432, was applied aiming a high therapeutic gain. C3H/HeN mice bearing SCC VII tumors in their legs were irradiated locally 40 min after administration of 200 mg/kg RP-170 orally. OK-432 was administered at 2KE one day before irradiation, at 4KE immediately after irradiation, and 4KE 6 days later. After this multimodal treatment, its TCD50 (the radiation dose to control 50% of irradiated tumor) reduced markedly and as a result, dose modifying factor (DMF) increased to more than 2. Moreover, this combination therapy could reduce the dose of RP-170; radiotherapy with 50 mg/kg RP-170 and OK-432 could produce the same DMF as that from irradiation with 150 mg/kg of RP-170. The higher antitumor effect in this study could also be demonstrated by the significantly increased autologous tumor-cell killing (ATK) activity in tumor infiltrating lymphocyte. (author)

  2. Synthesis and biological evaluation of 90Y-labeled porphyrin-DOTA conjugate for targeted tumor therapy

    International Nuclear Information System (INIS)

    Development of tumor-avid substances has received considerable attention in current cancer diagnostic and therapeutic protocols. Among the various substances exhibiting tumor specificity, hematoporphyrin and its derivatives have been extensively investigated with the aim to identifying potential agents for targeted tumor diagnosis and therapy. Working in this direction, a water soluble unsymmetrical porphyrin, namely 5-(4-(3-amino)-n-propyloxyphenyl)-10,15,20-tris-(4 carboxymethyleneoxyphenyl)porphyrin was synthesized and subsequently coupled with a bi-functional chelating agent (BFCA), namely p-isothiocyanato-benzyl-1,4,7,10 -tetraazacyclododecane- 1,4,7,10-tetraacetic acid (p-NCS-benzyl-DOTA), for its radiolabeling with 90Y. 90Y was chosen as a therapeutic radionuclide owing to its suitable nuclear decay characteristics (Eβmax= 2.28 MeV, T1/2= 64h) and easy availability in high radionuclidic purity from a 90Sr-90Y generator. The emission of high energy β- particle makes it a suitable candidate for therapy in large-sized tumors

  3. Treatment plan comparison of Linac step and shoot,Tomotherapy, RapidArc, and Proton therapy for prostate cancer using dosimetrical and biological index

    CERN Document Server

    Lee, Suk; Chang, Kyung Hwan; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook; Shin, Dongho

    2015-01-01

    The purpose of this study was to use various dosimetrical indices to determine the best IMRT modality technique for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. Intensity modulated radiation therapy plans were designed to include different modalities, including the linac step and shoot, Tomotherapy, RapidArc, and Proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), conformation number (CN), critical organ scoring index (COSI), and quality factor (QF) were determined to compare the different treatment plans. Biological indices such as the generalized equivalent uniform dose (gEUD), based tumor control probability (TCP), and normal tissue complication probability (NTCP) were also calculated and used to compare the treatment plans. The RapidArc plan attained better PTV coverage, as evidenc...

  4. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    Energy Technology Data Exchange (ETDEWEB)

    David W. Nigg; Amanda E. Schwint; John K. Hartwell; Elisa M. Heber; Veronica Trivillin; Jorge Castillo; Luis Wentzeis; Patrick Sloan; Charles A. Wemple

    2004-10-01

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  5. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    Energy Technology Data Exchange (ETDEWEB)

    Nigg, D.W.; Schwint, A.E.; Hartwell, J.K.; Heber, E.M.; Trivillin, V.; Castillo, J.; Wentzeis, L.; Sloan, P.; Wemple, C.A.

    2004-10-04

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  6. 葡萄膜炎的生物治疗进展%Advance in the biological therapy of uveitis

    Institute of Scientific and Technical Information of China (English)

    李燕利; 杨炜

    2013-01-01

    葡萄膜炎多发于青壮年,多为自身免疫性疾病,常反复发作.研究表明,生物制剂可以干扰机体内引起炎症反应过程的具有特定分子或途径,在葡萄膜炎的发病过程中发挥了关键的治疗作用,以达到治疗葡萄膜炎的目的.本文意在探讨抗肿瘤坏死因子制剂、白细胞介素受体拮抗剂、干扰素、抗淋巴细胞特异性抑制剂等生物制剂在葡萄膜炎治疗过程中的治疗进展.%Most of uveitis is a kind of autoimmune diseases. Uveitis often occurs in the young adults and frequently relapses. Studies show that biological preparations can interfere with the specific molecules or pathways which cause inflammatory reaction process in the body, which play a critical role in the treatment of onset progress of uveitis to achieve the purpose of treatment of uveitis. This paper discusses the progress of biological preparations such as anti tumor necrosis factor agents, interleukin receptor antagonists, interferon and anti lymphocyte specific inhibitors applied in the treatment of uveitis.

  7. Effects of radiation therapy for Hodgkin's disease in a child with ataxia telangiectasia: a clinical, biological and pathologic study

    International Nuclear Information System (INIS)

    Stage I lymphocyte-predominant Hodgkin's disease was diagnosed in a 44-month-old girl. Although immune deficiency was suspected and IgA deficiency demonstrated, the diagnosis of an ataxia-telangiectasia (AT)-like syndrome was not confirmed until eight weeks later when results of studies on the radiosensitivity of cultured skin fibroblasts were available. The child had none of the usual physical stigmata of AT. Severe acute radiation damage followed the treatment of this child with standard doses of radiation therapy. Clinical, pathologic, and radiobiologic correlations are drawn. The diagnosis of a malignant lymphoma disorder in children under the age of five should alert clinicians to the possibility of immune deficiency and, even in the absence of classical physical signs, to AT in particular. Suggestions for the management of future similar cases are put forward

  8. Serum brain-derived neurotrophic factor (BDNF) levels in patients with panic disorder: as a biological predictor of response to group cognitive behavioral therapy.

    Science.gov (United States)

    Kobayashi, Keisuke; Shimizu, Eiji; Hashimoto, Kenji; Mitsumori, Makoto; Koike, Kaori; Okamura, Naoe; Koizumi, Hiroki; Ohgake, Shintaro; Matsuzawa, Daisuke; Zhang, Lin; Nakazato, Michiko; Iyo, Masaomi

    2005-06-01

    Little is known about biological predictors of treatment response in panic disorder. Our previous studies show that the brain-derived neurotrophic factor (BDNF) may play a role in the pathophysiology of major depressive disorders and eating disorders. Assuming that BDNF may be implicated in the putative common etiologies of depression and anxiety, the authors examined serum BDNF levels of the patients with panic disorder, and its correlation with therapeutic response to group cognitive behavioral therapy (CBT). Group CBT (10 consecutive 1 h weekly sessions) was administered to the patients with panic disorder after consulting the panic outpatient special service. Before treatment, serum concentrations of BDNF and total cholesterol were measured. After treatment, we defined response to therapy as a 40% reduction from baseline on Panic Disorder Severity Scale (PDSS) score as described by [Barlow, D.H., Gorman, J.M., Shear, M.K., Woods, S.W., 2000. Cognitive-behavioral therapy, imipramine, or their combination for panic disorder: A randomized controlled trial. JAMA. 283, 2529-2536]. There were 26 good responders and 16 poor responders. 31 age- and sex-matched healthy normal control subjects were also recruited in this study. The serum BDNF levels of the patients with poor response (25.9 ng/ml [S.D. 8.7]) were significantly lower than those of the patients with good response (33.7 ng/ml [S.D. 7.5]). However, there were no significant differences in both groups of the patients, compared to the normal controls (29.1 ng/ml [S.D. 7.1]). No significant differences of other variables including total cholesterol levels before treatment were detected between good responders and poor responders. These results suggested that BDNF might contribute to therapeutic response of panic disorder. A potential link between an increased risk of secondary depression and BDNF remains to be investigated in the future. PMID:15905010

  9. Optimal schedules of fractionated radiation therapy by way of the greedy principle: biologically-based adaptive boosting

    International Nuclear Information System (INIS)

    We revisit a long-standing problem of optimization of fractionated radiotherapy and solve it in considerable generality under the following three assumptions only: (1) repopulation of clonogenic cancer cells between radiation exposures follows linear birth-and-death Markov process; (2) clonogenic cancer cells do not interact with each other; and (3) the dose response function s(D) is decreasing and logarithmically concave. Optimal schedules of fractionated radiation identified in this work can be described by the following ‘greedy’ principle: give the maximum possible dose as soon as possible. This means that upper bounds on the total dose and the dose per fraction reflecting limitations on the damage to normal tissue, along with a lower bound on the time between successive fractions of radiation, determine the optimal radiation schedules completely. Results of this work lead to a new paradigm of dose delivery which we term optimal biologically-based adaptive boosting (OBBAB). It amounts to (a) subdividing the target into regions that are homogeneous with respect to the maximum total dose and maximum dose per fraction allowed by the anatomy and biological properties of the normal tissue within (or adjacent to) the region in question and (b) treating each region with an individual optimal schedule determined by these constraints. The fact that different regions may be treated to different total dose and dose per fraction mean that the number of fractions may also vary between regions. Numerical evidence suggests that OBBAB produces significantly larger tumor control probability than the corresponding conventional treatments. (paper)

  10. Treatment plan comparison of linac step and shoot, tomotherapy, rapidarc, and proton therapy for prostate cancer by using the dosimetrical and the biological indices

    Science.gov (United States)

    Lee, Suk; Cao, Yuan Jie; Chang, Kyung Hwan; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook; Shin, Dongho

    2015-07-01

    The purpose of this study was to use various dosimetrical indices to determine the best intensitymodulated radiation therapy (IMRT) modality - for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. IMRT plans were designed to include different modalities, including the linac step and shoot, tomotherapy, RapidArc, and proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), conformation number (CN), critical organ scoring index (COSI), and quality factor (QF), were determined to compare the different treatment plans. Biological indices, such as the generalized equivalent uniform dose (gEUD) based the tumor control probability (TCP), and the normal tissue complication probability (NTCP), were also calculated and used to compare the treatment plans. The RapidArc plan attained better PTV coverage, as evidenced by its superior PITV, CI, TCI, MHI, and CN values. Regarding organ at risks (OARs), proton therapy exhibited superior dose sparing for the rectum and the bowel in low dose volumes, whereas the tomotherapy and RapidArc plans achieved better dose sparing in high dose volumes. The QF scores showed no significant difference among these plans (p = 0.701). The average TCPs for prostate tumors in the RapidArc, linac and proton plans were higher than the average TCP for Tomotherapy (98.79%, 98.76%, and 98.75% vs. 98.70%, respectively). Regarding the rectum NTCP, RapidArc showed the most favorable result (0.09%) whereas linac resulted in the best bladder NTCP (0.08%).

  11. 3D-personalized Monte Carlo dosimetry in 90Y-microspheres therapies of primary and secondary hepatic cancers: absorbed dose and biological effective dose considerations

    International Nuclear Information System (INIS)

    Full text of publication follows. Purpose: a 3D-Personalized Monte Carlo Dosimetry (PMCD) was developed for treatment planning in nuclear medicine. The method was applied to Selective Internal Radiation Therapy (SIRT) using 90Y-microspheres for unresectable hepatic cancers. Methods: The PMCD method was evaluated for 20 patients treated for hepatic metastases or hepatocellular carcinoma at the European Hospital Georges Pompidou (Paris). First, regions of interest were outlined on the patient CT images. Using the OEDIPE software, patient-specific voxel phantoms were created. 99mTc-MAA SPECT data were then used to generate 3D-matrices of cumulated activity. Absorbed doses and Biologically Effective Dose (BED) were calculated at the voxel scale using the MCNPX Monte Carlo transport code. Finally, OEDIPE was used to determine the maximum injectable activity (MIA) for tolerance criteria on organs at risk (OARs), i.e. the lungs and non tumoral liver (NTL). Tolerance criteria based on mean absorbed doses, mean BED, Dose-Volume Histograms (DVHs) or BED-Volume Histograms (BVHs) were considered. Those MIAs were compared to the Partition Model with tolerance criteria on mean absorbed doses, which is a conventional method applied in clinical practice. Results: compared to Partition Model recommendations, performing dosimetry using the PMCD method enables to increase the activity prescription while ensuring OARs' radiation protection. Moreover, tolerance criteria based on DVHs allow us to enhance treatment planning efficiency by taking advantage of the parallel characteristic of the liver and the lungs, whose functions are not impaired if the level of irradiation to a fraction of the organ is kept sufficiently low. Finally, multi-cycle treatments based on tolerance criteria on mean BED and BVHs, were considered to go further in the dose optimization, taking into account biological considerations such as cell repair or radiosensitivity. Conclusion: besides its feasibility

  12. Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

    International Nuclear Information System (INIS)

    Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCPr) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, α/β values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all α/β values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCPr by less than 3%. This is especially true when multiple (two or three) markers are used

  13. Biological effect of dose distortion by fiducial markers in spot-scanning proton therapy with a limited number of fields: A simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Matsuura, Taeko; Maeda, Kenichiro; Sutherland, Kenneth; Takayanagi, Taisuke; Shimizu, Shinichi; Takao, Seishin; Miyamoto, Naoki; Nihongi, Hideaki; Toramatsu, Chie; Nagamine, Yoshihiko; Fujimoto, Rintaro; Suzuki, Ryusuke; Ishikawa, Masayori; Umegaki, Kikuo; Shirato, Hiroki [Department of Medical Physics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638 (Japan); Hitachi, Ltd., Hitachi Research Laboratory, 7-2-1 Omika-cho, Hitachi-shi, Ibaraki 319-1221 (Japan); Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638 (Japan); Department of Medical Physics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638 (Japan); Hitachi, Ltd., Hitachi Works, 3-1-1 Saiwai-cho, Hitachi-shi, Ibaraki 317-8511 (Japan); Hitachi, Ltd., Hitachi Research Laboratory, 7-2-1 Omika-cho, Hitachi-shi, Ibaraki 319-1221 (Japan); Department of Medical Physics, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638 (Japan); Department of Radiation Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, 060-8638 (Japan)

    2012-09-15

    Purpose: In accurate proton spot-scanning therapy, continuous target tracking by fluoroscopic x ray during irradiation is beneficial not only for respiratory moving tumors of lung and liver but also for relatively stationary tumors of prostate. Implanted gold markers have been used with great effect for positioning the target volume by a fluoroscopy, especially for the cases of liver and prostate with the targets surrounded by water-equivalent tissues. However, recent studies have revealed that gold markers can cause a significant underdose in proton therapy. This paper focuses on prostate cancer and explores the possibility that multiple-field irradiation improves the underdose effect by markers on tumor-control probability (TCP). Methods: A Monte Carlo simulation was performed to evaluate the dose distortion effect. A spherical gold marker was placed at several characteristic points in a water phantom. The markers were with two different diameters of 2 and 1.5 mm, both visible on fluoroscopy. Three beam arrangements of single-field uniform dose (SFUD) were examined: one lateral field, two opposite lateral fields, and three fields (two opposite lateral fields + anterior field). The relative biological effectiveness (RBE) was set to 1.1 and a dose of 74 Gy (RBE) was delivered to the target of a typical prostate size in 37 fractions. The ratios of TCP to that without the marker (TCP{sub r}) were compared with the parameters of the marker sizes, number of fields, and marker positions. To take into account the dependence of biological parameters in TCP model, {alpha}/{beta} values of 1.5, 3, and 10 Gy (RBE) were considered. Results: It was found that the marker of 1.5 mm diameter does not affect the TCPs with all {alpha}/{beta} values when two or more fields are used. On the other hand, if the marker diameter is 2 mm, more than two irradiation fields are required to suppress the decrease in TCP from TCP{sub r} by less than 3%. This is especially true when multiple

  14. Range modulation in proton therapy planning: a simple method for mitigating effects of increased relative biological effectiveness at the end-of-range of clinical proton beams

    International Nuclear Information System (INIS)

    The increase in relative biological effectiveness (RBE) of proton beams at the distal edge of the spread out Bragg peak (SOBP) is a well-known phenomenon that is difficult to quantify accurately in vivo. For purposes of treatment planning, disallowing the distal SOBP to fall within vulnerable tissues hampers sparing to the extent possible with proton beam therapy (PBT). We propose the distal RBE uncertainty may be straightforwardly mitigated with a technique we call “range modulation”. With range modulation, the distal falloff is smeared, reducing both the dose and average RBE over the terminal few millimeters of the SOBP. One patient plan was selected to serve as an example for direct comparison of image-guided radiotherapy plans using non-range modulation PBT (NRMPBT), and range-modulation PBT (RMPBT). An additional plan using RMPBT was created to represent a re-treatment scenario (RMPBTrt) using a vertex beam. Planning statistics regarding dose, volume of the planning targets, and color images of the plans are shown. The three plans generated for this patient reveal that in all cases dosimetric and device manufacturing advantages are able to be achieved using RMPBT. Organ at risk (OAR) doses to critical structures such as the cochleae, optic apparatus, hypothalamus, and temporal lobes can be selectively spared using this method. Concerns about the location of the RBE that did significantly impact beam selection and treatment planning no longer have the same impact on the process, allowing these structures to be spared dose and subsequent associated issues. This present study has illustrated that RMPBT can improve OAR sparing while giving equivalent coverage to target volumes relative to traditional PBT methods while avoiding the increased RBE at the end of the beam. It has proven easy to design and implement and robust in our planning process. The method underscores the need to optimize treatment plans in PBT for both traditional energy dose in gray (Gy) and

  15. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Tomohiko, E-mail: matsutomo_llp@yahoo.co.jp [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan); Kogo, Kasei [Kumamoto Radiosurgery Clinic, Kumamoto (Japan); Oya, Natsuo [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan)

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  16. Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

    International Nuclear Information System (INIS)

    Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD5) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a comparable

  17. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy10. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients

  18. Biologic therapies for chronic inflammatory bowel disease Tratamientos biológicos en la enfermedad inflamatoria crónica intestinal

    Directory of Open Access Journals (Sweden)

    M. P. Martínez-Montiel

    2006-04-01

    Full Text Available Crohn's disease (CD and ulcerative colitis (UC make up the so-called chronic inflammatory bowel disease (IBD. Advances in the understanding of IBD pathophysiologic mechanisms in the last few years have allowed the development of novel therapies such as biologic therapies, which at least theoretically represent a more specific management of this disease with fewer side effects. Currently, the only effective and widely accepted biologic therapy for the treatment of intraluminal, fistulizing CD, both for remission induction and maintenance, is infliximab. The role of other monoclonal antibodies such as adalimumab is not clearly established. It could be deemed an alternative for patients with allergic reactions to infliximab, and for those with lost response because of anti-infliximab antibody development. However, relevant issues such as dosage and administration regimen remain to be established. Anti-integrin α4 therapies, despite encouraging results in phase-3 studies, are still unavailable, as their marketing authorization was held back in view of a number of reports regarding progressive multifocal leukoencephalopathy cases. Immunostimulating therapy may be highly relevant in the near future, as it represents a novel strategy against disease with the inclusion of granulocyte-monocyte colony-stimulating factors. Regarding ulcerative colitis, results from the ACT-1 and ACT-2 studies showed that infliximab is also useful for the management of serious UC flare-ups not responding to standard treatment, which will lead to a revision of therapeutic algorithms, where this drug should be given preference before intravenous cyclosporine. In the next few years, the role of anti-CD3 drugs (vilisilizumab, T-cell inhibiting therapies, and epithelial repair and healing stimulating factors will be established.La enfermedad de Crohn (EC y la colitis ulcerosa (CU constituyen la denominada enfermedad inflamatoria crónica intestinal (EII. Los avances producidos

  19. Clinical, biological, histological features and treatment of oral mucositis induced by radiation therapy: a literature review; Aspectos clinicos, biologicos, histopatologicos e tratamentos propostos para a mucosite oral induzida por radioterapia: revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Bonan, Paulo Rogerio Ferreti [Universidade Estadual de Montes Claros e Faculdades Unidas do Norte de Minas, MG (Brazil). Dept. de Odontologia]. E-mail: pbonan@yahoo.com; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de [Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP (Brazil). Faculdade de Odontologia. Dept. de Diagnostico Oral; Alves, Fabio de Abreu [Hospital do Cancer AC Camargo, Sao Paulo, SP (Brazil). Dept. de Estomatologia

    2005-07-01

    The oral mucositis is a main side effect of radiotherapy on head and neck, initiating two weeks after the beginning of the treatment. It is characterized by sensation of local burning to intense pain, leading in several cases, to the interruption of the treatment. The purpose of this work is to review the main published studies that discuss the clinical, biological and histopathological features of oral mucositis induced by radiation therapy and to describe the main approaches recommended to prevent or to treat it. Although the clinical features of mucositis are intensively described in the literature, few studies address the histopathological alterations in oral mucositis and only recently, its biological processes have been investigated. The biological mechanisms involved in the radiation tissue damage have been only recently discussed and there is no consensus among treatment modalities. Yet, the progressive knowledge in the histopathology and biological characteristics of oral mucositis probably will lead to more effective in prevention and control strategies. (author)

  20. Synthetic biology: advancing biological frontiers by building synthetic systems

    OpenAIRE

    Chen, Yvonne Yu-Hsuan; Galloway, Kate E.; Smolke, Christina D.

    2012-01-01

    Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field.

  1. Direct evaluation of radiobiological parameters from clinical data in the case of ion beam therapy: an alternative approach to the relative biological effectiveness

    International Nuclear Information System (INIS)

    The relative biological effectiveness (RBE) concept is commonly used in treatment planning for ion beam therapy. Whether models based on in vitro/in vivo RBE data can be used to predict human response to treatments is an open issue. In this work an alternative method, based on an effective radiobiological parameterization directly derived from clinical data, is presented. The method has been applied to the analysis of prostate cancer trials with protons and carbon ions. Prostate cancer trials with proton and carbon ion beams reporting 5 year-local control (LC5) and grade 2 (G2) or higher genitourinary toxicity rates (TOX) were selected from literature to test the method. Treatment simulations were performed on a representative subset of patients to produce dose and linear energy transfer distribution, which were used as explicative physical variables for the radiobiological modelling. Two models were taken into consideration: the microdosimetric kinetic model (MKM) and a linear model (LM). The radiobiological parameters of the LM and MKM were obtained by coupling them with the tumor control probability and normal tissue complication probability models to fit the LC5 and TOX data through likelihood maximization. The model ranking was based on the Akaike information criterion. Results showed large confidence intervals due to the limited variety of available treatment schedules. RBE values, such as RBE = 1.1 for protons in the treated volume, were derived as a by-product of the method, showing a consistency with current approaches. Carbon ion RBE values were also derived, showing lower values than those assumed for the original treatment planning in the target region, whereas higher values were found in the bladder. Most importantly, this work shows the possibility to infer the radiobiological parametrization for proton and carbon ion treatment directly from clinical data. (paper)

  2. The Biology of Aging.

    Science.gov (United States)

    Sprott, Richard L.; And Others

    1992-01-01

    Thirteen articles in this special issue discuss aging theories, biomarkers of aging, aging research, disease, cancer biology, Alzheimer's disease, stress, oxidation of proteins, gene therapy, service delivery, biogerontology, and ethics and aging research. (SK)

  3. Combined tumor therapy

    International Nuclear Information System (INIS)

    This comprehensive survey of current methods and achievements first takes a look at the two basic therapies, devoting a chapter each to the surgery and radiotherapy of tumors. The principal subjects of the book, however, are the systemic, adjuvant therapy, biological therapies, hyperthermia and various other therapies (as e.g. treatment with ozone, oxygen, or homeopathic means), and psychotherapy. (MG) With 54 figs., 86 tabs

  4. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... skin cells called melanocytes that produce skin color ( melanin ). Radiation therapy is used mostly for melanomas that ... in addition to surgery, chemotherapy or biologic therapy. Hair Epidermis Dermis Subcutaneous Hair Follicle Vein Artery © ASTRO ...

  5. Boron determination in biological samples - Intercomparison of three analytical methods to assist development of a treatment protocol for neoplastic diseases of the liver with Boron Neutron Capture Therapy

    OpenAIRE

    Schütz, Christian L.

    2012-01-01

    Die Bor-Neuroneneinfang-Therapie (engl.: Boron Neutron Capture Therapy, BNCT) ist eine indirekte Strahlentherapie, welche durch die gezielte Freisetzung von dicht ionisierender Strahlung Tumorzellen zerstört. Die freigesetzten Ionen sind Spaltfragmente einer Kernreaktion, bei welcher das Isotop 10B ein niederenergetisches (thermisches) Neutron einfängt. Das 10B wird durch ein spezielles Borpräparat in den Tumorzellen angereichert, welches selbst nicht radioaktiv ist. rnAn der Johannes Gutenbe...

  6. Family therapy

    Directory of Open Access Journals (Sweden)

    Shaikh Altamash

    2013-01-01

    Full Text Available Another major force not letting us succeed in the treatment of diabetes remains right inside the patients home, their family members. Hence, it is important to know the perception of the close family members about this simple and strong tool in diabetes, ′insulin′. The drug is nearing its century, it has not fully being accepted gracefully even in todays electronic savvy society. So, we need to strongly discover the reason for its non-acceptance, while trials are out inventing new drugs. One vital thing that can change this attitude is increasing the understanding of this drug, insulin in depth to close people around the patient, the ′family′. Underestimating family′s perception about disease and treatment for diabetes is detrimental to both diseased and the doctor. This consists of a biopsychosocial model; biological, psychological and social factors. Family forms the most important part of it. The strategies in family therapy include psychodynamic, structural, strategic, and cognitive-behavioral component. Diabetes has and will continue to rise, so will be the treatment options. From the clinicians side its to fix fasting first but from patients its fix family first. Family therapy demonstrates the importance of insulin initiation and maintenance in insulin naive patients, and continuation for others. The specific needs of such patients and their impact on family life are met with family therapy. Who needs family therapy? Benefits of family therapy and a case based approach is covered.

  7. Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom

    DEFF Research Database (Denmark)

    Guyot, Patricia; Taylor, Peter C; Christensen, Robin;

    2012-01-01

    To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom.......To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom....

  8. Clinical response to anti-TNFα therapy in patients with rheumatoid arthritis faulted or intolerance in non-biological DMARD in the Hospital San Juan de Dios in the period January 2006 to December 2011

    International Nuclear Information System (INIS)

    Various clinical studies are performed globally using anti-TNFα therapy and has proven its clinical effectiveness in the management of rheumatoid arthritis patients, that have failed or have presented intolerance to the use of non-biological DMARDs. The clinical response to treatment of anti-TNFα was determined in patients with rheumatoid arthritis who have presented without respond, have showed intolerance or secondary effects to DMARDs no biological, in the Servicio de Reumatologia del Hospital San Juan de Dios, in the period January 2006 to December 2011. Study has been descriptive, retrospective, observational, by reviewing dossiers of patients with rheumatoid arthritis to initiate anti-TNFα therapy where has valued the DAS28 and initial VES, then at 6 months and 12 months after starting treatment. In the period analyzed, 47 patients evaluated with traditional DMARD failure who have received anti-TNFα therapy, according to DAS28, 32 patients were cataloged as severe activity and 15 of them with moderate activity. A total of 41 patients have used etanercept, with adalimumab 6 patients. The DAS28 initial average was 5,63 in all patients, 6,16 in the subgroup of patients with severe activity, and 4,49 in the subgroup of moderate activity. After 6 months of treatment, the DAS28 has descended to 3,25 in all patients, with 3,67 in the subgroup of severe clinical activity, and 2,35 in the subgroup of moderate clinical activity. One year after treatment values DAS28 have been 3,13 for all patients, 3,53 in severe activity and 2,28 in the subgroup of activity clinical moderate. In all groups and subgroups of patients, difference was demonstrated statistically significant at p less than 0,05. Between the subgroups of patients according to clinical activity is keeped without significant difference, or the type of anti-TNFα therapy employed. The anti-TNFα therapy has proven to be effective for improvement of clinical activity of rheumatoid arthritis, regardless of

  9. Biological effects

    International Nuclear Information System (INIS)

    Following an introduction into the field of cellular radiation effect considering the most important experimental results, the biological significance of the colony formation ability is brought out. The inactivation concept of stem cells does not only prove to be good, according to the present results, in the interpretation of the pathogenesis of acute radiation effects on moult tissue, it also enables chronicle radiation injuries to be interpreted through changes in the fibrous part of the organs. Radiation therapy of tumours can also be explained to a large extent by the radiation effect on the unlimited reproductiveness of tumour cells. The more or less similar dose effect curves for healthy and tumour tissue in practice lead to intermittent irradiation. The dependence of the intermittent doses and intervals on factors such as Elkind recovery, synchronisation, redistribution, reoxygenation, repopulation and regeneration are reviewed. (ORU/LH)

  10. Inadequate response or intolerability to oral methotrexate: Is it optimal to switch to subcutaneous methotrexate prior to considering therapy with biologics?

    Science.gov (United States)

    Yadlapati, Sujani; Efthimiou, Petros

    2016-05-01

    Methotrexate (MTX) is considered an anchor drug in the treatment of rheumatoid arthritis. It is also the first-line therapy in a multitude of rheumatologic conditions. Low-dose oral MTX is the preliminary modality of treatment for rheumatoid arthritis due to its affordability, favorable outcomes, and limited risks. However, patients refractory to low-dose MTX therapy may require larger doses of oral MTX. Several studies in the past have demonstrated variability in bioavailability of oral MTX at high doses. This warrants a subsequent switch to parenteral MTX. Widely used among the parenteral preparations of MTX is subcutaneous (SC) MTX. SC MTX provides dependable efficacy, predictable bioavailability, sustained clinical outcomes, and minimal GI adverse effects. It is useful either singularly or in combination therapy regimens. Although SC MTX and intramuscular MTX have similar pharmacokinetics, SC MTX may be preferred by most patients. Development of prefilled syringes and auto-injectors have enabled self-administration of the medication providing the patients with a sense of independence and improved general well-being. Hence, SC MTX can prove to be more efficacious in patients refractory to oral MTX therapy or in patients experiencing severe gastrointestinal adverse effects. PMID:26936262

  11. Synthetic Biology for Therapeutic Applications

    OpenAIRE

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2014-01-01

    Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug d...

  12. Biological Threats

    Science.gov (United States)

    ... Workplace Plans School Emergency Plans Main Content Biological Threats Biological agents are organisms or toxins that can ... for Disease Control and Prevention . Before a Biological Threat Unlike an explosion, a biological attack may or ...

  13. Ablation and Other Local Therapy for Kidney Cancer

    Science.gov (United States)

    ... for kidney cancer Targeted therapies for kidney cancer Biologic therapy (immunotherapy) for kidney cancer Chemotherapy for kidney cancer Pain control for kidney cancer Treatment choices by stage for ...

  14. Toward cell therapy using placenta-derived cells: Disease mechanisms, cell biology, preclinical studies, and regulatory aspects at the round table

    OpenAIRE

    Parolini, O.; Alviano, F; Bergwerf, I; Boraschi, D.; De Bari, C; De Waele, P; Dominici, M; Evangelista, M; Falk, W; Hennerbichler, S; Hess, D C; G. Lanzoni; B. Liu; Marongiu, F; Mc Guckin, C

    2010-01-01

    Among the many cell types which may prove useful to regenerative medicine, mounting evidence suggests that human term placenta-derived cells will join the list of significant contributors. In making new cell therapy-based strategies a clinical reality, it is fundamental that no a priori claims are made regarding which cell source is preferable for a particular therapeutic application. Rather, ongoing comparisons of the potentiality and characteristics of cells from different sources should be...

  15. Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis

    OpenAIRE

    Yokomizo, Lauren; Limketkai, Berkeley; Park, K. T.

    2016-01-01

    Background There are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first-line agents to induce clinical remission and mucosal healing (MH) in UC. Methods We constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and ...

  16. Openness to and preference for attributes of biologic therapy prior to initiation among patients with rheumatoid arthritis: patient and rheumatologist perspectives and implications for decision making

    OpenAIRE

    Bolge SC; Goren A; Brown D.; Ginsberg S; Allen I

    2016-01-01

    Susan C Bolge,1 Amir Goren,2 Duncan Brown,2 Seth Ginsberg,3 Isabel Allen4 1Health Economics & Outcomes Research, Janssen Scientific Affairs, LLC, Raritan, NJ, 2Health Outcomes Practice, Kantar Health, New York, 3Global Healthy Living Foundation, Upper Nyack, NY, 4Department of Biostatistics & Epidemiology, University of California San Francisco, San Francisco, CA, USA Purpose: Despite American College of Rheumatology recommendations, appropriate and timely initiation of biologic the...

  17. The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy

    OpenAIRE

    Leist, Marcel; Bremer, Susanne; Brundin, Patrik; Hescheler, Jürgen; Kirkeby, Agnete; Krause, Karl-Heinz; Pörzgen, Peter; Pucéat, Michel; Schmidt, Mathias; Schrattenholz, André; Zak, Naomi B.; Hentze, Hannes

    2008-01-01

    Human embryonic stem cells (hESC) are now routinely cultured in many laboratories, and differentiation protocols are available to generate a large variety of cell types. In an ongoing ethical debate opinions of different groups are based on varying sets of religious, historical, cultural and scientific arguments as well as on widely differing levels of general information. We here give an overview of the biological background for non-specialists, and address all is- sues of the current stem c...

  18. Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis

    OpenAIRE

    Hazlewood, Glen S; Barnabe, Cheryl; Tomlinson, George; Marshall, Deborah; Devoe, Dan; Bombardier, Claire

    2016-01-01

    Objective To compare methotrexate based disease modifying antirheumatic drug (DMARD) treatments for rheumatoid arthritis in patients naive to or with an inadequate response to methotrexate. Design Systematic review and Bayesian random effects network meta-analysis of trials assessing methotrexate used alone or in combination with other conventional synthetic DMARDs, biologic drugs, or tofacitinib in adult patients with rheumatoid arthritis. Data sources Trials were identified from Medline, Em...

  19. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy

    OpenAIRE

    Jurkić Lela Munjas; Cepanec Ivica; Pavelić Sandra Kraljević; Pavelić Krešimir

    2013-01-01

    Abstract Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and wit...

  20. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  1. Study of the interaction of boron-containing amino acids for the neutron capture therapy with biologically interesting compounds by using 'three-spot zone electrophoresis'

    International Nuclear Information System (INIS)

    As the boron carriers for boron neutron capture therapy, p-borono phenylalanine (BPA) is the boron compound which has been clinically used together with sodium borocaptate. It was found by the electrophoresis behavior that the BPA interacted with organic carboxylic acids in its dissolved state. In this paper, the electrophoresis behavior of general amino acids as seen in three-spot zone electrophoresis and the peculiar interaction of the amino acids having dihydroxyboryl radical are described. Zone electrophoresis has been developed as separation means, and three-spot process excludes the errors due to accidental factors as far as possible. The behaviors of zone electrophoresis of ordinary neutral amino acids, orthoboric acid and p-BPA are reported. For utilizing the features of boron neutron capture therapy, it is necessary to develop the carrier which is singularly taken into cancer cells. There is not a good method for discriminating normal cells and cancer cells. As for the administration of BPA to patients, its solubility is insufficient, therefore, its fructose complex has been used. The research on the biochemical peculiarity of boron is important. (K.I.)

  2. Molecular Biology of Medulloblastoma

    OpenAIRE

    J Gordon Millichap

    2007-01-01

    Current methods of diagnosis and treatment of medulloblastoma, and the influence of new biological advances in the development of more effective and less toxic therapies are reviewed by researchers at Children’s National Medical Center, The George Washington University, Washington, DC.

  3. Antiprotons get biological

    CERN Multimedia

    2003-01-01

    After its final run in September, the first results of the Antiproton Cell Experiment (ACE) look very promising. It was the first experiment to take data on the biological effects of antiproton beams to evaluate the potential of antiprotons in radiation therapy.

  4. Technical Note: Implementation of biological washout processes within GATE/GEANT4—A Monte Carlo study in the case of carbon therapy treatments

    International Nuclear Information System (INIS)

    Purpose: The imaging of positron emitting isotopes produced during patient irradiation is the only in vivo method used for hadrontherapy dose monitoring in clinics nowadays. However, the accuracy of this method is limited by the loss of signal due to the metabolic decay processes (biological washout). In this work, a generic modeling of washout was incorporated into the GATE simulation platform. Additionally, the influence of the washout on the β+ activity distributions in terms of absolute quantification and spatial distribution was studied. Methods: First, the irradiation of a human head phantom with a 12C beam, so that a homogeneous dose distribution was achieved in the tumor, was simulated. The generated 11C and 15O distribution maps were used as β+ sources in a second simulation, where the PET scanner was modeled following a detailed Monte Carlo approach. The activity distributions obtained in the presence and absence of washout processes for several clinical situations were compared. Results: Results show that activity values are highly reduced (by a factor of 2) in the presence of washout. These processes have a significant influence on the shape of the PET distributions. Differences in the distal activity falloff position of 4 mm are observed for a tumor dose deposition of 1 Gy (Tini = 0 min). However, in the case of high doses (3 Gy), the washout processes do not have a large effect on the position of the distal activity falloff (differences lower than 1 mm). The important role of the tumor washout parameters on the activity quantification was also evaluated. Conclusions: With this implementation, GATE/GEANT 4 is the only open-source code able to simulate the full chain from the hadrontherapy irradiation to the PET dose monitoring including biological effects. Results show the strong impact of the washout processes, indicating that the development of better models and measurement of biological washout data are essential

  5. Biological and therapeutic effects of ortho-silicic acid and some ortho-silicic acid-releasing compounds: New perspectives for therapy

    Directory of Open Access Journals (Sweden)

    Jurkić Lela Munjas

    2013-01-01

    Full Text Available Abstract Silicon (Si is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4, as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K, the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel, silica gel (amorphous silicon dioxide, and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4 in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

  6. Do changes in prescription practice in patients with rheumatoid arthritis treated with biological agents affect treatment response and adherence to therapy? Results from the nationwide Danish DANBIO Registry

    DEFF Research Database (Denmark)

    Hetland, M L; Lindegaard, H M; Hansen, A;

    2008-01-01

    BACKGROUND: Prescription practice for tumour necrosis factor alpha (TNFalpha) inhibitors has changed towards treating patients with lower disease activity. OBJECTIVE: To determine the trend in treatment response in cohorts of patients with rheumatoid arthritis who started TNFalpha inhibitor...... treatment between 2000 and 2005. METHODS: 1813 patients with RA starting treatment with biological agents in 2000-5 were registered prospectively in the nationwide DANBIO Registry. Baseline disease activity and 12 months' treatment responses were determined in cohorts based on start year (2000/1; 2002; 2003...

  7. Involvement of the Artemis Protein in the Relative Biological Efficiency Observed With the 76-MeV Proton Beam Used at the Institut Curie Proton Therapy Center in Orsay

    Energy Technology Data Exchange (ETDEWEB)

    Calugaru, Valentin [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France); Nauraye, Catherine [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Cordelières, Fabrice P. [Institut Curie, Centre Universitaire, Orsay (France); Biard, Denis [Centre d' Etude Atomique, Direction des Sciences du Vivant, Institut des Maladies Emergentes et des Thérapies Innovantes, Service d' Etude des Prions et des Infections Atypiques, Fontenay-aux-Roses (France); De Marzi, Ludovic [Institut Curie Centre de Protonthérapie d' Orsay, Centre Universitaire, Orsay (France); Hall, Janet; Favaudon, Vincent [Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France); Mégnin-Chanet, Frédérique, E-mail: frederique.megnin@inserm.fr [Institut Curie, Centre Universitaire, Orsay (France); INSERM U612, Centre Universitaire, Orsay (France)

    2014-09-01

    Purpose: Previously we showed that the relative biological efficiency for induced cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To investigate the repair pathways underlying this increase, we used an isogenic human cell model in which individual DNA repair proteins have been depleted, and techniques dedicated to precise measurements of radiation-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). Methods and Materials: The 3-Gy surviving fractions of HeLa cells individually depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway) or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were determined at the 3 positions previously defined in the SOBP. Quantification of incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D) immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells. Results: We showed that the amount of SSBs and DSBs depends directly on the particle fluence and that the increase in relative biological efficiency observed in the distal part of the SOBP is due to a subset of lesions generated under these conditions, leading to cell death via a pathway in which the Artemis protein plays a central role. Conclusions: Because therapies like proton or carbon beams are now being used to treat cancer, it is even more important to dissect the mechanisms implicated in the repair of the lesions generated by these particles. Additionally, alteration of the expression or activity of the Artemis protein could be a novel therapeutic tool before high linear energy transfer irradiation treatment.

  8. Involvement of the Artemis Protein in the Relative Biological Efficiency Observed With the 76-MeV Proton Beam Used at the Institut Curie Proton Therapy Center in Orsay

    International Nuclear Information System (INIS)

    Purpose: Previously we showed that the relative biological efficiency for induced cell killing by the 76-MeV beam used at the Institut Curie Proton Therapy Center in Orsay increased with depth throughout the spread-out Bragg peak (SOBP). To investigate the repair pathways underlying this increase, we used an isogenic human cell model in which individual DNA repair proteins have been depleted, and techniques dedicated to precise measurements of radiation-induced DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). Methods and Materials: The 3-Gy surviving fractions of HeLa cells individually depleted of Ogg1, XRCC1, and PARP1 (the base excision repair/SSB repair pathway) or of ATM, DNA-PKcs, XRCC4, and Artemis (nonhomologous end-joining pathway) were determined at the 3 positions previously defined in the SOBP. Quantification of incident SSBs and DSBs by the alkaline elution technique and 3-dimensional (3D) immunofluorescence of γ-H2AX foci, respectively, was performed in SQ20 B cells. Results: We showed that the amount of SSBs and DSBs depends directly on the particle fluence and that the increase in relative biological efficiency observed in the distal part of the SOBP is due to a subset of lesions generated under these conditions, leading to cell death via a pathway in which the Artemis protein plays a central role. Conclusions: Because therapies like proton or carbon beams are now being used to treat cancer, it is even more important to dissect the mechanisms implicated in the repair of the lesions generated by these particles. Additionally, alteration of the expression or activity of the Artemis protein could be a novel therapeutic tool before high linear energy transfer irradiation treatment

  9. Hadron therapy

    International Nuclear Information System (INIS)

    -defined range of proton beams offer a solution to these problems through their superior dose distribution properties. In recent years the term 'Hadron Therapy' has been coined to describe cancer treatments involving heavy particles including neutrons, protons and heavy charged particles such as 12C, 20Ne, 28Si, etc. While protons offer a dose distribution advantage, neutrons, which are exponentially attenuated, offer therapeutic advantages derived from differences in cellular response to the different types of radiation depending on cell kinetics and physiology. These differences are attributed to the high stopping power (or 'linear energy transfer') of the secondary particles set in motion in tissue by the primary neutron beam. Heavy charged particle beams (12C, etc) combine the dose distribution advantages of the Bragg peak with the biological advantages of high linear energy transfer (LET). Research in neutron therapy has shown that the biological advantages of this therapy can only be realized for a limited number of disease sites and histologies. The dose distribution advantages of proton therapy, however, are more widely applicable and realizable. It can be argued that, because of the basic physical differences in the dose distribution mechanisms for x ray and proton beams, proton beams can always give a better dose distribution; i.e. more uniform dose in the tumor volume and less dose to the surrounding normal tissues. In spite of the large capital costs of proton facilities, several large facilities, which incorporate a single accelerator and multiple treatment rooms have been built or are planned. It is argued that such large facilities operated over 20-25 years can provide a cost effective and superior cancer treatment in comparison with x ray therapy. The rationales for hadron therapy and the modern accelerator, computing and imaging technologies necessary for it's successful application to cancer therapy will be presented and discussed in detail

  10. The Biological Effects of Low Level Laser Therapy on Osteoblasts:An Update%低能量激光治疗对成骨细胞的生物效应研究进展

    Institute of Scientific and Technical Information of China (English)

    李秋实; 陈英新; 周延民

    2011-01-01

    低能量激光治疗(Low level laser therapy,LLLT)对体内外成骨细胞的作用是激光医学领域的研究热点,本文为近年来LLLT对成骨细胞的生物效应及光生物调节作用机制研究进展的综述.LLLT可以活化成骨细胞,促进骨修复.LLLT可能对涉及骨组织修复的学科如口腔种植学具有重要意义.%The effect of low level laser therapy ( LLLT) on in vitro and in vivo osteoblasts has been a hot issue in laser medical area. This review briefly reports the biological effects of LLLT on osteoblasts and the mechanism of photobiomodulation is discussed too. It is pointed out in this review that LLLT can activate osteoblasts and then promote bone repair. LLLT could be very important to the clinical application in the subjects involved with bone tissue healing such as oral implantology.

  11. A Preliminary, Open Label, Single-arm Study of Calcipotriene/Betamethasone Topical Suspension as a Supplement to Non-biologic Systemic Therapy for Psoriasis

    Science.gov (United States)

    Kupetsky, Erine; Houston, Neil A.M.

    2016-01-01

    Background: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. Methods: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient’s Global Assessment from baseline to Week 12. Results: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient’s Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. Conclusion: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019. PMID:27462386

  12. Biological evaluation of 153Sm and 166Ho complexes with macrocyclic ligands containing acetate pendant arms as potential agents for therapy

    International Nuclear Information System (INIS)

    For the development of therapeutic radiopharmaceuticals it is essential to choose the appropriate beta-emitter as well as the carrier biomolecule. Different carrier biomolecules, namely antibodies and peptides, have been linked to different beta-emitters (153Sm, 166Ho and 177Lu) using tetraaza macrocycles as bifunctional chelators. The cavity size of these chelators, the rigidity of the macrocyclic backbone and the nature of the pendant arms seems to play an important role on the thermodynamic stability and kinetic inertness of the radiocomplexes and on their biological behaviour. In our research group we have been exploring the possibility of using tetraazamacrocycles with different cavity size, pendant arms and rigidity for preparing 153Sm and 166Ho complexes useful for therapeutical applications and/or bone pain palliation. In this communication we present the results obtained when we reacted trita and teta with 153Sm and 166Ho. The complexes are formed in good yields (> 98%), are hydrophilic and present an overall negative charges, as well as low plasmatic protein binding. Good in vitro stability in physiological media and human serum was also found for all the complexes. The biodistribution studies in mice are also presented and have shown that 153Sm/166Ho-trita and 166Ho-teta have rapid tissue clearance, comparably to the corresponding dota complexes. In contrast, 153Sm-teta has a significant lower total excretion and a significant liver and muscle uptake. Our results indicate that 153Sm/166Ho-trita form very stable complexes in vivo. However, teta, which has a larger cavity size, forms less stable complexes with the larger ion Sm3+. The biological profile of 153Sm/166Ho-trita is very interesting for the evaluation of these complexes as therapeutical agents when conjugated to biomolecules

  13. A paradigm for viewing biologic systems as scale-free networks based on energy efficiency: implications for present therapies and the future of evolution.

    Science.gov (United States)

    Yun, Anthony J; Lee, Patrick Y; Doux, John D

    2006-01-01

    A network constitutes an abstract description of the relationships among entities, respectively termed links and nodes. If a power law describes the probability distribution of the number of links per node, the network is said to be scale-free. Scale-free networks feature link clustering around certain hubs based on preferential attachments that emerge due either to merit or legacy. Biologic systems ranging from sub-atomic to ecosystems represent scale-free networks in which energy efficiency forms the basis of preferential attachments. This paradigm engenders a novel scale-free network theory of evolution based on energy efficiency. As environmental flux induces fitness dislocations and compels a new meritocracy, new merit-based hubs emerge, previously merit-based hubs become legacy hubs, and network recalibration occurs to achieve system optimization. To date, Darwinian evolution, characterized by innovation sampling, variation, and selection through filtered termination, has enabled biologic progress through optimization of energy efficiency. However, as humans remodel their environment, increasing the level of unanticipated fitness dislocations and inducing evolutionary stress, the tendency of networks to exhibit inertia and retain legacy hubs engender maladaptations. Many modern diseases may fundamentally derive from these evolutionary displacements. Death itself may constitute a programmed adaptation, terminating individuals who represent legacy hubs and recalibrating the network. As memes replace genes as the basis of innovation, death itself has become a legacy hub. Post-Darwinian evolution may favor indefinite persistence to optimize energy efficiency. We describe strategies to reprogram or decommission legacy hubs that participate in human disease and death. PMID:16580786

  14. Basic radiotherapy physics and biology

    CERN Document Server

    Chang, David S; Das, Indra J; Mendonca, Marc S; Dynlacht, Joseph R

    2014-01-01

    This book is a concise and well-illustrated review of the physics and biology of radiation therapy intended for radiation oncology residents, radiation therapists, dosimetrists, and physicists. It presents topics that are included on the Radiation Therapy Physics and Biology examinations and is designed with the intent of presenting information in an easily digestible format with maximum retention in mind. The inclusion of mnemonics, rules of thumb, and reader-friendly illustrations throughout the book help to make difficult concepts easier to grasp. Basic Radiotherapy Physics and Biology is a

  15. Tratamiento biológico en psoriasis: Revisión bibliográfica Biologic therapy of psoriasis: Literature review

    Directory of Open Access Journals (Sweden)

    MS Lorenzetti

    2012-06-01

    ; there can be possible 8-MOP toxicity and risk of neoplasia. Biological psoriasis treatments are targeted against lymphocytes surface proteins or cytokines which act on the psoriasis physiopathogenic mechanisms. A bibliographic-like research was conducted to acquire international experience in biological agents, specially focused on etanercept, infliximab and adalimumab. These proved to be effective and to have a relative safety with regards to infectious and neoplastic complications.

  16. Epicardial Fat Thickness as Cardiovascular Risk Factor and Therapeutic Target in Patients with Rheumatoid Arthritis Treated with Biological and Nonbiological Therapies

    Directory of Open Access Journals (Sweden)

    Marcos M. Lima-Martínez

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA is a chronic inflammatory disease associated with high cardiovascular morbidity and mortality. Epicardial adipose tissue (EAT thickness may act as a therapeutic target during treatments with drugs modulating the adipose tissue. We evaluate EAT thickness in RA patients treated with biological and nonbiological disease-modifying antirheumatic drugs (DMARDs. A cross-sectional study was conducted with a cohort of 34 female RA patients and 16 controls matched for age and body mass index (BMI. Plasma glucose, basal insulin, plasma lipids, and high-sensitivity C-reactive protein (hs-CRP were assessed. EAT thickness and left ventricular mass (LVM were measured by echocardiography. No significant differences in waist circumference (WC, blood pressure, fasting blood glucose, basal insulin, and lipid parameters were found between the groups. The control group showed lower concentrations (P=0.033 of hs-CRP and LVM (P=0.0001 than those of the two RA groups. Patients treated with TNF-α inhibitors showed significantly lower EAT thickness than those treated with nonbiological DMARDs (8.56 ± 1.90 mm versus 9.71 ± 1.45 mm; P=0.04. Women with no RA revealed reduced EAT thickness (5.39 ± 1.52 mm as compared to all RA patients (P=0.001. Results suggest that RA patients have greater EAT thickness than controls regardless of BMI and WC.

  17. Thermal and biological properties of the Schiff base N,N‧-bis(salicylidene)-1,2-phenylenediamine, a potential adjuvant to antibiotic therapy

    Science.gov (United States)

    de Toledo, T. A.; da Costa, R. C.; da Silva, L. E.; Teixeira, A. M. R.; Lima, V. N.; Sena, D. M.; Coutinho, H. D. Melo; Freire, P. T. C.; Pizani, P. S.

    2016-07-01

    Schiff base N,N‧-bis(salicylidene)-1,2-phenylenediamine, salophen, is a substance that presents synergism when combined with amikacin against Staphylococcus aureus and Escherichia coli. Measurements of temperature dependence of the Raman spectra of salophen combined with thermal analysis investigations are presented. The room temperature crystalline structure seems to be stable up to the temperature where the phase transition from solid to liquid (433-443 K) is observed. The Raman spectra in the temperature range 433-443 K were observed to be characterized by the loss of external vibrational modes, in accordance with thermal analysis curves. According to thermogravimetric analysis, salophen shows a weight loss variation in the temperature range 300-453 K corresponding to 5% loss in weight, which is attributed to dehydration and materials melting temperature. The enthalpy (ΔH) obtained from the integration of the differential scanning calorimetry peak at melting (Tm = 438 K) and decomposition temperature (Td = 484 K) is founded to be - 91 J/g and 239 J/g, respectively. Finally, it was carried out biological assays to evaluate the antibacterial potential of the salophen.

  18. The photo biological effect of low level laser therapy on serum level of leptin, cholesterol and triglycerides in overweight and obese females

    International Nuclear Information System (INIS)

    The use of low level laser for body contouring and weight reduction depends on the photochemical non thermal effect of laser light on the adipose tissue. LLLT was reported to liquefy or release stored fat in adipocytes by the opening of specialized yet not identified cell membrane-associated pores after a brief treatment The concentration of leptin in adipose tissue and serum closely parallel the mass of adipose tissue and adipocyte size and triglycerides content. Thus, leptin increases in obesity and falls with weight loss. The current study was conducted to evaluate the effect of the low level laser therapy (LLLT) on leptin hormone, Cholesterol and triglyceride in both overweight and obese females. Twenty women were included in this study. Their ages ranged from 30-40 years. They were divided into two equal groups. Group A (Overweight group): included 10 females with BMI between 25 and 29.9 Kg/m2 -Group B (Obese group): included 10 females with BMI . 30. Both groups received LLL to the abdomen using laser scanner for uniform distribution of the beam above and below the umbilicus. Duration of treatment was 30 minutes, 2 times per week for 8 weeks as a total period of treatment. Serum level of leptin was estimated by radioimmunoassay (RIA). As regards serum cholesterol and triglyceride they were determined by enzymatic colorimetric test. Biochemical assessments were done before and after treatment. Results of the present study showed that in the overweight group laser treatment resulted in highly significant reduction in leptin serum level accompanied by highly significant increase in serum triglycerides level. Meanwhile, the increase in cholesterol level was insignificant. As regards the obese group, alteration in serum leptin level caused by laser treatment was not significant. In this group the increase in triglycerides and cholesterol serum levels after treatment were highly significant

  19. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Stenmark, Matthew H. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Cai Xuwei [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shanghai Cancer Hospital, Fudan University, Shanghai (China); Shedden, Kerby [Department of Biostatistics, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Hayman, James A. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Yuan Shuanghu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Radiation Oncology, Shangdong Cancer Hospital, Jinan (China); Ritter, Timothy [Veterans Affairs Medical Center, Ann Arbor, Michigan (United States); Ten Haken, Randall K.; Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Kong Fengming, E-mail: fengkong@med.umich.edu [Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, Michigan (United States); Veterans Affairs Medical Center, Ann Arbor, Michigan (United States)

    2012-10-01

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1{beta}), IL-6, IL-8, tumor necrosis factor alpha (TNF-{alpha}), and transforming growth factor beta1 (TGF-{beta}1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ss1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ss1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  20. Combining Physical and Biologic Parameters to Predict Radiation-Induced Lung Toxicity in Patients With Non-Small-Cell Lung Cancer Treated With Definitive Radiation Therapy

    International Nuclear Information System (INIS)

    Purpose: To investigate the plasma dynamics of 5 proinflammatory/fibrogenic cytokines, including interleukin-1beta (IL-1β), IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta1 (TGF-β1) to ascertain their value in predicting radiation-induced lung toxicity (RILT), both individually and in combination with physical dosimetric parameters. Methods and Materials: Treatments of patients receiving definitive conventionally fractionated radiation therapy (RT) on clinical trial for inoperable stages I-III lung cancer were prospectively evaluated. Circulating cytokine levels were measured prior to and at weeks 2 and 4 during RT. The primary endpoint was symptomatic RILT, defined as grade 2 and higher radiation pneumonitis or symptomatic pulmonary fibrosis. Minimum follow-up was 18 months. Results: Of 58 eligible patients, 10 (17.2%) patients developed RILT. Lower pretreatment IL-8 levels were significantly correlated with development of RILT, while radiation-induced elevations of TGF-ß1 were weakly correlated with RILT. Significant correlations were not found for any of the remaining 3 cytokines or for any clinical or dosimetric parameters. Using receiver operator characteristic curves for predictive risk assessment modeling, we found both individual cytokines and dosimetric parameters were poor independent predictors of RILT. However, combining IL-8, TGF-ß1, and mean lung dose into a single model yielded an improved predictive ability (P<.001) compared to either variable alone. Conclusions: Combining inflammatory cytokines with physical dosimetric factors may provide a more accurate model for RILT prediction. Future study with a larger number of cases and events is needed to validate such findings.

  1. A novel algorithm for the calculation of physical and biological irradiation quantities in scanned ion beam therapy: the beamlet superposition approach

    Science.gov (United States)

    Russo, G.; Attili, A.; Battistoni, G.; Bertrand, D.; Bourhaleb, F.; Cappucci, F.; Ciocca, M.; Mairani, A.; Milian, F. M.; Molinelli, S.; Morone, M. C.; Muraro, S.; Orts, T.; Patera, V.; Sala, P.; Schmitt, E.; Vivaldo, G.; Marchetto, F.

    2016-01-01

    The calculation algorithm of a modern treatment planning system for ion-beam radiotherapy should ideally be able to deal with different ion species (e.g. protons and carbon ions), to provide relative biological effectiveness (RBE) evaluations and to describe different beam lines. In this work we propose a new approach for ion irradiation outcomes computations, the beamlet superposition (BS) model, which satisfies these requirements. This model applies and extends the concepts of previous fluence-weighted pencil-beam algorithms to quantities of radiobiological interest other than dose, i.e. RBE- and LET-related quantities. It describes an ion beam through a beam-line specific, weighted superposition of universal beamlets. The universal physical and radiobiological irradiation effect of the beamlets on a representative set of water-like tissues is evaluated once, coupling the per-track information derived from FLUKA Monte Carlo simulations with the radiobiological effectiveness provided by the microdosimetric kinetic model and the local effect model. Thanks to an extension of the superposition concept, the beamlet irradiation action superposition is applicable for the evaluation of dose, RBE and LET distributions. The weight function for the beamlets superposition is derived from the beam phase space density at the patient entrance. A general beam model commissioning procedure is proposed, which has successfully been tested on the CNAO beam line. The BS model provides the evaluation of different irradiation quantities for different ions, the adaptability permitted by weight functions and the evaluation speed of analitical approaches. Benchmarking plans in simple geometries and clinical plans are shown to demonstrate the model capabilities.

  2. Incorporating biologic measurements (SF2, CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy

    International Nuclear Information System (INIS)

    Purpose: To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF2) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. Methods and Materials: Measurements of SF2 and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcpα,ρ). Regression analysis was performed to assess the prognostic power of tcpα,ρ vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF2 and CFE measurements alone. Results: In a univariate regression analysis of 44 patients, tcpα,ρ was a better prognostic factor for both local control and survival (p2 alone (p=0.009 for local control, p=0.29 for survival) or CFE alone (p=0.015 for local control, p=0.38 for survival). In multivariate analysis, tcpα,ρ emerged as the most important prognostic factor for local control (pα,ρ, CFE was still a significant independent prognostic factor for local control, whereas SF2 was not. The sensitivities of tcpα,ρ and SF2 as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. Conclusions: A Poisson tcp model incorporating individual SF2, CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients

  3. Spondyloarthritides: evolving therapies

    OpenAIRE

    Barr, Andrew; Keat, Andrew

    2010-01-01

    TNF blockade therapy has substantially advanced the treatment of peripheral spondyloarthritides but revolutionised the treatment of severe ankylosing spondylitis. The capacity of biologic treatment to improve dramatically symptoms and quality of life in patients with spinal disease is undoubted, although important questions remain. Notable amongst these are concerns about skeletal disease modification and the true balance between costs and effectiveness. Guidelines for the biologic treatment ...

  4. Cell therapy of refractory Crohn's disease.

    Science.gov (United States)

    Knyazev, O V; Parfenov, A I; Shcherbakov, P L; Ruchkina, I N; Konoplyannikov, A G

    2013-11-01

    We analyzed medium-term efficiency and safety of biological therapy of Crohn's disease, in particular transplantation of allogenic mesenchymal stromal bone marrow cells and anticytokine therapy with selective immunosuppressive agents. It was found that both methods of biological therapy of refractory Crohn's disease resulted in clinical and in some cases endoscopic remission. In most cases, clinical remission was maintained without steroid hormone therapy. Thus, both methods produce comparable clinical results. It was concluded that transplantation of mesenchymal stromal bone marrow cells could be considered as a promising method in the therapy of refractory Crohn's disease comparable by its efficiency with infliximab therapy. PMID:24319711

  5. The use of positron emission tomography/computed tomography imaging in radiation therapy: a phantom study for setting internal target volume of biological target volume

    International Nuclear Information System (INIS)

    Fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is an important method for detecting tumours, planning radiotherapy treatment, and evaluating treatment responses. However, using the standardized uptake value (SUV) threshold with PET imaging may be suitable not to determine gross tumour volume but to determine biological target volume (BTV). The aim of this study was to extract internal target volume of BTV from PET images. Three spherical densities of 18F-FDG were employed in a phantom with an air or water background with repetitive motion amplitudes of 0–30 mm. The PET data were reconstructed with attenuation correction (AC) based on CT images obtained by slow CT scanning (SCS) or helical CT scanning (HCS). The errors in measured SUVmax and volumes calculated using SUV threshold values based on SUVmax (THmax) in experiments performed with varying extents of respiratory motion and AC were analysed. A partial volume effect (PVE) was not observed in spheres with diameters of ≥ 28 mm. When calculating SUVmax and THmax, using SCS for AC yielded smaller variance than using HCS (p < 0.05). For spheres of 37- and 28-mm diameters in the phantom with either an air or water background, significant differences were observed when mean THmax of 30-, 20-, or 10-mm amplitude were compared with the stationary conditions (p < 0.05). The average THmax values for 37-mm and 28-mm spheres with an air background were 0.362 and 0.352 in non-motion, respectively, and the mean THmax values for 37-mm and 28-mm spheres with a water background were 0.404 and 0.387 in non-motion and 0.244 and 0.263 in motion, respectively. When the phantom background was air, regardless of sphere concentration or size, THmax was dependent only on motion amplitude. We found that there was no PVE for spheres with ≥ 28-mm diameters, and differences between SUVmax and THmax were reduced by using SCS for AC. In the head-and-neck and the abdomen, the standard values of

  6. Drug therapies in dermatology.

    Science.gov (United States)

    Aslam, Arif; Griffiths, Christopher E M

    2014-02-01

    This article explores the current and emerging therapies for skin disease, with a particular focus on chronic plaque psoriasis and metastatic malignant melanoma. We discuss the current biological therapies used for psoriasis and those on the horizon, including small molecules and biosimilars. We also summarise the recent advances in the use of novel therapeutic agents in other dermatological diseases and outline the promise of translational research and stratified medicine approaches in dermatology. Better matching of patients with therapies is anticipated to have a major effect on both clinical practice and the development of new drugs and diagnostics. PMID:24532745

  7. Mathematical modeling of biological processes

    CERN Document Server

    Friedman, Avner

    2014-01-01

    This book on mathematical modeling of biological processes includes a wide selection of biological topics that demonstrate the power of mathematics and computational codes in setting up biological processes with a rigorous and predictive framework. Topics include: enzyme dynamics, spread of disease, harvesting bacteria, competition among live species, neuronal oscillations, transport of neurofilaments in axon, cancer and cancer therapy, and granulomas. Complete with a description of the biological background and biological question that requires the use of mathematics, this book is developed for graduate students and advanced undergraduate students with only basic knowledge of ordinary differential equations and partial differential equations; background in biology is not required. Students will gain knowledge on how to program with MATLAB without previous programming experience and how to use codes in order to test biological hypothesis.

  8. Lung Stem cell biology

    OpenAIRE

    Ardhanareeswaran, Karthikeyan; Mirotsou, Maria

    2013-01-01

    Over the past few years new insights have been added to the study of stem cells in the adult lung. The exploration of the endogenous lung progenitors as well as the study of exogenously delivered stem cell populations holds promise for advancing our understanding of the biology of lung repair mechanisms. Moreover, it opens new possibilities for the use of stem cell therapy for the development of regenerative medicine approaches for the treatment of lung disease. Here, we discuss the main type...

  9. Biotoxins in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    İlker Kelle

    2007-01-01

    Full Text Available The search for biological antitumor agents has been pursued for over half a century. Among the biological agents which have antitumoral activity, snake and scorpion venoms have been shown to possess a wide spectrum of biological activities. Venom components exhibit an antitumoral activity by means of direct cytolytic and cytostatic effects or indirect mechanisms such as amplifying of immune response against cancerous cells. These peptides constitute a potent antitumoral activity throughout their thrapeutic usages while they cause any significant side effects. Therefore it has been emphasized that natural venom peptides or their synthetic analogues will be valuable agents in replacement of classical antineoplastic drugs in cancer therapy in the future.

  10. Proteomic Investigations into Hemodialysis Therapy

    OpenAIRE

    Mario Bonomini; Vittorio Sirolli; Luisa Pieroni; Paolo Felaco; Luigi Amoroso; Andrea Urbani

    2015-01-01

    The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and m...

  11. Proton Therapy

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Proton Therapy Proton therapy delivers radiation to tumor tissue ... feel during and after the procedure? What is proton therapy and how is it used? Protons are ...

  12. [Biologics and mycobacterial diseases].

    Science.gov (United States)

    Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

    2013-03-01

    developing TB. Lastly, Dr. Matsumoto stressed the risk of discontinuing TNF-alpha inhibitor during treatment for tuberculosis. He showed from his clinical experience that TNF-alpha inhibitor can be safely used in active TB patient receiving effective antituberculosis chemotherapy and it is even more effective for prevention of paradoxical response. Active discussion was done about the four topics, including the matter beyond present guidelines. We hope these discussions will form the basis for the establishment of new guideline for the management of mycobacterial disease when using immunosuppressive agents including biologics. 1. The risk of developing tuberculosis (TB) and situations of screening for TB risk at administration of biologics-the case of rheumatoid arthritis: Shigeto TOHMA (Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital) We calculated the standardized incidence ratio (SIR) of TB from the clinical data on National Database of Rheumatic Diseases by iR-net in Japan (NinJa) and compared with the SIR of TB from the data of the post-marketing surveillances of five biologics. Among 43584 patient-years, forty patients developed TB. The SIR of TB in NinJa was 4.34 (95%CI: 3.00-5.69). According to the post-marketing surveillances of 5 biologics, the SIR of TB were 3.62-34.4. The incidence of TB in patients with RA was higher than general population in Japan, and was increased more by some biologics. We have to recognize the risk of TB when we start biologics therapy to patients with RA. Although the frequency of implementation of QuantiFERON test (QFT) had gradually increased, it was still limited to 41%. In order to predict the risk of developing TB and to prevent TB, it might be better to check all RA patients by QFT at time time of biologics administration. 2. Biologics and nontuberculous mycobacterial diseases: Hitoshi TOKUDA (Social Insurance Central General Hospital) Several topics about the

  13. Regenerative Therapy for Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Narsis Daftarian

    2010-01-01

    Full Text Available Major advances in various disciplines of basic sciences including embryology, molecular and cell biology, genetics, and nanotechnology, as well as stem cell biology have opened new horizons for regenerative therapy. The unique characteristics of stem cells prompt a sound understanding for their use in modern regenerative therapies. This review article discusses stem cells, developmental stages of the eye field, eye field transcriptional factors, and endogenous and exogenous sources of stem cells. Recent studies and challenges in the application of stem cells for retinal pigment epithelial degeneration models will be summarized followed by obstacles facing regenerative therapy.

  14. Biologics in Paediatric Crohn's Disease

    OpenAIRE

    Oliver Gouldthorpe; Anthony G Catto-Smith; George Alex

    2011-01-01

    Crohn's disease affects increasing numbers of children worldwide. Generally, childhood-onset disease runs a more severe course than in adults and has a greater impact on quality of life. Therapy in children must take account of a different set of risks for toxicity compared to adults, but also to their longevity. Biologic drugs present remarkable advantages in terms of disease control for children, especially in those whose disease cannot be controlled with conventional therapies, but their l...

  15. Biological Effects of Low Level Laser Therapy

    OpenAIRE

    Farivar, Shirin; Malekshahabi, Talieh; Shiari, Reza

    2014-01-01

    The use of low level laser to reduce pain, inflammation and edema, to promote wound, deeper tissues and nerves healing, and to prevent tissue damage has been known for almost forty years since the invention of lasers. This review will cover some of the proposed cellular mechanisms responsible for the effect of visible light on mammalian cells, including cytochrome c oxidase (with absorption peaks in the Near Infrared (NIR)). Mitochondria are thought to be a likely site for the initia...

  16. Integrative radiation systems biology.

    Science.gov (United States)

    Unger, Kristian

    2014-01-01

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer" of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology. PMID:24411063

  17. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Maximisation of the ratio of normal tissue preservation and tumour cell reduction is the main concept of radiotherapy alone or combined with chemo-, immuno- or biologically targeted therapy. The foremost parameter influencing this ratio is radiation sensitivity and its modulation towards a more efficient killing of tumour cells and a better preservation of normal tissue at the same time is the overall aim of modern therapy schemas. Nevertheless, this requires a deep understanding of the molecular mechanisms of radiation sensitivity in order to identify its key players as potential therapeutic targets. Moreover, the success of conventional approaches that tried to statistically associate altered radiation sensitivity with any molecular phenotype such as gene expression proofed to be somewhat limited since the number of clinically used targets is rather sparse. However, currently a paradigm shift is taking place from pure frequentistic association analysis to the rather holistic systems biology approach that seeks to mathematically model the system to be investigated and to allow the prediction of an altered phenotype as the function of one single or a signature of biomarkers. Integrative systems biology also considers the data from different molecular levels such as the genome, transcriptome or proteome in order to partially or fully comprehend the causal chain of molecular mechanisms. An example for the application of this concept currently carried out at the Clinical Cooperation Group “Personalized Radiotherapy in Head and Neck Cancer” of the Helmholtz-Zentrum München and the LMU Munich is described. This review article strives for providing a compact overview on the state of the art of systems biology, its actual challenges, potential applications, chances and limitations in radiation oncology research working towards improved personalised therapy concepts using this relatively new methodology

  18. Biology Notes.

    Science.gov (United States)

    School Science Review, 1982

    1982-01-01

    Presents procedures, exercises, demonstrations, and information on a variety of biology topics including labeling systems, biological indicators of stream pollution, growth of lichens, reproductive capacity of bulbous buttercups, a straw balance to measure transpiration, interaction of fungi, osmosis, and nitrogen fixation and crop production. (DC)

  19. Spondyloarthritides: evolving therapies.

    Science.gov (United States)

    Barr, Andrew; Keat, Andrew

    2010-01-01

    TNF blockade therapy has substantially advanced the treatment of peripheral spondyloarthritides but revolutionised the treatment of severe ankylosing spondylitis. The capacity of biologic treatment to improve dramatically symptoms and quality of life in patients with spinal disease is undoubted, although important questions remain. Notable amongst these are concerns about skeletal disease modification and the true balance between costs and effectiveness. Guidelines for the biologic treatment of ankylosing spondylitis and psoriatic arthritis have been introduced in North America and Europe with considerable consensus. However, the absence of clear criteria for the diagnosis of early disease leaves the issue of biologic treatment of ankylosing spondylitis at the pre-radiographic stage unresolved. Newer biologic agents are entering the field, although superiority over TNF blockers will be difficult to demonstrate. PMID:21205283

  20. Rethinking biologics in lupus nephritis.

    Science.gov (United States)

    Venuturupalli, S

    2016-09-01

    Lupus nephritis (LN) is a chronic and devastating complication of systemic lupus erythematosus. Despite advances in our understanding of LN and the availability of effective therapies, LN remains a difficult clinical problem, and progression to end stage renal disease remains a significant challenge. Though the advent of biologics has revolutionized the treatment of many rheumatological conditions, and several clinical trials of biologics have been conducted in LN, the promise of biologics remains unfulfilled. The experience gained from these initial clinical trials can help tailor approaches in future clinical trials, and the lessons learned can be applied to find a cure for this condition. PMID:27497255

  1. Cancer Therapy with Antiprotons

    Science.gov (United States)

    Bassler, Niels; Holzscheiter, Michael H.; Ad-4 Collaboration

    2005-10-01

    Starting in 2003 the AD-4/ACE collaboration has studied the biological effects of antiprotons annihilating in a human tissue like material on live V-79 Chinese Hamster cells. The main goal of the work is to prove the efficacy of antiprotons for cancer therapy. In this report we discuss a critical point to be considered carefully for all particle beam radiation therapies, namely the loss of primary particles from the beam on the way to a tumor seated some distance below the surface.

  2. Quantum Biology

    Directory of Open Access Journals (Sweden)

    Alessandro Sergi

    2009-06-01

    Full Text Available A critical assessment of the recent developmentsof molecular biology is presented.The thesis that they do not lead to a conceptualunderstanding of life and biological systems is defended.Maturana and Varela's concept of autopoiesis is briefly sketchedand its logical circularity avoided by postulatingthe existence of underlying living processes,entailing amplification from the microscopic to the macroscopic scale,with increasing complexity in the passage from one scale to the other.Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces,is criticized. It is suggested that the correct interpretationof quantum dispersion forces (van der Waals, hydrogen bonding, and so onas quantum coherence effects hints at the necessity of includinglong-ranged forces (or mechanisms for them incondensed matter theories of biological processes.Some quantum effects in biology are reviewedand quantum mechanics is acknowledged as conceptually important to biology since withoutit most (if not all of the biological structuresand signalling processes would not even exist. Moreover, it is suggested that long-rangequantum coherent dynamics, including electron polarization,may be invoked to explain signal amplificationprocess in biological systems in general.

  3. Translational Approaches towards Cancer Gene Therapy: Hurdles and Hopes

    OpenAIRE

    Yadollah Omidi; Jaleh Barar

    2012-01-01

    Introduction: Of the cancer gene therapy approaches, gene silencing, suicide/apoptosis inducing gene therapy, immunogene therapy and targeted gene therapy are deemed to sub­stantially control the biological consequences of genomic changes in cancerous cells. Thus, a large number of clinical trials have been conducted against various malignancies. In this review, we will discuss recent translational progresses of gene and cell therapy of cancer. Methods: Essential information on gene therapy o...

  4. Quantum Biology

    CERN Document Server

    Sergi, Alessandro

    2009-01-01

    A critical assessment of the recent developments of molecular biology is presented. The thesis that they do not lead to a conceptual understanding of life and biological systems is defended. Maturana and Varela's concept of autopoiesis is briefly sketched and its logical circularity avoided by postulating the existence of underlying {\\it living processes}, entailing amplification from the microscopic to the macroscopic scale, with increasing complexity in the passage from one scale to the other. Following such a line of thought, the currently accepted model of condensed matter, which is based on electrostatics and short-ranged forces, is criticized. It is suggested that the correct interpretation of quantum dispersion forces (van der Waals, hydrogen bonding, and so on) as quantum coherence effects hints at the necessity of including long-ranged forces (or mechanisms for them) in condensed matter theories of biological processes. Some quantum effects in biology are reviewed and quantum mechanics is acknowledge...

  5. Radiation Therapy

    Science.gov (United States)

    ... therapy. At this time, you will have a physical exam , talk about your medical history , and maybe have imaging tests . Your doctor or nurse will discuss external beam radiation therapy, its benefits and side effects, and ways you can care ...

  6. Proton and carbon ion therapy

    CERN Document Server

    Lomax, Tony

    2013-01-01

    Proton and Carbon Ion Therapy is an up-to-date guide to using proton and carbon ion therapy in modern cancer treatment. The book covers the physics and radiobiology basics of proton and ion beams, dosimetry methods and radiation measurements, and treatment delivery systems. It gives practical guidance on patient setup, target localization, and treatment planning for clinical proton and carbon ion therapy. The text also offers detailed reports on the treatment of pediatric cancers, lymphomas, and various other cancers. After an overview, the book focuses on the fundamental aspects of proton and carbon ion therapy equipment, including accelerators, gantries, and delivery systems. It then discusses dosimetry, biology, imaging, and treatment planning basics and provides clinical guidelines on the use of proton and carbon ion therapy for the treatment of specific cancers. Suitable for anyone involved with medical physics and radiation therapy, this book offers a balanced and critical assessment of state-of-the-art...

  7. Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non–Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

    International Nuclear Information System (INIS)

    Purpose: Patients treated with chemoradiotherapy for locally advanced non–small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials: This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray’s proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results: A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis (p < 0.0001). A 1-Gy BED increase in radiotherapy dose intensity was statistically significantly associated with approximately 4% relative improvement in survival; this is another way of expressing the finding that the pool-adjusted hazard ratio for survival as a function of BED was 0.96. Similarly, a 1-Gy tBED increase in radiotherapy dose intensity was statistically significantly associated with approximately 3% relative improvement in local-regional control; this is another way of expressing the finding that the pool-adjusted hazard ratio as a function of tBED was 0.97. Conclusions: Higher radiotherapy dose intensity is associated with improved local-regional control

  8. Introduction to radiation biology

    International Nuclear Information System (INIS)

    This book is arranged in a logical sequence, starting from radiation physics and radiation chemistry, followed by molecular, subcellular and cellular effects and going on to the level of organism. Topics covered include applied radiobiology like modifiers of radiosensitivity, predictive assay, health physics, human genetics and radiopharmaceuticals. The topics covered are : 1. Radiation Physics, 2. Detection and Measurement of Radiation, 3. Radiation Chemistry, 4. DNA Damage and Repair, 5. Chromosomal Aberrations and Gene Mutations, 6. Cellular Radiobiology 7. Acute Radiation Effects, 8. Delayed Effects of Radiation, 9. Biological Basis of Radiotherapy, 10. Chemical Modifiers of Radiosensitivity, 11. Hyperthermia, 12. High LET Radiations in Cancer, Therapy, 13. Predictive Assays, 14. Radiation Effects on Embryos, 15. Human Radiation Genetics, 16. Radiolabelled Compounds in Biology and Medicine and 17. Radiological Health

  9. Therapy Services.

    Science.gov (United States)

    Austin Independent School District, TX.

    Reviewed are the goals and activities of the therapy services in the Austin Early Childhood Special Education Program. Specific sections detail activities for speech therapy (such as diagnostic assessment, habilitation, consultation, and reporting procedures), occupational therapy (including identification and assessment, and services to children,…

  10. DSG型生物信息红外肝病治疗仪促进小鼠肝脏微循环的实验研究%DSG biological information infrared liver disease therapy instrument improves liver microcirculation in mice

    Institute of Scientific and Technical Information of China (English)

    田甜; 徐列明

    2009-01-01

    目的 研究DSG型生物信息红外肝病治疗仪(BILT肝病治疗仪)对小鼠肝脏微循环的影响.方法 将40只SPF小鼠造模后随机均分为未照射模型组、冷光源照射模型组、红外线照射模犁组和BILT肝病治疗仪照射模型组,另取20只正常小鼠作为对照.每组分别以激光多普勒血流仪测定肝脏血流量并以显微活体视频技术观察肝脏微循环血流速度,同时进行肝脏病理学检查和血清生化学检查.结果 BILT肝病治疗仪照射模型组肝脏平均血流灌注量与未照射模型组比较明显增加(P=0.004),而冷光源、红外线照射模型组与未照射模型组比均无明显增加血流量作用(P=0.713和0.465).未照射正常组较未照射模型组小鼠肝脏微血管内红细胞平均流速快,差异有统计学意义(P=0.001);BILT肝病治疗仪照射模型组肝脏微循环平均流速较未照射模型组、冷光源照射模型组和红外线照射模型组的流速也有所增加,差异有统计学意义(P=0.004、0.020和0.030).BILT肝病治疗仪照射模型组AST活性较未照射模型组明显降低(P=0.027),该组羟脯氨酸(Hyp)平均含量低于未照射模型组,但差异无统计学意义(P=0.433).结论 BILT肝病治疗仪可改善肝纤维化小鼠肝脏的微循环并降低肝纤维化小鼠血清AST活性,改善肝脏病理状态.%Objective To investigate the effect of DSG biologic information infrared liver disease therapy instrument(BILT liver disease therapy instrument)on liver microcirculations in mice.Methods Liver fibrosis was induced in 40 SPF mice which were randomized into 4 groups:without irradiation group,coht light irradiation group,infrared light irradiation group and BILT group(10 in each group).Twenty healthy mice were taken as the control.Liver blood flow of each group was observed by laser-Doppler flow instrument,and blood flow rate of liver microcirculation in each group was observed by intravital microscopy

  11. Biological Oceanography

    Science.gov (United States)

    Abbott, M. R.

    1984-01-01

    Within the framework of global biogeochemical cycles and ocean productivity, there are two areas that will be of particular interest to biological oceanography in the 1990s. The first is the mapping in space time of the biomass and productivity of phytoplankton in the world ocean. The second area is the coupling of biological and physical processes as it affects the distribution and growth rate of phytoplankton biomass. Certainly other areas will be of interest to biological oceanographers, but these two areas are amenable to observations from satellites. Temporal and spatial variability is a regular feature of marine ecosystems. The temporal and spatial variability of phytoplankton biomass and productivity which is ubiquitous at all time and space scales in the ocean must be characterized. Remote sensing from satellites addresses these problems with global observations of mesocale (2 to 20 days, 10 to 200 km) features over a long period of time.

  12. Biological preconcentrator

    Science.gov (United States)

    Manginell, Ronald P.; Bunker, Bruce C.; Huber, Dale L.

    2008-09-09

    A biological preconcentrator comprises a stimulus-responsive active film on a stimulus-producing microfabricated platform. The active film can comprise a thermally switchable polymer film that can be used to selectively absorb and desorb proteins from a protein mixture. The biological microfabricated platform can comprise a thin membrane suspended on a substrate with an integral resistive heater and/or thermoelectric cooler for thermal switching of the active polymer film disposed on the membrane. The active polymer film can comprise hydrogel-like polymers, such as poly(ethylene oxide) or poly(n-isopropylacrylamide), that are tethered to the membrane. The biological preconcentrator can be fabricated with semiconductor materials and technologies.

  13. Biomedicines—Moving Biologic Agents into Approved Treatment Options

    Directory of Open Access Journals (Sweden)

    Kenneth Cornetta

    2013-03-01

    Full Text Available The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and Europe. Bioengineering of new agents capitalizing on microRNA biology, nanoparticle technology, stem cell biology, and an increasing understanding of immunology predict a rich future for product development. [...

  14. Biological imaging in radiation oncology

    Energy Technology Data Exchange (ETDEWEB)

    Grosu, A.L.; Wiedenmann, N.; Molls, M. [Klinik und Poliklinik fuer Strahlentherapie und Radiologische Onkologie Klinikum rechts der Isar, Technical Univ. of Munich (Germany)

    2005-07-01

    The goal of this study was to discuss the value of integrating biological imaging (PET, SPECT, MRS etc.) in radiation treatment planning and monitoring. Studies in patients with brain tumors have shown that, compared to CT and MRI alone, the image fusion of CT/MRI and amino acid SPECT or PET allows a more correct delineation of gross tumor volume (GTV) and planning target volume (PTV). For FDG-PET, comparable results with different techniques are reported in the literature also for bronchial carcinoma, ear-nose-and-throat tumors, and cervical carcinoma, or, in the case of MRS, for prostate cancer. Imaging of hypoxia, cell proliferation, apoptosis, tumor angiogenesis, and gene expression leads to the identification of differently aggressive areas of a biologically inhomogeneous tumor mass that can be individually and more appropriately targeted using innovative IMRT. Thus, a biological, inhomogeneous dose distribution can be generated, the so-called dose painting. In addition, the biological imaging can play a significant role in the evaluation of the therapy response after radiochemotherapy. Clinical studies in ear-nose-and-throat tumors, bronchial carcinoma, esophagus carcinoma, and cervical carcinoma suggest that the sensitivity and specificity of FDG-PET for the therapy response are higher compared to anatomical imaging (CT and MRI). Clinical and experimental studies are required to define the real impact of these investigations in radiation treatment planning, and especially in the evaluation of therapy response. (orig.)

  15. Marine Biology

    Science.gov (United States)

    Dewees, Christopher M.; Hooper, Jon K.

    1976-01-01

    A variety of informational material for a course in marine biology or oceanology at the secondary level is presented. Among the topics discussed are: food webs and pyramids, planktonic blooms, marine life, plankton nets, food chains, phytoplankton, zooplankton, larval plankton and filter feeders. (BT)

  16. Biology Notes.

    Science.gov (United States)

    School Science Review, 1983

    1983-01-01

    Describes laboratory procedures, demonstrations, and classroom activities/materials, including water relation exercise on auxin-treated artichoke tuber tissue; aerobic respiration in yeast; an improved potometer; use of mobiles in biological classification, and experiments on powdery mildews and banana polyphenol oxidase. Includes reading lists…

  17. Proton therapy

    International Nuclear Information System (INIS)

    Proton therapy has become a subject of considerable interest in the radiation oncology community and it is expected that there will be a substantial growth in proton treatment facilities during the next decade. I was asked to write a historical review of proton therapy based on my personal experiences, which have all occurred in the United States, so therefore I have a somewhat parochial point of view. Space requirements did not permit me to mention all of the existing proton therapy facilities or the names of all of those who have contributed to proton therapy. (review)

  18. Treatment of psoriasis with biologic agents in Malta

    OpenAIRE

    Mercieca, Liam; Boffa, Michael J.; Clark, Eileen; Scerri, Lawrence; Aquilina, Susan

    2016-01-01

    Introduction: Biologic therapy has revolutionalised the treatment of moderate to severe psoriasis leading to improved clinical outcomes and quality of life scores. This study aims to determine current biologic use in psoriatic patients at our Dermatology department at Sir Paul Boffa hospital, Malta. Method: All patients who were administered biologic therapy for psoriasis in Malta until the end of 2014 were included. Data included demographic details, disease dur...

  19. Mesoscopic biology

    Indian Academy of Sciences (India)

    G V Shivashankar

    2002-02-01

    In this paper we present a qualitative outlook of mesoscopic biology where the typical length scale is of the order of nanometers and the energy scales comparable to thermal energy. Novel biomolecular machines, governed by coded information at the level of DNA and proteins, operate at these length scales in biological systems. In recent years advances in technology have led to the study of some of the design principles of these machines; in particular at the level of an individual molecule. For example, the forces that operate in molecular interactions, the stochasticity involved in these interactions and their spatio-temporal dynamics are beginning to be explored. Understanding such design principles is opening new possibilities in mesoscopic physics with potential applications.

  20. Biological programming

    OpenAIRE

    Ramsden, Jeremy J.; Bándi, Gergely

    2010-01-01

    Biology offers a tremendous set of concepts that are potentially very powerfully usable for the software engineer, but they have been barely exploited hitherto. In this position paper we propose a fresh attempt to create the building blocks of a programming technology that could be as successful as life. A key guiding principle is to develop and make use of unambiguous definitions of the essential features of life.

  1. Biological radioprotector

    International Nuclear Information System (INIS)

    According to the patent description, the biological radioprotector is deuterium depleted water, DDW, produced by vacuum distillation with an isotopic content lower than natural value. It appears as such or in a mixture with natural water and carbon dioxide. It can be used for preventing and reducing the ionizing radiation effects upon humans or animal organisms, exposed therapeutically, professionally or accidentally to radiation. The most significant advantage of using DDW as biological radioprotector results from its way of administration. Indeed no one of the radioprotectors currently used today can be orally administrated, what reduces the patients' compliance to prophylactic administrations. The biological radioprotector is an unnoxious product obtained from natural water, which can be administrated as food additive instead of drinking water. Dose modification factor is according to initial estimates around 1.9, what is a remarkable feature when one takes into account that the product is toxicity-free and side effect-free and can be administrated prophylactically as a food additive. A net radioprotective action of the deuterium depletion was evidenced experimentally in laboratory animals (rats) hydrated with DDW of 30 ppm D/(D+H) concentration as compared with normally hydrated control animals. Knowing the effects of irradiation and mechanisms of the acute radiation disease as well as the effects of administration of radiomimetic chemicals upon cellular lines of fast cell division, it appears that the effects of administrating DDW result from stimulation of the immunity system. In conclusion, the biological radioprotector DDW presents the following advantages: - it is obtained from natural products without toxicity; - it is easy to be administrated as a food additive, replacing the drinking water; - besides radioprotective effects, the product has also immunostimulative and antitumoral effects

  2. Marine biology

    International Nuclear Information System (INIS)

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index

  3. Marine biology

    Energy Technology Data Exchange (ETDEWEB)

    Thurman, H.V.; Webber, H.H.

    1984-01-01

    This book discusses both taxonomic and ecological topics on marine biology. Full coverage of marine organisms of all five kingdoms is provided, along with interesting and thorough discussion of all major marine habitats. Organization into six major parts allows flexibility. It also provides insight into important topics such as disposal of nuclear waste at sea, the idea that life began on the ocean floor, and how whales, krill, and people interact. A full-color photo chapter reviews questions, and exercises. The contents are: an overview marine biology: fundamental concepts/investigating life in the ocean; the physical ocean, the ocean floor, the nature of water, the nature and motion of ocean water; general ecology, conditions for life in the sea, biological productivity and energy transfer; marine organisms; monera, protista, mycota and metaphyta; the smaller marine animals, the large animals marine habitats, the intertidal zone/benthos of the continental shelf, the photic zone, the deep ocean, the ocean under stress, marine pollution, appendix a: the metric system and conversion factors/ appendix b: prefixes and suffixes/ appendix c: taxonomic classification of common marine organisms, and glossary, and index.

  4. Gene therapy.

    OpenAIRE

    Mota Biosca, Anna

    1992-01-01

    Applications of gene therapy have been evaluated in virtually every oral tissue, and many of these have proved successful at least in animal models. While gene therapy will not be used routinely in the next decade, practitioners of oral medicine should be aware of the potential of this novel type of treatment that doubtless will benefit many patients with oral diseases.

  5. Third workshop on heavy charged particles in biology and medicine

    International Nuclear Information System (INIS)

    The book of abstracts contains 67 papers presented at the workshop. Main topics are: Physics, chemistry, DNA, cell biology, cellular and molecular repair, space biology, tumor and tissue biology, predictive assays, cancer therapy, and new projects. Separate entries in the database are prepared for all of these papers. (MG)

  6. Cold Spring Harbor symposia on quantitative biology: Volume 51, Molecular biology of /ital Homo sapiens/

    International Nuclear Information System (INIS)

    This volume is the second part of a collection of papers submitted by the participants to the 1986 Cold Spring Harbor Symposium on Quantitative Biology entitled Molecular Biology of /ital Homo sapiens/. The 49 papers included in this volume are grouped by subject into receptors, human cancer genes, and gene therapy. (DT)

  7. Human Gene Therapy: Genes without Frontiers?

    Science.gov (United States)

    Simon, Eric J.

    2002-01-01

    Describes the latest advancements and setbacks in human gene therapy to provide reference material for biology teachers to use in their science classes. Focuses on basic concepts such as recombinant DNA technology, and provides examples of human gene therapy such as severe combined immunodeficiency syndrome, familial hypercholesterolemia, and…

  8. Biological Databases

    Directory of Open Access Journals (Sweden)

    Kaviena Baskaran

    2013-12-01

    Full Text Available Biology has entered a new era in distributing information based on database and this collection of database become primary in publishing information. This data publishing is done through Internet Gopher where information resources easy and affordable offered by powerful research tools. The more important thing now is the development of high quality and professionally operated electronic data publishing sites. To enhance the service and appropriate editorial and policies for electronic data publishing has been established and editors of article shoulder the responsibility.

  9. Biological biomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Jorge-Herrero, E. [Servicio de Cirugia Experimental. Clinica Puerta de Hierro, Madrid (Spain)

    1997-05-01

    There are a number of situations in which substances of biological origin are employed as biomaterials. Most of them are macromolecules derived from isolated connective tissue or the connective tissue itself in membrane form, in both cases, the tissue can be used in its natural form or be chemically treated. In other cases, certain blood vessels can be chemically pretreated and used as vascular prostheses. Proteins such as albumin, collagen and fibrinogen are employed to coat vascular prostheses. Certain polysaccharides have also been tested for use in controlled drug release systems. Likewise, a number of tissues, such as dura mater, bovine pericardium, procine valves and human valves, are used in the preparation of cardiac prostheses. We also use veins from animals or humans in arterial replacement. In none of these cases are the tissues employed dissimilar to the native tissues as they have been chemically modified, becoming a new bio material with different physical and biochemical properties. In short, we find that natural products are being utilized as biomaterials and must be considered as such; thus, it is necessary to study both their chemicobiological and physicomechanical properties. In the present report, we review the current applications, problems and future prospects of some of these biological biomaterials. (Author) 84 refs.

  10. Yoga therapy for Schizophrenia

    Directory of Open Access Journals (Sweden)

    N Gangadhar Bangalore

    2012-01-01

    Full Text Available Schizophrenia is one of the most severe mental disorders. Despite significant advances in pharmacotherapy, treatment remains sub-optimal, with many patients having persisting deficits, especially in cognitive and social functioning. Yoga as a therapy has proven to be effective as a sole or additional intervention in psychiatric disorders such as depression and anxiety. Recently, there has been significant interest in the application of yoga therapy in psychosis and schizophrenia. To review a the evidence for the use of yoga therapy in patients with schizophrenia b studies which have been done in this area, c the barriers for reaching yoga to patients, and d future directions, an English language literature search of PubMed/MEDLINE, Google Scholar, and EBSCO as well as grey literature was done. Research reports have demonstrated the feasibility and efficacy of yoga as an add-on therapy in schizophrenia, particularly in improving negative symptomatology and social cognition. However, the biological underpinnings of this effect remain unclear, although there are some indications that hormones like oxytocin may contribute to the changes in social cognition.

  11. Enzyme Therapy: Current Perspectives.

    Science.gov (United States)

    UmaMaheswari, Thiyagamoorthy; Hemalatha, Thiagarajan; Sankaranarayanan, Palavesam; Puvanakrishnan, Rengarajulu

    2016-01-01

    Enzymes control all metabolic processes in human system from simple digestion of food to highly complex immune response. Physiological reactions occuring in healthy individuals are disturbed when enzymes are deficient or absent. Enzymes are administered for normalizing biological function in certain pathologies. Initially, crude proteolytic enzymes were used for the treatment of gastrointestinal disorders. Recent advances have enabled enzyme therapy as a promising tool in the treatment of cardiovascular, oncological and hereditary diseases. Now, a spectrum of other diseases are also covered under enzyme therapy. But, the available information on the use of enzymes as therapeutic agents for different diseases is scanty. This review details the enzymes which have been used to treat various diseases/disorders. PMID:26891548

  12. Physical Therapy and Occupational Therapy in Progeria

    Science.gov (United States)

    Physical Therapy and Occupational Therapy in Progeria Information for Families and Caretakers from The Progeria Research Foundation Written ... accelerated aging in children. Children with Progeria need Physical Therapy (PT) and Occupational Therapy (OT) as often as ...

  13. Oxygen Therapy

    Science.gov (United States)

    Oxygen therapy is a treatment that provides you with extra oxygen. Oxygen is a gas that your body needs to function. Normally, your lungs absorb oxygen from the air you breathe. But some conditions ...

  14. Oxygen Therapy

    Science.gov (United States)

    ... therapy works, it helps to understand how your respiratory system works. This system is a group of organs and tissues that help you breathe. The respiratory system includes the airways and lungs. The airways carry ...

  15. Targeted cancer gene therapy : the flexibility of adenoviral gene therapy vectors

    NARCIS (Netherlands)

    Rots, MG; Curiel, DT; Gerritsen, WR; Haisma, HJ

    2003-01-01

    Recombinant adenoviral vectors are promising reagents for therapeutic interventions in humans, including gene therapy for biologically complex diseases like cancer and cardiovascular diseases. In this regard, the major advantage of adenoviral vectors is their superior in vivo gene transfer efficienc

  16. Targeted Radionuclide Therapy of Human Tumors

    Science.gov (United States)

    Gudkov, Sergey V.; Shilyagina, Natalya Yu.; Vodeneev, Vladimir A.; Zvyagin, Andrei V.

    2015-01-01

    Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed. PMID:26729091

  17. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  18. Association of a complement receptor 1 gene variant with baseline erythrocyte sedimentation rate levels in patients starting anti-TNF therapy in a UK rheumatoid arthritis cohort: results from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort

    OpenAIRE

    Bluett, J; I Ibrahim; Plant, D.; Hyrich, K L; Morgan, A.W.; A G Wilson; Isaacs, J.D.; [...; Gaston, H; Mulherin, D; Price, T; Sheeran, T; Chalam, V; S. Baskar; Emery, P

    2013-01-01

    Eligibility for anti-tumour necrosis factor (TNF) therapy in most European countries is restricted to severe, active rheumatoid arthritis (RA). The DAS28 score is a marker of disease severity and incorporates one of two inflammatory markers, erythrocyte sedimentation rate (ESR) or C-reactive protein. We aimed to determine the relation between genetic variants known to affect ESR and levels of ESR in patients with active RA. DNA samples were genotyped for four single-nucleotide polymorphisms (...

  19. Creating biological nanomaterials using synthetic biology

    International Nuclear Information System (INIS)

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems. (review)

  20. Creating biological nanomaterials using synthetic biology

    Directory of Open Access Journals (Sweden)

    MaryJoe K Rice

    2014-01-01

    Full Text Available Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic biology, discusses how biological systems naturally produce materials, and then presents examples and strategies for incorporating synthetic biology approaches in the development of new materials. In particular, strategies for using synthetic biology to produce both organic and inorganic nanomaterials are discussed. Ultimately, synthetic biology holds the potential to dramatically impact biological materials science with significant potential applications in medical systems.

  1. Maintenance Therapy in IBD

    Science.gov (United States)

    ... Help Center Home > Resources > Maintenance Therapy Go Back Maintenance Therapy Email Print + Share The term "maintenance therapy" ... are referred to as "maintenance therapies." Why is Maintenance Therapy Needed in IBD? Both Crohn's disease and ...

  2. Structural Biology Fact Sheet

    Science.gov (United States)

    ... Home > Science Education > Structural Biology Fact Sheet Structural Biology Fact Sheet Tagline (Optional) Middle/Main Content Area What is structural biology? Structural biology is a field of science focused ...

  3. Mammalian synthetic biology: emerging medical applications

    OpenAIRE

    Kis, Zoltán; Pereira, Hugo Sant'Ana; Homma, Takayuki; Pedrigi, Ryan M.; Krams, Rob

    2015-01-01

    In this review, we discuss new emerging medical applications of the rapidly evolving field of mammalian synthetic biology. We start with simple mammalian synthetic biological components and move towards more complex and therapy-oriented gene circuits. A comprehensive list of ON–OFF switches, categorized into transcriptional, post-transcriptional, translational and post-translational, is presented in the first sections. Subsequently, Boolean logic gates, synthetic mammalian oscillators and tog...

  4. Simulating Biological and Non-Biological Motion

    Science.gov (United States)

    Bruzzo, Angela; Gesierich, Benno; Wohlschlager, Andreas

    2008-01-01

    It is widely accepted that the brain processes biological and non-biological movements in distinct neural circuits. Biological motion, in contrast to non-biological motion, refers to active movements of living beings. Aim of our experiment was to investigate the mechanisms underlying mental simulation of these two movement types. Subjects had to…

  5. A Brief Introduction to Chinese Biological Biological

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Chinese Biological Abstracts sponsored by the Library, the Shanghai Institutes for Biological Sciences, the Biological Documentation and Information Network, all of the Chinese Academy of Sciences, commenced publication in 1987 and was initiated to provide access to the Chinese information in the field of biology.

  6. Chitosan Nanoparticles-Mediated Wild-Type p53 Gene Delivery for Cancer Gene Therapy: Improvement in Pharmaceutical & Biological Properties (Enhance in Loading, Release, Expression and Stability of P53 Plasmid and Induction of Apoptosis in Carcinoma Cell Line

    Directory of Open Access Journals (Sweden)

    Mehrdad Hamidi

    2008-05-01

    Full Text Available Efficient non-viral vectors for gene delivery based on chitosan polymer is dependent on a variety of factors, e.g. loading and lelease capacity, stability in biological system and complex size. This system may have low loading, release and stability capacity. Biodegradable and biocompatible nanoparticles formulated using a chitosan polymer has the potential for sustained and controlled gene delivery. Our hypothesis is that nanoparticles-mediated wild-type p53 gene delivery would result in sustained gene expression, and hence better efficacy with a therapeutic gene. In this study, we have determined the pharmaceutical and biological characterization of Chitosan nanoparticles containing wild-type p53. Nanoparticles containing plasmid were formulated using a microemulsion reverse micellar and ionic gelation techniques. In conclusion, chitosan nanoparticles- p53 complex gene delivery results in sustained and better antiproliferative activity, which could be therapeutically beneficial in cancer treatment.

  7. Monoclonal antibodies in targeted therapy

    Directory of Open Access Journals (Sweden)

    Beata Powroźnik

    2012-09-01

    Full Text Available Targeted therapy is a new therapeutic method consisting in the inhibition of specific molecular pathways. In modern therapy, the key role is played by monoclonal antibodies, included in the group of biological agents. The success of molecularly targeted therapy is to define the proper “molecular target”, selecting the right drug active against a specific “target” and selecting a group of patients who benefit from treatment. Introduction of targeted therapy resulted in improved results of the treatment of many serious and chronic diseases. In general, targeted molecular therapies have good toxicity profiles, but some patients are exquisitely sensitive to these drugs and can develop particular and severe toxicities. Patient selection and proper monitoring significantly decrease the risk of life-threatening adverse events. Data concerning late side effects are still unavailable because of the short follow-up of molecularly targeted therapy. Currently in the U.S. and Europe there are approximately 31 registered therapeutic monoclonal antibodies, while 160 are subjected to clinical trials. This paper presents an overview of therapeutic monoclonal antibodies currently used in therapy and the present state of knowledge about them. 

  8. Cell and gene therapy in Australia.

    Science.gov (United States)

    Martiniello-Wilks, R; Rasko, J E J

    2007-01-01

    The expansion of human cells to produce cell therapeutic products for the treatment of disease is, with few exceptions, an experimental therapy. Because cell therapies involve a biological product, often with some genetic or other modification, they require extensive pre-clinical research and development. Cell therapy production processes and premises require licensing by the Therapeutic Goods Administration. In this review, timed to coincide with the international meetings of the ISCT and ISSCR in Australia, we describe some promising cell therapies currently under development. PMID:17464751

  9. Immuno-gene therapy in hepatocarcinoma

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    @@Hepatocarcinoma is a disease that threatens human health. To date,the known etiology of hepatocarcinomahas not been narrowed down to just one factor. It is possible that there are their own causes in different areas.Thus, there are no absolute, but relative therapy to cure all kinds of hepatocarcinoma. Presently,there exists other treatment for the hepatocarcinoma which cannot be operated by surgery, such as cryosurgery,photodynamic therapy,immunotherapy,interventional radiotherapy and targeting therapy. With the development of molecular biology ,gene therapy offers new possibilities in the treatment of genetic diseases,tumors,AIDS and other gene defect disease.

  10. Creating biological nanomaterials using synthetic biology

    OpenAIRE

    MaryJoe K Rice; Ruder, Warren C.

    2014-01-01

    Synthetic biology is a new discipline that combines science and engineering approaches to precisely control biological networks. These signaling networks are especially important in fields such as biomedicine and biochemical engineering. Additionally, biological networks can also be critical to the production of naturally occurring biological nanomaterials, and as a result, synthetic biology holds tremendous potential in creating new materials. This review introduces the field of synthetic bi...

  11. Music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    alternate with clear and lucid mental states. These states are important as it is here that it is possible to meet the person’s psychosocial needs. Ketil Normann’s conceps of periods of lucidity are presented and connected to clinical music therapy practice and how it is possible to use music in order...... as a consequence of person-centred care. Umeå University Medical Dissertations. New Series. Ridder, H.M. (2005). Music therapy as a way to enhance lucidity in persons with dementia in advanced stages. In: Esch, A.; Frohne-Hagemann, I.; Laqua, M.; Schirmer, H.; Seitz, E. (Eds.) Jahrbuch Musicktherapie. Forschung...... und Entwicklung Music Therapy Annual. Research and Development. 2005 (1), pp. 25-40. Reichert Verlag Wiesbaden....

  12. Art Therapy

    DEFF Research Database (Denmark)

    Skov, Vibeke; Pedersen, Inge Nygaard

    2014-01-01

    Abstract Based on a Jungian approach, this article will introduce an integrative model to therapeutic change using art therapy methods as practical tools, with the aim of improving quality of life and in the prevention of depression. In a research study involving six participants, painting, clay...... work and drumming were used together with imagination and personal dialogues linked to the artwork. These art therapy processes attempted to combine the participant’s experience of inner and outer reality. The effect of gaining more knowledge about their inner reality using dreams and symbols......, was that participants gained a new understanding about their personal life. In addition, some participants were able to continue to use art therapy experiences as selfdevelopmental tools after the research study terminated. Jung’s description of the interactive relationship between the two living parts of the psyche...

  13. Nuclear physics and particle therapy

    Science.gov (United States)

    Battistoni, G.

    2016-05-01

    The use of charged particles and nuclei in cancer therapy is one of the most successful cases of application of nuclear physics to medicine. The physical advantages in terms of precision and selectivity, combined with the biological properties of densely ionizing radiation, make charged particle approach an elective choice in a number of cases. Hadron therapy is in continuous development and nuclear physicists can give important contributions to this discipline. In this work some of the relevant aspects in nuclear physics will be reviewed, summarizing the most important directions of research and development.

  14. What Is Music Therapy?

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login About Music Therapy & AMTA What is Music Therapy? Definition and Quotes ... is Music Therapy? Print Email Share What is Music Therapy What is Music Therapy? Music Therapy is the ...

  15. Biologicals and switch in rheumatoid arthritis throughout time - are we being more aggressive? Biologicals and switch in rheumatoid arthritis throughout time - are we being more aggressive?

    NARCIS (Netherlands)

    S. Ramiro; R. Roque; F. Vinagre; A. Cordeiro; V. Tavares; A. van Tubergen; J. Silva; R. Landewé; M.J. Santos

    2011-01-01

    Objectives: To investigate the switches performed in patients with rheumatoid arthritis under biolo-gical therapy and specifically comparing the swi-tches from earlier days with more recent switches. Patients and methods: Patients with rheumatoid arthritis under biological therapy followed at Hospi-

  16. Dance Therapy.

    Science.gov (United States)

    Leventhal, Marcia B.

    1980-01-01

    Dance therapy deals with personal growth via body-mind interaction. A change in movement expression is believed to result in a personality or behavior change. The therapist is trained to become sensitive to movement expression as it relates to the psychological, motor, and cognitive development of the child. (JN)

  17. DNA nanovehicles and the biological barriers

    DEFF Research Database (Denmark)

    Okholm, Anders Hauge; Kjems, Jørgen

    2016-01-01

    modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also be...

  18. DNA nanovehicles and the biological barriers

    DEFF Research Database (Denmark)

    Okholm, Anders Hauge; Kjems, Jørgen

    2016-01-01

    modules. The applications of DNA nanostructures are still in its infancy, but one of the high expectations are to deliver solutions for targeted therapy. Nucleic acids, however, do not easily enter cells unassisted and biological barriers and harsh nucleolytic conditions in the human body must also...

  19. Principles and practice of proton beam therapy

    CERN Document Server

    Das, Indra J

    2015-01-01

    Commissioned by The American Association of Physicists in Medicine (AAPM) for their June 2015 Summer School, this is the first AAPM monograph printed in full color. Proton therapy has been used in radiation therapy for over 70 years, but within the last decade its use in clinics has grown exponentially. This book fills in the proton therapy gap by focusing on the physics of proton therapy, including beam production, proton interactions, biology, dosimetry, treatment planning, quality assurance, commissioning, motion management, and uncertainties. Chapters are written by the world's leading medical physicists who work at the pioneering proton treatment centers around the globe. They share their understandings after years of experience treating thousands of patients. Case studies involving specific cancer treatments show that there is some art to proton therapy as well as state-of-the-art science. Even though the focus lies on proton therapy, the content provided is also valuable to heavy charged particle th...

  20. Anecdotal therapies.

    Science.gov (United States)

    Millikan, L E

    1999-01-01

    Traditionally, many advances in medicine have been serendipitous. Are serendipitous and anecdotal synonymous? Many of our materia medica today relate to initial probes and anecdotal reports that matured to full investigation and therapeutic indications. The recent situation regarding Skin Cap is one that highlights the downside of this scenario. Several drugs in the US continue usage largely related to anecdotal indications, and anecdotal extension of legend indications is a standard for American Dermatology. The situation with systemic drugs, such as Trental, zinc preparations, imidazoles for extended indications, lysine and melatonin, all will be discussed. Topical preparations such as skin cap, cantharone, Vioform, all also are included in this category. It is important to place this topic in perspective in regards to geographic variation and therapeutic need. Many diseases lacking specific therapy are important targets for anecdotal therapy, and this will foster continued approaches in this area. The growing standardization of medicine and pharmaceutical regulation, threatens the anecdotal approach, but it provides still an important link to the future for some forms of therapy in diseases that are difficult to treat. Traditionally, the anecdote has been the first step in the therapeutic chain. Withering discovery of the benefits of the common fox glove in dropsy, was followed by many other anecdotes arriving via folk-medicine in the New World. This approach of utilizing folk medicine has now reached new heights, with very active searches by major pharmaceutical companies throughout the third world for remedies that may have potential. Couched with this is the history of anecdotal "snake-oil" remedies, that clearly had no benefit to anyone except the huckster marketing same. The excesses in this area of unproven and false therapies, led to the gradual organization of therapeutic trials and the Food and Drug Administration in the US as we know it today. The

  1. Retinoids in experimental neuroblastoma therapy

    OpenAIRE

    Ponthan, Frida

    2003-01-01

    Retinoids are analogues of vitamin A, with documented activity against various malignant cell types. Neuroblastoma is a childhood tumour of the sympathetic nervous system that shows a complex clinical and biological heterogeneity, often with poor outcome despite intensive multimodal therapy. The aim of the thesis was to investigate effects of retinoid treatment in vitro on human neuroblastoma cells, and in vivo on human neuroblastoma xenografts in nude rats. The ultimate...

  2. Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy--a single centre, open-label study.

    LENUS (Irish Health Repository)

    Pontifex, Eliza K

    2011-01-01

    With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent.

  3. Music Therapy

    DEFF Research Database (Denmark)

    Sanfi, Ilan

    2012-01-01

    may cause detrimental long-term effects. Three studies have examined the effect of music therapy procedural support (MTPS) under needle procedures. Consequently, this study aims at examining the effects of MTPS in an RCT. Moreover, the study addresses clinical aspects of the applied MT intervention...... and provides research-based clinical tools. Methods 41 children (1 to 10 years) were enrolled and underwent a single PIVA procedure. The children were randomly assigned to either an MT or a comparable control group receiving PIVA. In addition, the music therapy (MT) group received individualised MTPS (i.......e. music alternate engagement) before, during, and after PIVA. The intervention was performed by a trained music therapist and comprised preferred songs, improvised songs/music, and instrument playing. The study was carried out in accordance with the rules in force regarding research ethics and clinical MT...

  4. Music Therapy

    DEFF Research Database (Denmark)

    Trondalen, Gro; Bonde, Lars Ole

    2012-01-01

    Music therapy (MT) is most commonly defined as an intervention where “the therapist helps the client to promote health, using music experiences and the relationships developing through them” (Bruscia 1998). Also other definitions of MT agree that a therapeutic relationship is important for a music...... intervention to be considered MT. Other interventions that “use music for health-related goals, but in ways that do not qualify as music therapy” (Gold 2009), may be described as music medicine, or simply as music listening. In this text we elaborate on an overview chapter covering some of the different major...... music therapy orientations/models (Guided Imagery and Music, Nordoff-Robbins, Psychoanalytic, Cognitive-behavioral etc), their theoretical foundations and their practical approaches to health and wellbeing or ‘health musicking’. The relational context – the interplay of (expressive as well as receptive...

  5. Particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Raju, M.R.

    1993-09-01

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics.

  6. Particle therapy

    International Nuclear Information System (INIS)

    Particle therapy has a long history. The experimentation with particles for their therapeutic application got started soon after they were produced in the laboratory. Physicists played a major role in proposing the potential applications in radiotherapy as well as in the development of particle therapy. A brief review of the current status of particle radiotherapy with some historical perspective is presented and specific contributions made by physicists will be pointed out wherever appropriate. The rationale of using particles in cancer treatment is to reduce the treatment volume to the target volume by using precise dose distributions in three dimensions by using particles such as protons and to improve the differential effects on tumors compared to normal tissues by using high-LET radiations such as neutrons. Pions and heavy ions combine the above two characteristics

  7. Radioiodine therapy

    International Nuclear Information System (INIS)

    For over 40 years now, radioiodine (131I) has remained one of the most useful radionuclide for diagnosis and therapy in Nuclear Medicine. The wide application of radioiodine in the study of the thyroid gland and in the management of its disorders has been most rewarding. The medical literature is replete with reports of its efficacy, failures, and complications, but most of these studies have been conducted among Caucasian persons and in relatively affluent societies. Very few reports are available from the less developed and economically depressed areas of the world where thyroid disorders abound or and are even endemic. This chapter is an attempt to highlight the use of radioactive iodine therapy in the developing countries, particularly those in the Asian region

  8. Gene therapy

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005147 CNHK200-hA-a gene-viral therapeutic system and its antitumor effect on lung cancer. WANG Wei-guo(王伟国),et al. Viral & Gene Ther Center, Eastern Hepatobilli Surg Instit 2nd Milit Univ, Shanghai 200438. Chin J Oncol,2005:27(2):69-72. Objective: To develop a novel vector system, which combines the advantages of the gene therapy,

  9. State of the Art in Hadron Therapy

    International Nuclear Information System (INIS)

    Charged particle beams offer an improved dose conformation to the target volume as compared to photon radiotherapy, with better sparing of normal tissue structures close to the target. In addition, beams of ions heavier than helium exhibit a strong increase of the Linear Energy Transfer (LET) in the Bragg peak as compared to the entrance region. These physical and biological properties make ion beams more favorable for radiation therapy of cancer than photon beams. As a consequence, particle therapy with protons and heavy ions has gained increasing interest worldwide. This contribution summarizes the physical and biological principles of charged particle therapy with ion beams and highlights some of the developments in the field of beam delivery, the principles of treatment planning and the determination of absorbed dose in ion beams. The clinical experience gathered so far with carbon ion therapy is briefly reviewed

  10. The working principle of magnetic resonance therapy

    CERN Document Server

    Brizhik, Larissa; Fermi, Enrico

    2015-01-01

    In this paper we describe briefly the basic aspects of magnetic resonance therapy, registered as TMR therapy. Clinical studies have shown that application of this therapy significantly accelerates wound healing and, in particular, healing of the diabetic foot disease. To understand the working principle of this therapy, we analyze relevant to it biological effects produced by magnetic fields. Based on these data, we show that there is a hierarchy of the possible physical mechanisms, which can produce such effects. The mutual interplay between the mechanisms can lead to a synergetic outcome delayed in time, which can affect the physiological state of the organism. In particular, we show that soliton mediated charge transport during the redox processes in living organisms is sensitive to magnetic fields, so that such fields can facilitate redox processes in particular, and can stimulate the healing effect of the organism in general. This and other non-thermal resonant mechanisms of the biological effects of mag...

  11. Change in CD3 positive T-cell expression in psoriatic arthritis synovium correlates with change in DAS28 and magnetic resonance imaging synovitis scores following initiation of biologic therapy - a single centre, open-label study

    LENUS (Irish Health Repository)

    Pontifex, Eliza K

    2011-01-27

    Abstract Introduction With the development of increasing numbers of potential therapeutic agents in inflammatory disease comes the need for effective biomarkers to help screen for drug efficacy and optimal dosing regimens early in the clinical trial process. This need has been recognized by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group, which has established guidelines for biomarker validation. To seek a candidate synovial biomarker of treatment response in psoriatic arthritis (PsA), we determined whether changes in immunohistochemical markers of synovial inflammation correlate with changes in disease activity scores assessing 28 joints (ΔDAS28) or magnetic resonance imaging synovitis scores (ΔMRI) in patients with PsA treated with a biologic agent. Methods Twenty-five consecutive patients with PsA underwent arthroscopic synovial biopsies and MRI scans of an inflamed knee joint at baseline and 12 weeks after starting treatment with either anakinra (first 10 patients) or etanercept (subsequent 15 patients) in two sequential studies of identical design. DAS28 scores were measured at both time points. Immunohistochemical staining for CD3, CD68 and Factor VIII (FVIII) was performed on synovial samples and scored by digital image analysis (DIA). MRI scans performed at baseline and at 12 weeks were scored for synovitis semi-quantitatively. The ΔDAS28 of the European League Against Rheumatism good response definition (>1.2) was chosen to divide patients into responder and non-responder groups. Differences between groups (Mann Whitney U test) and correlations between ΔDAS28 with change in immunohistochemical and MRI synovitis scores (Spearman\\'s rho test) were calculated. Results Paired synovial samples and MRI scans were available for 21 patients (8 anakinra, 13 etanercept) and 23 patients (8 anakinra, 15 etanercept) respectively. Change in CD3 (ΔCD3) and CD68 expression in the synovial sublining layer (ΔCD68sl) was significantly greater in

  12. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    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)

  13. Molecular biology of Homo sapiens: Abstracts of papers presented at the 51st Cold Spring Harbor symposium on quantitative biology

    International Nuclear Information System (INIS)

    This volume contains abstracts of papers presented at the 51st Cold Springs Harbor Symposium on Quantitative Biology. The topic for this meeting was the ''Molecular Biology of Homo sapiens.'' Sessions were entitled Human Gene Map, Human Cancer Genes, Genetic Diagnosis, Human Evolution, Drugs Made Off Human Genes, Receptors, and Gene Therapy. (DT)

  14. Molecular biology of Homo sapiens: Abstracts of papers presented at the 51st Cold Spring Harbor symposium on quantitative biology

    Energy Technology Data Exchange (ETDEWEB)

    Watson, J.D.; Siniscalco, M.

    1986-01-01

    This volume contains abstracts of papers presented at the 51st Cold Springs Harbor Symposium on Quantitative Biology. The topic for this meeting was the ''Molecular Biology of Homo sapiens.'' Sessions were entitled Human Gene Map, Human Cancer Genes, Genetic Diagnosis, Human Evolution, Drugs Made Off Human Genes, Receptors, and Gene Therapy. (DT)

  15. Music Therapy: A Career in Music Therapy

    Science.gov (United States)

    About Music Therapy & Music Therapy Training M usic therapy is a healthcare profession that uses music to help individuals of all ages improve physical, ... grateful I chose a career as rewarding as music therapy. I love what I do each day!” Where ...

  16. Systems biology of fungal infection

    Directory of Open Access Journals (Sweden)

    Fabian eHorn

    2012-04-01

    Full Text Available Elucidation of pathogenicity mechanisms of the most important human pathogenic fungi, Aspergillus fumigatus and Candida albicans, has gained great interest in the light of the steadily increasing number of cases of invasive fungal infections.A key feature of these infections is the interaction of the different fungal morphotypes with epithelial and immune effector cells in the human host. Because of the high level of complexity, it is necessary to describe and understand invasive fungal infection by taking a systems biological approach, i.e., by a comprehensive quantitative analysis of the non-linear and selective interactions of a large number of functionally diverse, and frequently multifunctional, sets of elements, e.g., genes, proteins, metabolites, which produce coherent and emergent behaviours in time and space. The recent advances in systems biology will now make it possible to uncover the structure and dynamics of molecular and cellular cause-effect relationships within these pathogenic interactions.We review current efforts to integrate omics and image-based data of host-pathogen interactions into network and spatio-temporal models. The modelling will help to elucidate pathogenicity mechanisms and to identify diagnostic biomarkers and potential drug targets for therapy and could thus pave the way for novel intervention strategies based on novel antifungal drugs and cell therapy.

  17. [Genetic therapy in oncology: ethical aspects].

    Science.gov (United States)

    Bucci, L M; Fazio, V M

    2001-01-01

    The more advanced oncologic therapies are directing toward new frontiers, on account of the remarkable undesirable effects of chemio- and radio-therapies. This new therapeutic experiences are of type biological (vaccines), or genic (substitution again genes with shutters meaning-tumoral). This therapies involve, to be effected, some ethical shrewdnesses: choice of the patient, the engineering modality of the genes, the transfer of the genes in cells of the exclusively somatic line, the elimination of the pathogenic risk of the vector virus, the obligatory use of sterile rooms, the attention to the administration of the drug, a legal issue of the judgment of notoriety. PMID:11725612

  18. Fundamental Concepts in Radionuclide Therapy. Chapter 2

    International Nuclear Information System (INIS)

    A short overview of the basic concepts and principles of radionuclide therapy is presented in this chapter. After introducing the most important radionuclides currently employed in therapeutic applications and new promising radioisotopes such as α emitters, this review covers the various types of vector molecules and biological approaches for targeting specific cancer cells. These applications include the use of receptor specific pharmacophores such as antibodies and peptides, and DNA targeting agents. The potential advantages of combining methods developed for radionuclide therapy with gene therapy and nanotechnology are also discussed. (author)

  19. Biological conversion system

    Science.gov (United States)

    Scott, C.D.

    A system for bioconversion of organic material comprises a primary bioreactor column wherein a biological active agent (zymomonas mobilis) converts the organic material (sugar) to a product (alcohol), a rejuvenator column wherein the biological activity of said biological active agent is enhanced, and means for circulating said biological active agent between said primary bioreactor column and said rejuvenator column.

  20. Synthetic biology: insights into biological computation.

    Science.gov (United States)

    Manzoni, Romilde; Urrios, Arturo; Velazquez-Garcia, Silvia; de Nadal, Eulàlia; Posas, Francesc

    2016-04-18

    Organisms have evolved a broad array of complex signaling mechanisms that allow them to survive in a wide range of environmental conditions. They are able to sense external inputs and produce an output response by computing the information. Synthetic biology attempts to rationally engineer biological systems in order to perform desired functions. Our increasing understanding of biological systems guides this rational design, while the huge background in electronics for building circuits defines the methodology. In this context, biocomputation is the branch of synthetic biology aimed at implementing artificial computational devices using engineered biological motifs as building blocks. Biocomputational devices are defined as biological systems that are able to integrate inputs and return outputs following pre-determined rules. Over the last decade the number of available synthetic engineered devices has increased exponentially; simple and complex circuits have been built in bacteria, yeast and mammalian cells. These devices can manage and store information, take decisions based on past and present inputs, and even convert a transient signal into a sustained response. The field is experiencing a fast growth and every day it is easier to implement more complex biological functions. This is mainly due to advances in in vitro DNA synthesis, new genome editing tools, novel molecular cloning techniques, continuously growing part libraries as well as other technological advances. This allows that digital computation can now be engineered and implemented in biological systems. Simple logic gates can be implemented and connected to perform novel desired functions or to better understand and redesign biological processes. Synthetic biological digital circuits could lead to new therapeutic approaches, as well as new and efficient ways to produce complex molecules such as antibiotics, bioplastics or biofuels. Biological computation not only provides possible biomedical and

  1. Academic Training Lecture Regular Programme: Particle Therapy

    CERN Multimedia

    2012-01-01

    Particle Therapy using Proton and Ion Beams - From Basic Principles to Daily Operations and Future Concepts by Andreas Peter (Head of Accelerator Operations, Heidelberg Ion Beam Theraps Centre (HIT), Germany) Part I: Tuesday, September 11, 2012 from 11:00 to 12:00 (Europe/Zurich) at CERN ( 222-R-001 - Filtration Plant ) • An introduction about the historical developments of accelerators and their use for medical applications: tumour treatment from X-rays to particle therapy • Description of the underlying physics and biology of particle therapy; implications on the requirements for the needed beam parameters (energy, intensity, focus, beam structure) • Accelerator technology used for particle therapy so far: cyclotrons and synchrotrons • Particle therapy facilities worldwide: an overview and some examples in detail: PSI/Switzerland, Loma Linda/USA, HIMAC/Japan, HIT/Heidelberg, CNAO/Italy Part II: Wednesday, September 12, 2012 from 11:00 to 12:00 (Europe/Zurich) at CER...

  2. Optimal use of biologics in the management of Crohn’s disease

    OpenAIRE

    Panaccione, Remo; Ghosh, Subrata

    2010-01-01

    Crohn’s disease (CD) is a chronic relapsing and remitting disorder of the gastrointestinal tract with no known cure. The inflammation that drives the disease can lead to debilitating symptoms and a number of complications that may lead to surgery. The introduction of biologic therapy a decade ago has offered a new option for patients failing conventional therapy. Over time, biologic therapy has also led to the desire to achieve treatment goals beyond the control of symptoms. In order to achie...

  3. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; May, Elebeoba E.; Leitão, Andrei; Tropsha, Alexander

    2011-01-01

    There is a critical need for improving the level of chemistry awareness in systems biology. The data and information related to modulation of genes and proteins by small molecules continue to accumulate at the same time as simulation tools in systems biology and whole body physiologically-based pharmacokinetics (PBPK) continue to evolve. We called this emerging area at the interface between chemical biology and systems biology systems chemical biology, SCB (Oprea et al., 2007).

  4. Pictures of Synthetic Biology

    OpenAIRE

    Cserer, Amelie; Seiringer, Alexandra

    2009-01-01

    This article is concerned with the representation of Synthetic Biology in the media and by biotechnology experts. An analysis was made of German-language media articles published between 2004 and 2008, and interviews with biotechnology-experts at the Synthetic Biology conference SB 3.0 in Zurich 2007. The results have been reflected in terms of the definition of Synthetic Biology, applications of Synthetic Biology and the perspectives of opportunities and risks. In the media, Synthetic Biolog...

  5. Principles of radiation therapy

    International Nuclear Information System (INIS)

    Radiation oncology now represents the integration of knowledge obtained over an 80-year period from the physics and biology laboratories and the medical clinic. Such integration is recent; until the supervoltage era following World War II, the chief developments in these three areas for the most part were realized independently. The physics and engineering laboratories have now developed a dependable family of sources of ionizing radiations that can be precisely directed at tumor volumes at various depths within the body. The biology laboratory has provided the basic scientific support underlying the intensive clinical experience and currently is suggesting ways of using ionizing radiations more effectively, such as modified fractionation schedules relating to cell cycle kinetics and the use of drugs and chemicals as modifiers of radiation response and normal tissue reaction. The radiation therapy clinic has provided the patient stratum on which the acute and chronic effects of irradiation have been assessed, and the patterns of treatment success and failure identified. The radiation therapist has shared with the surgeon and medical oncologist the responsibility for clarifying the natural history of a large number of human neoplasms, and through such clarifications, has developed more effective treatment strategies. Several examples of this include the improved results in the treatment of Hodgkin's disease, squamous cell carcinoma of the cervix, seminoma, and epithelial neoplasms of the upper aerodigestive tract

  6. Stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Comprehensive an up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. Examines in detail retrospective studies and prospective clinical trials for various organ sites from around the world. Written by world-renowned experts in SBRT from North America, Asia and Europe. Stereotactic body radiation therapy (SBRT) has emerged as an innovative treatment for various primary and metastatic cancers, and the past five years have witnessed a quantum leap in its use. This book provides a comprehensive and up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. It will serve as a detailed resource for this rapidly developing treatment modality. The organ sites covered include lung, liver, spine, pancreas, prostate, adrenal, head and neck, and female reproductive tract. Retrospective studies and prospective clinical trials on SBRT for various organ sites from around the world are examined, and toxicities and normal tissue constraints are discussed. This book features unique insights from world-renowned experts in SBRT from North America, Asia, and Europe. It will be necessary reading for radiation oncologists, radiation oncology residents and fellows, medical physicists, medical physics residents, medical oncologists, surgical oncologists, and cancer scientists.

  7. Meson radiobiology and therapy

    International Nuclear Information System (INIS)

    High-linear energy transfer radiation (neutrons, heavy ions, and pions) have a greater relative biological effectiveness than low-linear energy transfer radiation by depositing a high density of ionization in irradiated cells. This overcomes the protective effect of oxygen; decreases the variation in sensitivity among the several stages of the cell cycles; and, inhibits the repair of sublethal damage as compared to x-rays, gamma rays, electrons and protons. Negative pi mesons (pions), appear particularly suited for radiation therapy as their penetration and depth-dose profiles lend themselves to shaping the high dose area to the tumor size and location. Preliminary biological experiments with pions produced at the Los Alamos Meson Physics Facility studied cell survival at various radiation depths and cell cycle sensitivity. Histologic study of data from the first human experiments indicated severe tumor cell destruction by pions as compared to x-rays in treating malignant melanoma skin nodules, without increased effects on dermal elements. (U.S.)

  8. Stereotactic body radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Simon S. [Univ. Hospitals Seidman Cancer Center, Cleveland, OH (United States). Dept. of Radiation Oncology; Case Western Reserve Univ., Cleveland, OH (United States). Case Comprehensive Cancer Center; Teh, Bin S. [The Methodist Hospital Cancer Center and Research Institute, Houston, TX (United States). Weill Cornell Medical College; Lu, Jiade J. [National Univ. of Singapore (Singapore). Dept. of Radiation Oncology; Schefter, Tracey E. (eds.) [Colorado Univ., Aurora, CO (United States). Dept. of Radiation Oncology

    2012-11-01

    Comprehensive an up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. Examines in detail retrospective studies and prospective clinical trials for various organ sites from around the world. Written by world-renowned experts in SBRT from North America, Asia and Europe. Stereotactic body radiation therapy (SBRT) has emerged as an innovative treatment for various primary and metastatic cancers, and the past five years have witnessed a quantum leap in its use. This book provides a comprehensive and up-to-date account of the physical/technological, biological, and clinical aspects of SBRT. It will serve as a detailed resource for this rapidly developing treatment modality. The organ sites covered include lung, liver, spine, pancreas, prostate, adrenal, head and neck, and female reproductive tract. Retrospective studies and prospective clinical trials on SBRT for various organ sites from around the world are examined, and toxicities and normal tissue constraints are discussed. This book features unique insights from world-renowned experts in SBRT from North America, Asia, and Europe. It will be necessary reading for radiation oncologists, radiation oncology residents and fellows, medical physicists, medical physics residents, medical oncologists, surgical oncologists, and cancer scientists.

  9. Camouflage therapy.

    Science.gov (United States)

    Rayner, V L

    1995-04-01

    Camouflage therapy is a system of cosmetic techniques designed for patients to use to assist themselves in coping constructively with the psychological and physical trauma of their disfigurements. It is described as a "system" because these techniques are interrelated. A camouflage therapist may teach the patient to use one, two, or all of the techniques at the same time in order to normalize their appearance. Four basic techniques have been described in this article. They are as follows: (1) the use of opaque, waterproof cover creams to conceal scarring; (2) the application of pancake makeup for patients with oily or acne-prone skin; (3) color correctors to obliterate discoloration from postoperative trauma; and (4) recreating imperfections on the skin. For more information about the use of cosmetics to normalize the appearance of physical disfigurements, the following books are recommended. PMID:7600717

  10. Intrapleural therapy.

    Science.gov (United States)

    Huggins, J Terrill; Doelken, Peter; Sahn, Steven A

    2011-08-01

    Numerous intrapleural therapies have been adopted to treat a vast array of pleural diseases. The first intrapleural therapies proposed focused on the use of fibrinolytics and DNase to promote fluid drainage in empyema. Numerous case series and five randomized controlled trials have been published to determine the outcomes of fibrinolytics in empyema treatment. In the largest randomized trial, the use of streptokinase had no reduction in mortality, decortication rates or hospital days compared with placebo in the treatment of empyema. Criticism over study design and patient selection may have potentially affected the outcomes in this study. The development of dyspnoea is common in the setting of malignant pleural effusions. Pleural fluid evacuation followed by pleurodesis is often attempted. Numerous sclerosing agents have been studied, with talc emerging as the most effective agent. Small particle size of talc should be avoided because of increased systemic absorption potentiating toxicity, such as acute lung injury. Over the past several years, the use of chronic indwelling pleural catheters have emerged as the preferred modality in the treating a symptomatic malignant pleural effusion. For patients with malignant-related lung entrapment, pleurodesis often fails due to the presence of visceral pleural restriction; however, chronic indwelling pleural catheters are effective in palliation of dyspnoea. Finally, the use of staphylococcal superantigens has been proposed as a therapeutic model for the treatment of non-small lung cancer. Intrapleural instillation of staphylococcal superantigens increased median survival by 5 months in patients with non-small cell lung cancer with a malignant pleural effusion. PMID:21672085

  11. Emerging frontiers in radiation biology

    International Nuclear Information System (INIS)

    Radiation biology owes its origin to the spectacular success in the treatment of human diseases by x-rays and radium, just after their respective discoveries in 1895-96. From the very inception it has attracted researchers from all disciplines of science. The target and hit theory developed by physicists, dominated the scene till the advent of radiation chemistry concepts which offered an entirely different perspective to the mechanisms involved in biological effects of radiations and their modification by endogenous and exogenous agents like radioprotectors and radiosensitisers including hyperthermia. The applied aspect of radiation biology mainly relates to radiation therapy of cancer which, in spite of its long existence, is still to achieve scientific perfection. Nevertheless, it did not wait -and fortunately so-, for its radiobiological rationality but continued its development to be the main modality for cancer treatment today. Several approaches are now being attempted to improve its efficacy by selectively damaging the cancerous cells while sparing the normal tissues and also by devising suitable predictive assays for radioresponse of different tumours to enable individualisation of treatment schedules. (author). 99 refs., 1 fig., 2 tabs

  12. Biology and management of ependymomas.

    Science.gov (United States)

    Wu, Jing; Armstrong, Terri S; Gilbert, Mark R

    2016-07-01

    Ependymomas are rare primary tumors of the central nervous system in children and adults that comprise histologically similar but genetically distinct subgroups. The tumor biology is typically more associated with the site of origin rather than being age-specific. Genetically distinct subgroups have been identified by genomic studies based on locations in classic grade II and III ependymomas. They are supratentorial ependymomas with C11orf95-RELA fusion or YAP1 fusion, infratentorial ependymomas with or without a hypermethylated phenotype (CIMP), and spinal cord ependymomas. Myxopapillary ependymomas and subependymomas have different biology than ependymomas with typical WHO grade II or III histology. Surgery and radiotherapy are the mainstays of treatment, while the role of chemotherapy has not yet been established. An in-depth understanding of tumor biology, developing reliable animal models that accurately reflect tumor molecule features, and high throughput drug screening are essential for developing new therapies. Collaborative efforts between scientists, physicians, and advocacy groups will enhance the translation of laboratory findings into clinical trials. Improvements in disease control underscore the need to incorporate assessment and management of patients' symptoms to ensure that treatment advances translate into improvement in quality of life. PMID:27022130

  13. Can Shockwave Therapy Improve Tendon Metabolism?

    NARCIS (Netherlands)

    Zwerver, Johannes; Waugh, Charlotte; van der Worp, Henk; Scott, Alex

    2016-01-01

    Shockwave treatments are commonly used in the management of tendon injuries and there is increasing evidence for its clinical effectiveness. There is a paucity of fundamental (in vivo) studies investigating the biological action of shockwave therapy. Destruction of calcifications, pain relief and me

  14. Innovative Approaches to Plasminogen Activator Therapy

    Science.gov (United States)

    Haber, Edgar; Quertermous, Thomas; Matsueda, Gary R.; Runge, Marschall S.

    1989-01-01

    Plasminogen activator therapy for acute myocardial infarction has become standard medical practice. Bleeding complications, however, limit the utility of the currently available agents. This article reviews how the tools of molecular biology and protein engineering are being used to develop safer and more effective plasminogen activators.

  15. Gene therapy for gastric cancer: Is it promising?

    OpenAIRE

    Sutter, Andreas P; Fechner, Henry

    2006-01-01

    Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer, including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological t...

  16. American Music Therapy Association

    Science.gov (United States)

    American Music Therapy Association Home Contact News Help/FAQ Members Only Login Quick Links Facts About Music Therapy Qualifications ... with AMTA Sponsor AMTA Events Social Networking Support Music Therapy When you shop at AmazonSmile, Amazon will ...

  17. Radioactive Iodine (Radioiodine) Therapy

    Science.gov (United States)

    ... lymph nodes and other parts of the body. Radioactive iodine therapy improves the survival rate of patients with papillary ... and benefits of RAI therapy with your doctor. Radioactive iodine therapy cannot be used to treat anaplastic (undifferentiated) and ...

  18. Occupational Therapy (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Occupational Therapy KidsHealth > For Parents > Occupational Therapy Print A A ... for some kids. continue Kids Who Might Need Occupational Therapy According to the AOTA, kids with these medical ...

  19. External Beam Therapy (EBT)

    Science.gov (United States)

    ... Physician Resources Professions Site Index A-Z External Beam Therapy (EBT) External beam therapy (EBT) is a ... follow-up should I expect? What is external beam therapy and how is it used? External beam ...

  20. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  1. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Science.gov (United States)

    2010-10-01

    ... following drugs and biologicals that are furnished as part of an outpatient hospital service: (1) Orphan... biological as an outpatient hospital service was being made on August 1, 2000. (2) Cancer therapy drugs and... services if payment for the drug or biological as an outpatient hospital service was being made on August...

  2. 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.

  3. 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.

  4. Physical basis of heavy ion radiation therapy

    International Nuclear Information System (INIS)

    Physical foundation of a heavy ion radio-therapy was discussed, especially on a designing a spread Bragg peak with a ridge filter. A large radiobiological effectiveness will be positively utilized in the heavy ion radio-therapy. The biological effectiveness will be different depending on the depth in human body. This fact gives us difficult problems when we aim to kill uniformly the target cells in human body. As a first step to solve these problems, biological effectiveness of a mixed beam using monoenergetic low and high LET beams was examined and try to understand the results by the amorphous image of the track structure of the heavy ions. A research on a microscopic pattern of energy deposition will be important to solve biophysical problem in heavy ion radio-therapy. (author)

  5. Targeted Therapies in Epithelial Ovarian Cancer

    International Nuclear Information System (INIS)

    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

  6. Intermediate physics for medicine and biology

    CERN Document Server

    Hobbie, Russell K

    2015-01-01

    This classic text has been used in over 20 countries by advanced undergraduate and beginning graduate students in biophysics, physiology, medical physics, neuroscience, and biomedical engineering. It bridges the gap between an introductory physics course and the application of physics to the life and biomedical sciences. Extensively revised and updated, the fifth edition incorporates new developments at the interface between physics and biomedicine. New coverage includes cyclotrons, photodynamic therapy, color vision, x-ray crystallography, the electron microscope, cochlear implants, deep brain stimulation, nanomedicine, and other topics highlighted in the National Research Council report BIO2010. As with the previous edition, the first half of the text is primarily biological physics, emphasizing the use of ideas from physics to understand biology and physiology, and the second half is primarily medical physics, describing the use of physics in medicine for diagnosis (mainly imaging) and therapy. Among the m...

  7. Cryoprecipitate therapy.

    Science.gov (United States)

    Nascimento, B; Goodnough, L T; Levy, J H

    2014-12-01

    Cryoprecipitate, originally developed as a therapy for patients with antihaemophilic factor deficiency, or haemophilia A, has been in use for almost 50 yr. However, cryoprecipitate is no longer administered according to its original purpose, and is now most commonly used to replenish fibrinogen levels in patients with acquired coagulopathy, such as in clinical settings with haemorrhage including cardiac surgery, trauma, liver transplantation (LT), or obstetric haemorrhage. Cryoprecipitate is a pooled product that does not undergo pathogen inactivation, and its administration has been associated with a number of adverse events, particularly transmission of blood-borne pathogens and transfusion-related acute lung injury. As a result of these safety concerns, along with emerging availability of alternative fibrinogen preparations, cryoprecipitate has been withdrawn from use in a number of European countries. Compared with the plasma from which it is prepared, cryoprecipitate contains a high concentration of coagulation factor VIII, coagulation factor XIII, and fibrinogen. Cryoprecipitate is usually licensed by regulatory authorities for the treatment of hypofibrinogenaemia, and recommended for supplementation when plasma fibrinogen levels decrease below 1 g litre(-1); however, this threshold is empiric and is not based on solid clinical evidence. Consequently, there is uncertainty over the appropriate dosing and optimal administration of cryoprecipitate, with some guidelines from professional societies to guide clinical practice. Randomized, controlled trials are needed to determine the clinical efficacy of cryoprecipitate, compared with the efficacy of alternative preparations. These trials will allow the development of evidence-based guidelines in order to inform physicians and guide clinical practice. PMID:24972790

  8. Advances in Biological Science.

    Science.gov (United States)

    Oppenheimer, Steven B.; And Others

    1988-01-01

    Reviews major developments in areas that are at the cutting edge of biological research. Areas include: human anti-cancer gene, recombinant DNA techniques for the detection of Huntington disease carriers, and marine biology. (CW)

  9. Biology of Blood

    Science.gov (United States)

    ... Mail Facebook TwitterTitle Google+ LinkedIn Home Blood Disorders Biology of Blood Overview of Blood Medical Dictionary Also ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  10. Biologics in Pediatric Rheumatology: Quo Vadis?

    Science.gov (United States)

    Sterba, Yonit; Ilowite, Norman

    2016-07-01

    The past two decades have brought immense satisfaction to pediatric rheumatologists and families of children with rheumatologic diseases. We have been able to better classify, recognize, and diagnose rheumatologic diseases, but most importantly, the discovery of biologic therapies and their efficacy and relative safety in treating multiple rheumatologic conditions, improving quality of life for the patients we care for. We will review the advances of the past two decades and discuss potential areas for new discoveries. PMID:27306623

  11. Biologic agents in juvenile spondyloarthropathies.

    Science.gov (United States)

    Katsicas, María Martha; Russo, Ricardo

    2016-01-01

    The juvenile spondyloarthropathies (JSpA) are a group of related rheumatic diseases characterized by involvement of peripheral large joints, axial joints, and entheses (enthesitis) that begin in the early years of life (prior to 16(th) birthday).The nomenclature and concept of spondyloarthropathies has changed during the last few decades. Although there is not any specific classification of JSpA, diseases under the spondyloarthropathy nomenclature umbrella in the younger patients include: the seronegative enthesitis and arthropathy (SEA) syndrome, juvenile ankylosing spondylitis, reactive arthritis, and inflammatory bowel disease-associated arthritis. Moreover, the ILAR criteria for Juvenile Idiopathic Arthritis includes two categories closely related to spondyloarthritis: Enthesitis-related arthritis and psoriatic arthritis.We review the pathophysiology and the use of biological agents in JSpA. JSpA are idiopathic inflammatory diseases driven by an altered balance in the proinflammatory cytokines. There is ample evidence on the role of tumor necrosis factor (TNF) and interleukin-17 in the physiopathology of these entities. Several non-biologic and biologic agents have been used with conflicting results in the treatment of these complex diseases. The efficacy and safety of anti-TNF agents, such as etanercept, infliximab and adalimumab, have been analysed in controlled and uncontrolled trials, usually showing satisfactory outcomes. Other biologic agents, such as abatacept, tocilizumab and rituximab, have been insufficiently studied and their role in the therapy of SpA is uncertain. Interleukin-17-blocking agents are promising alternatives for the treatment of JSpA patients in the near future. Recommendations for the treatment of patients with JSpA have recently been proposed and are discussed in the present review. PMID:26968522

  12. Engineering scalable biological systems

    OpenAIRE

    Lu, Timothy K.

    2010-01-01

    Synthetic biology is focused on engineering biological organisms to study natural systems and to provide new solutions for pressing medical, industrial, and environmental problems. At the core of engineered organisms are synthetic biological circuits that execute the tasks of sensing inputs, processing logic, and performing output functions. In the last decade, significant progress has been made in developing basic designs for a wide range of biological circuits in bacteria, yeast, and mammal...

  13. Systems interface biology

    OpenAIRE

    Francis J Doyle; Stelling, Jörg

    2006-01-01

    The field of systems biology has attracted the attention of biologists, engineers, mathematicians, physicists, chemists and others in an endeavour to create systems-level understanding of complex biological networks. In particular, systems engineering methods are finding unique opportunities in characterizing the rich behaviour exhibited by biological systems. In the same manner, these new classes of biological problems are motivating novel developments in theoretical systems approaches. Henc...

  14. Biological Races in Humans

    OpenAIRE

    Templeton, Alan R.

    2013-01-01

    Races may exist in humans in a cultural sense, but biological concepts of race are needed to access their reality in a non-species-specific manner and to see if cultural categories correspond to biological categories within humans. Modern biological concepts of race can be implemented objectively with molecular genetic data through hypothesis-testing. Genetic data sets are used to see if biological races exist in humans and in our closest evolutionary relative, the chimpanzee. Using the two m...

  15. Delivery systems for gene therapy

    Directory of Open Access Journals (Sweden)

    Shrikant Mali

    2013-01-01

    Full Text Available The structure of DNA was unraveled by Watson and Crick in 1953, and two decades later Arber, Nathans and Smith discovered DNA restriction enzymes, which led to the rapid growth in the field of recombinant DNA technology. From expressing cloned genes in bacteria to expressing foreign DNA in transgenic animals, DNA is now slated to be used as a therapeutic agent to replace defective genes in patients suffering from genetic disorders or to kill tumor cells in cancer patients. Gene therapy provides modern medicine with new perspectives that were unthinkable two decades ago. Progress in molecular biology and especially, molecular medicine is now changing the basics of clinical medicine. A variety of viral and non-viral possibilities are available for basic and clinical research. This review summarizes the delivery routes and methods for gene transfer used in gene therapy.

  16. Fractionated radiation therapy after Strandqvist

    International Nuclear Information System (INIS)

    Models for predicting the total dose required to produce tolerable normal-tissue damage in radiation therapy are becoming less empirical, more realistic, and more specific for different tissue reactions. The progression is described from the 'cube root law', through STRANDQVIST'S well known graph to NSD, TDF and CRE and more recently to biologically based time factors and linear-quadratic dose-response curves. New applications of the recent approach are reviewed together with their implications for non-standard fractionation in radiation therapy. It is concluded that accelerated fractionation is an important method to be investigated, as well as hyperfractionation; and that more data are required about the proliferation rates of clonogenic cells in human tumours. (orig.)

  17. Upgrading Undergraduate Biology Education

    Science.gov (United States)

    Musante, Susan

    2011-01-01

    On many campuses throughout the country, undergraduate biology education is in serious need of an upgrade. During the past few decades, the body of biological knowledge has grown exponentially, and as a research endeavor, the practice of biology has evolved. Education research has also made great strides, revealing many new insights into how…

  18. Biology Myth-Killers

    Science.gov (United States)

    Lampert, Evan

    2014-01-01

    "Biology Myth-Killers" is an activity designed to identify and correct common misconceptions for high school and college introductory biology courses. Students identify common myths, which double as biology misconceptions, and use appropriate sources to share the "truth" about the myths. This learner-centered activity is a fun…

  19. Designing synthetic biology.

    Science.gov (United States)

    Agapakis, Christina M

    2014-03-21

    Synthetic biology is frequently defined as the application of engineering design principles to biology. Such principles are intended to streamline the practice of biological engineering, to shorten the time required to design, build, and test synthetic gene networks. This streamlining of iterative design cycles can facilitate the future construction of biological systems for a range of applications in the production of fuels, foods, materials, and medicines. The promise of these potential applications as well as the emphasis on design has prompted critical reflection on synthetic biology from design theorists and practicing designers from many fields, who can bring valuable perspectives to the discipline. While interdisciplinary connections between biologists and engineers have built synthetic biology via the science and the technology of biology, interdisciplinary collaboration with artists, designers, and social theorists can provide insight on the connections between technology and society. Such collaborations can open up new avenues and new principles for research and design, as well as shed new light on the challenging context-dependence-both biological and social-that face living technologies at many scales. This review is inspired by the session titled "Design and Synthetic Biology: Connecting People and Technology" at Synthetic Biology 6.0 and covers a range of literature on design practice in synthetic biology and beyond. Critical engagement with how design is used to shape the discipline opens up new possibilities for how we might design the future of synthetic biology. PMID:24156739

  20. Biological Water or Rather Water in Biology?

    Czech Academy of Sciences Publication Activity Database

    Jungwirth, Pavel

    2015-01-01

    Roč. 6, č. 13 (2015), s. 2449-2451. ISSN 1948-7185 Institutional support: RVO:61388963 Keywords : biological water * protein * interface Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 7.458, year: 2014

  1. Prosthodontic management of implant therapy.

    Science.gov (United States)

    Thalji, Ghadeer; Bryington, Matthew; De Kok, Ingeborg J; Cooper, Lyndon F

    2014-01-01

    Implant-supported dental restorations can be screw-retained, cement-retained, or a combination of both, whereby a metal superstructure is screwed to the implants and crowns are individually cemented to the metal frame. Each treatment modality has advantages and disadvantages. The use of computer-aided design/computer-assisted manufacture technologies for the manufacture of implant superstructures has proved to be advantageous in the quality of materials, precision of the milled superstructures, and passive fit. Maintenance and recall evaluations are an essential component of implant therapy. The longevity of implant restorations is limited by their biological and prosthetic maintenance requirements. PMID:24286654

  2. Synthetic biological networks

    International Nuclear Information System (INIS)

    Despite their obvious relationship and overlap, the field of physics is blessed with many insightful laws, while such laws are sadly absent in biology. Here we aim to discuss how the rise of a more recent field known as synthetic biology may allow us to more directly test hypotheses regarding the possible design principles of natural biological networks and systems. In particular, this review focuses on synthetic gene regulatory networks engineered to perform specific functions or exhibit particular dynamic behaviors. Advances in synthetic biology may set the stage to uncover the relationship of potential biological principles to those developed in physics. (review article)

  3. 76 FR 81513 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2011-12-28

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue, and Gene Therapies Advisory Committee..., Tissue, and Gene Therapies Advisory Committee. General Function of the Committee: To provide advice and... Gene Therapies, Center for Biologics Evaluation and Research, FDA. FDA intends to make...

  4. About radiation therapy

    International Nuclear Information System (INIS)

    Explained are the history and outline of technology in radiation therapy (RT), characteristics of dose distribution of major radiations in RT and significance of biological effective dose (BED) from aspects of radiation oncology and therapeutic prediction. The history is described from the first X-ray RT documented in 1896 to the latest (1994) RT with National Institute of Radiological Sciences (NIRS) carbon beam for tumors in trunk. X-ray RT has aimed to make the energy high because target tumors are generally present deep in the body and an ideal RT, the intensity modulated RT, has been developed to assure the desirable dose distribution (or, dose-volume histogram) based on precise planning with X-CT and computing. Low energy gamma ray emitted from radioisotopes provides also an ideal RT mean because of its excellent focusing to the internal target; however, problems remain of invasion and long lodging of the isotope in the body. Heavy ion RT is conducted on the planning on X-CT image and computation utilizing Bragg's principle and is superior for minimizing the exposure of normal, non-cancerous tissues. Boron neutron capture therapy is a promising RT as the local control is always possible at 10B ratio of the lesion/normal tissue >2.5, which is measurable by PET with 18F-boronophenylalanine. In the current oncology, BED is estimated by the linear quadratic model, α(nd)+β(nd)2, where d is a total irradiation dose and n, number of fractionation, and is a planning basis for the effect prediction in RT above. Physical problems in future involve the system development of more efficient dose focusing and convenient dose impartation, and development of more easily operable system and cost reduction is awaited. (R.T.)

  5. Future development of biologically relevant dosimetry.

    Science.gov (United States)

    Palmans, H; Rabus, H; Belchior, A L; Bug, M U; Galer, S; Giesen, U; Gonon, G; Gruel, G; Hilgers, G; Moro, D; Nettelbeck, H; Pinto, M; Pola, A; Pszona, S; Schettino, G; Sharpe, P H G; Teles, P; Villagrasa, C; Wilkens, J J

    2015-01-01

    Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented. PMID:25257709

  6. Quantum biological information theory

    CERN Document Server

    Djordjevic, Ivan B

    2016-01-01

    This book is a self-contained, tutorial-based introduction to quantum information theory and quantum biology. It serves as a single-source reference to the topic for researchers in bioengineering, communications engineering, electrical engineering, applied mathematics, biology, computer science, and physics. The book provides all the essential principles of the quantum biological information theory required to describe the quantum information transfer from DNA to proteins, the sources of genetic noise and genetic errors as well as their effects. Integrates quantum information and quantum biology concepts; Assumes only knowledge of basic concepts of vector algebra at undergraduate level; Provides a thorough introduction to basic concepts of quantum information processing, quantum information theory, and quantum biology; Includes in-depth discussion of the quantum biological channel modelling, quantum biological channel capacity calculation, quantum models of aging, quantum models of evolution, quantum models o...

  7. Nonclinical safety strategies for stem cell therapies

    Energy Technology Data Exchange (ETDEWEB)

    Sharpe, Michaela E., E-mail: michaela_sharpe@yahoo.com [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom); Morton, Daniel [Exploratory Drug Safety, Drug Safety Research and Development, Pfizer Inc, Cambridge, 02140 (United States); Rossi, Annamaria [Investigative Toxicology, Drug Safety Research and Development, Pfizer Ltd, Ramsgate Road, Sandwich, CT13 9NJ (United Kingdom)

    2012-08-01

    Recent breakthroughs in stem cell biology, especially the development of the induced pluripotent stem cell techniques, have generated tremendous enthusiasm and efforts to explore the therapeutic potential of stem cells in regenerative medicine. Stem cell therapies are being considered for the treatment of degenerative diseases, inflammatory conditions, cancer and repair of damaged tissue. The safety of a stem cell therapy depends on many factors including the type of cell therapy, the differentiation status and proliferation capacity of the cells, the route of administration, the intended clinical location, long term survival of the product and/or engraftment, the need for repeated administration, the disease to be treated and the age of the population. Understanding the product profile of the intended therapy is crucial to the development of the nonclinical safety study design.

  8. Art Therapy Verses Psychotherapy

    Science.gov (United States)

    Del Giacco, Maureen

    2009-01-01

    The purpose of my paper is to identify the difference between psychotherapy and art therapy. Then to introduce a technique within the field of art therapy that is relevant to neuro-plasticity Del Giacco Neuro Art Therapy. The paper identifies the importance of the amygdala and the hippocampus within the role of art therapy. Supporting…

  9. Physical Therapy (For Parents)

    Science.gov (United States)

    ... Story" 5 Things to Know About Zika & Pregnancy Physical Therapy KidsHealth > For Parents > Physical Therapy Print A A ... Finding a Physical Therapist en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) for ...

  10. Overview of light-ion beam therapy

    International Nuclear Information System (INIS)

    This overview of light-ion beam therapy covers the following topics: a history of hadron therapy, light-ion beam therapy, beam fragmentation, the biological rationale for the clinical use of light ions, the physical parameters of clinical beams, distributions of relative biological effectiveness (RBE) and linear energy transfer (LET), verification of treatment planning and delivery using charged particle beams, ion beam research in space biology, clinical trials using light ions, and the relationship between the present report and other IAEA and ICRU reports. There are plans for four national centres using light ions, in Germany, France, Austria, and Italy. There is an increasing interest in further initiatives and more countries are expressing interest in creating national projects, in particular Sweden, the Netherlands, Belgium, Spain and the UK. In Japan, another carbon-ion therapy facility project has started, and three additional facilities are planned. There are other initiatives for light-ion facilities in several locations in the USA, in China, and in Korea. (author)

  11. Inflammatory mediators: Parallels between cancer biology and stem cell therapy

    OpenAIRE

    Rameshwar, Pranela

    2009-01-01

    Shyam A Patel1,2,3, Andrew C Heinrich2,3, Bobby Y Reddy2, Pranela Rameshwar21Graduate School of Biomedical Sciences, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 2Department of Medicine – Division of Hematology/Oncology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA; 3These authors contributed equally to this workAbstract: Inflammation encompasses diverse molecular pathways, and it is intertwined with a wide ar...

  12. Updates in biological therapies for knee injuries: bone

    OpenAIRE

    Kfuri, Mauricio; de Freitas, Rafael Lara; Batista, Bruno Bellaguarda; Salim, Rodrigo; Castiglia, Marcello Teixeira; Tavares, Ricardo Antonio; Araújo, Paulo Henrique

    2014-01-01

    Bone is a unique tissue because of its mechanical properties, ability for self-repair, and enrollment in different metabolic processes such as calcium homeostasis and hematopoietic cell production. Bone barely tolerates deformation and tends to fail when overloaded. Fracture healing is a complex process that in particular cases is impaired. Osteoprogenitor cells proliferation, growth factors, and a sound tridimensional scaffold at fracture site are key elements for new bone formation and depo...

  13. Stem cells - biological update and cell therapy progress

    OpenAIRE

    GIRLOVANU, MIHAI; Susman, Sergiu; Soritau, Olga; RUS-CIUCA, DAN; MELINCOVICI, CARMEN; CONSTANTIN, ANNE-MARIE; Carmen Mihaela MIHU

    2015-01-01

    In recent years, the advances in stem cell research have suggested that the human body may have a higher plasticity than it was originally expected. Until now, four categories of stem cells were isolated and cultured in vivo: embryonic stem cells, fetal stem cells, adult stem cells and induced pluripotent stem cells (hiPSCs). Although multiple studies were published, several issues concerning the stem cells are still debated, such as: the molecular mechanisms of differentiation, the methods t...

  14. Stem cell biology in thyroid cancer: Insights for novel therapies

    Institute of Scientific and Technical Information of China (English)

    Parisha; Bhatia; Koji; Tsumagari; Zakaria; Y; Abd; Elmageed; Paul; Friedlander; Joseph; F; Buell; Emad; Kandil

    2014-01-01

    Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

  15. Waldenström macroglobulinemia: biology, genetics, and therapy

    OpenAIRE

    Ansell, Stephen; Paludo, Jonas

    2016-01-01

    Jonas Paludo,1,2 Stephen M Ansell,1 1Division of Hematology, 2Division of Medical Oncology, Mayo Clinic, Rochester, MN, USA Abstract: Waldenström macroglobulinemia (WM) is a distinct clinicopathologic entity characterized by the presence of a lymphoplasmacytic lymphoma, a non-Hodgkin lymphoma, and IgM monoclonal gammopathy. WM is an indolent, uncommon malignancy mostly affecting the elderly. Patient outcomes have modestly improved since the introduction of rituximab to conventional c...

  16. Nuclear Physics meets Medicine and Biology: Boron Neutron Capture Therapy

    CERN Document Server

    F. Ballarini, F; S. Bortolussi, S; P. Bruschi, P; A.M. Clerici, A M; A. De Bari, A; P. Dionigi, P; C. Ferrari, C; M.A. Gadan, M A; N. Protti, N; S. Stella, S; C. Zonta, C; A. Zonta, A; S. Altieri, S

    2010-01-01

    BNCT is a tumour treatment based on thermal-neutron irradiation of tissues enriched with 10B, which according to the 10B(n, )7Li reaction produces particles with high Linear Energy Transfer and short range. Since this treatment can deliver a therapeutic tumour dose sparing normal tissues, BNCT represents an alternative for diffuse tumours and metastases, which show poor response to surgery and photontherapy. In 2001 and 2003, in Pavia BNCT was applied to an isolated liver, which was infused with boron, explanted, irradiated and re-implanted. A new project was then initiated for lung tumours, developing a protocol for Boron concentration measurements and performing organ-dose Monte Carlo calculations; in parallel, radiobiology studies are ongoing to characterize the BNCT effects down to cellular level. After a brief introduction, herein we will present the main activities ongoing in Pavia including the radiobiological ones, which are under investigation not only experimentally but also theoretically, basing on...

  17. Biological Therapy in Treating Patients With Metastatic Cancer

    Science.gov (United States)

    2013-02-21

    Breast Cancer; Colorectal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Head and Neck Cancer; Liver Cancer; Lung Cancer; Metastatic Cancer; Ovarian Cancer; Pancreatic Cancer; Testicular Germ Cell Tumor

  18. Treatment planning for light ions: how to take into account relative biological effectivness (RBE)

    International Nuclear Information System (INIS)

    A new treatment planning program was developed for the heavy ion therapy facility at GSI, which is tailored to the special needs for an active beam delivery using a magnetic raster scanner. It also includes a biological model for the estimation of biological effective dose for carbon ions and realizes a fully biological treatment planning. Biological effective dose distributions and RBE maps can be displayed and assessed from the graphical user interface. (orig.)

  19. Prescribing patterns of biologic immunomodulating medicine in the South African private health care sector / Ilanca Roux

    OpenAIRE

    Roux, Ilanca

    2010-01-01

    Advances in molecular immunology and rapid technical evolution during the past two decades have led to a new class of medicines called biologics. Recently, a large number of biologics, or biologic immunomodulators, directed towards an array of immune–mediated diseases, have entered the market. This has lead to a dramatic change in the immunotherapy of autoimmune diseases, as biologics present new potential to improve or substitute conventional immunosuppressive therapies. Accor...

  20. American Society of Gene & Cell Therapy

    Science.gov (United States)

    ... Resources Clinical Trials Information Gene Therapy and Cell Therapy Terminology Gene Therapy & Cell Therapy Breakthroughs FAQs Gene Therapy and Cell Therapy Defined Gene Therapy and Cell Therapy for Diseases Sites of ...

  1. Anaemia and radiation therapy

    International Nuclear Information System (INIS)

    Anaemia is frequent in cancer and may increase tumour hypoxia that stimulates angiogenesis. However, erythropoietin is a hypoxia-inducible stimulator of erythropoiesis which seems to improve quality of life in cancer patients. Two recent phase III randomized studies showed negative results using erythropoietin in head and neck cancer patients and in metastatic breast cancer patients with impaired specific survival. In vitro and in vivo experiments have provided erythropoietin-receptor expression in endothelial cancer cells including malignant tumours of the breast, prostate, cervix, lung, head and neck, ovary, melanoma, stomach, gut, kidney etc. Biologic effect of erythropoietin and its receptor linkage induces proliferation of human breast cancer and angiogenesis and may limit anti-tumour effect of cancer treatment, in part, by tumour vascularization improvement. In addition, the use of exogenous erythropoietin could be able to favour tumour progression by improving tumour oxygenation and nutriment supply. If erythropoietin receptor were functional in human cancer. the assessment of erythropoietin receptor expression on tumour cell may help to select patients benefiting from exogenous erythropoietin. However. the relationship between erythropoietin receptor expression, tumour growth and exogenous erythropoietin. requires more studies. The results of recent clinical trials suggest that using erythropoietin should be avoided in non-anemic patients and discussed in patients receiving curative therapy. (authors)

  2. Intracoronary radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Dae Hyuk; Oh, Seung Jun; Lee, Hee Kung; Park, Seong Wook; Hong, Myeong Ki [College of Medicine, Ulsan Univ., Seoul (Korea, Republic of); Bom, Hee Seung [College of Medicine, Chonnam National Univ., Kwangju (Korea, Republic of)

    2001-07-01

    Restenosis remains a major limitation of percutaneous coronary interventions. Numerous Studies including pharmacological approaches and new devices failed to reduce restenosis rate except coronary stenting. Since the results of BENESTENT and STRESS studies came out, coronary stenting has been the most popular interventional strategy in the various kinds of coronary stenotic lesions, although the efficacy of stending was shown only in the discrete lesion of the large coronary artery. The widespread use of coronary stending has improved the early and late outcomes after coronary intervention, but it has also led to a new and serious problem, e.g., in-stent restenosis. Intravascular radiation for prevention of restenosis is a new technology in the field of percutaneous coronary intervention. Recent animal experiments and human trials have demonstrated that local irradiation, in conjunction with coronary interventions, substantially diminished the rate of restenosis. This paper reviews basic radiation biology of intracoronary radiation and its role in the inhibition of restenosis. The current status of intracoronary radiation therapy using Re-188 liquid balloon is also discussed.

  3. Laser therapy in sinusitis

    International Nuclear Information System (INIS)

    The sinusitis is an inflammation of one or more breasts peri-nasals. It is common in the months of winter and it can last months or years if it is not treat. At the moment we have several means that try to offer our patients a better treatment. One of these instruments is the low power laser that for their properties to the interaction with the biological tissues offers therapeutic effects on the alive tissues, achieving at the level cellular important changes for a quick answer of the damaged tissue. We intended to demonstrate the effectiveness of the treatment with low power laser in patient with sinusitis. It was carried out an explanatory and retrospective study, where it was applied as treatment the low power laser, for that which a team of model Cuban production Fisser 21. The feminine sex, the affected age group prevailed it was among 36 to 50 years for both groups, the maxillary sinusitis prevailed regarding the frontal. The migraine, the nasal obstruction and the sensation of congestion of the head were present in most of the cases. 75% of the patients' treaties noticed improvement of the symptoms between the 1st and 3rd sessions. At the end 80% cured without necessity of a second treatment cycle. The accompanying symptoms almost disappeared in their entirety. We recommend using the treatment of low power laser, as therapy of first line for the treatment of sinusitis of infectious cause. (Author)

  4. Branching processes in biology

    CERN Document Server

    Kimmel, Marek

    2015-01-01

    This book provides a theoretical background of branching processes and discusses their biological applications. Branching processes are a well-developed and powerful set of tools in the field of applied probability. The range of applications considered includes molecular biology, cellular biology, human evolution and medicine. The branching processes discussed include Galton-Watson, Markov, Bellman-Harris, Multitype, and General Processes. As an aid to understanding specific examples, two introductory chapters, and two glossaries are included that provide background material in mathematics and in biology. The book will be of interest to scientists who work in quantitative modeling of biological systems, particularly probabilists, mathematical biologists, biostatisticians, cell biologists, molecular biologists, and bioinformaticians. The authors are a mathematician and cell biologist who have collaborated for more than a decade in the field of branching processes in biology for this new edition. This second ex...

  5. Spectroscopy of biological nanocrystals

    OpenAIRE

    Ortac, Inanc; Severcan, Feride

    2007-01-01

    Nanocrystals have gained much interest in recent years, due to their unusual properties allowing interesting applications in physical and biological science. In this literature review, biological nanocrystals are discussed from the spectroscopic point of view. Firstly, the theory behind the outstanding abilities of the nanocrystals is described. Secondly, the spectroscopic properties of biological nanocrystals are mentioned. Lastly, the use of nanocrystals with various spectroscopic applicati...

  6. Biological detector and method

    Energy Technology Data Exchange (ETDEWEB)

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

    2014-04-15

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  7. Biological detector and method

    Energy Technology Data Exchange (ETDEWEB)

    Sillerud, Laurel; Alam, Todd M.; McDowell, Andrew F.

    2015-11-24

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  8. Introducing Aquatic Biology

    OpenAIRE

    Kinne, Otto; Browman, Howard I.; Seaman, Matthias

    2007-01-01

    The Inter-Research Science Center (IR) journals Marine Ecology Progress Series (MEPS) and Aquatic Microbial Ecology (AME) have been receiving increasing numbers of high-quality manuscripts that are principally biological, rather than ecological. With regret, we have had to turn these submissions away. Also, leading limnologists have for many years suggested that IR should provide an outlet for top quality articles on freshwater biology and ecology. Aquatic Biology (...

  9. Biological detector and method

    Science.gov (United States)

    Sillerud, Laurel; Alam, Todd M; McDowell, Andrew F

    2013-02-26

    A biological detector includes a conduit for receiving a fluid containing one or more magnetic nanoparticle-labeled, biological objects to be detected and one or more permanent magnets or electromagnet for establishing a low magnetic field in which the conduit is disposed. A microcoil is disposed proximate the conduit for energization at a frequency that permits detection by NMR spectroscopy of whether the one or more magnetically-labeled biological objects is/are present in the fluid.

  10. Glycobiology Current Molecular Biology

    OpenAIRE

    Sabire KARAÇALI

    2003-01-01

    Carbohydrate chemistry evolved into carbohydrate biochemistry and gradually into the biology of carbohydrates, or glycobiology, at the end of the last century. Glycobiology is the new research area of modern molecular biology, and it investigates the structure, biosynthesis and biological functions of glycans. The numbers, linkage types (a or b), positions, binding points and functional group differences of monosaccharides create microheterogeneity. Thus, numerous glycoforms with precise stru...

  11. Foundations of biology

    OpenAIRE

    Sikorav, Jean-Louis; Braslau, Alan; Goldar, Arach

    2014-01-01

    It is often stated that there are no laws in biology, where everything is contingent and could have been otherwise, being solely the result of historical accidents. Furthermore, the customary introduction of fundamental biological entities such as individual organisms, cells, genes, catalysts and motors remains largely descriptive; constructive approaches involving deductive reasoning appear, in comparison, almost absent. As a consequence, both the logical content and principles of biology ne...

  12. Current research in Radiation Biology and Biochemistry Division

    International Nuclear Information System (INIS)

    The Radiation Biology and Biochemistry Division, Bhabha Atomic Research Centre, Bombay has been engaged in research in the frontier areas of (i) radiation biology related to tumour therapy and injury caused by free radicals; (ii) molecular basis of diseases of physiological origin; (iii) molecular aspects of chemical carcinogenesis and (iv) structure of genome and genome related functions. The gist of research and development activities carried out in the Division during the last two years are documented

  13. Therapy of malignant brain tumors

    International Nuclear Information System (INIS)

    The tumors of the brain claim for a separate position in scientific medicine regarding biology, morphology, features of clinical manifestation, diagnostics and therapy. During the past years due to rapid progress in medical biotechnics the situation of the neuroclinician in front of brain tumors has been dramatically changed. The prerequisites for early and accurate diagnosis as well as for successful treatment also of malignant neoplasms have increased and remarkably improved. At the same time the information necessary for an appropriate pragmatic use of the available cognitive methods and therapeutic means increased along the same scale. These facts necessitate the preparation of publications in which the state of the art is presented in possible completeness, systematic order and proper dis-posability for rational management and therapeutic strategies. The primary aim of the present book is to serve these purposes. With 8 chapters, two of them are indexed for INIS, the collective of competent authors deal on the biology, pathology and immunology of malignant brain tumors of adults and of children including relevant basic and recent data of experimental research; further on the available methods of therapy: neurosurgery, radiology and chemotherapy, the fundamental principals of their efficacy and the differing models of single respective combined application, in comprehensive critical form. 111 figs

  14. Biological aerosol background characterization

    Science.gov (United States)

    Blatny, Janet; Fountain, Augustus W., III

    2011-05-01

    To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

  15. 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.

  16. Proteomic Investigations into Hemodialysis Therapy

    Directory of Open Access Journals (Sweden)

    Mario Bonomini

    2015-12-01

    Full Text Available The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane’s performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane’s bio(incompatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research.

  17. Aroma therapy and medfly SIT

    International Nuclear Information System (INIS)

    A summary of the main findings of the research program on the biological competence of mass-reared, sterile males of the Mediterranean fruit fly (med fly), Ceratitis capitata (Wied.) and the development and implementation of the sterile insect technique (SIT) against this pest is presented. The potential application of aroma therapy to improve the mating success of sterile med fly males is studied. The report assumes a loosely chronological framework as it documents progression along two experimental scales: the number of males simultaneously exposed to ginger root oil, starting with small groups of 25 males and ending with rooms with nearly 200 million males; the experimental arena used to test the effects of aroma therapy, progressing from standard field-cages to large field enclosures to the open field. In addition, brief comments are offered regarding the potential negative effects of GRO exposure, the mechanisms underlying GRO-mediated improvement in male mating success, and the financial costs of GRO aroma therapy. (MAC)

  18. Aroma therapy and medfly SIT

    Energy Technology Data Exchange (ETDEWEB)

    Shelly, Todd E., E-mail: todd.e.shelly@aphis.usda.go [U.S. Department of Agriculture (USDA-APHIS), HI (United States). Animal and Plant Health Inspection

    2006-07-01

    A summary of the main findings of the research program on the biological competence of mass-reared, sterile males of the Mediterranean fruit fly (med fly), Ceratitis capitata (Wied.) and the development and implementation of the sterile insect technique (SIT) against this pest is presented. The potential application of aroma therapy to improve the mating success of sterile med fly males is studied. The report assumes a loosely chronological framework as it documents progression along two experimental scales: the number of males simultaneously exposed to ginger root oil, starting with small groups of 25 males and ending with rooms with nearly 200 million males; the experimental arena used to test the effects of aroma therapy, progressing from standard field-cages to large field enclosures to the open field. In addition, brief comments are offered regarding the potential negative effects of GRO exposure, the mechanisms underlying GRO-mediated improvement in male mating success, and the financial costs of GRO aroma therapy. (MAC)

  19. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  20. Pharmacologic Therapies for Rheumatologic and Autoimmune Conditions.

    Science.gov (United States)

    Bays, Alison M; Gardner, Gregory

    2016-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are commonly prescribed by rheumatologists to reduce disease activity and induce remission in autoimmune conditions such as systemic lupus erythematosus and rheumatoid arthritis. Steroids are sometimes used in combination with DMARD therapy and should be used at the lowest effective dose for the least amount of time. There are many biologic agents available for use for inflammatory arthritis and other autoimmune conditions. Care should be taken when prescribing and managing DMARDS, steroids and biologic agents medications with a careful eye towards screening for infectious disease, vaccination, bone heath and lab monitoring. PMID:27235612

  1. Biological Clocks & Circadian Rhythms

    Science.gov (United States)

    Robertson, Laura; Jones, M. Gail

    2009-01-01

    The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian…

  2. Experimenting with Mathematical Biology

    Science.gov (United States)

    Sanft, Rebecca; Walter, Anne

    2016-01-01

    St. Olaf College recently added a Mathematical Biology concentration to its curriculum. The core course, Mathematics of Biology, was redesigned to include a wet laboratory. The lab classes required students to collect data and implement the essential modeling techniques of formulation, implementation, validation, and analysis. The four labs…

  3. Bioinformatics and School Biology

    Science.gov (United States)

    Dalpech, Roger

    2006-01-01

    The rapidly changing field of bioinformatics is fuelling the need for suitably trained personnel with skills in relevant biological "sub-disciplines" such as proteomics, transcriptomics and metabolomics, etc. But because of the complexity--and sheer weight of data--associated with these new areas of biology, many school teachers feel…

  4. Biological Macromolecule Crystallization Database

    Science.gov (United States)

    SRD 21 Biological Macromolecule Crystallization Database (Web, free access)   The Biological Macromolecule Crystallization Database and NASA Archive for Protein Crystal Growth Data (BMCD) contains the conditions reported for the crystallization of proteins and nucleic acids used in X-ray structure determinations and archives the results of microgravity macromolecule crystallization studies.

  5. Biological pretreatment sewages water

    OpenAIRE

    Veselý, Václav

    2009-01-01

    Bachelor's thesis deals with waste water purification at the stage of pre-inflow of water into the biological waste water treatment plants. It is divided into two parts, a theoretical and calculation. The theoretical part deals about sewage water and the method of biological treatment. Design proposal is part of the activation tank for quantity EO.

  6. Integrated Biological Control

    International Nuclear Information System (INIS)

    Biological control is any activity taken to prevent, limit, clean up, or remediate potential environmental, health and safety, or workplace quality impacts from plants, animals, or microorganisms. At Hanford the principal emphasis of biological control is to prevent the transport of radioactive contamination by biological vectors (plants, animals, or microorganisms), and where necessary, control and clean up resulting contamination. Other aspects of biological control at Hanford include industrial weed control (e.g.; tumbleweeds), noxious weed control (invasive, non-native plant species), and pest control (undesirable animals such as rodents and stinging insects; and microorganisms such as molds that adversely affect the quality of the workplace environment). Biological control activities may be either preventive (apriori) or in response to existing contamination spread (aposteriori). Surveillance activities, including ground, vegetation, flying insect, and other surveys, and apriori control actions, such as herbicide spraying and placing biological barriers, are important in preventing radioactive contamination spread. If surveillance discovers that biological vectors have spread radioactive contamination, aposteriori control measures, such as fixing contamination, followed by cleanup and removal of the contamination to an approved disposal location are typical response functions. In some cases remediation following the contamination cleanup and removal is necessary. Biological control activities for industrial weeds, noxious weeds and pests have similar modes of prevention and response

  7. Biological sample collector

    Science.gov (United States)

    Murphy, Gloria A.

    2010-09-07

    A biological sample collector is adapted to a collect several biological samples in a plurality of filter wells. A biological sample collector may comprise a manifold plate for mounting a filter plate thereon, the filter plate having a plurality of filter wells therein; a hollow slider for engaging and positioning a tube that slides therethrough; and a slide case within which the hollow slider travels to allow the tube to be aligned with a selected filter well of the plurality of filter wells, wherein when the tube is aligned with the selected filter well, the tube is pushed through the hollow slider and into the selected filter well to sealingly engage the selected filter well and to allow the tube to deposit a biological sample onto a filter in the bottom of the selected filter well. The biological sample collector may be portable.

  8. Optics of Biological Particles

    CERN Document Server

    Hoekstra, Alfons; Videen, Gorden

    2007-01-01

    This book covers the optics of single biological particles, both theory and experiment, with emphasis on Elastic Light Scattering and Fluorescence. It deals with the optics of bacteria (bio-aerosols), marine particles (selected phytoplankton communities) and red and white blood cells. Moreover, there are dedicated chapters on a general theory for scattering by a cell, and modelling and simulation of scattering by inhomogeneous biological cells. Finally, one chapter is dedicated to astro-biological signatures, discussing the possibilities for detecting non-terrestrial biological material. The volume has up-to-date discussions on new experimental and numerical techniques, and many examples of applications of these techniques in real-life systems, as used to detect and characterize e.g. biological warfare agents or human blood cells.

  9. Frontiers in mathematical biology

    CERN Document Server

    1994-01-01

    Volume 100, which is the final volume of the LNBM series serves to commemorate the acievements in two decades of this influential collection of books in mathematical biology. The contributions, by the leading mathematical biologists, survey the state of the art in the subject, and offer speculative, philosophical and critical analyses of the key issues confronting the field. The papers address fundamental issues in cell and molecular biology, organismal biology, evolutionary biology, population ecology, community and ecosystem ecology, and applied biology, plus the explicit and implicit mathematical challenges. Cross-cuttting issues involve the problem of variation among units in nonlinear systems, and the related problems of the interactions among phenomena across scales of space, time and organizational complexity.

  10. Psoriatic arthritis treatment: biological response modifiers.

    Science.gov (United States)

    Mease, P J; Antoni, C E

    2005-03-01

    In recent years there has been a surge of interest in the treatment of chronic inflammatory disorders as a result of the development and application of targeted biological therapies. The elucidation of the overlapping cellular and cytokine immunopathology of such diverse conditions as rheumatoid arthritis (RA), Crohn's disease, and psoriasis points to specific targets for bioengineered proteins or small molecules. Similar to clinical trials in RA, trials in psoriatic arthritis (PsA) have shown excellent clinical results with the tumour necrosis factor (TNF) blockers, etanercept, infliximab, and adalimumab in a variety of domains including the joints, quality of life, function, and slowing of disease progress as evidenced radiologically. In addition, these agents have shown benefit in domains more unique to PsA, such as the skin lesions of psoriasis, enthesitis, and dactylitis, pointing out the similar pathogenesis of the disease in the skin, the tendons, and the synovial membrane. This therapy has been generally safe and well tolerated in clinical trials of PsA. Other logical candidates for targeted therapy in development include other anti-TNF agents, costimulatory blockade agents that affect T cell function, blockers of other cytokines such as interleukin (IL)-1, 6, 12, 15, or 18, and B cell modulatory medicines. Also, it will be useful to learn more about the effects of combining traditional disease modifying drugs and the newer biologicals. PMID:15708944

  11. Hyperbaric oxygen therapy

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/002375.htm Hyperbaric oxygen therapy To use the sharing features on this page, please enable JavaScript. Hyperbaric oxygen therapy uses a special pressure chamber to increase ...

  12. External Radiation Therapy

    Medline Plus

    Full Text Available ... older the treatment that is frequently used is radiation therapy. Gunnar Zagars, M.D.: There are different forms ... prostate. [beeping] Narrator: The more common form of radiation therapy is external beam. A typical treatment takes seven ...

  13. Therapy and Counseling

    Science.gov (United States)

    ... feelings and behavior. Behavior therapy is sometimes called behavior modification therapy. This kind of treatment focuses on changing unwanted or unhealthy behaviors and replacing them with healthy ones. This treatment ...

  14. Genes and Gene Therapy

    Science.gov (United States)

    ... correctly, a child can have a genetic disorder. Gene therapy is an experimental technique that uses genes to ... or prevent disease. The most common form of gene therapy involves inserting a normal gene to replace an ...

  15. Hormone Replacement Therapy

    Science.gov (United States)

    ... before and during menopause, the levels of female hormones can go up and down. This can cause ... hot flashes and vaginal dryness. Some women take hormone replacement therapy (HRT), also called menopausal hormone therapy, ...

  16. Virtual particle therapy centre

    CERN Multimedia

    2015-01-01

    Particle therapy is an advanced technique of cancer radiation therapy, using protons or other ions to target the cancerous mass. This advanced technique requires a multi-disciplinary team working in a specialised centre. 3D animation: Nymus3D

  17. Laser therapy for cancer

    Science.gov (United States)

    Laser therapy uses a very narrow, focused beam of light to shrink or destroy cancer cells. It ... to cut out tumors without damaging other tissue. Laser therapy is often given through a thin, lighted ...

  18. Role of biologics in intractable urticaria

    Directory of Open Access Journals (Sweden)

    Cooke A

    2015-04-01

    Full Text Available Andrew Cooke,1 Adeeb Bulkhi,1,2 Thomas B Casale1 1Department of Internal Medicine, Division of Allergy and Immunology, University of South Florida, Tampa, FL, USA; 2Department of Internal Medicine, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia Abstract: Chronic urticaria (CU is a common condition faced by many clinicians. CU has been estimated to affect approximately 0.5%–1% of the population, with nearly 20% of sufferers remaining symptomatic 20 years after onset. Antihistamines are the first-line therapy for CU. Unfortunately, nearly half of these patients will fail this first-line therapy and require other medication, including immune response modifiers or biologics. Recent advances in our understanding of urticarial disorders have led to more targeted therapeutic options for CU and other urticarial diseases. The specific biologic agents most investigated for antihistamine-refractory CU are omalizumab, rituximab, and intravenous immunoglobulin (IVIG. Of these, the anti-IgE monoclonal antibody omalizumab is the best studied, and has recently been approved for the management of CU. Other agents, such as interleukin-1 inhibitors, have proved beneficial for Schnitzler syndrome and cryopyrin-associated periodic syndromes (CAPS, diseases associated with urticaria. This review summarizes the relevant data regarding the efficacy of biologics in antihistamine-refractory CU. Keywords: chronic urticaria, omalizumab, intravenous immunoglobulin, anakinra, canakinumab

  19. Medical Art Therapy

    OpenAIRE

    Aydın, Birgül

    2012-01-01

    Art therapy is a form of expressive therapy that uses art materials. Art therapy combines traditional psychotherapeutic theories and techniques with an understanding of the psychological aspects of the creative process, especially the affective properties of the different art materials. Medical art therapy has been defined as the clinical application of art expression and imagery with individuals who are physically ill, experiencing physical trauma or undergoing invasive or aggressive medical...

  20. Applications of dynamical systems in biology and medicine

    CERN Document Server

    Radunskaya, Ami

    2015-01-01

    This volume highlights problems from a range of biological and medical applications that can be interpreted as questions about system behavior or control.  Topics include drug resistance in cancer and malaria, biological fluid dynamics, auto-regulation in the kidney, anti-coagulation therapy, evolutionary diversification and photo-transduction.  Mathematical techniques used to describe and investigate these biological and medical problems include ordinary, partial and stochastic differentiation equations, hybrid discrete-continuous approaches, as well as 2 and 3D numerical simulation. .