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Sample records for biological therapy

  1. Biological therapies for spondyloarthritis

    OpenAIRE

    Bruner, Vincenzo; Atteno, Mariangela; Spanò, Angelo; Scarpa, Raffaele; Peluso, Rosario

    2014-01-01

    Biological therapies and new imaging techniques have changed the therapeutic and diagnostic approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α (TNFα) inhibitor treatment is currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) has failed. TNFα inhibitor treatment is more effective in preventing articular damage in peripheral joints than in axial ones. It is important to tr...

  2. 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.

  3. Biological therapy and dentistry

    Science.gov (United States)

    Radfar, Lida; Ahmadabadi, Roshanak E; Masood, Farah; Scofield, R Hal

    2016-01-01

    In recent years, a new class of drugs has revolutionized the treatment of autoimmune, allergic, infectious and many more diseases. These drugs are classified into three groups, cytokines, monoclonal antibodies and fusion proteins. Biological drugs have less side effects compared to conventional drugs, and may target special damaged cells, but not all the cells. There may be side effects such as infection, hypersensitivity, hematological disorders, cancer, hepatotoxicity and neurological disorders, but there is not enough evidence or long term studies of the mechanism of action and side effects of these drugs. Patients on biological therapy may need some special consideration in dentistry. This paper is a review regarding the classification, mechanism of action and side effects of these drugs, and dental consideration for patients on biological therapy. PMID:26372436

  4. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  5. Cardiovascular toxicities of biological therapies

    DEFF Research Database (Denmark)

    Ryberg, Marianne

    2013-01-01

    The development of biological therapy is based on growing knowledge regarding the molecular changes required in cells for the development and progression of cancer to occur. Molecular targeted therapy is designed to inhibit the major molecular pathways identified as essential for a specific...

  6. 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.

  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. 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.

  9. Book review: Safety of Biologics Therapy

    Directory of Open Access Journals (Sweden)

    Robak T

    2017-01-01

    Full Text Available Tadeusz Robak Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, PolandSafety of Biologics Therapy: Monoclonal Antibodies, Cytokines, Fusion Proteins, Hormones, Enzymes, Coagulation Proteins, Vaccines, Botulinum Toxins (Cham, Switzerland: Springer International Publishing; 2016 by Brian A Baldo from the Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, and the Department of Medicine, University of Sydney, Australia, is a book that belongs on the shelf of everyone in the field of biologic therapies research and clinical practice. In writing this book, the author’s intention was to produce an up-to-date text book on approved biologic therapies, as far as that is possible in this time of rapidly evolving developments in biotherapeutic research and the introduction of new and novel agents for clinical use.The monograph comprises 610 pages in 13 chapters, each including a summary and further reading suggestions. All chapters include a discussion of basic and clinical material. Well-designed, comprehensive tables and color figures are present throughout the book. The book itself examines the biologic products that have regulatory approval in the USA and/or European Union and that show every indication of remaining important therapies. It covers in great detail all the latest work on peptide hormones and enzymes, monoclonal antibodies, fusion proteins, and cytokine therapies. Beyond that, it also presents the latest information on blood coagulation proteins, vaccines, botulinum neurotoxins, and biosimilars. 

  10. The Use of Biologic Therapies in Uveitis.

    Science.gov (United States)

    Schwartzman, Sergio; Schwartzman, Monica

    2015-12-01

    Therapy for autoimmune ophthalmic disease is currently evolving. The improved understanding of the abnormal immune response in the various forms of uveitis has resulted in targeted therapy. The aberrations of the immune system have been characterized by atypical cell populations, cytokine expression, and cell-cell interactions. Different patterns of cytokine expression have now been delineated in the abnormal uveal tract with exaggerated and/or abnormal expression of TNF, IL-1, IL-2, IL-6, and IL-17. The development of therapies for other conditions in which these cytokines play an important role has resulted in the availability of biological agents that have been adopted for use in the therapy for uveitis. Adalimumab and infliximab have been the best studied anti-TNF agents and indeed have now been recommended by an expert panel as first-line treatment of ocular manifestations of Behçet's disease and second-line treatment for other forms of uveitis (Levy-Clarke et al. (Ophthalmology, 2013). Other anti-TNF agents have been studied as well. Daclizumab, a monoclonal antibody directed against the IL-2 receptor, has also demonstrated utility in treating uveitis as have some of the anti-IL1 agents. Gevokizumab has been granted orphan drug designation for the treatment of resistant forms of uveitis. Therapies affecting IL-6, including tocilizumab are being studied, and available medications that block antigen presenting cell and T cell interaction such as abatacept have been reported to be effective in uveitis. Interferons as well as rituximab have also been evaluated in small studies. Although these biologic therapies have provided a larger armamentarium to treat uveitis, challenges remain. Uveitis is not a single illness; rather, it is a manifestation of many potential systemic diseases that may have very specific individual therapeutic targets. Identifying and characterizing these underlying diseases is not always achieved, and more importantly, the most effective

  11. 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.

  12. Biologic therapies for chronic inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    M. P. Martínez-Montiel

    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.

  13. Biologic Therapy in Psoriasis: Safety Profile.

    Science.gov (United States)

    Campanati, Anna; Ganzetti, Giulia; Giuliodori, K; Molinelli, Elisa; Offidani, A

    2016-01-01

    This review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis.

  14. Biologic therapy in inflammatory bowel disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    In luminal Crohn's disease with moderate to severe inflammatory activity, infliximab and adalimumab can be used in the case of treatment failure with conventional therapies, such as systemic steroids and immunosuppressive therapy or if this treatment is not tolerated. Further treatment strategy d...

  15. Biologic therapy in inflammatory bowel disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    In luminal Crohn's disease with moderate to severe inflammatory activity, infliximab and adalimumab can be used in the case of treatment failure with conventional therapies, such as systemic steroids and immunosuppressive therapy or if this treatment is not tolerated. Further treatment strategy...... 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...

  16. Metastasis in renal cell carcinoma: Biology and implications for therapy

    Directory of Open Access Journals (Sweden)

    Jun Gong

    2016-10-01

    Full Text Available Although multiple advances have been made in systemic therapy for renal cell carcinoma (RCC, metastatic RCC remains incurable. In the current review, we focus on the underlying biology of RCC and plausible mechanisms of metastasis. We further outline evolving strategies to combat metastasis through adjuvant therapy. Finally, we discuss clinical patterns of metastasis in RCC and how distinct systemic therapy approaches may be considered based on the anatomic location of metastasis.

  17. 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.

  18. Gene engineering biological therapy for juvenile arthritis

    Directory of Open Access Journals (Sweden)

    Kh Mikhel's

    2011-01-01

    However, GEBA therapy cannot completely cure the disease as before despite the progress achieved. GEBAs have potentially a number of serious side effects, among which there are severe infections and there is a risk of developing malignancies and autoimmune processes. Their administration requires careful monitoring to reveal the early development of serious adverse reactions, thus preventing a poor outcome.

  19. Principles of biological therapy in psoriasis.

    Science.gov (United States)

    Caca Biljanovska, N; V'lckova Laskoska, M

    2013-01-01

    Psoriasis is a chronic, systemic T-cell mediated autoimmune skin disease, potentially associated with arthritis. The new understanding of immunopathogenesis and inflammatory cytokine pathways was actually the rationale for developing and introducing biological drugs in the treatment of moderate to severe psoriasis and psoriatic arthritis. Different from the traditional systemic drugs that impact the entire immune system, bio-logics target only specific points of the immune system. This review focuses on five biologics which target either T-cells (alefacept) or TNF-alpha (etanercept, adalimumab and infliximab) or interleukin IL-12/IL-23 (ustekinumab)--their efficacy, safety, patient monitoring and recommended dosage. The purpose of the treatment guidelines presented here is to provide a high standard of continuing care of psoriasis and psoriatic arthritis patients.

  20. Synthetic biology: applying biological circuits beyond novel therapies.

    Science.gov (United States)

    Dobrin, Anton; Saxena, Pratik; Fussenegger, Martin

    2016-04-18

    Synthetic biology, an engineering, circuit-driven approach to biology, has developed whole new classes of therapeutics. Unfortunately, these advances have thus far been undercapitalized upon by basic researchers. As discussed herein, using synthetic circuits, one can undertake exhaustive investigations of the endogenous circuitry found in nature, develop novel detectors and better temporally and spatially controlled inducers. One could detect changes in DNA, RNA, protein or even transient signaling events, in cell-based systems, in live mice, and in humans. Synthetic biology has also developed inducible systems that can be induced chemically, optically or using radio waves. This induction has been re-wired to lead to changes in gene expression, RNA stability and splicing, protein stability and splicing, and signaling via endogenous pathways. Beyond simple detectors and inducible systems, one can combine these modalities and develop novel signal integration circuits that can react to a very precise pre-programmed set of conditions or even to multiple sets of precise conditions. In this review, we highlight some tools that were developed in which these circuits were combined such that the detection of a particular event automatically triggered a specific output. Furthermore, using novel circuit-design strategies, circuits have been developed that can integrate multiple inputs together in Boolean logic gates composed of up to 6 inputs. We highlight the tools available and what has been developed thus far, and highlight how some clinical tools can be very useful in basic science. Most of the systems that are presented can be integrated together; and the possibilities far exceed the number of currently developed strategies.

  1. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  2. Biologicals and Fetal Cell Therapy for Wound and Scar Management

    OpenAIRE

    Hirt-Burri, Nathalie; Ramelet, Albert-Adrien; Raffoul, Wassim; de Buys Roessingh, Anthony; Scaletta, Corinne; Pioletti, Dominique; Applegate, Lee Ann

    2011-01-01

    Few biopharmaceutical preparations developed from biologicals are available for tissue regeneration and scar management. When developing biological treatments with cellular therapy, selection of cell types and establishment of consistent cell banks are crucial steps in whole-cell bioprocessing. Various cell types have been used in treatment of wounds to reduce scar to date including autolog and allogenic skin cells, platelets, placenta, and amniotic extracts. Experience with fetal cells show ...

  3. Photodynamic therapy (PDT) as a biological modifier

    Science.gov (United States)

    Obochi, Modestus; Tao, Jing-Song; Hunt, David W. C.; Levy, Julia G.

    1996-04-01

    The capacity of photosensitizers and light to ablate cancerous tissues and unwanted neovasculature constitutes the classical application of photodynamic therapy (PDT). Cell death results from either necrotic or apoptotic processes. The use of photosensitizers and light at doses which do not cause death has been found to affect changes in certain cell populations which profoundly effect their expression of cell surface molecules and secretion of cytokines, thereby altering the functional attributes of the treated cells. Cells of the immune system and the skin may be sensitive to modulation by 'sub-lethal PDT.' Ongoing studies have been conducted to assess, at the molecular level, changes in both lymphocytes and epidermal cells (EC) caused by treatment with low levels of benzoporphyrin derivative monoacid ring A (BPD) (a photosensitizer currently in clinical trials for cancer, psoriasis, endometriosis and age-related macular degeneration) and light. Treatment of skin with BPD and light, at levels which significantly enhanced the length of murine skin allograft acceptance, have been found to down-regulate the expression of Langerhans cell (LC) surface antigen molecules [major histocompatibility complex (MHC) class II and intracellular adhesion molecule (ICAM)-1] and the formation of some cytokines (tumor necrosis factor-alpha (TNF- (alpha) ).

  4. 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.

  5.  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.

  6. Reactivation of latent viruses after treatment with biological therapies

    Directory of Open Access Journals (Sweden)

    Asthana AK

    2014-06-01

    Full Text Available Anil Kumar Asthana,1 John Samuel Lubel2,31Department of Gastroenterology, The Alfred Hospital, Melbourne, 2Department of Gastroenterology and Hepatology, Eastern Health, 3Eastern Health Clinical School, Monash University, Melbourne, VIC, AustraliaAbstract: Biological therapies are used extensively for malignant (eg, lymphoma and autoimmune (eg, rheumatoid arthritis conditions. These agents include anti-tumor necrosis factor antagonists, such as infliximab, and B-cell-depleting therapies, such as rituximab. In the past decade, there has been an explosion in the types and numbers of agents being used. One of the known risks with these agents is infection. In particular, there is increasing awareness regarding latent virus reactivation. This occurs when a latent virus is reactivated into its active replicative phase as a result of an internal or external trigger, such as immunosuppression. It is challenging, however, to quantitatively attribute the risk of reactivation to biological therapy alone because the underlying malignant or autoimmune condition could also be a contributing factor. There is well documented evidence regarding the reactivation of viruses such as hepatitis B virus and cytomegalovirus with drugs such as rituximab. Long-term data are lacking; such data are essential to guide risk stratification and chemoprophylaxis. Universally accepted viral screening guidelines prior to commencement of immunosuppression are lacking. As an example, the US Centers for Disease Control and Prevention have published recommendations regarding hepatitis B virus screening prior to commencing immunosuppression, but this action has not translated into universally accepted guidelines. Some of the other relevant viruses involved include cytomegalovirus, hepatitis C virus, varicella zoster virus, Epstein–Barr virus, and other members of the herpes family. This article reviews the current literature on the risk of latent viral reactivation with biological

  7. Biological therapies in moderate and severe psoriasis: perspectives and certainties.

    Science.gov (United States)

    Constantin, M M; Poenaru, E; Constantin, T; Poenaru, C; Purcarea, V L; Mateescu, B R

    2014-01-01

    An inflammatory, proliferative condition with chronic evolution and systemic response, psoriasis, is positioned today among the most common inflammatory skin diseases affecting the Caucasian population worldwide. With a significant incidence, psoriasis has been increasingly defined as a disease with a major impact on the patient's life and the society to which he/she belongs. This paper conducts an analysis of the currently available therapies for the treatment of moderate and severe psoriasis, therapies with biological agents obtained through sophisticated genetic engineering technologies. Recent research and the increasing interest in therapeutic methods as complete and efficient as possible make us optimistic and confident in the future.

  8. 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

  9. [Special features of biological drug therapy in children].

    Science.gov (United States)

    Aalto, Kristiina; Leinonen, Sanna; Kolho, Kaija-Leena; Lahdenne, Pekka

    2016-01-01

    Several new biological drugs, of which TNFα blockers are being used most extensively, have in recent years been adopted for the treatment of pediatric inflammatory diseases such as juvenile arthritis and associated chronic iritis, and inflammatory bowel diseases. In special situations the children will be prescribed off-label also other drugs affecting cytokines, e.g. IL-1 and IL-6 blockers. Tailoring of the treatment is possible today with the help of drug level measurements and anti-drug antibody determinations. Severe safety hazards associated with biological drug therapy in children are very rare.

  10. Plasmonic Photothermal Therapy in Third and Fourth Biological Windows

    CERN Document Server

    Onal, E Doruk

    2016-01-01

    The recently reported 3rd and 4th biological transparency windows located respectively at 1.6-1.9um and 2.1-2.3um promise deeper tissue penetration and reduced collateral photodamage, yet they haven't been utilized in photothermal therapy applications. Nanoparticle based plasmonic photothermal therapy poses a nontrivial optimization problem in which the light absorption efficiency of the nanoparticle has to be maximized subject to various constraints that are imposed by application environment. Upscaling the typical absorber-dominant nanoparticle designs (rod, sphere etc.) that operate in the 1st and 2nd transparency windows is not a viable option as their size gets prohibitively large for cell intrusion and they become scatterer-dominant. The present study addresses this issue and suggests a versatile approach for designing both lithography based and self-assembling absorber dominant nanostructures for the new transparency windows, while keeping their size relatively small. The proposed nanoparticles demonst...

  11. 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.

  12. Biological Therapies for Atrial Fibrillation: Ready for Prime Time?

    Science.gov (United States)

    Donahue, J Kevin

    2016-01-01

    Atrial fibrillation is a prominent cause of morbidity and mortality in developed countries. Treatment strategies center on controlling atrial rhythm or ventricular rate. The need for anticoagulation is an independent decision from the rate versus rhythm control debate. This review discusses novel biological strategies that have potential utility in the management of atrial fibrillation. Rate controlling strategies predominately rely on G-protein gene transfer to enhance cholinergic or suppress adrenergic signaling pathways in the atrioventricular node. Calcium channel blocking gene therapy and fibrosis enhancing cell therapy have also been reported. Rhythm controlling strategies focus on disrupting reentry by enhancing conduction or suppressing repolarization. Efforts to suppress inflammation and apoptosis are also under study. Resistance to blood clot formation has been shown with thrombomodulin. These strategies are in various stages of preclinical development.

  13. 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.

  14. Biology, prognosis, and therapy of Waldenström Macroglobulinemia.

    Science.gov (United States)

    Castillo, Jorge J; Ghobrial, Irene M; Treon, Steven P

    2015-01-01

    Waldenström Macroglobulinemia (WM) is a rare B-cell lymphoma characterized by the uncontrolled accumulation of malignant lymphoplasmacytic cells, mainly in the bone marrow, and monoclonal IgM production. Despite its rarity, our understanding of the biology of this disease has improved significantly in recent years with the identification of recurrent mutations in the MYD88 and CXCR4 genes. Based on the diversity of clinical features observed in WM patients, therapy should be highly personalized having into account several factors such as age, co-morbidities, IgM levels, and presence of hyperviscosity, coagulopathy, cryoglobulinemia, or cold agglutinin disease. In this chapter, we review the recent advances in the biology of WM and the current therapeutic options for untreated and relapsed WM patients. Finally, we discuss the role of prognostic factors and current evidence supporting an improvement in the survival of WM patients in the last decade.

  15. Biological therapy for dermatological manifestations of inflammatory bowel disease.

    Science.gov (United States)

    Zippi, Maddalena; Pica, Roberta; De Nitto, Daniela; Paoluzi, Paolo

    2013-05-16

    Ulcerative colitis and Crohn's disease are the two forms of inflammatory bowel disease (IBD). The advent of biological drugs has significantly changed the management of these conditions. Skin manifestations are not uncommon in IBD. Among the reactive lesions (immune-mediated extraintestinal manifestations), erythema nodosum (EN) and pyoderma gangrenosum (PG) are the two major cutaneous ills associated with IBD, while psoriasis is the dermatological comorbidity disease observed more often. In particular, in the last few years, anti-tumor necrosis factor (TNF)-α agents have been successfully used to treat psoriasis, especially these kinds of lesions that may occur during the treatment with biological therapies. The entity of the paradoxical manifestations has been relatively under reported as most lesions are limited and a causal relationship with the treatment is often poorly understood. The reason for this apparent side-effect of the therapy still remains unclear. Although side effects may occur, their clinical benefits are undoubted. This article reviews the therapeutic effects of the two most widely used anti-TNF-α molecules, infliximab (a fusion protein dimer of the human TNF-α receptor) and adalimumab (a fully human monoclonal antibody to TNF-α), for the treatment of the major cutaneous manifestations associated with IBD (EN, PG and psoriasis).

  16. Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics.

    Science.gov (United States)

    Moghadam-Kia, Siamak; Oddis, Chester V; Aggarwal, Rohit

    2017-02-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies including biologics that target various pathways involved in the pathogenesis of IIMs. In a large clinical trial of rituximab in adult and juvenile myositis, the primary outcome was not met, but the definition of improvement was met by most of this refractory group of myositis patients. Rituximab use was also associated with a significant glucocorticoid-sparing effect. Intravenous immune globulin (IVIg) can be used for refractory IIMs or those with severe dysphagia or concomitant infections. Anti-tumor necrosis factor (anti-TNF) utility in IIMs is generally limited by previous negative studies along with recent reports suggesting their potential for inducing myositis. Further research is required to assess the role of new therapies such as tocilizumab (anti-IL6), ACTH gel, sifalimumab (anti-IFNα), and abatacept (inhibition of T cell co-stimulation) given their biological plausibility and encouraging small case series results. Other potential novel therapies include alemtuzumab (a humanized monoclonal antibody which binds CD52 on B and T lymphocytes), fingolimod (a sphingosine 1-phosphate receptor modulator that traps T lymphocytes in the lymphoid organs), eculizumab, and basiliximab. The future investigations in IIMs will depend on well-designed controlled clinical trials using validated consensus core set measures and improvements in myositis classification schemes based on serologic and histopathologic features.

  17. Basics of particle therapy II biologic and dosimetric aspects of clinical hadron therapy.

    Science.gov (United States)

    Rong, Yi; Welsh, James

    2010-12-01

    Besides photons and electrons, high-energy particles like protons, neutrons, ⁴He ions or heavier ions (C, Ne, etc) have been finding increasing applications in the treatment of radioresistant tumors and tumors located near critical structures. The main difference between photons and hadrons is their different biologic effect and depth-dose distribution. Generally speaking, protons are superior in dosimetric aspects whereas neutrons have advantages in biologic effectiveness because of the high linear energy transfer. In 1946 Robert Wilson first published the physical advantages in dose distribution of ion particles for cancer therapy. Since that time hadronic radiotherapy has been intensively studied in physics laboratories worldwide and clinical application have gradually come to fruition. Hadron therapy was made possible by the advances in accelerator technology, which increases the particles' energy high enough to place them at any depth within the patient's body. As a follow-up to the previous article Introduction to Hadrons, this review discusses certain biologic and dosimetric aspects of using protons, neutrons, and heavy charged particles for radiation therapy.

  18. Biological therapy induces expression changes in Notch pathway in psoriasis.

    Science.gov (United States)

    Skarmoutsou, Evangelia; Trovato, Chiara; Granata, Mariagrazia; Rossi, Giulio A; Mosca, Ambra; Longo, Valentina; Gangemi, Pietro; Pettinato, Maurizio; D'Amico, Fabio; Mazzarino, Maria Clorinda

    2015-12-01

    Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.

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

    Directory of Open Access Journals (Sweden)

    G. R. Akhunova

    2013-01-01

    Full Text Available 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 therapy was evaluated 24 weeks after therapy.Results. In 15.2 % of patients with AS were diagnosed thyroid gland disorders. The level of anti-thyroid antibodies, thyroid stimulating hormone (thyroid function were correlated with active AS (index BASDAI, and the level of anti-thyroid antibodies were correlated with Creactive protein and erythrocyte sedimentation rate, the intensity of pain in the joints, number of swollen joints and inflamed enthesis.Therapy with non-steroidal anti-inflammatory drug is not provided significant effect on the structural and functional state of the thyroidgland, contributing to a downward trend in the level of antibodies to thyroid peroxidase. Treatment with Infliximab reduced the levels ofantibodies to thyroid peroxidase, thyroid stimulating hormone. This treatment was more effective in improving the structural and functionalstate of the thyroid gland.Conclusions. Against the background of the therapy in patients with AS is marked improvement in thyroid function, reduction of antithyroid antibodies, accompanied by a decrease in activity and improvement of clinical and laboratory parameters of AS.

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

    Directory of Open Access Journals (Sweden)

    G. R. Akhunova

    2014-07-01

    Full Text Available 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 therapy was evaluated 24 weeks after therapy.Results. In 15.2 % of patients with AS were diagnosed thyroid gland disorders. The level of anti-thyroid antibodies, thyroid stimulating hormone (thyroid function were correlated with active AS (index BASDAI, and the level of anti-thyroid antibodies were correlated with Creactive protein and erythrocyte sedimentation rate, the intensity of pain in the joints, number of swollen joints and inflamed enthesis.Therapy with non-steroidal anti-inflammatory drug is not provided significant effect on the structural and functional state of the thyroidgland, contributing to a downward trend in the level of antibodies to thyroid peroxidase. Treatment with Infliximab reduced the levels ofantibodies to thyroid peroxidase, thyroid stimulating hormone. This treatment was more effective in improving the structural and functionalstate of the thyroid gland.Conclusions. Against the background of the therapy in patients with AS is marked improvement in thyroid function, reduction of antithyroid antibodies, accompanied by a decrease in activity and improvement of clinical and laboratory parameters of AS.

  1. 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.

  2. Stem cells - biological update and cell therapy progress.

    Science.gov (United States)

    Girlovanu, Mihai; Susman, Sergiu; Soritau, Olga; Rus-Ciuca, Dan; Melincovici, Carmen; Constantin, Anne-Marie; Mihu, Carmen Mihaela

    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 to prevent teratoma formation or the ethical and religious issues regarding especially the embryonic stem cell research. The direct differentiation of stem cells into specialized cells: cardiac myocytes, neural cells, pancreatic islets cells, may represent an option in treating incurable diseases such as: neurodegenerative diseases, type I diabetes, hematologic or cardiac diseases. Nevertheless, stem cell-based therapies, based on stem cell transplantation, remain mainly at the experimental stages and their major limitation is the development of teratoma and cancer after transplantation. The induced pluripotent stem cells (hiPSCs) represent a prime candidate for future cell therapy research because of their significant self-renewal and differentiation potential and the lack of ethical issues. This article presents an overview of the biological advances in the study of stem cells and the current progress made in the field of regenerative medicine.

  3. The Changing Landscape of Breast Cancer: How Biology Drives Therapy

    Directory of Open Access Journals (Sweden)

    Sarah Friend

    2016-01-01

    Full Text Available Breast cancer is the most prevalent life-threatening cancer in women. Optimizing therapy to increase cure rates in early stage disease, and improving life expectancy and palliation for advanced stages, are goals driving major areas of research. The armamentarium of targeted treatments for breast cancer is ever expanding as understanding of breast cancer biology deepens. A revolution in our treatment was heralded a decade ago by the introduction of trastuzumab for human epidermal receptor-2 positive (HER2+ disease resulting in remarkable reductions in recurrence and improvements in overall survival (OS. Advances continue to be made in other breast cancer subtypes targeting key activating pathways for therapeutic development. However, for these other targeted agents, improvement in OS has been elusive. This article focuses on the development of targeted therapy in breast cancer focusing primarily on the last 5 years, to illustrate that as we understand the complex pathways allowing the dysregulated cell to become malignant, it also propels us closer towards the promise of precision and personalized medicine.

  4. A short history of biological therapy for psoriatic arthritis.

    Science.gov (United States)

    Mease, Philip

    2015-01-01

    Psoriatic arthritis (PsA) is an inflammatory disease characterised by the clinical domains of arthritis, enthesitis, dactylitis, spondylitis, and psoriasis, often causing significant functional disability, loss of quality of life, and premature mortality. Prior to the introduction of targeted biologic medications, such as TNF inhibitors, the capacity to control disease activity was limited, with only modest effects noted in most patients with traditional oral medications such as methotrexate and sulfasalazine. The introduction of TNF inhibitors substantially changed the outlook of PsA patients, yielding significant response in all relevant clinical domains and demonstrating the capacity to inhibit progressive structural damage of joints. However, not all patients responded to these agents and many patients displayed initial response which waned over time, partly due to immunogenicity (development of antibodies which blocked full therapeutic effect of the biologic protein), or because of poor tolerability and/or adverse events. Thus, it has been important to develop new medicines which target other key cytokines and immunologic pathways, including ustekinumab which inhibits both IL12 and IL23 and thus is felt to work in both the TH1 and TH7 pathways of inflammation, has been approved for the treatment of PsA as well as psoriasis. IL17 inhibitors, including secukinumab and ixekizumab have demonstrated significant effectiveness in psoriasis and PsA; abatacept, which modulates T cell activity via inhibition the second signal of T cell activation is under study. This article provides an historical overview of this revolution; details of specific biological therapies will be provided in adjacent articles in this supplement.

  5. Low cost biological lung volume reduction therapy for advanced emphysema

    Directory of Open Access Journals (Sweden)

    Bakeer M

    2016-08-01

    Full Text Available Mostafa Bakeer,1 Taha Taha Abdelgawad,1 Raed El-Metwaly,1 Ahmed El-Morsi,1 Mohammad Khairy El-Badrawy,1 Solafa El-Sharawy2 1Chest Medicine Department, 2Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt Background: Bronchoscopic lung volume reduction (BLVR, using biological agents, is one of the new alternatives to lung volume reduction surgery.Objectives: To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue.Methods: Enrolled patients were divided into two groups: group A (seven patients in which autologous blood was used and group B (eight patients in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications.Results: In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted (P-value: <0.001 and 0.038, respectively. In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted (P-value: 0.005 and 0.004, respectively. All patients tolerated the procedure with no mortality.Conclusion: BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. Keywords: BLVR, bronchoscopy, COPD, interventional pulmonology

  6. Biologic therapy with or without topical treatment in psoriasis: what does the current evidence say?

    Science.gov (United States)

    Jensen, J Daniel; Delcambre, Macey Renault; Nguyen, Gloria; Sami, Naveed

    2014-10-01

    Biologic therapy represents a relatively new class of drugs which have revolutionized the treatment of psoriasis and are used with increasing frequency in order to control this chronic, systemic inflammatory disease. However, it is unclear what role there is for combination therapy of biologics with traditional topical agents. The purpose of this article is to assess the literature on the role of topical agents as adjuvants to biological treatments in the treatment of psoriasis and identify areas for further research. A MEDLINE search was performed in order to identify English-language publications from 1996 to 2014 examining combination biologic therapy with topical medications in the treatment of psoriasis. Data from these clinical studies are summarized and the outcomes are discussed. In general, the addition of adjuvant topical therapy to systemic biologic therapy allowed for a reduction in dosage and side effects of both agents, maintenance of initial response to biologics, treatment of recalcitrant lesions in partial responders, and potential acceleration of response to biologic therapies. The current data, though limited, suggest that using topical therapies as adjunct treatment to biologics is a well tolerated and effective means of controlling psoriasis and improving quality of life for patients. However, the treating physician should remain attentive to signs of adverse events and seek opportunities to reduce the dose or treatment frequency during chronic use.

  7. Inflammatory bowel disease nurse specialists for patients on biological therapies: a nationwide Italian survey

    Science.gov (United States)

    Guarini, Alessandra; Marinis, Francesca De; Kohn, Anna; Orzes, Nicoletta; D’Incà, Renata; Iannone, Teresa; Giaquinto, Antonella; Rivara, Cinzia; Ridola, Lorenzo; Lorenzetti, Roberto; Zullo, Angelo

    2016-01-01

    Background Management of inflammatory bowel disease (IBD) patients requires a multidisciplinary approach. Among the working team, the role of IBD nurse is expected to be particularly relevant when managing patients receiving biological therapies. We performed a survey to assess the presence of IBD nurse in centers where patients were receiving biologics. Methods For this Italian nationwide survey a specific questionnaire was prepared. IBD nurse was defined as a nurse directly involved in all phases of biological therapy, from pre-therapy screening, administration and monitoring during therapy, to follow up performed by a dedicated helpline, completed a specific training on biological therapy therapy, and observed international guidelines. Results A total of 53 Italian IBD centers participated in the survey, and 91 valid questionnaires were collected. Overall, 34 (37.4%) nurses could be classified as IBD specialists. IBD nurses had a significantly higher educational level than other nurses, they were more frequently operating in Central or Southern than in Northern Italy, they were working in an Academic center rather than in a General hospital, and in IBD centers with >25 patients on biological therapy. On the contrary, mean age, gender distribution, years of nursing, and years working in the IBD unit did not significantly differ between IBD and other nurses. Conclusions Our nationwide survey showed that the presence of an IBD nurse is still lacking in the majority of Italian IBD centers where patients receive biological therapies, suggesting a prompt implementation. PMID:27708516

  8. 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

  9. Use of biologic agents in combination with other therapies for the treatment of psoriasis.

    Science.gov (United States)

    Cather, Jennifer C; Crowley, Jeffrey J

    2014-12-01

    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)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.

  10. A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

    Science.gov (United States)

    Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

    In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

  11. Cardiovascular risk factors in high-need psoriasis patients and its implications for biological therapies.

    NARCIS (Netherlands)

    Driessen, R.J.B.; Boezeman, J.B.M.; Kerkhof, P.C.M. van de; Jong, E.M.G.J. de

    2009-01-01

    BACKGROUND: The associations between psoriasis and cardiovascular risk factors are reported to be stronger as psoriasis severity increases. This makes studying cardiovascular risk factors in high-need psoriasis patients, eligible for biological therapy, interesting. OBJECTIVE: To survey the prevalen

  12. Breakthrough disease during interferon-[beta] therapy in MS: No signs of impaired biologic response

    DEFF Research Database (Denmark)

    Hesse, D; Krakauer, M; Lund, H;

    2010-01-01

    Disease activity is highly variable in patients with multiple sclerosis (MS), both untreated and during interferon (IFN)-beta therapy. Breakthrough disease is often regarded as treatment failure; however, apart from neutralizing antibodies (NAbs), no blood biomarkers have been established...... as reliable indicators of treatment response, despite substantial, biologically measurable effects. We studied the biologic response to treatment in a cohort of NAb-negative patients to test whether difference in responsiveness could segregate patients with and without breakthrough disease during therapy....

  13. 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...... simultaneously in therapy....

  14. 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.

  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. Alterations in immune function with biologic therapies for autoimmune disease.

    Science.gov (United States)

    Her, Minyoung; Kavanaugh, Arthur

    2016-01-01

    Autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and others, are characterized by dysregulation of various aspects of normal immunity and inflammation. Biologic agents targeting key components of the dysregulated immune response have dramatically improved patient outcomes and transformed treatment paradigms for a number of systemic inflammatory autoimmune diseases. Despite their excellent efficacy, because they do affect normal immune responsiveness, biologic agents can potentially be associated with a variety of adverse effects. Important potential adverse effects related to the use of biologic agents include immunosuppression, which might result in outcomes such as infection, and autoimmunity, that could result in paradoxical inflammation or even autoimmune disease. In this article the current clinical evidence and immunologic mechanisms of the adverse effects related to biologic agents are discussed.

  17. Biologics: the role of delivery systems in improved therapy

    Directory of Open Access Journals (Sweden)

    Škalko-Basnet N

    2014-03-01

    Full Text Available Nataša Škalko-Basnet Drug Transport and Delivery Research Group, Department of Pharmacy, University of Tromsø, Tromsø, Norway Abstract: The beginning of the 21st century saw numerous protein and peptide therapeuticals both on the market and entering the final stages of clinical studies. They represent a new category of biologically originated drugs termed biologics or biologicals. Their main advantages over conventional drugs can be summarized by their high selectivity and potent therapeutic efficacy coupled with limited side effects. In addition, they exhibit more predictable behavior under in vivo conditions. However, up to now most of the formulations of biologics are designed and destined for the parenteral route of administration. As a consequence, many suffer from short plasma half-lives, resulting in their frequent administration and ultimately poor patient compliance. This review represents an attempt to address some of the challenges and promises in the product development of biologics both for parenteral and noninvasive administration. Some of the products currently in the pipeline of pharmaceutical development and corresponding perspectives are discussed in more detail. Keywords: biologics, drug delivery systems, medical devices

  18. The risk of herpes zoster during biological therapy for psoriasis and other inflammatory conditions.

    Science.gov (United States)

    Adelzadeh, L; Jourabchi, N; Wu, J J

    2014-07-01

    Recent advances in biological therapies have proved highly effective in treating psoriasis and other inflammatory conditions, including psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis. However, adverse effects related to their immunosuppression have been observed, including an increased propensity to viral infections. This review evaluates the evidence of herpes zoster (HZ) risk from biologics based on clinical reports, cohort studies and randomized controlled studies. The risk of HZ associated with these agents remains controversial, especially when comparing their risk with non-biological therapy used to treat the same inflammatory conditions. This review specifically assesses the risk of the TNF inhibitors etanercept, adalimumab and infliximab, as well as interleukin-12/23 inhibitor ustekinumab. We found multiple cohort studies, randomized controlled trials and case reports that suggest infliximab increases risk of HZ, whereas adalimumab, etanercept and ustekinumab HZ risk remain controversial. Nevertheless, HZ vaccination should be considered prior to initiation of biological therapy, particularly infliximab.

  19. Biologic Therapy in Inflammatory Immunomediated Systemic Diseases: Safety Profile.

    Science.gov (United States)

    Moroncini, Gianluca; Albani, Lisa; Nobili, Lorenzo; Gabrielli, Armando

    2016-01-01

    The discovery of some key molecular mechanisms underlying the dysregulation of the immune system responsible for inflammatory systemic diseases as severe as Systemic Lupus Erythematosus (SLE), Systemic Sclerosis (SSc), and Systemic Vasculitides, led to the development and subsequent introduction into clinical practice of biological drugs which are significantly improving the management of such complex disorders. This novel molecular targeted therapeutics represents in fact a valid alternative or complementary treatment to conventional immunosuppressive strategies, characterized by broad, unspecific actions and severe adverse effects. Main advantages of the use of biologic drugs reside in their steroid-sparing effect and in the ability of inducing remission of refractory disease states or curing specific organ involvements. Aim of this article is to review and briefly discuss the scientific evidence supporting the use of biologics in these diseases, with a particular emphasis on their efficacy and safety profile compared to the canonical drugs.

  20. Modern Therapies for Idiopathic Inflammatory Myopathies (IIMs): Role of Biologics

    OpenAIRE

    Moghadam-Kia, Siamak; Oddis, Chester V.; Aggarwal, Rohit

    2017-01-01

    Despite the lack of placebo-controlled trials, glucocorticoids are considered the mainstay of initial treatment for idiopathic inflammatory myopathy (IIMs) and myositis-associated ILD (MA-ILD). Glucocorticoid-sparing agents are often given concomitantly with other immunosuppressive agents, particularly in patients with moderate or severe disease. As treatment of refractory cases of idiopathic inflammatory myopathies has been challenging, there is growing interest in evaluating newer therapies...

  1. Emerging Stem Cell Therapies: Treatment, Safety, and Biology

    Directory of Open Access Journals (Sweden)

    Joel Sng

    2012-01-01

    Full Text Available Stem cells are the fundamental building blocks of life and contribute to the genesis and development of all higher organisms. The discovery of adult stem cells has led to an ongoing revolution of therapeutic and regenerative medicine and the proposal of novel therapies for previously terminal conditions. Hematopoietic stem cell transplantation was the first example of a successful stem cell therapy and is widely utilized for treating various diseases including adult T-cell leukemia-lymphoma and multiple myeloma. The autologous transplantation of mesenchymal stem cells is increasingly employed to catalyze the repair of mesenchymal tissue and others, including the lung and heart, and utilized in treating various conditions such as stroke, multiple sclerosis, and diabetes. There is also increasing interest in the therapeutic potential of other adult stem cells such as neural, mammary, intestinal, inner ear, and testicular stem cells. The discovery of induced pluripotent stem cells has led to an improved understanding of the underlying epigenetic keys of pluripotency and carcinogenesis. More in-depth studies of these epigenetic differences and the physiological changes that they effect will lead to the design of safer and more targeted therapies.

  2. The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Larsen L

    2016-10-01

    Full Text Available Lone Larsen,1 Michael Dam Jensen,2 Michael Due Larsen,3 Rasmus Gaardskær Nielsen,4 Niels Thorsgaard,5 Ida Vind,6 Signe Wildt,7 Jens Kjeldsen8 1Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg,2Department of Internal Medicine, Section of Gastroenterology, Lillebaelt Hospital Vejle, Vejle, 3Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, 4Department of Paediatrics, Hans Christian Andersen Children's Hospital, Odense University Hospital, Odense C, 5Department of Internal Medicine, Section of Gastroenterology, Hospital Unit West, Herning, 6Department of Gastroenterology, Copenhagen University Hospital, Hvidovre, 7Department of Medicine, Section of Gastroenterology, Køge Hospital, Køge, 8Department of Medical Gastroenterology, Odense University Hospital, Odense C, Denmark Aim: The aims of The Danish National Registry for Biological Therapy in Inflammatory Bowel Disease are to ensure that biological therapy and the clinical management of patients with inflammatory bowel disease (IBD receiving biological treatment are in accordance with the national clinical guidelines and, second, the database allows register-based clinical epidemiological research. Study population: The study population comprises all Danish patients with IBD (both children and adults with ulcerative colitis, Crohn's disease, and IBD unclassified who receive biological therapy. Patients will be enrolled consecutively when biological treatment is initiated. Main variables: The variables in the database are: diagnosis, time of diagnosis, disease manifestation, indication for biological therapy, previous biological and nonbiological therapy, date of visit, clinical indices, physician's global assessment, pregnancy and breastfeeding (women, height (children, weight, dosage (current biological agent, adverse events, surgery, endoscopic procedures, and radiology. Descriptive data: Eleven clinical indicators

  3. RNA Systems Biology for Cancer: From Diagnosis to Therapy.

    Science.gov (United States)

    Amirkhah, Raheleh; Farazmand, Ali; Wolkenhauer, Olaf; Schmitz, Ulf

    2016-01-01

    It is due to the advances in high-throughput omics data generation that RNA species have re-entered the focus of biomedical research. International collaborate efforts, like the ENCODE and GENCODE projects, have spawned thousands of previously unknown functional non-coding RNAs (ncRNAs) with various but primarily regulatory roles. Many of these are linked to the emergence and progression of human diseases. In particular, interdisciplinary studies integrating bioinformatics, systems biology, and biotechnological approaches have successfully characterized the role of ncRNAs in different human cancers. These efforts led to the identification of a new tool-kit for cancer diagnosis, monitoring, and treatment, which is now starting to enter and impact on clinical practice. This chapter is to elaborate on the state of the art in RNA systems biology, including a review and perspective on clinical applications toward an integrative RNA systems medicine approach. The focus is on the role of ncRNAs in cancer.

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

    OpenAIRE

    Fakhri, Hamid Reza; Janket, Sok Ja; Jackson, Elizabeth A.; Alison E Baird; 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” ...

  5. 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.

  6. Embryonic stem cells: prospects for developmental biology and cell therapy.

    Science.gov (United States)

    Wobus, Anna M; Boheler, Kenneth R

    2005-04-01

    Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation.

  7. Ozone- A Biological Therapy in Dentistry- Reality or Myth?????

    Science.gov (United States)

    Naik, Saraswathi V; K, Rajeshwari; Kohli, Shivani; Zohabhasan, Sayyad; Bhatia, Shekhar

    2016-01-01

    The usage of ozone in dentistry has been proposed because of its antimicrobial, disinfectant, biocompatibility and healing properties. In the last decade a number of therapeutic protocols with ozone have been developed to address common dental infections associated with periodontal disease, RCT and caries. Despite these advantages, therapeutic ozone's application in dentistry is limited because of its possible side effects. Hence, dental practitioners need to know the proper usage of ozone therapy that can provide better patient care and considerably cut down the time and cost of the treatment.

  8. 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.

  9. 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

  10. 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.

  11. Stem cell biology and cell transplantation therapy in the retina.

    Science.gov (United States)

    Osakada, Fumitaka; Hirami, Yasuhiko; Takahashi, Masayo

    2010-01-01

    Embryonic stem (ES) cells, which are derived from the inner cell mass of mammalian blastocyst stage embryos, have the ability to differentiate into any cell type in the body and to grow indefinitely while maintaining pluripotency. During development, cells undergo progressive and irreversible differentiation into specialized adult cell types. Remarkably, in spite of this restriction in potential, adult somatic cells can be reprogrammed and returned to the naive state of pluripotency found in the early embryo simply by forcing expression of a defined set of transcription factors. These induced pluripotent stem (iPS) cells are molecularly and functionally equivalent to ES cells and provide powerful in vitro models for development, disease, and drug screening, as well as material for cell replacement therapy. Since functional impairment results from cell loss in most central nervous system (CNS) diseases, recovery of lost cells is an important treatment strategy. Although adult neurogenesis occurs in restricted regions, the CNS has poor potential for regeneration to compensate for cell loss. Thus, cell transplantation into damaged or diseased CNS tissues is a promising approach to treating various neurodegenerative disorders. Transplantation of photoreceptors or retinal pigment epithelium cells derived from human ES cells can restore some visual function. Patient-specific iPS cells may lead to customized cell therapy. However, regeneration of retinal function will require a detailed understanding of eye development, visual system circuitry, and retinal degeneration pathology. Here, we review the current progress in retinal regeneration, focusing on the therapeutic potential of pluripotent stem cells.

  12. 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.

  13. Role of conventional therapies in the era of biological treatment in Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Paolo Gionchetti; Fernando Rizzello; Carlo Calabrese; Rosy Tambasco; Ramona Brugnera; Giulia Straforini; Giuseppina Liguori; Giulia Spuri Fornarini; Donatella Riso; Massimo Campieri

    2011-01-01

    Outstanding progress regarding the pathophysiology of Crohn's disease (CD) has led to the development of innovative therapeutic concepts.Numerous controlled trials have been performed in CD.This review concentrates on the results of randomized, placebo-controlled trials, and meta-analyses when available, that provide the highest degree of evidence.Current guidelines on the management of CD recommend a step-up approach to treatment involving the addition of more powerful therapies as the severity of disease and refractoriness to therapy increase.The advent of biological drugs has opened new therapeutic horizons for treating CD, modifying the treatment goals.However, the large majority of patients with CD will be managed through conventional therapy, even if they are a prelude to biological therapy.

  14. In vivo biological response to extracorporeal shockwave therapy in human tendinopathy:Response of tendinopathy to shockwave therapy

    OpenAIRE

    Waugh, Charlotte; Morrissey, Dylan; Jones, Eleanor; Riley, Graham; Langberg, Henning; SCREEN, Hazel

    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....

  15. 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...

  16. Summary of the primer on tumor immunology and the biological therapy of cancer

    OpenAIRE

    Margolin Kim; Liu Shujuan; Li Yufeng; Hwu Patrick

    2009-01-01

    Abstract The International Society for Biological Therapy of Cancer (iSBTc) is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this pro...

  17. 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.

  18. 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.

  19. Combination therapy with leflunomide and genetic engineering biological agents

    Directory of Open Access Journals (Sweden)

    Nataliya Vladimirovna Chichasova

    2011-06-01

    Full Text Available The paper gives data on the use of a combination of genetic engineering biological agents (GEBAs and leflunomide in patients with rheumatoid arthritis (RA. In accordance with the international guidelines, the majority of GEBAs should be given in a combination with methotrexate (MTX, which increases the efficacy of a number of GEBAs (tumor necrosis factor-α inhibitors, rituximab and affects tolerability (remikeid, humira. However, MTX cannot be always used in real practice. The data given in the paper on the efficiency and safety of the coadministration of leflunomide and a GEBA in patients with active RA, which are based on the results of randomized studies and national registers, including the Russian one, point to the compatibility of the results of treatment with this and GEBA-MTX combinations.

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

    OpenAIRE

    Urba Walter J; Hwu Patrick; Balwit James M; Marincola Francesco M

    2011-01-01

    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 ...

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

    Institute of Scientific and Technical Information of China (English)

    WilliamH.D.Hallett; WilliamJ.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.

  2. 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.

  3. Isoniazid toxicity and TB development during biological therapy of patients with psoriasis in Colombia.

    Science.gov (United States)

    Cataño, Juan; Morales, Milena

    2016-10-01

    Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up.

  4. Summary of the primer on tumor immunology and the biological therapy of cancer

    Directory of Open Access Journals (Sweden)

    Margolin Kim

    2009-01-01

    Full Text Available Abstract The International Society for Biological Therapy of Cancer (iSBTc is one of the "premier destinations for interaction and innovation in the cancer biologics community". It provides a primer course each year during the annual meeting to address the most important areas of tumor immunology and immunotherapy. The course has been given by prominent investigators in the area of interest, covering the core principles of cancer immunology and immunotherapy. The target audience for this program includes investigators from academic, regulatory, and biopharmaceutical venues. The program goal is to enable the attendees to learn the current status and the most recent advances in biologic therapies, and to leverage this knowledge towards the improvement of cancer therapy. The 2008 immunologic primer course was held on October 30 at the 23rd Annual meeting of iSBTc in San Diego, CA. Nine internationally renowned investigators gave excellent presentations on different topics. The topics covered in this primer included: (1 cytokines in cancer immunology; (2 anti-angiogenic therapy; (3 end stage: immune killing of tumors; (4 blocking T cell checkpoints; (5 approach to identification and therapeutic exploitation of tumor antigens; (6 T regulatory cells; (7 adoptive T cell therapy; (8 immune monitoring of cancer immunotherapy; and (9 immune adjuvants. We summarized the topics in this primer for public education. The related topic slides and schedule can be accessed online http://www.isbtc.org/meetings/am08/primer08.

  5. 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

  6. Biologic Therapies: From Complexity to Clinical Practice in a Changing Environment

    Directory of Open Access Journals (Sweden)

    Remo Panaccione

    2015-12-01

    Full Text Available This symposium provided an opportunity for global experts to discuss the challenges posed by the introduction of biosimilars. The impact of the manufacturing process on clinical outcomes, maintaining treatment responses over the long term, and issues surrounding patient management in a changing environment were addressed. The symposium was opened by Prof Panaccione describing the evolution of inflammatory bowel disease (IBD treatment in the last 20 years and how biologics have improved outcomes. Prof D’Haens provided an explanation of the complexity surrounding biologic drug development and the hurdles facing drug manufacturers when ensuring high quality and consistently performing products over time. Prof Panaccione discussed the clinical challenges in balancing the transition from induction to maintenance therapy in order to provide a clinically relevant and sustained response to therapy. He also discussed the evidence for long-term outcomes with adalimumab for IBD. Prof Feagan highlighted the issues faced by clinicians treating patients with biologics, including the ability to switch between biologics without loss of efficacy or impact on safety, and the need to consider interchangeability between biologic therapies and the potential risk and impact of immunogenicity.

  7. Mesenchymal Stem Cells as a Biological Drug for Heart Disease: Where Are We With Cardiac Cell-Based Therapy?

    Science.gov (United States)

    Sanina, Cristina; Hare, Joshua M

    2015-07-17

    Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine.

  8. Centralised Biological Therapy Registry for Moderate to Severe Plaque Psoriasis – Overview and Methodology

    Directory of Open Access Journals (Sweden)

    Sutka R

    2016-04-01

    Full Text Available The introduction of new pharmacotherapy entities in the last decade accentuate the necessity to set up treatment guidelines based on real life evidence. Randomized controlled trials remain golden standard of a research. Data derived from studies aiming on daily clinical practice should bring needed, added value. Disease prevalence growth, due to increased life expectancy, better diagnostic procedures and earlier medical intervention, as well as ever growing demand for highly priced, sophistically produced drugs put stress on healthcare budgets even in developed countries. Large databases commonly called - therapy registries are implemented to collect data on therapy effectivity in terms of effectiveness, safety and patient long-term on therapy survival. Registries importance rose together with biological therapies introduction. New in class molecules entered the market conditionally being obliged to provide additional e.g. safety data. Such procedures require involvement of many different professionals, e.g. physicians, professional medical bodies, IT experts, database administrators, statisticians and government institutions. Paper based, followed by computer based forms were distributed among physicians to collect these data. eHealth technologies provide physicians with centralized, more intuitive applications. The particularities of different diagnosis caused great variations within each specific registry launched. Important information was missing since they were pointed out as optional and many were redundant causing frustration among physicians due to inadequate administrative workload. The main objective of this work was to set up the therapy registry standards and procedures. Methodology of „ideal“ moderate to severe plaque psoriasis biology therapy registry development, introduction, administration and evaluation was prepared to assist any government institution or professional body when planning registry deployment. Electronic

  9. Management of infections in rheumatic patients receiving biological therapies. The Portuguese Society of Rheumatology recommendations.

    Directory of Open Access Journals (Sweden)

    Teixeira L

    2016-12-01

    Full Text Available Introduction: Infections are a major cause of morbi dity and mortality in systemic inflammatory rheumatic di - seases and the management of infectious complications in patients under biological therapies deserves parti - cular attention. Objective: Develop evidence-based recommendations for the management of infections in rheumatic patients receiving biological therapies. Methods: A search in PubMed (until 10 November 2014 and EMBASE (until 20 December 2014 databases was performed. Patients with systemic inflammatory rheumatic diseases treated with approved biologics in whom infections occurred were included. Search results were submitted to title and abstract selection, followed by detailed review of suitable studies. Information regarding presentation of the infectious complication, its diagnosis, treatment, and outcome, as well as maintenance or discontinuation of the biological agent was extracted and subsequently pooled according to the type of infection considered. Results of literature review were presented and critically reviewed in a dedi - cated meeting by a multidisciplinary panel. Recommendations were then formulated using the Delphi method. Finally, the level of agreement among rheumatologists was voted using an online survey. Results: Fifteen recommendations were issued. Nine general recommendations concerned the assessment of infectious risk before and while on biologics, the procedures in case of suspected infection and the mana - gement of biologics during infectious complications. Six specific recommendations were developed for respiratory, urinary, gastrointestinal, skin, osteoarticular and disseminated infections. Conclusion: These fifteen recommendations are intended to help rheumatologists in the management of infections in patients on biological therapy. They integrate an extensive literature review, expert opinion and inputs from Portuguese rheumatologists.

  10. Leukemia, an effective model for chemical biology and target therapy1

    Institute of Scientific and Technical Information of China (English)

    Guo-qiang CHEN; Li-shun WANG; Ying-li WU; Yun YU

    2007-01-01

    The rapid rise of chemical biology aimed at studying signaling networks for basic cellular activities using specific, active small molecules as probes has greatly accelerated research on pathological mechanisms and target therapy of diseases.This research is especially important for malignant tumors such as leukemia, a heterogeneous group of hematopoietic malignancies that occurs worldwide. With the use of a chemical approach combined with genetic manipulation, great progresshas been achieved over the past few decades on the biological, molecular and cytogenetic aspects of leukemia, and in its diagnosis and therapy. In particular,discoveries of the clinical effectiveness of all-trans rctinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia and the kinase inhibitorsImatinib and Dasatinib in the treatment of chronic myelogenous leukemia not only make target therapy of leukemia a reality, but also push mechanisms of leukemo-genesis and leukemic cell activities forward. This review will outline advances in chemical biology that help our understanding of the molecular mechanisms of cell differentiation and apoptosis induction and target therapy of leukemia.

  11. Current trends in management of hepatitis B virus reactivation in the biologic therapy era

    Institute of Scientific and Technical Information of China (English)

    Claudio M Mastroianni; Miriam Lichtner; Rita Citton; Cosmo Del Borgo; Angela Rago; Helene Martini; Giuseppe Cimino; Vincenzo Vullo

    2011-01-01

    Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk of HBV reactivation is heightened by the use monoclonal antibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. Emerging data indicate that HBV reactivation could also develop following the use of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is diagnosed, it is mandatory to suspend biologic treatment and start antiviral agents immediately. However, pre-emptive antiviral therapy prior to monoclonal antibody administration is crucial in preventing HBV reactivation and its clinical consequences. Several lines of evidence have shown that risk of HBV reactivation is greatly reduced by the identification of high-risk patients and the use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.

  12. 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...... significantly elevated for four hours post-ESWT (p 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...

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

    OpenAIRE

    CM Waugh; Morrissey, D.; E. Jones; GP Riley; H Langberg; HRC Screen

    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 3...

  14. 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.

  15. 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.

  16. Hormono-biological therapy in metastatic breast cancer: preclinical evidence, clinical studies and future directions.

    Science.gov (United States)

    Tonini, Giuseppe; Schiavon, Gaia; Fratto, Maria Elisabetta; Vincenzi, Bruno; Santini, Daniele

    2008-02-01

    Breast cancer growth is regulated by coordinated actions of the estrogen receptor (ER) and various growth factor receptor signalling pathways. This complex interactive signalling potentially explains some of the reasons behind endocrine therapy action and resistance. Recent research into the molecular biology of ER signalling has revealed new molecular targets which, if present in cancer cells, might be additionally targeted using various signal transduction inhibitors to overcome or prevent resistance to endocrine therapy. The dynamic inverse relationship between the expression of ER and growth factor receptors brings more excitement to the potential of restoring ER expression in apparently ER-negative cells by inhibition of growth factor signalling. The multiple pathways involved in activating ERs also provide a rationale for combining endocrine and non-endocrine therapies that block different signalling pathways. Ongoing clinical trials promise to further improve the present care for breast cancer patients.

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. [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.

  3. 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.

  4. Melatonin as a promising agent of regulating stem cell biology and its application in disease therapy.

    Science.gov (United States)

    Zhang, Shuo; Chen, Simon; Li, Yuan; Liu, Yu

    2017-03-01

    Stem cells have emerged as an important approach to repair and regenerate damaged tissues or organs and show great therapeutic potential in a variety of diseases. However, the low survival of engrafted stem cells still remains a major challenge for stem cell therapy. As a major hormone from the pineal gland, melatonin has been shown to play an important role in regulating the physiological and pathological functions of stem cells, such as promoting proliferation, migration and differentiation. Thus, melatonin combined with stem cell transplantation displayed promising application potential in neurodegenerative diseases, liver cirrhosis, wound healing, myocardial infarction, kidney ischemia injury, osteoporosis, etc. It exerts its physiological and pathological functions through its anti-oxidant, anti-inflammatory, anti-apoptosis and anti-ageing properties. Here, we summarize recent advances on exploring the biological role of melatonin in stem cells, and discuss its potential applications in stem cell-based therapy.

  5. Pollutional haze and COPD: etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.

    Science.gov (United States)

    Wang, Fei; Ni, Song-Shi; Liu, Hua

    2016-01-01

    In recent years, serious pollutional haze occurs in the mainland of China thanks to the development of urbanization and industrialization. There is a close relationship between air pollution and the occurrence and development of chronic obstructive pulmonary disease (COPD), but there are some new characteristics in some aspects of COPD associated with pollutional haze compared with COPD induced by traditional physical and chemical factors. This article attempts to summarize the new progress from these new features of COPD related to pollutional haze, focus on etiology, epidemiology, pathogenesis, pathology, biological markers and therapy.

  6. Safety of biological therapies for psoriasis: effects on reproductive potential and outcomes in male and female patients.

    Science.gov (United States)

    Yiu, Z Z N; Griffiths, C E M; Warren, R B

    2014-09-01

    The effects of biological therapies for psoriasis on pregnancy outcomes and lactation, and male fertility and mutagenicity are common concerns in the clinical setting. There is relatively little evidence to guide the clinician and patient. Here, we review the safety profile of the commonly used biological therapies for psoriasis in individuals of reproductive potential. Safety data were derived from large-scale registries, adverse event reporting databases, clinical trials and case reports. We assessed the effect of each therapy on adverse pregnancy outcomes including congenital malformations, and lactation with maternal administration, and male fertility and potential mutagenicity with paternal administration. We provide applicable guidance to inform clinician and patient before and after conception.

  7. 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. [

  8. 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

  9. Preliminary biological study of SPA residue after therapy and its agricultural us

    Directory of Open Access Journals (Sweden)

    Teresa Kłapeć

    2013-12-01

    Full Text Available Introduction: Spa residue is an undehydrated therapeutic peat, which belongs to the group of peloids, a natural organic material widely used in spa therapy. Once used for therapy, it cannot be reused due to the loss of adsorptive properties. The aim of the study was the biological and parasitological assessment of spa residue to view the chances for fertilization of soils. Material and methods: In this study 80 samples of spa residues, from 7 spa resorts in Poland were investigated for Salmonella bacteria, bacteria of the general and faecal coliform group, anaerobic sulphites-reducing bacteria of Clostridium perfringens type and the eggs of intestinal nematodes (Ascaris, Trichuris and Toxocara. Microbiological and parasitological analyses of the residue were conducted based on the Polish Standards: PN-Z-19000-1/2001, PN-Z-19000- 4/2001, and Microbiological and Parasitological Guidelines for Sanitary Evaluation of Soils, Institute of Rural Health, Lublin 1995. Results: In the investigated samples of the residue neither Salmonella bacteria nor the eggs of intestinal nematodes Ascaris, Trichuris or Toxocara were found. The titres of coliform group bacteria, fecal coli bacteria, and Clostridium perfringens bacteria were within the range 1–1012, and did not exceed the limit values set for fertilizers and soils. Conclusions: Therefore, it is suggested to reuse spa residue after therapy for agricultural purposes (e.g. soil fertilization.

  10. 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.

  11. [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.

  12. When do tissues and cells become products? Regulatory oversight of emerging biological therapies.

    Science.gov (United States)

    Farrugia, Albert

    2006-01-01

    Although therapeutics derived from biological sources have been subjected to regulatory oversight for some time, the products used in transplantation procedures have historically been exempt from this oversight. These products have been viewed as being part of medical practice rather than as the result of mainstream pharmaceutical manufacture. Furthermore, their unique source makes them difficult to assess in traditional regulatory systems based on the tenets of pharmaceutical quality control. With the increasing use of transplantation therapies to both replace dysfunctional organs and to influence genetic and metabolic processes, public health concerns on these therapies have increased. In addition, it is recognized that therapeutic claims for some of these interventions need to be properly assessed. These considerations have led the established regulatory agencies of the developed world to develop new regulatory paradigms for the products of transplantation practice. While a number of concerns have driven these developments, the minimization of infectious disease risk remains the paramount driver for introducing these regulatory systems. More than the regulation of medicines and medical devices manufactured in traditional pharmaceutical modes, the regulation of cell and tissue products is intimately linked to areas of public health policy and funding. This places regulators in a challenging position as they attempt to reconcile their roles as independent assessors with the needs of the overall public health framework. This is particularly difficult when considering measures which may affect access to life saving therapies. Regulators have recognized the need to assess these therapies through systems which incorporate consideration of risk-benefit ratios and include mechanisms for transparent and accountable release of products when full compliance to traditional concepts of manufacturing practice is not possible.

  13. 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...

  14. Pilot study of sexual dysfunction in patients with psoriasis: Influence of biologic therapy

    Directory of Open Access Journals (Sweden)

    Ricardo Ruiz-Villaverde

    2011-01-01

    Full Text Available Background: Psoriasis is a chronic skin disease that affects 1 to 3% of the population in most industrialized countries. It is commonly associated with a variety of psychological problems including low self-esteem, depression, suicidal thoughts, and sexual dysfunction. Materials and Methods : We have performed a pilot study in which we have tried to assess the impact on sexual dysfunction in patients with psoriasis who have started treatment with biological therapy using validated indexes in Spanish: International Index of Erectile Function for men and female sexual function index in women. Results : Considering the men and women from our study, an improvement in FSFI by an average of 9.5 and 6.3 points is observed, respectively. Conclusion: We considered our series as a first step for a more detailed approach to the study of sexual function in patients with psoriasis.

  15. Hepatitis C virus and non-Hodgkin’s lymphoma: biology, epidemiology and therapy

    Directory of Open Access Journals (Sweden)

    Gabriele Pozzato

    2011-11-01

    Full Text Available Although the association between the hepatitis C virus and B-cell non-Hodgkin’s lymphomas is still controversial, there is increasing evidence of the role of this virus in several B-cell lymphoproliferative disorders, whose prototype is mixed cryoglobulinemia. The aim of the present paper was to provide an overview of the biological mechanisms involved in the development of B-cell disorders in the course of chronic hepatitis C virus infection. The link between this virus and non-Hodgkin’s lymphomas is also considered from an epidemiological point of view, and the great regional differences in the prevalence of hepatitis C-associated lymphomas are discussed. Finally, the role of antiviral therapy and suggestions about the most appropriate, currently available, therapeutic approaches are also discussed.

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

    Science.gov (United States)

    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 disintegrate tissues, but rather to microscopically cause interstitial and extracellular biological responses and tissue regeneration. The researchers are interesting to investigate the biological effects which support the clinical successes. Some authors speculated that shockwaves relieve pain in insertional tendinopathy by hyper-stimulation analgesia. Many recent studies demonstrated the modulations of shockwave treatment including neovascularization, differentiation of mesenchymal stem cells and local release of angiogenetic factors. The experimental findings confirm that ESWT decrease the expression of high levels of inflammatory mediators (matrix metalloproteinases and inter-leukins). Therefore, ESWT produces a regenerative and tissue-repairing effect in musculoskeletal tissues, not merely a mechanical disintegrative effect as generally before assumed. Based on the encouraging results of clinical and experimental studies, the potential of ESWT appears to be emerging. The promising outcome after this non-invasive treatment option in tendinitis care justifies the indication of shockwave therapy. Further studies have to be performed in order or determine optimum treatment parameters and will bring about an improvement in accordance with evidence-based medicine. Finally, meta-analysis studies are necessary to demonstrate the efficacy and safety of ESWT in treating tendinopathies.

  17. Combination therapy with biologic agents in rheumatic diseases: current and future prospects

    Science.gov (United States)

    Inui, Kentaro; Koike, Tatsuya

    2016-01-01

    Strategies in rheumatoid arthritis (RA) based on ‘treat to target’ aim to control disease activity, minimize structural damage, and promote longer life. Several disease-modifying antirheumatic drugs (DMARDs) have been shown to be effective including biological DMARDs (bDMARDs). Treatment guidelines and recommendations for RA have also been published. According to those guidelines, conventional synthetic DMARDs (csDMARDs), as monotherapy or combination therapy, should be used in DMARD-naïve patients, irrespective of the addition of glucocorticoids (GCs). Combination therapies with bDMARDs are also essential for conducting treatment strategies for RA, because in every recommendation or guideline for the management of RA, combination therapies of csDMARDs with bDMARDs are recommended for RA patients with moderate or high disease activity after failure of csDMARD treatment. bDMARDs are more efficacious if used concomitantly with methotrexate (MTX) than with MTX monotherapy or bDMARD monotherapy. Thus, retention has been reported to be longer when combined with MTX. The superior efficacy of combination therapy compared with MTX monotherapy or bDMARD monotherapy could be because: (1) it could help to minimize MTX toxicity by reducing the dose of MTX, thus retention rate of the same therapeutic regimen would become high; (2) anti-bDMARD antibodies are observed at lower concentrations when using MTX concomitantly, so less clearance of bDMARDs via less formation of bDMARD and an anti-bDMARD immune complex; (3) of the additive effects of MTX to bDMARD, especially the combination of tumor necrosis factor inhibitors (TNFis) with MTX. Hence, evidence suggests that combination therapy with bDMARDs is more efficacious than monotherapy using a csDMARD or bDMARD, and that MTX is the best drug for this purpose (if MTX is not contraindicated). Finding the most effective drug regimen at the lowest cost will be the aim of RA treatment in the future. PMID:27721905

  18. Monoclonal gammopathy of undetermined significance in patients with psoriasis: is it really a side effect of biological therapy?

    Science.gov (United States)

    Conti, Andrea; Esposito, Ilaria; Lasagni, Claudia; Miglietta, Roberta; Padalino, Claudia; Fabiano, Antonella; Pellacani, Giovanni

    2014-11-01

    Moderate-to-severe psoriasis is treated using biological drugs targeting cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor alpha (TNF-α) (adalimumab, infliximab, etanercept) and interleukin 12/23 (IL 12/23) (ustekinumab). There is a slight risk of developing hematological malignancies, such as monoclonal gammopathy of undetermined significance (MGUS) with anti TNF-α agents. There are no data available on anti-IL12/23 drugs. This retrospective study of data from 191 patients describes the appearance and follow-up of MGUS in three patients with psoriasis receiving long-term biological therapy. Since the appearance of MGUS occurred after about 6 years of anti-TNFα treatment in only three subjects, it was deemed unlikely to be due to the biological treatment. The decision not to suspend biological therapy after the appearance of MGUS was taken after careful assessment of the possible risks and benefits.

  19. 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.

  20. Synthetic biology and therapeutic strategies for the degenerating brain: Synthetic biology approaches can transform classical cell and gene therapies, to provide new cures for neurodegenerative diseases.

    Science.gov (United States)

    Agustín-Pavón, Carmen; Isalan, Mark

    2014-10-01

    Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from combining 'protect and repair' strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site-specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long-term therapies for many brain diseases in human patients.

  1. 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

  2. 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.

  3. The complex biology and contribution of Staphylococcus aureus in atopic dermatitis, current and future therapies.

    Science.gov (United States)

    Hepburn, L; Hijnen, D J; Sellman, B R; Mustelin, T; Sleeman, M A; May, R D; Strickland, I

    2016-10-25

    Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of UK children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonised with Staphylococcus aureus (S. aureus) and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitisation, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection. S. aureus generates exoproteins that enable invasion and dissemination within the host skin but can also damage the skin and activate the host immune system. Antibiotics are often used by dermatologists to aid clearance of S. aureus; however, these are becoming less effective and chronic usage discouraged with the emergence of multiple antibiotic-resistant strains. New ways to target S. aureus using monoclonal antibodies and vaccines are now being developed. This review will attempt to evaluate the key biology of S. aureus, current treatment of S. aureus infections in atopic dermatitis and recent advances in developing new anti-S. aureus therapies that have potential in severe AD. This article is protected by copyright. All rights reserved.

  4. 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.

  5. 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

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

    Science.gov (United States)

    Waugh, C M; Morrissey, D; Jones, E; Riley, G P; Langberg, H; Screen, H R C

    2015-05-15

    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 help to

  7. 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

  8. Correlation between BMI and PASI in patients affected by moderate to severe psoriasis undergoing biological therapy.

    Science.gov (United States)

    Bardazzi, F; Balestri, R; Baldi, E; Antonucci, A; De Tommaso, S; Patrizi, A

    2010-01-01

    Obesity is common in psoriatic patients, and it has been shown to be important for many aspects of the condition. In particular, low-calorie diets can improve the symptoms and response to treatment in pustular psoriasis. The present study investigates the influence of body-weight alteration on the disease's clinical manifestations in moderate to severe psoriasis patients treated with biological drugs. Finally, the influence of a caloric restriction was assessed. This observational transversal study enrolled 33 patients attending our Severe Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass Index (BMI) was used as a diagnostic indicator of being overweight and of obesity. Waist circumference was also measured. Body weight and Psoriasis Area Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months. Nonparametric test of Mann-Whitney was used to detect the differences between patient groups. Fisher's exact test was performed to evaluate the different results depending on the therapeutic changes of BMI. There was a strong prevalence of overweight-obese individuals in the group with a mean BMI of 30.59 +/- 6.94. Waist circumference was also above normal in the majority of the patients. Obese patients had a PASI index higher than the average of the whole group (25.03 +/- 12.43), with grade III obese patients having an average PASI of 44 +/- 3.37. At the first and second follow-ups, patients who put on weight did not achieve PASI 50; patients who had a stable weight presented variable response to treatment, while patients who decreased their weight achieved PASI 90 or PASI 75 even when not responding at the first. Further studies are needed to understand if the poor response observed in heavier patients is due to biological drugs pharmacokinetics or because therapy should be BMI based rather than administered in fixed doses, posing then an ethical consideration.

  9. 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.

  10. Role of regulatory T cells in pathogenesis and biological therapy of multiple sclerosis.

    Science.gov (United States)

    Buc, Milan

    2013-01-01

    Multiple sclerosis (MS) is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. It is caused by an autoimmune response to self-antigens in a genetically susceptible individual induced by unknown environmental factors. Principal cells of the immune system that drive the immunopathological processes are T cells, especially of TH1 and TH17 subsets. However, in recent years, it was disclosed that regulatory T cells took part in, too. Subsequently, there was endeavour to develop ways how to re-establish their physiological functions. In this review, we describe known mechanisms of action, efficacy, and side-effects of contemporary and emerging MS immunotherapeutical agents on Treg cells and other cells of the immune system involved in the immunopathogenesis of the disease. Furthermore, we discuss how laboratory immunology can offer physicians its help in the diagnosis process and decisions what kind of biological therapy should be used.

  11. Biology, Risk Stratification, and Therapy of Pediatric Acute Leukemias: An Update

    Science.gov (United States)

    Pui, Ching-Hon; Carroll, William L.; Meshinchi, Soheil; Arceci, Robert J.

    2011-01-01

    Purpose We review recent advances in the biologic understanding and treatment of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), identify therapeutically challenging subgroups, and suggest future directions of research. Methods A review of English literature on childhood acute leukemias from the past 5 years was performed. Results Contemporary treatments have resulted in 5-year event-free survival rates of approximately 80% for childhood ALL and almost 60% for pediatric AML. The advent of high-resolution genome-wide analyses has provided new insights into leukemogenesis and identified many novel subtypes of leukemia. Virtually all ALL and the vast majority of AML cases can be classified according to specific genetic abnormalities. Cooperative mutations involved in cell differentiation, cell cycle regulation, tumor suppression, drug responsiveness, and apoptosis have also been identified in many cases. The development of new formulations of existing drugs, molecularly targeted therapy, and immunotherapies promises to further advance the cure rates and improve quality of life of patients. Conclusion The application of new high-throughput sequencing techniques to define the complete DNA sequence of leukemia and host normal cells and the development of new agents targeted to leukemogenic pathways promise to further improve outcome in the coming decade. PMID:21220611

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

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.; Fois, G.; Edouard, M.; Nemoz, C.; Renier, M.; Requardt, H.; Esteve, F.; Adam, JF.; Elleaume, H.; Bravin, A., E-mail: prezado@esrf.fr [ID17 Biomedical Beamline, European Synchrotron Radiation Facility (ESRF), 6 rue Jules Horowitz, BP 220, 38043 Grenoble Cedex (France)

    2009-03-15

    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.

  13. Role of Regulatory T Cells in Pathogenesis and Biological Therapy of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Milan Buc

    2013-01-01

    Full Text Available Multiple sclerosis (MS is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms. It is caused by an autoimmune response to self-antigens in a genetically susceptible individual induced by unknown environmental factors. Principal cells of the immune system that drive the immunopathological processes are T cells, especially of TH1 and TH17 subsets. However, in recent years, it was disclosed that regulatory T cells took part in, too. Subsequently, there was endeavour to develop ways how to re-establish their physiological functions. In this review, we describe known mechanisms of action, efficacy, and side-effects of contemporary and emerging MS immunotherapeutical agents on Treg cells and other cells of the immune system involved in the immunopathogenesis of the disease. Furthermore, we discuss how laboratory immunology can offer physicians its help in the diagnosis process and decisions what kind of biological therapy should be used.

  14. Physics fundamentals and biological effects of synchrotron radiation therapy; Fundamentos fisicos y efectos biologicos de la radioterapia con radiacion sincrotron

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.

    2010-07-01

    The main goal of radiation therapy is to deposit a curative dose in the tumor without exceeding the tolerances in the nearby healthy tissues. For some radioresistant tumors, like gliomas, requiring high doses for complete sterilization, the major obstacle for curative treatment with ionizing radiation remains the limited tolerance of the surrounding healthy tissue. This limitation is particularly severe for brain tumors and, especially important in children, due to the high risk of complications in the development of the central nervous system. In addition, the treatment of tumors close to an organ at risk, like the spinal cord, is also restricted. One possible solution is the development of new radiation therapy techniques exploiting radically different irradiation modes and modifying, in this way, the biological equivalent doses. This is the case of synchrotron radiation therapy (SR T). In this work the three new radiation therapy techniques under development at the European Synchrotron Radiation Facility (ESR F), in Grenoble (France) will be described, namely: synchrotron stereotactic radiation therapy (Ssr), microbeam radiation therapy (MR T) and mini beam radiation therapy. The promising results in the treatment of the high grade brain tumors obtained in preclinical studies have paved the way to the clinical trials. The first patients are expected in the fall of 2010. (Author).

  15. 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.

  16. 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

  17. Chemical and biological warfare: Biochemistry, therapy, and treatment. (Latest citations from the NTIS bibliographic database). Published Search

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The bibliography contains citations concerning biochemistry, therapy, and treatment of the effects of military chemical and biological warfare agents. References include surveys and studies of immunizing agents and drugs, the efficacy of these drugs, and the effect of the drugs on the patient. Also included are biochemical studies, assay techniques, and antidote development, some of which is supported by animal studies. Citations concerning detection and warning, defoliants, protection, biology and toxicology, and general studies are covered in separate bibliographies.(Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  18. Chemical and biological warfare: Biochemistry, therapy, and treatment. (Latest citations from the NTIS bibliographic database). Published Search

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    The bibliography contains citations concerning biochemistry, therapy, and treatment of the effects of military chemical and biological warfare agents. References include surveys and studies of immunizing agents and drugs, the efficacy of these drugs, and the effect of the drugs on the patient. Also included are biochemical studies, assay techniques, and antidote development, some of which is supported by animal studies. Citations concerning detection and warning, defoliants, protection, biology and toxicology, and general studies are covered in separate bibliographies.(Contains 50-250 citations and includes a subject term index and title list.) (Copyright NERAC, Inc. 1995)

  19. Protocols for assessing radiofrequency interactions with gold nanoparticles and biological systems for non-invasive hyperthermia cancer therapy.

    Science.gov (United States)

    Corr, Stuart J; Cisneros, Brandon T; Green, Leila; Raoof, Mustafa; Curley, Steven A

    2013-08-28

    Cancer therapies which are less toxic and invasive than their existing counterparts are highly desirable. The use of RF electric-fields that penetrate deep into the body, causing minimal toxicity, are currently being studied as a viable means of non-invasive cancer therapy. It is envisioned that the interactions of RF energy with internalized nanoparticles (NPs) can liberate heat which can then cause overheating (hyperthermia) of the cell, ultimately ending in cell necrosis. In the case of non-biological systems, we present detailed protocols relating to quantifying the heat liberated by highly-concentrated NP colloids. For biological systems, in the case of in vitro experiments, we describe the techniques and conditions which must be adhered to in order to effectively expose cancer cells to RF energy without bulk media heating artifacts significantly obscuring the data. Finally, we give a detailed methodology for in vivo mouse models with ectopic hepatic cancer tumors.

  20. Development and application of biological techniques to two-photon photodynamic therapy

    Science.gov (United States)

    Khurana, Mamta; Karotki, Aliaksandr; Moriyama, Eduardo H.; Akens, Margarete K.; Wilson, Brian C.

    2007-06-01

    Two-photon (2-γ) photodynamic therapy (PDT) as opposed to "standard" one-photon (1-γ) PDT with Visudyne has recently been suggested as a targeted treatment alternative for wet-form age-related macular degeneration (AMD) and other neovascular diseases. AMD is a major cause of severe vision loss in the older population. It occurs due to growth of new leaky blood vessels (neovasculature) from the choriocapillaris, which results in destruction of photoreceptors in the fovea and loss of central vision. Damage outside the diseased region is always a concern, due to photosensitizer accumulation and its 1-γ excitation. Highly targeted 2-γ excitation, due to its non-linear intensity dependence, intrinsically avoids out-of-focus damage to healthy tissues and so could be valuable for wet-AMD. We have previously developed a quantitative approach for comparing the 2-γ efficacy of photosensitizers in vitro. In this study, we report further the development of ex vivo and in vivo techniques. A mouse mesenteric vessel has been investigated as the ex vivo model of neovasculature. For the in vivo studies, we have explored a mouse dorsal skin-fold window chamber model. Two-photon PDT is delivered using tightly focused ~300 fs laser pulses from a Ti:sapphire laser operating at 850 nm with 90 MHz pulse repetition rate. Confocal microscopy coupled to the laser was used to visualize the vessel's/cell's response before, during and after the treatment. We are able to demonstrate quantitative biological techniques to evaluate efficacy of 2-γ PDT photosensitizers in vivo.

  1. Review of the treatment of psoriatic arthritis with biological agents: choice of drug for initial therapy and switch therapy for non-responders

    Directory of Open Access Journals (Sweden)

    D'Angelo S

    2017-03-01

    Full Text Available Salvatore D’Angelo,1 Giuseppina Tramontano,1 Michele Gilio,1 Pietro Leccese,1 Ignazio Olivieri1,2 1Rheumatology Institute of Lucania (IRel - Rheumatology Department of Lucania, San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza and Matera, 2Basilicata Ricerca Biomedica (BRB Foundation, Potenza, Italy Abstract: Psoriatic arthritis (PsA is a heterogeneous chronic inflammatory disease with a broad clinical spectrum and variable course. It can involve musculoskeletal structures as well as skin, nails, eyes, and gut. The management of PsA has changed tremendously in the last decade, thanks to an earlier diagnosis, an advancement in pharmacological therapies, and a wider application of a multidisciplinary approach. The commercialization of tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab as well as interleukin (IL-12/23 (ustekinumab and IL-17 (secukinumab inhibitors is representative of a revolution in the treatment of PsA. No evidence-based strategies are currently available for guiding the rheumatologist to prescribe biological drugs. Several international and national recommendation sets are currently available with the aim to help rheumatologists in everyday clinical practice management of PsA patients treated with biological therapy. Since no specific biological agent has been demonstrated to be more effective than others, the drug choice should be made according to the available safety data, the presence of extra-articular manifestations, the patient’s preferences (e.g., administration route, and the drug price. However, future studies directly comparing different biological drugs and assessing the efficacy of treatment strategies specific for PsA are urgently needed. Keywords: psoriatic arthritis, treatment, biological drugs, TNF inhibitors, ustekinumab, secukinumab

  2. Gain in Quality-adjusted Life-years in Patients with Rheumatoid Arthritis During 1 Year of Biological Therapy

    DEFF Research Database (Denmark)

    Linde, Louise; Sørensen, Jan; Østergaard, Mikkel;

    2013-01-01

    The quality-adjusted life-year (QALY) is used to measure outcome in rheumatoid arthritis (RA) studies; identification of drivers of a gain in QALY might help predict a treatment response. We investigated how changes in components of the Disease Activity Score-28 joints (DAS28) were associated...... with the European League Against Rheumatism (EULAR) and European Quality of Life 5 Dimensions (EQ-5D) responses; and what baseline variables predicted the change in QALY following 1 year of biological therapy....

  3. 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

  4. Induced hemocompatibility and bone formation as biological scaffold for cell therapy implant

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

    Full Text Available Although stem cells can become almost any type of specialized cell in the human body and may have the potential to generate replacement cells for tissues and organs, the transplantation of these cells are hindered by immune rejection and teratoma formation. However, scientists have found a promising solution for these problems-they have discovered the ability to isolate stem cells from a patient’s umbilical cord blood or bone marrow. Even more recently, small stem cells, such as spore-like stem cells, Blastomere-Like Stem Cells (BLSCs, and Very-Small Embryonic-Like stem cells (VSELs isolated directly from the peripheral blood have beeninvestigated as a novel approach to stem cell therapy as they can be isolated directly from the peripheral blood. A newly-discovered population of multipotent stem cells in this class has been dubbed StemBios (SB cells. The potential therapeutic uses of such stem cells have been explored in many ways, one of which includes dental remodeling and construction. Using adult stem cells, scientists have engineered and cultivated teeth in mice that may one day be used for human implantation.It follows that such regeneration may be possible, to a certain degree, in human patients as well. This idea leads to the present study on the effect of SB cell therapy on early osseointegrationof dental implants. Titanium (Ti dental implants have been proven to be a reliable and predictable treatment for restoration of edentulous regions. The osseointegration process can be described in two stages: primary stability (mechanical stability and secondary stability (biological stability. The mechanical stabilization of the implant reflects the interaction between the bone density and the features of the implant designs and can be determined after implant insertion. Alternatively,the biological stabilization of the implant is a physiologic healing process. It is couple to the biological interaction between the external surface of the

  5. Stem cells, cell therapies, and bioengineering in lung biology and diseases. Comprehensive review of the recent literature 2010-2012.

    Science.gov (United States)

    Weiss, Daniel J

    2013-10-01

    A conference, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," was held July 25 to 28, 2011 at the University of Vermont 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 rapidly expanding areas of study that 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, to discuss and debate current controversies, and to identify future research directions and opportunities for basic and translational research in cell-based therapies for lung diseases. The goal of this article, which accompanies the formal conference report, is to provide a comprehensive review of the published literature in lung regenerative medicine from the last conference report through December 2012.

  6. 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.

  7. Extracorporeal blood oxygenation and ozonation: clinical and biological implications of ozone therapy.

    Science.gov (United States)

    Di Paolo, N; Gaggiotti, E; Galli, F

    2005-01-01

    Some lines of evidence have suggested that the challenge to antioxidants and biomolecules provoked by pro-oxidants such as ozone may be used to generate a controlled stress response of possible therapeutic relevance in some immune dysfunctions and chronic, degenerative conditions. Immune and endothelial cells have been proposed to be elective targets of the positive molecular effects of ozone and its derived species formed during blood ozonation. On the bases of these underlying principles and against often prejudicial scepticism and concerns about its toxicity, ozone has been used in autohemotherapy (AHT) for four decades with encouraging results. However, clinical application and validation of AHT have been so far largely insufficient. Latterly, a new and more effective therapeutic approach to ozone therapy has been established, namely extracorporeal blood oxygenation and ozonation (EBOO). This technique, first tested in vitro and then in vivo in sheep and humans (more than 1200 treatments performed in 82 patients), is performed with a high-efficiency apparatus that makes it possible to treat with a mixture of oxygen-ozone (0.5-1 microg/ml oxygen) in 1 h of extracorporeal circulation up to 4800 ml of heparinized blood without technical or clinical problems, whereas only 250 ml of blood can be treated with ozone by AHT. The EBOO technique can be easily adapted for use in hemodialysis also. The standard therapeutic cycle lasts for 7 weeks in which 14 treatment sessions of 1 h are performed. After a session of EBOO, the interaction of ozone with blood components results in 4-5-fold increased levels of thiobarbituric acid reactants and a proportional decrease in plasma protein thiols without any appreciable erythrocyte haemolysis. On the basis of preliminary in vitro evidence, these simple laboratory parameters may represent a useful complement in the routine monitoring of biological compliance to the treatment. The clinical experience gained so far confirms the

  8. A model of study for human cancer: Spontaneous occurring tumors in dogs. Biological features and translation for new anticancer therapies.

    Science.gov (United States)

    Ranieri, G; Gadaleta, C D; Patruno, R; Zizzo, N; Daidone, M G; Hansson, M G; Paradiso, A; Ribatti, D

    2013-10-01

    Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. Interestingly, several murine cancer models also exhibit heterogeneity, genomic instability and an intact immune system. However, they do not adequately represent several features that define cancer in humans, including long periods of latency, the complex biology of cancer recurrence and metastasis and outcomes to novel therapies. Therefore, additional models that better investigate the human disease are needed. In the pet population, with special references to the dog, cancer is a spontaneous disease and dogs naturally develop cancers that share many characteristics with human malignancies. More than 40 years ago, optimization of bone marrow transplantation protocols was undertaken in dogs and recently novel targeted therapies such as liposomal muramyl tripeptide phosphatidylethanolamine and several tyrosine kinase inhibitors, namely masitinib (AB1010) and toceranib phosphate (SU11654), have been developed to treat dog tumors which have then been translated to human clinical trials. In this review article, we will analyze biological data from dog tumors and comparative features with human tumors, and new therapeutic approaches translated from dog to human cancer.

  9. Evaluation of Novel Targeted Therapies in Aggressive Biology Sarcoma Patients after progression from US FDA approved Therapies

    Science.gov (United States)

    Subbiah, Vivek; Hess, Kenneth R.; Khawaja, Muhammad Rizwan; Wagner, Michael J.; Tang, Chad; Naing, Aung; Fu, Siqing; Janku, Filip; Piha-Paul, Sarina; Tsimberidou, Apostolia M.; Herzog, Cynthia E.; Ludwig, Joseph A.; Patel, Shreyaskumar; Ravi, Vinod; Benjamin, Robert S.; Meric-Bernstam, Funda; Hong, David S.

    2016-01-01

    Prognosis of patients with advanced sarcoma after progression from FDA approved therapies remains grim. In this study, clinical outcomes of 100 patients with advanced sarcoma who received treatment on novel targeted therapy trials were evaluated. Outcomes of interest included best response, clinical benefit rate, progression-free survival (PFS) and overall survival (OS). Median patient age was 48 years (range 14–80). Patients had received a median of 2 prior lines of systemic treatment. Phase I treatments were anti-VEGF–based (n = 45), mTOR inhibitor–based (n = 15), and anti-VEGF + mTOR inhibitor–based (n = 17) or involved other targets (n = 23). Best responses included partial response (n = 4) and stable disease (n = 57). Clinical benefit rate was 36% (95% confidence interval 27–46%). Median OS was 9.6 months (95% Confidence Interval 8.1–14.2); median PFS was 3.5 months (95% Confidence Interval 2.4–4.7). RMH prognostic score of 2 or 3 was associated with lower median OS (log-rank p-value < 0.0001) and PFS (log-rank p-value 0.0081). Receiving cytotoxic chemotherapy as part of phase I trial was also associated with shorter median OS (log-rank p-value 0.039). Patients with advanced sarcoma treated on phase I clinical trials had a clinical benefit rate of 36% and RMH score predicted survival. PMID:27748430

  10. Consistent control of psoriasis by continuous long-term therapy: the promise of biological treatments.

    NARCIS (Netherlands)

    Kerkhof, P.C.M. van de

    2006-01-01

    Psoriasis is a chronic, incurable disease that frequently requires long-term treatment. Although many patients benefit from effective traditional systemic therapies, namely methotrexate, cyclosporin, retinoids and fumaric acid esters, and some patients achieve long-term disease control, unrestricted

  11. 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.

  12. Public versus Private Drug Insurance and Outcomes of Patients Requiring Biologic Therapies for Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Amir Rumman

    2017-01-01

    Full Text Available Background. Antitumor necrosis factor (anti-TNF therapy is a highly effective but costly treatment for inflammatory bowel disease (IBD. Methods. We conducted a retrospective cohort study of IBD patients who were prescribed anti-TNF therapy (2007–2014 in Ontario. We assessed if the insurance type was a predictor of timely access to anti-TNF therapy and nonroutine health utilization (emergency department visits and hospitalizations. Results. There were 268 patients with IBD who were prescribed anti-TNF therapy. Public drug coverage was associated with longer median wait times to first dose than private one (56 versus 35 days, P=0.002. After adjusting for confounders, publicly insured patients were less likely to receive timely access to anti-TNF therapy compared with those privately insured (adjusted hazard ratio, 0.66; 95% CI: 0.45–0.95. After adjustment for demographic and clinical characteristics, publicly funded subjects were more than 2-fold more likely to require hospitalization (incidence rate ratio [IRR], 2.30; 95% CI: 1.19–4.43 and ED visits (IRR 2.42; 95% CI: 1.44–4.08 related to IBD. Conclusions. IBD patients in Ontario with public drug coverage experienced greater delays in access to anti-TNF therapy than privately insured patients and have a higher rate of hospitalizations and ED visits related to IBD.

  13. Public versus Private Drug Insurance and Outcomes of Patients Requiring Biologic Therapies for Inflammatory Bowel Disease

    Science.gov (United States)

    Rumman, Amir; Candia, Roberto; Sam, Justina J.; Croitoru, Kenneth; Silverberg, Mark S.; Steinhart, A. Hillary

    2017-01-01

    Background. Antitumor necrosis factor (anti-TNF) therapy is a highly effective but costly treatment for inflammatory bowel disease (IBD). Methods. We conducted a retrospective cohort study of IBD patients who were prescribed anti-TNF therapy (2007–2014) in Ontario. We assessed if the insurance type was a predictor of timely access to anti-TNF therapy and nonroutine health utilization (emergency department visits and hospitalizations). Results. There were 268 patients with IBD who were prescribed anti-TNF therapy. Public drug coverage was associated with longer median wait times to first dose than private one (56 versus 35 days, P = 0.002). After adjusting for confounders, publicly insured patients were less likely to receive timely access to anti-TNF therapy compared with those privately insured (adjusted hazard ratio, 0.66; 95% CI: 0.45–0.95). After adjustment for demographic and clinical characteristics, publicly funded subjects were more than 2-fold more likely to require hospitalization (incidence rate ratio [IRR], 2.30; 95% CI: 1.19–4.43) and ED visits (IRR 2.42; 95% CI: 1.44–4.08) related to IBD. Conclusions. IBD patients in Ontario with public drug coverage experienced greater delays in access to anti-TNF therapy than privately insured patients and have a higher rate of hospitalizations and ED visits related to IBD. PMID:28239601

  14. 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.

  15. An official American Thoracic Society workshop report: stem cells and cell therapies in lung biology and diseases.

    Science.gov (United States)

    Weiss, Daniel J; Chambers, Daniel; Giangreco, Adam; Keating, Armand; Kotton, Darrell; Lelkes, Peter I; Wagner, Darcy E; Prockop, Darwin J

    2015-04-01

    The University of Vermont College of Medicine and the Vermont Lung Center, in collaboration with the NHLBI, Alpha-1 Foundation, American Thoracic Society, European Respiratory Society, International Society for Cell Therapy, and the Pulmonary Fibrosis Foundation, convened a workshop, "Stem Cells and Cell Therapies in Lung Biology and Lung Diseases," held July 29 to August 1, 2013 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 conference was a follow-up to four previous biennial conferences held at the University of Vermont in 2005, 2007, 2009, and 2011. 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.

  16. 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.

  17. 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.

  18. A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field

    Science.gov (United States)

    Mairani, A.; Dokic, I.; Magro, G.; Tessonnier, T.; Bauer, J.; Böhlen, T. T.; Ciocca, M.; Ferrari, A.; Sala, P. R.; Jäkel, O.; Debus, J.; Haberer, T.; Abdollahi, A.; Parodi, K.

    2017-02-01

    Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LET D ) as an indicator of the physical properties of the proton radiation field. The LET D values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z  =  1) and He fragments (3He and 4He, Z  =  2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear–quadratic model parameters for the reference radiation {{≤ft(α /β \\right)}\\text{ph}} , predicts, when integrated in an MC code, higher RBE values in comparison to LET D -based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low {{≤ft(α /β \\right)}\\text{ph}} tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z  =  2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

  19. 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

  20. Systems biology analysis unravels the complementary action of combined rosuvastatin and ezetimibe therapy

    NARCIS (Netherlands)

    Verschuren, L.; Radonjic, M.; Wielinga, P.Y.; Kelder, T.; Kooistra, T.; Ommen, B. van; Kleemann, R.

    2012-01-01

    AIMS: Combination-drug therapy takes advantage of the complementary action of their individual components, thereby potentiating its therapeutic effect. Potential disadvantages include side effects that are not foreseen on basis of the data available from drug monotherapy. Here, we used a systems bio

  1. 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

  2. Monotherapy and combined therapy of new potential antitumor compounds: antiproliferative activities and biological targets

    OpenAIRE

    Marques, Mara Lisa Miranda

    2014-01-01

    Review article Martins, P., Marques, M., Coito, L., Pombeiro, A.J.L., Baptista, P.V., Fernandes, A.R. 2014. Organometallic Compounds in Cancer Therapy: Past Lessons and Future Directions. Anti-cancer Agents in Medicinal Chemistry 14. PMID: 25173559

  3. 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...... handed out among RA patients during their planned visits. Values for DAS28 were obtained from the DANBIO registry. Demographic data and data on patients' medical treatment, disease duration, serological and radiological status were retrieved from patients' files. The χ(2) test and an unpaired t-test were...... with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms....

  4. Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy.

    Science.gov (United States)

    Kadosawa, Tsuyoshi; Ohashi, Fumihito; Nishimura, Ryohei; Sasaki, Nobuo; Saito, Isao; Wakabayashi, Hiroaki; Takeuchi, Akira

    2003-10-01

    To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.

  5. 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.

  6. 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

    2011-06-03

    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.

  7. 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.

  8. 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...

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gruen, Rebecca Antonia

    2014-06-03

    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. 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 ...

  12. 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 

  13. 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.

  14. 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.

  15. 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...

  16. Molecular biology of cancer-associated fibroblasts: can these cells be targeted in anti-cancer therapy?

    Science.gov (United States)

    Gonda, Tamas A; Varro, Andrea; Wang, Timothy C; Tycko, Benjamin

    2010-02-01

    It is increasingly recognized that the non-neoplastic stromal compartment in most solid cancers plays an active role in tumor proliferation, invasion and metastasis. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types in the tumor stroma, and these cells are pro-tumorigenic. Evidence that CAFs are epigenetically and possibly also genetically distinct from normal fibroblasts is beginning to define these cells as potential targets of anti-cancer therapy. Here, we review the cell-of-origin and molecular biology of CAFs, arguing that such knowledge provides a rational basis for designing therapeutic strategies to coordinately and synergistically target both the stromal and malignant epithelial component of human cancers.

  17. Micro-masters of glioblastoma biology and therapy: increasingly recognized roles for microRNAs.

    Science.gov (United States)

    Floyd, Desiree; Purow, Benjamin

    2014-05-01

    MicroRNAs are small noncoding RNAs encoded in eukaryotic genomes that have been found to play critical roles in most biological processes, including cancer. This is true for glioblastoma, the most common and lethal primary brain tumor, for which microRNAs have been shown to strongly influence cell viability, stem cell characteristics, invasiveness, angiogenesis, metabolism, and immune evasion. Developing microRNAs as prognostic markers or as therapeutic agents is showing increasing promise and has potential to reach the clinic in the next several years. This succinct review summarizes current progress and future directions in this exciting and steadily expanding field.

  18. 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. 

  19. Towards personalized therapy for patients with malignant melanoma: molecular insights into the biology of BRAF mutations.

    Science.gov (United States)

    Bradish, Joshua R; Montironi, Rodolfo; Lopez-Beltran, Antonio; Post, Kristin M; MacLennan, Gregory T; Cheng, Liang

    2013-02-01

    BRAF mutations have been identified as the most common oncogene mutation in melanomas, especially important in those originating on nonchronically sun-damaged skin. There is a large and continually growing body of evidence regarding the importance of this mutation in targeted therapy for melanoma. In this review, we outline these findings including: molecular pathways used by BRAF, the importance in nonmalignant neoplasms, histologic associations, the relationship of BRAF to KIT and NRAS mutations, and their impact on survival, as well as resistance mechanisms to BRAF inhibitors employed by melanoma. Understanding these topics and how they relate to one another may facilitate the development of new treatments and eventually improve the prognosis for those patients afflicted with this disease.

  20. 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...

  1. 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

  2. [Molecular biology of renal cancer: bases for genetic directed therapy in advanced disease].

    Science.gov (United States)

    Maroto Rey, José Pablo; Cillán Narvaez, Elena

    2013-06-01

    There has been expansion of therapeutic options in the management of metastatic renal cell carcinoma due to a better knowledge of the molecular biology of kidney cancers. There are different tumors grouped under the term renal cell carcinoma, being clear cell cancer the most frequent and accounting for 80% of kidney tumors. Mutations in the Von Hippel-Lindau gene can be identified in up to 80% of sporadic clear cell cancer, linking a genetically inheritable disease where vascular tumors are frequent, with renal cell cancer. Other histologic types present specific alterations in molecular pathways, like c-MET in papillary type I tumors, and Fumarase Hydratase in papillary type II tumors. Identification of the molecular alteration for a specific tumor may offer an opportunity for treatment selection based on biomarkers, and, in the future, for developing an engineering designed genetic treatment.

  3. 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 sporadic cases of IBD. However, patients with familial CD had significantly higher risk of major surgery than sporadic CD cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced time from diagnosis to first...... tumor necrosis factor-α inhibitor treatment among familial CD and UC cases as compared with sporadic cases. CONCLUSION: We found only minor differences in surgery rates and tumor necrosis factor exposure, between familial and sporadic cases of IBD. These findings may represent purely social rather than...

  4. 银屑病生物治疗研究进展%Biologic therapies of psoriasis

    Institute of Scientific and Technical Information of China (English)

    张希琳; 顾军

    2012-01-01

    With the progress in the understanding of immunological mechanisms and susceptibility genes of psoriasis,an increasing number of targeted biological agents have been developed over the past decade.According to the mechanism of action,these agents are mainly divided into two groups,including costimulatory signal-blocking agents and inflammatory mediator-inhibiting agents.Inflammatory mediators targeted by these agents mainly include tumor necrosis factor α,interleukin-12 and interleukin-23.This review introduces the mechanism,clinical efficacy and safety of many biological agents which have been approved or unapproved but have shown vast potential for treating psoriasis in Europe and America.%近10年来,随着对银屑病免疫学机制和易感基因研究的不断深入,越来越多针对关键发病环节的靶向性生物制剂被研发出来用于控制这一顽疾.根据作用机制的不同,银屑病生物制剂主要分为阻断共刺激信号和抑制炎症介质两种.其中,肿瘤坏死因子α、白介素12及白介素23为其主要的炎症介质靶点.对目前欧美已经批准上市和尚未批准,但较有潜力的多种银屑病生物制剂的作用机制、临床疗效及安全性进行阐述.

  5. 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.

  6. Dynamic infrared imaging for biological and medical applications in Boron neutron capture therapy

    Science.gov (United States)

    Santa Cruz, Gustavo A.; González, Sara J.; Dagrosa, Alejandra; Schwint, Amanda E.; Carpano, Marina; Trivillin, Verónica A.; Boggio, Esteban F.; Bertotti, José; Marín, Julio; Monti Hughes, Andrea; Molinari, Ana J.; Albero, Miguel

    2011-05-01

    Boron Neutron Capture Therapy (BNCT) is a treatment modality, currently focused on the treatment of cancer, which involves a tumor selective 10B compound and a specially tuned neutron beam to produce a lethal nuclear reaction. BNCT kills target cells with microscopic selectivity while sparing normal tissues from potentially lethal doses of radiation. In the context of the Argentine clinical and research BNCT projects at the National Atomic Energy Commission and in a strong collaboration with INVAP SE, we successfully implemented Dynamic Infrared Imaging (DIRI) in the clinical setting for the observation of cutaneous melanoma patients and included DIRI as a non invasive methodology in several research protocols involving small animals. We were able to characterize melanoma lesions in terms of temperature and temperature rate-of-recovery after applying a mild cold thermal stress, distinguishing melanoma from other skin pigmented lesions. We observed a spatial and temporal correlation between skin acute reactions after irradiation, the temperature pattern and the dose distribution. We studied temperature distribution as a function of tumor growth in mouse xenografts, observing a significant correlation between tumor temperature and drug uptake; we investigated temperature evolution in the limbs of Wistar rats for a protocol of induced rheumatoid arthritis (RA), DIRI being especially sensitive to RA induction even before the development of clinical signs and studied surface characteristics of tumors, precancerous and normal tissues in a model of oral cancer in the hamster cheek pouch.

  7. Vessel-associated stem cells from skeletal muscle: From biology to future uses in cell therapy.

    Science.gov (United States)

    Sancricca, Cristina; Mirabella, Massimiliano; Gliubizzi, Carla; Broccolini, Aldobrando; Gidaro, Teresa; Morosetti, Roberta

    2010-06-26

    Over the last years, the existence of different stem cells with myogenic potential has been widely investigated. Besides the classical skeletal muscle progenitors represented by satellite cells, numerous multipotent and embryologically unrelated progenitors with a potential role in muscle differentiation and repair have been identified. In order to conceive a therapeutic approach for degenerative muscle disorders, it is of primary importance to identify an ideal stem cell endowed with all the features for a possible use in vivo. Among all emerging populations, vessel-associated stem cells are a novel and promising class of multipotent progenitors of mesodermal origin and with high myogenic potential which seem to best fit all the requirements for a possible cell therapy. In vitro and in vivostudies have already tested the effectiveness and safety of vessel-associated stem cells in animal models. This leads to the concrete possibility in the future to start pilot human clinical trials, hopefully opening the way to a turning point in the treatment of genetic and acquired muscle disorders.

  8. 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.

  9. Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy

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    Benjamin L. Franc

    2003-10-01

    Full Text Available The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.

  10. New Ru(II) pincer complexes: synthesis, characterization and biological evaluation for photodynamic therapy.

    Science.gov (United States)

    Tabrizi, Leila; Chiniforoshan, Hossein

    2016-11-15

    Three new ruthenium(ii) complexes of NCN pincer and phenylcyanamide derivative ligands of the formula [Ru(L)(Ph2phen)(3,5-(NO2)2pcyd)], 1, [Ru(L)(Me2phen)(3,5-(NO2)2pcyd)], 2, and [Ru(L)(Cl2phen)(3,5-(NO2)2pcyd)], 3 (HL: 5-methoxy-1,3-bis(1-methyl-1H-benzo[d]imidazol-2-yl)benzene, 3,5-(NO2)2pcyd: 3,5-(NO2)2pcyd, Ph2phen: 4,7-diphenyl-1,10-phenanthroline, Me2phen: 4,7-dimethyl-1,10-phenanthroline, Cl2phen: 4,7-dichloro-1,10-phenanthroline) have been synthesized and studied as potential photosensitizers (PSs) in photodynamic therapy (PDT). The complexes exhibited promising (1)O2 production quantum yields comparable with PSs available on the market. The DNA-binding interactions of the complexes with calf thymus DNA have been studied by absorption, emission, and viscosity measurements. All complexes cleave SC-DNA efficiently on photoactivation at 350 nm with the formation of singlet oxygen ((1)O2) and hydroxyl radicals (˙OH) in type-II and photoredox pathways. Complexes 1-3 showed very good uptake in cervical cancer cells (HeLa). The compounds studied were found to exhibit low toxicity against HeLa cells (IC50 > 300 μM) and, remarkably, on non-cancerous MRC-5 cells (IC50 > 100 μM) in the dark. However, 1 showed very promising behavior with an increment of about 90 times, in its cytotoxicity upon light illumination at 420 nm in addition to very good human plasma stability.

  11. Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

    Science.gov (United States)

    Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

    2014-04-01

    CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

  12. Stabilized nanosystem of nanocarriers with an immobilized biological factor for anti-tumor therapy

    Science.gov (United States)

    Kwiatkowska, Angelika; Grzeczkowicz, Anna; Stachowiak, Radosław; Kamiński, Michał; Grubek, Zuzanna; Bielecki, Jacek; Strawski, Marcin; Szklarczyk, Marek

    2017-01-01

    Objective The inadequate efficiency of existing therapeutic anti-cancer regiments and the increase in the multidrug resistance of cancer cells underscore the need to investigate novel anticancer strategies. The induction of apoptosis in tumors by cytotoxic agents produced by pathogenic microorganisms is an example of such an approach. Nevertheless, even the most effective drug should be delivered directly to targeted sites to reduce any negative impact on other cells. Accordingly, the stabilized nanosystem (SNS) for active agent delivery to cancer cells was designed for further application in local anti-tumor therapy. A product of genetically modified Escherichia coli, listeriolysin O (LLO), was immobilized within the polyelectrolyte membrane (poly(ethylenimine)|hyaluronic acid) shells of ‘LLO nanocarriers’ coupled with the stabilizing element of natural origin. Methods and results The impact of LLO was evaluated in human leukemia cell lines in vitro. Correspondingly, the influence of the SNS and its elements was assessed in vitro. The viability of targeted cells was evaluated by flow cytometry. Visualization of the system structure was performed using confocal microscopy. The membrane shell applied to the nanocarriers was analyzed using atomic force microscopy and Fourier transform infrared spectroscopy techniques. Furthermore, the presence of a polyelectrolyte layer on the nanocarrier surface and/or in the cell was confirmed by flow cytometry. Finally, the structural integrity of the SNS and the corresponding release of the fluorescent solute listeriolysin were investigated. Conclusion The construction of a stabilized system offers LLO release with a lethal impact on model eukaryotic cells. The applied platform design may be recommended for local anti-tumor treatment purposes. PMID:28166290

  13. Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients

    NARCIS (Netherlands)

    Sonis, S.T.; Hashemi, S.; Epstein, J.B.; Nair, R.G.; Raber-Durlacher, J.E.

    2016-01-01

    Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our in

  14. The use of biologically related model (Eclipse for the intensity-modulated radiation therapy planning of nasopharyngeal carcinomas.

    Directory of Open Access Journals (Sweden)

    Monica W K Kan

    Full Text Available Intensity-modulated radiation therapy (IMRT is the most common treatment technique for nasopharyngeal carcinoma (NPC. Physical quantities such as dose/dose-volume parameters are used conventionally for IMRT optimization. The use of biological related models has been proposed and can be a new trend. This work was to assess the performance of the biologically based IMRT optimization model installed in a popular commercial treatment planning system (Eclipse as compared to its dose/dose volume optimization model when employed in the clinical environment for NPC cases.Ten patients of early stage NPC and ten of advanced stage NPC were selected for this study. IMRT plans optimized using biological related approach (BBTP were compared to their corresponding plans optimized using the dose/dose volume based approach (DVTP. Plan evaluation was performed using both biological indices and physical dose indices such as tumor control probability (TCP, normal tissue complication probability (NTCP, target coverage, conformity, dose homogeneity and doses to organs at risk. The comparison results of the more complex advanced stage cases were reported separately from those of the simpler early stage cases.The target coverage and conformity were comparable between the two approaches, with BBTP plans producing more hot spots. For the primary targets, BBTP plans produced comparable TCP for the early stage cases and higher TCP for the advanced stage cases. BBTP plans reduced the volume of parotid glands receiving doses of above 40 Gy compared to DVTP plans. The NTCP of parotid glands produced by BBTP were 8.0 ± 5.8 and 7.9 ± 8.7 for early and advanced stage cases, respectively, while those of DVTP were 21.3 ± 8.3 and 24.4 ± 12.8, respectively. There were no significant differences in the NTCP values between the two approaches for the serial organs.Our results showed that the BBTP approach could be a potential alternative approach to the DVTP approach for NPC.

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

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    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

  16. Biological therapy of salivary adenoid cystic carcinoma%生物治疗涎腺腺样囊性癌的研究进展

    Institute of Scientific and Technical Information of China (English)

    李敏敏; 徐明菊; 孙万邦

    2014-01-01

    Adenoid cystic carcinoma is one of the most common malignant tumors of the salivary gland.Two biological characteristics of the tumors with significant:high perineural-invasion and metastatic lung.These two biological characteristics have a direct impact on the treatment and prognosis of adenoid cystic carcinoma.Surgical therapy,radiotherapy and chemotherapy effect of the tumor are not very satisfactory.Therefore,The tumor biological characteristics and study on biologic therapy has attracted wide attention from scholars at home and abroad,and has made some achievements.Now make a review of the progress of biological therapy in recent years,.%涎腺腺样囊性癌是目前最为常见的涎腺恶性肿瘤之一,该肿瘤具有显著的两大生物学特性:嗜神经侵袭性和肺高转移性,而这两大生物学特性也直接影响着涎腺腺样囊性癌的治疗和预后.该肿瘤对手术、放射治疗及化学药物治疗效果均不十分理想,因此,生物治疗引起了国内外学者的广泛关注研究,并取得了一定的成果.

  17. 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.

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

    Science.gov (United States)

    Baechler, Sébastien; Hobbs, Robert F; Prideaux, Andrew R; Wahl, Richard L; Sgouros, George

    2008-03-01

    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 alpha/beta), 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

  19. A pathogenetic approach to autoimmune skin disease therapy: psoriasis and biological drugs, unresolved issues, and future directions.

    Science.gov (United States)

    Ayroldi, Emira; Bastianelli, Alessandra; Cannarile, Lorenza; Petrillo, Maria Grazia; Delfino, Domenico V; Fierabracci, Alessandra

    2011-01-01

    Psoriasis is a chronic inflammatory disease with a complex pathophysiology and a multigenic background. Autoimmunity and genetic hallmarks couple to confer the disease, which is characterized by chronic plaques (85-90% of all cases) and/or psoriasis arthritis (PsA), and involve the peripheral and sacro-iliac joints, nails, and skeleton. Dissecting the ethiopathogenetic mechanisms of psoriasis and PsA is a major basic research challenge. One important question is whether a single inflammatory mediator can be responsible for the interactive network that forms between immune cells and cytokines in this disease. Despite much progress, no research has yet been able to define a single model to explain the multifaceted pathogenesis of psoriasis and PsA. It is known that both the innate and adaptive immune systems are involved, antigen presenting cells and T lymphocytes play a prominent role, and that the deregulation of the T helper (Th)- 1/Th-2/Th-17/Th-23 axis is directly implicated in disease pathogenesis. Pharmacological therapy for psoriasis has evolved with the development of human knowledge of the disease pathophysiology. Thus, the first "ethiopathogenetic" drugs (e.g., methotrexate, cyclosporin, and alefacept) inhibited T-cell activation directly or targeted co-accessory molecules implicated in T-cell activation. When the mechanism underlying psoriatic inflammation was accepted as a cytokine network disorder, more specific biologics were studied in murine models and were later used clinically. Tumor necrosis factor was the first successful target of cytokine inhibition therapy for psoriasis and PsA (e.g., infliximab, adalimumab, and etanercept). With the recently discovered role for Th-17 in autoimmunity, drugs targeting interleukin-23 (ustekinumab) have become accepted for the pharmacological treatment of psoriasis. The expansion of pharmacological treatment options for psoriasis is not complete. As the knowledge of pathogenetic mechanisms increases, it may be

  20. Biological therapy in the treatment of moderate-to-severe ulcerative colitis patients: can colectomy be prevented?

    Directory of Open Access Journals (Sweden)

    Fábio Vieira Teixeira

    2011-12-01

    Full Text Available Ulcerative colitis treatment intends to induce remission, and its maintenance. Biological drugs, such as infliximab, have been indicated in moderate and severe cases of the disease, which are unresponsive to conventional medication. Randomized controlled trials proved the efficacy of biological treatment with high rates of sustained disease remission and mucosal healing. Recently, the concept of mucosal healing has been inversely associated with surgical treatment. Patients treated with infliximab have lower colectomy rates than those receiving conventional therapies. We suppose that earlier use of biological drugs in disease's course would lead to better clinical control and mucosal healing, with a consequent reduction in colectomy rates. To support this hypothesis, a literature review from January, 1996 to April, 2011 was performed.O tratamento da colite ulcerativa tem como objetivo induzir a remissão, além da manutenção da remissão da doença. Agentes biológicos como o infliximabe têm sido indicados em casos moderados e graves da doença, os quais não respondem à medicação convencional. Ensaios clínicos randomizados comprovaram a eficácia do tratamento biológico com altas taxas de remissão da doença e cicatrização sustentada da mucosa. Recentemente, o conceito de cicatrização da mucosa tem sido inversamente associado com o tratamento cirúrgico. Pacientes tratados com infliximabe têm taxas mais baixas de colectomia se comparados com aqueles que receberam terapias convencionais. Supõe-se que quanto mais cedo for introduzida a terapia biológica no curso da doença, melhor seriam o controle clínico e a cicatrização da mucosa, com consequente redução nas taxas de colectomia. Para apoiar esta hipótese, foi realizada uma revisão da literatura entre janeiro de 1996 e abril de 2011.

  1. Pharmacological treatment of spondyloarthritis: exploring the effectiveness of nonsteroidal anti-inflammatory drugs, traditional disease-modifying antirheumatic drugs and biological therapies

    Science.gov (United States)

    Caso, Francesco; Costa, Luisa; Del Puente, Antonio; Di Minno, Matteo Nicola Dario; Lupoli, Gelsy; Scarpa, Raffaele; Peluso, Rosario

    2015-01-01

    Spondyloarthritis represents a heterogeneous group of articular inflammatory diseases that share common genetic, clinical and radiological features. The therapy target of spondyloarthritis relies mainly in improving patients’ quality of life, controlling articular inflammation, preventing the structural joints damage and preserving the functional abilities, autonomy and social participation of patients. Among these, traditional disease-modifying antirheumatic drugs have been demonstrated to be effective in the management of peripheral arthritis; moreover, in the last decade, biological therapies have improved the approach to spondyloarthritis. In patients with axial spondyloarthritis, tumor necrosis factor α inhibitors are currently the only effective therapy in patients for whom conventional therapy with nonsteroidal anti-inflammatory drugs has failed. The aim of this review is to summarize the current experience and evidence about the pharmacological approach in spondyloarthritis patients. PMID:26568809

  2. Synthesis, characterization and biological evaluation of carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture therapy.

    Science.gov (United States)

    da Silva, A Filipa F; Seixas, Raquel S G R; Silva, Artur M S; Coimbra, Joana; Fernandes, Ana C; Santos, Joana P; Matos, António; Rino, José; Santos, Isabel; Marques, Fernanda

    2014-07-28

    Herein we present the synthesis and characterization of benzo[b]acridin-12(7H)-ones bearing carboranyl moieties and test their biological effectiveness as boron neutron capture therapy (BNCT) agents in cancer treatment. The cellular uptake of these novel compounds into the U87 human glioblastoma cells was evaluated by boron analysis (ICP-MS) and by fluorescence imaging (confocal microscopy). The compounds enter the U87 cells exhibiting a similar profile, i.e., preferential accumulation in the cytoskeleton and membranes and a low cytotoxic activity (IC50 values higher than 200 μM). The cytotoxic activity and cellular morphological alterations after neutron irradiation in the Portuguese Research Reactor (6.6 × 10(7) neutrons cm(-2) s(-1), 1 MW) were evaluated by the MTT assay and by electron microscopy (TEM). Post-neutron irradiation revealed that BNCT has a higher cytotoxic effect on the cells. Accumulation of membranous whorls in the cytoplasm of cells treated with one of the compounds correlates well with the cytotoxic effect induced by radiation. Results provide a strong rationale for considering one of these compounds as a lead candidate for a new generation of BNCT agents.

  3. A regulatory perspective of clinical trial applications for biological products with particular emphasis on Advanced Therapy Medicinal Products (ATMPs).

    Science.gov (United States)

    Jones, David R; McBlane, James W; McNaughton, Graham; Rajakumaraswamy, Nishanthan; Wydenbach, Kirsty

    2013-08-01

    The safety of trial subjects is the tenet that guides the regulatory assessment of a Clinical Trial Authorization application and applies equally to trials involving small molecules and those with biological/biotechnological products, including Advanced Therapy Medicinal Products. The objective of a regulator is to ensure that the potential risk faced by a trial subject is outweighed by the potential benefit to them from taking part in the trial. The focus of the application review is to assess whether risks have been identified and appropriate steps taken to alleviate these as much as possible. Other factors are also taken into account during a review, such as regulatory requirements, and emerging non-clinical and clinical data from other trials on the same or similar products. This paper examines the regulatory review process of a Clinical Trial Authorization application from the perspectives of Quality, Non-Clinical and Clinical Regulatory Assessors at the Medicines and Healthcare products Regulatory Agency. It should be noted that each perspective has highlighted specific issues from their individual competence and that these can be different between the disciplines.

  4. 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.

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

    Science.gov (United States)

    Rigon, Roberta B; Fachinetti, Naiara; Severino, Patrícia; Santana, Maria H A; Chorilli, Marlus

    2016-01-20

    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.

  6. Herbal Therapies for Type 2 Diabetes Mellitus: Chemistry, Biology, and Potential Application of Selected Plants and Compounds

    Directory of Open Access Journals (Sweden)

    Cicero L. T. Chang

    2013-01-01

    Full Text Available Diabetes mellitus has been recognized since antiquity. It currently affects as many as 285 million people worldwide and results in heavy personal and national economic burdens. Considerable progress has been made in orthodox antidiabetic drugs. However, new remedies are still in great demand because of the limited efficacy and undesirable side effects of current orthodox drugs. Nature is an extraordinary source of antidiabetic medicines. To date, more than 1200 flowering plants have been claimed to have antidiabetic properties. Among them, one-third have been scientifically studied and documented in around 460 publications. In this review, we select and discuss blood glucose-lowering medicinal herbs that have the ability to modulate one or more of the pathways that regulate insulin resistance, β-cell function, GLP-1 homeostasis, and glucose (reabsorption. Emphasis is placed on phytochemistry, anti-diabetic bioactivities, and likely mechanism(s. Recent progress in the understanding of the biological actions, mechanisms, and therapeutic potential of compounds and extracts of plant origin in type 2 diabetes is summarized. This review provides a source of up-to-date information for further basic and clinical research into herbal therapy for type 2 diabetes. Emerging views on therapeutic strategies for type 2 diabetes are also discussed.

  7. Cost-effectiveness of biological therapy compared with methotrexate in the treatment for rheumatoid arthritis in Colombia.

    Science.gov (United States)

    Valle-Mercado, Carolina; Cubides, Maria-Fernanda; Parra-Torrado, Monica; Rosselli, Diego

    2013-12-01

    The objectives of the study are to develop a cost-effectiveness model comparing biological therapy (BT) with methotrexate (MTX) alone, in the treatment for rheumatoid arthritis (RA), combining clinical and quality-of-life data from international trials with local costs and local epidemiological data. We designed a six-month cycle Markov model with five functional states, based on Health Assessment Questionnaire, with patients initiating treatment in any of the predefined states, based on a sample of 150 local RA patients. Simulations ran for 10 and 20 years, and for the whole life span. Utilities, in quality-adjusted life years (QALY), were taken from international literature. Discount rate was 3 % for costs and utilities. We calculated direct and indirect costs using a combination of international and local data. Results are presented as incremental cost-effectiveness ratios (ICER). ICERs in euros per QALY were 143,072 for 10 years; 139,332 for 20 years; and 137,712 for the whole life span. Total costs with MTX were lower than with BT, despite higher out of pocket, productivity, and complication costs. Under conventional thresholds, and for the "average" RA patient, BT would not be cost-effective in Colombia. BT compared to MTX provides more QALYs, but at a high cost. When ICERs were estimated for Colombia, BT would not be cost-effective. We propose different thresholds for different conditions, perhaps prioritizing chronic diseases that lead to disability.

  8. Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/biological therapy are predictors of disease behavior change in patients with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    Peter Laszlo Lakatos; Zsofia Czegledi; Tamas Szamosi; Janos Banai; Gyula David; Ferenc Zsigmond; Tunde Pandur; Zsuzsanna Erdelyi; Orsolya Gemela; Janos Papp; Laszlo Lakatos

    2009-01-01

    AIM: To assess the combined effect of disease phenotype, smoking and medical therapy [steroid, azathioprine (AZA), AZA/biological therapy] on the probability of disease behavior change in a Caucasian cohort of patients with Crohn's disease (CD). METHODS: Three hundred and forty well-characterized, unrelated, consecutive CD patients were analyzed (M/F: 155/185, duration: 9.4 ± 7.5 years) with a complete clinical follow-up. Medical records including disease phenotype according to the Montreal classification, extraintestinal manifestations, use of medications and surgical events were analyzed retrospectively. Patients were interviewed on their smoking habits at the time of diagnosis and during the regular follow-up visits. RESULTS: A change in disease behavior was observed in 30.8% of patients with an initially non-stricturing, non-penetrating disease behavior after a mean disease duration of 9.0 ± 7.2 years. In a logistic regression analysis corrected for disease duration, perianal disease, smoking, steroid use, early AZA or AZA/ biological therapy use were independent predictors of disease behavior change. In a subsequent Kaplan-Meier survival analysis and a proportional Cox regression analysis, disease location ( P = 0.001), presence of perianal disease ( P < 0.001), prior steroid use ( P = 0.006), early AZA ( P = 0.005) or AZA/biological therapy ( P = 0.002), or smoking ( P = 0.032) were independent predictors of disease behavior change. CONCLUSION: Our data suggest that perianal disease, small bowel disease, smoking, prior steroid use, early AZA or AZA/biological therapy are all predictors of disease behavior change in CD patients.

  9. 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

  10. Biological Therapies for Cancer

    Science.gov (United States)

    ... Medicine 2009;7:11. [PubMed Abstract] Pardoll D. Cancer immunology. In: Abeloff M, Armitage J, Niederhuber J, Kastan ... 363(5):411-422. [PubMed Abstract] Finn OJ. Cancer immunology. New England Journal of Medicine 2008;358(25): ...

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

    Directory of Open Access Journals (Sweden)

    Tsai-Ling Liao

    Full Text Available 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 ≧ 5 mg/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.

  12. Baseline Comorbidities in a Population-Based Cohort of Rheumatoid Arthritis Patients Receiving Biological Therapy: Data from the Australian Rheumatology Association Database

    Directory of Open Access Journals (Sweden)

    Andrew M. Briggs

    2009-01-01

    Methods. Descriptive analysis from the Australian Rheumatology Association Database (ARAD. Results. Up to October 2006, there were 681 RA patients taking biologics enrolled in ARAD. Baseline data were available for 624 (72% female, mean (SD age 57.0 (12.5 years. Of these, 59.5% reported at least one comorbid condition, most commonly hypertension (35.7% and osteoporosis (30.4%; 61 (9.8% had a history of malignancy (35 nonmelanoma skin, 5 breast, 4 bowel, 5 cervix, 3 melanoma, 3 prostate and 1 each of lip, lung, myeloma, testis, uterus, vagina. Self-reported infections within the previous 6 months were common (71.5%. Conclusions. History of comorbidities, including recent infections, is common among Australian RA patients commencing biologics, and 10% have a history of malignancy. This may impact future evaluations of health outcomes among this population, including attribution of adverse events of biologic therapy.

  13. Nodal Melanoma Metastasis under Infliximab Therapy in a Patient with Nevoid Melanoma First Misdiagnosed as Benign Nevus: A Potentially Dangerous Diagnostic Pitfall in the Era of Biologic Therapies

    Directory of Open Access Journals (Sweden)

    Gilles Safa

    2013-10-01

    Full Text Available We report the case of a 53-year-old Caucasian woman who developed nodal melanoma metastasis under infliximab therapy 2 years after the removal of a nevoid melanoma, which was initially misdiagnosed as a benign compound nevus. This case illustrates the potential link between tumor necrosis factor (TNF-α inhibition and the reactivation of latent melanoma. Furthermore, this case highlights the need for a complete skin examination before using anti-TNF-α therapy to rule out atypical malignant lesions or melanomas that can easily be missed because of presentations such as nevoid melanoma.

  14. 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.

  15. 椎间盘退变生物治疗进展%The recent advances in biological therapy for intervertebral disc degeneration

    Institute of Scientific and Technical Information of China (English)

    石志远; 张超; 阮狄克

    2012-01-01

    in maintaining the water content in the discs and the matrix content of nucleus pulposus. Gene therapy overcomes the side effects of the exogenous application of the growth factors and inhibition of inflammatory factors, but it has such defects as short-term effects, instability and so on. It gradually becomes the hot point, to which the researchers pay close attention. However, gene therapy should be performed under strict safety guarantee. The successful construction of a novel regulatory system structured by adenos viruses provides a powerful guarantee for the safety of gene therapy. As the carriers of cells, factors and genes, scaffold materials are indispensable in biological therapy. However, the pathogenic mechanism of the intervertebral disc degeneration has not been completely clear, which makes the biological therapy lack of a definite object. Then how to break through the bottlenecks of the biological therapy depends on the further confirmation of the mechanism of the intervertebral disc degeneration. It is also the field that should be focused on and explored by researchers.

  16. Discovery of Innovative Therapies for Rare Immune-Mediated Inflammatory Diseases via Off-Label Prescription of Biologics: The Case of IL-6 Receptor Blockade in Castleman's Disease.

    Science.gov (United States)

    Musters, Anne; Assaf, Amira; Gerlag, Danielle M; Tak, Paul P; Tas, Sander W

    2015-01-01

    Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, inflammatory bowel diseases, and various hematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies, it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated using a case of multicentric Castleman's disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody) treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

  17. Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    Science.gov (United States)

    Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

    2014-03-01

    New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer.

  18. The dependency of compound biological effectiveness factors on the type and the concentration of administered neutron capture agents in boron neutron capture therapy

    OpenAIRE

    Masunaga, Shin-Ichiro; Sakurai, Yoshinori; Tanaka, Hiroki; Tano, Keizo; Suzuki, Minoru; Kondo, Natsuko; Narabayashi, Masaru; Nakagawa, Yosuke; Watanabe, Tsubasa; Maruhashi, Akira; ONO, KOJI

    2014-01-01

    Purpose To examine the effect of the type and the concentration of neutron capture agents on the values of compound biological effectiveness (CBE) in boron neutron capture therapy. Methods and materials After the subcutaneous administration of a 10 B-carrier, boronophenylalanine- 10 B (BPA) or sodium mercaptododecaborate- 10 B (BSH), at 3 separate concentrations, the 10 B concentrations in tumors were measured by γ-ray spectrometry. SCC VII tumor-bearing C3H/He mice received 5-bromo-2′-deoxyu...

  19. 系统应用生物制剂治疗关节病性银屑病进展%Biological agents in systemic therapy of psoriatic arthritis

    Institute of Scientific and Technical Information of China (English)

    施秀阳; 吴华香

    2008-01-01

    Psoriatic arthritis is a chronic, progressive inflammatory arthropathy associated with psoriasis. The specific etiology and pathogenesis of psoriatic arthritis is unknown at present, and some patients with severe psoriatic arthritis do not respond to conventional therapy. Biological agents, such as TNF antagonists, IL-1 antagonists, T cell specific biologic agent, have shown good effects in the treatment of psoriatic arthritis. Also, compared with disease modifying antirheumatic drugs, biologic agents are more effective, tolerable and safer, nevertheless, a variety of adverse reactions have been observed, choice and use of biological agents need to be cautious.%关节病性银屑病是一种与银屑病相关的慢性进行性炎性皮肤与关节疾病,其病因和发病机制不清,一些严重的关节病件银屑病患者对常规治疗无效.目前肿瘤坏死因子抑制剂、IL-1抑制剂、针对T细胞治疗等生物制剂治疗关节病性银屑病已显示出疗效,同时存在一定的不良反应,使用时需谨慎,但是与慢作用抗风湿药物相比,疗效更为明显,且具有更好的耐受性.

  20. Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

    Science.gov (United States)

    Manegold, Christian

    2014-09-01

    The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources.

  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

    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 rationale for using RTX; give an overview of the possible mechanisms of action; and give an account of its effects and side-effects when used in GD and TAO. Scant evidence, originating from only a few methodologically inhomogeneous studies, suggests that RTX may prolong remission for hyperthyroidism over...... 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. 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.…

  3. Gene Therapy for the Treatment of Parkinson’s Disease: The Nature of the Biologics Expands the Future Indications

    Directory of Open Access Journals (Sweden)

    Massimo S. Fiandaca

    2012-06-01

    Full Text Available The pharmaceutical industry’s development of therapeutic medications for the treatment of Parkinson’s disease (PD endures, as a result of the continuing need for better agents, and the increased clinical demand due to the aging population. Each new drug offers advantages and disadvantages to patients when compared to other medical offerings or surgical options. Deep brain stimulation (DBS has become a standard surgical remedy for the effective treatment of select patients with PD, for whom most drug regimens have failed or become refractory. Similar to DBS as a surgical option, gene therapy for the treatment of PD is evolving as a future option. In the four different PD gene therapy approaches that have reached clinical trials investigators have documented an excellent safety profile associated with the stereotactic delivery, viral vectors and doses utilized, and transgenes expressed. In this article, we review the clinically relevant gene therapy strategies for the treatment of PD, concentrating on the published preclinical and clinical results, and the likely mechanisms involved. Based on these presentations, we advance an analysis of how the nature of the gene therapy used may eventually expand the scope and utility for the management of PD.

  4. 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

  5. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organisation: pregnancy and pediatrics.

    Science.gov (United States)

    Mahadevan, Uma; Cucchiara, Salvatore; Hyams, Jeffrey S; Steinwurz, Flavio; Nuti, F; Travis, Simon P L; Sandborn, William J; Colombel, Jean-Frederio

    2011-02-01

    Women with inflammatory bowel disease (IBD) have similar rates of fertility to the general population, but have an increased rate of adverse pregnancy outcomes compared with the general population, which may be worsened by disease activity. Infertility is increased in those undergoing ileal pouch-anal anastomosis. Anti-tumor necrosis factor therapy in pregnancy is considered to be low risk and compatible with use during conception in men and women and during pregnancy in at least the first two trimesters. Infliximab (IFX) and certolizumab pegol are also compatible with breastfeeding, but safety data for adalimumab (ADA) are awaited. The safety of natalizumab during pregnancy is unknown. For children with Crohn's disease (CD), IFX is effective at inducing and maintaining remission. Episodic therapy is not as effective as scheduled infusions. Disease duration in children does not appear to affect the efficacy of IFX. IFX promotes growth in prepubertal and early pubertal Crohn's patients. It is also effective for the treatment of extraintestinal manifestations. ADA is effective for children with active CD and for maintaining remission, even if they have lost response to IFX, although there are fewer data. Vaccination of infants exposed to biological therapy in utero should be given at standard schedules during the first 6 months of life, except for live-virus vaccines such as rotavirus. Inactivated vaccines may be safely administered to children with IBD, even when immunocompromised.

  6. 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...

  7. HER3 comes of age: new insights into its functions and role in signaling, tumor biology, and cancer therapy.

    Science.gov (United States)

    Campbell, Marcia R; Amin, Dhara; Moasser, Mark M

    2010-03-01

    The human epidermal growth family (HER) of tyrosine kinase receptors underlies the pathogenesis of many types of human cancer. The oncogenic functions of three of the HER proteins can be unleashed through amplification, overexpression, or mutational activation. This has formed the basis for the development of clinically active targeted therapies. However, the third member HER3 is catalytically inactive, not found to be mutated or amplified in cancers, and its role and functions have remained shrouded in mystery. Recent evidence derived primarily from experimental models now seems to implicate HER3 in the pathogenesis of several types of cancer. Furthermore, the failure to recognize the central role of HER3 seems to underlie resistance to epidermal growth factor receptor (EGFR)- or HER2-targeted therapies in some cancers. Structural and biochemical studies have now greatly enhanced our understanding of signaling in the HER family and revealed the previously unrecognized activating functions embodied in the catalytically impaired kinase domain of HER3. This renewed interest and mechanistic basis has fueled the development of new classes of HER3-targeting agents for cancer therapy. However, identifying HER3-dependent tumors presents a formidable challenge and the success of HER3-targeting approaches depends entirely on the development and power of predictive tools.

  8. Mycobacterium kansasii Infection in a Patient Receiving Biologic Therapy-Not All Reactive Interferon Gamma Release Assays Are Tuberculosis.

    Science.gov (United States)

    Saleem, Nasir; Saba, Raya; Maddika, Srikanth; Weinstein, Mitchell

    2017-04-01

    Mycobacterium kansasii, a nontuberculous mycobacterium, can lead to lung disease similar to tuberculosis. Immunotherapeutic biologic agents predispose to infections with mycobacteria, including M kansasii. T-cell-mediated interferon gamma release assays like QuantiFERON-TB Gold Test (QFT) are widely used by clinicians for the diagnosis of infections with Mycobacterium tuberculosis; however, QFT may also show positive result with certain nontuberculous mycobacterial infections. We report a case of M kansasii pulmonary infection, with a positive QFT, in an immunocompromised patient receiving prednisone, leflunomide and tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody. This case highlights the risk of mycobacterial infections with the use of various biologic agents and the need for caution when interpreting the results of interferon gamma release assays.

  9. 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

    2015-10-21

    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.

  10. The onset of psoriasis during the treatment of inflammatory bowel diseases with infliximab: should biological therapy be suspended?

    Directory of Open Access Journals (Sweden)

    Rafael Denadai

    2012-06-01

    Full Text Available CONTEXT: Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD patients. OBJECTIVE: To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. METHODS: A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. RESULTS: Thirty-four studies (69 IBD patients met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%, was female (47.83%, had an average age of 27.11 years, and no reported history of psoriasis (84.05%. The patients developed primarily plaque-type psoriasis (40.58%. There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. CONCLUSION: As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

  11. Cutaneous lymphocyte-associated antigen as a novel predictive marker of TNF-alpha inhibitor biological therapy in psoriasis.

    Science.gov (United States)

    Jókai, Hajnalka; Szakonyi, József; Kontár, Orsolya; Barna, Gábor; Inotai, Dóra; Kárpáti, Sarolta; Holló, Péter

    2013-03-01

    A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.

  12. 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.

  13. The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Alessandro Comandone

    2011-12-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a. Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

  14. Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients.

    Science.gov (United States)

    Sonis, Stephen T; Hashemi, Sepehr; Epstein, Joel B; Nair, Raj G; Raber-Durlacher, Judith E

    2016-03-01

    Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways that have been strongly associated with negative tumor outcomes including proliferation, invasion, angiogenesis, metastases and cancer-treatment resistance. In light of these findings, we suggest an investigational strategy to assure that LLLT's anti-mucositis efficacy is independent of its possible potential to enhance threatening tumor behaviors. Included are appropriate pre-clinical modeling, short- and long-term follow-up of LLLT-treated patients, and the requirement for consistency of LLLT parameters.

  15. 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...

  16. Advances in the biology and therapy of chronic myeloid leukemia (CML): Proceedings from the 6th Post-ASH International CML and Myeloproliferative Neoplasms Workshop

    Science.gov (United States)

    Van Etten, Richard A.; Mauro, Michael; Radich, Jerald P.; Goldman, John M.; Saglio, Giuseppe; Jamieson, Catriona; Soverini, Simona; Gambacorti-Passerini, Carlo; Hehlmann, Rüdiger; Martinelli, Giovanni; Perrotti, Danilo; Scadden, David T.; Skorski, Tomasz; Tefferi, Ayalew; Mughal, Tariq I.

    2012-01-01

    Following the 53rd annual meeting of the American Society of Hematology in San Diego in December 2011, a group of clinical and laboratory investigators convened for the 6th post-ASH International Workshop on chronic myeloid leukemia (CML) and myeloproliferative neoplasms (MPN). The workshop took place on the 13th–14th December at the Estancia, La Jolla, California, USA. This report summarizes the most recent advances in the biology and therapy of CML that were presented at ASH and discussed at the Workshop. Preclinical studies focused on the CML stem cell and its niche, and on early results of deep sequencing of CML genomes. Clinical advances include updates on 2nd and 3rd generation TKIs, molecular monitoring, TKI discontinuation studies, and new therapeutic agents. A report summarizing the pertinent advances in MPN has been published separately. PMID:23121619

  17. ASSESSMENT OF THE RESPONSE OF PATIENTS WITH CROHN'S DISEASE TO BIOLOGICAL THERAPY USING NEW NON-INVASIVE MARKERS: lactoferrin and calprotectin

    Directory of Open Access Journals (Sweden)

    Islaine Martins NOGUEIRA

    2013-04-01

    Full Text Available Context The use of fecal markers to monitor Crohn's disease is crucial for assessing the response to treatment. Objective To assess the inflammatory activity of Crohn's disease by comparing fecal markers (calprotectin and lactoferrin, colonoscopy combined with biopsy, and the Crohn's disease activity index (CDAI, as well as serum markers, before treatment with infliximab, after the end of induction, and after the end of maintenance. Methods Seventeen patients were included who had been previously diagnosed with Crohn's disease and were using conventional treatment but required the introduction of biological therapy with infliximab. Each patient underwent a colonoscopy with biopsy, serum, and fecal (calprotectin and lactoferrin tests to assess inflammatory activity, and CDAI assessments before treatment with infliximab, after induction (week 8, and after maintenance (week 32. Results The calprotectin levels exhibited significant reductions (P = 0.04 between the assessment before treatment with infliximab and the end of induction, which did not occur after the end of the maintenance phase. Lactoferrin remained positive throughout the three phases of the study. Regarding the histological assessment, a significant difference was found only between the assessment before treatment and after the end of maintenance (P = 0.036, and 60% of the patients exhibited histological improvements after the completion of the follow-up period. The CDAI exhibited a significant difference between the assessment before treatment with infliximab and after induction, as well as before treatment and after maintenance (P<0.01. Conclusion Calprotectin and lactoferrin are not useful for monitoring inflammatory activity in Crohn's disease patients who are subjected to biological therapy.

  18. 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.

  19. A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis:sensitive to chemical and biological therapy

    Institute of Scientific and Technical Information of China (English)

    Yi-Qian Liu; Wei-You Zhu; Yong-Qian Shu; Yan-Hong Gu

    2012-01-01

    Mycosis fungoides is a common cutaneousT-cell lymphoma, which is usually characterized by chronic, indolence progression, with absence of typical symptoms in early stage, metastasis to lymph nodes, bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma. It can result in secondary skin infection which is a frequent cause of death. At present, no curative therapy existed. Therapeutic purpose is to induce remission, reduce tumor burden and protect immune function of patients. A case of patient with advanced severe mycosis fungoides receivingCHOP plus interferon α-2a was reported here, with disease-free survival of 7 months and overall survival of over17.0 months, and current status as well as developments of mycosis fungoides were briefly introduced.

  20. A case of advanced mycosis fungoides with comprehensive skin and visceral organs metastasis: sensitive to chemical and biological therapy.

    Science.gov (United States)

    Liu, Yi-Qian; Zhu, Wei-You; Shu, Yong-Qian; Gu, Yan-Hong

    2012-08-01

    Mycosis fungoides is a common cutaneous T-cell lymphoma, which is usually characterized by chronic, indolence progression, with absence of typical symptoms in early stage, metastasis to lymph nodes, bone marrow and visceral organs in later stage and ultimately progression to systemic lymphoma. It can result in secondary skin infection which is a frequent cause of death. At present, no curative therapy existed. Therapeutic purpose is to induce remission, reduce tumor burden and protect immune function of patients. A case of patient with advanced severe mycosis fungoides receiving CHOP plus interferon α-2a was reported here, with disease-free survival of 7 months and overall survival of over 17.0 months, and current status as well as developments of mycosis fungoides were briefly introduced.

  1. Experimental studies on the biological effects of extracorporeal shock wave therapy on tendon models. A review of the literature.

    Science.gov (United States)

    Visco, Vincenzo; Vulpiani, Maria Chiara; Torrisi, Maria Rosaria; Ferretti, Andrea; Pavan, Antonio; Vetrano, Mario

    2014-07-01

    Encouraging results using extracorporeal shock wave therapy (ESWT) for treating chronic tendinopathies were recently obtained, although the specific mechanisms by which it induces therapeutic effects remain largely unknown. In order to provide possible explications of such clinical efficacy, several reports have investigated the effects of ESWT on animal models and different kind of cultured cells. Our contribute in establishing the potential outcome of ESWT on human primary cultured tenocytes, derived from healthy compared to ruptured tendons, have supported the growing evidence that shock waves may supply faster post-injury recovery. The purpose of this review was to summarize and evaluate the available basic scientific evidences for using ESWT in tendon pathologies, suggesting possible shock waves-induced mechanisms of tissue repair.

  2. [Safety and efficacy of biologics directed against TNF-alpha and CD20 in the therapy of vasculitis and systemic lupus erythematosus].

    Science.gov (United States)

    Walker, Ulrich A; Hasler, Paul

    2008-05-01

    While the inhibition of TNF-alpha has been shown to improve vasculitis in vitro and in animal models, the clinical evidence for the efficacy of TNF-alpha blockade in most forms of vasculitis is mainly based on case reports and case series. Randomised controlled studies have so far not shown superiority of anti-TNF-alpha agents for Wegener's granulomatosis and giant cell arteritis. Moreover, in the context of Wegener's granulomatosis, a higher frequency and severity of infections are to be expected. In refractory cases of Behçet's disease therapy of uveitis and other organ manifestations is promising. Rituximab has achieved good effects in case reports of vasculitis. Results from controlled trials are not available. Observational studies indicate that in refractory systemic lupus erythematosus, and possibly also in several instances of small vessel vasculitis, rituximab can achieve good responses. The increased frequency of severe infections under TNF-alpha blockade requires a stringent benefit and risk assessment in addition to a multidisciplinary analysis of follow-up parameters. A detailed information of the patient regarding symptoms and signs of a possible infection are a prerequisite. Due to the complexity of the field and the danger of morbidity and mortality as a consequence of vasculitis or systemic lupus erythematosus on the one hand, and of the therapy on the other, biologics should only be used to treat these disorders in institutions fully equipped and staffed for this purpose.

  3. Synthesis, Photophysical Properties, and Biological Evaluation of trans-Bisthioglycosylated Tetrakis(fluorophenyl)chlorin for Photodynamic Therapy.

    Science.gov (United States)

    Hirohara, Shiho; Oka, Chio; Totani, Masayasu; Obata, Makoto; Yuasa, Junpei; Ito, Hiromu; Tamura, Masato; Matsui, Hirofumi; Kakiuchi, Kiyomi; Kawai, Tsuyoshi; Kawaichi, Masashi; Tanihara, Masao

    2015-11-12

    trans-Bisthioglycosylated tetrakis(fluorophenyl)chlorin (7) was designed as a powerful photodynamic therapy (PDT) photosensitizer based on the findings of our systematic studies. We show here that the trans-bisthioglycosylated structure of 7 enhanced its uptake by HeLa cells and that the chlorin ring of 7 increased the efficiency of reactive oxygen species generation under the standard condition of our photocytotoxicity test. The versatility of 7 in PDT treatment was established using weakly metastatic B16F1 melanoma cells, metastatic 4T1 breast cancer cells, the RGK-1 gastric carcinoma mucosal cell line, and three human glioblastoma cell lines (U87, U251, and T98G). The pharmacokinetics of 7 in mice bearing 4T1 breast cancer cells showed a high tumor-to-skin concentration ratio (approximately 60) at 24 h after intraperitoneal injection. The PDT efficacy of 7 in vivo was approximately 250-times higher than that of mono-l-aspartyl chlorin e6 (9) in mice bearing 4T1 breast cancer cells.

  4. Current Status of Herbal Medicines in Chronic Liver Disease Therapy: The Biological Effects, Molecular Targets and Future Prospects

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2015-12-01

    Full Text Available Chronic liver dysfunction or injury is a serious health problem worldwide. Chronic liver disease involves a wide range of liver pathologies that include fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The efficiency of current synthetic agents in treating chronic liver disease is not satisfactory and they have undesirable side effects. Thereby, numerous medicinal herbs and phytochemicals have been investigated as complementary and alternative treatments for chronic liver diseases. Since some herbal products have already been used for the management of liver diseases in some countries or regions, a systematic review on these herbal medicines for chronic liver disease is urgently needed. Herein, we conducted a review describing the potential role, pharmacological studies and molecular mechanisms of several commonly used medicinal herbs and phytochemicals for chronic liver diseases treatment. Their potential toxicity and side effects were also discussed. Several herbal formulae and their biological effects in chronic liver disease treatment as well as the underlying molecular mechanisms are also summarized in this paper. This review article is a comprehensive and systematic analysis of our current knowledge of the conventional medicinal herbs and phytochemicals in treating chronic liver diseases and on the potential pitfalls which need to be addressed in future study.

  5. Role of vitamin A in type 2 diabetes mellitus biology: effects of intervention therapy in a deficient state.

    Science.gov (United States)

    Iqbal, Sarah; Naseem, Imrana

    2015-01-01

    Diabetes has emerged as the biggest pandemic of our times, growing parallel to obesity. Insulin treatment regimens have been unable to completely inhibit protein glycation, which is responsible for the development of increased oxidative stress in diabetic tissues. Coupled with recent evidences that highlight the role of reactive oxygen species in the onset and progression of type 2 diabetes mellitus (T2DM), the antioxidants have taken prime focus as a possible intervention strategy. Studies have established a role of antioxidant vitamins C and E in improving patient condition in the past. Vitamin A, in addition to its role as an antioxidant, boasts a pleiotropic role in cell regulation through its action on gene regulation, maintenance of epithelial cell integrity, and resistance to infection. Studies have also ascribed a role to vitamin A in up-regulating the antioxidant enzyme functions in the body. Additionally, a link has been found between diabetes and deficient vitamin A levels indicating vitamin A supplementation may have a role in T2DM biology. This review therefore focuses on the vitamin A intervention in T2DM patients having deficient in vitamin A.

  6. Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy.

    Science.gov (United States)

    Schneider, Raphaël; Schmitt, Frédéric; Frochot, Céline; Fort, Yves; Lourette, Natacha; Guillemin, François; Müller, Jean-François; Barberi-Heyob, Muriel

    2005-04-15

    Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by 1H NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates 1 and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates 1 and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm2, respectively.

  7. Biological therapy of strontium-substituted bioglass for soft tissue wound-healing: responses to oxidative stress in ovariectomised rats.

    Science.gov (United States)

    Jebahi, S; Oudadesse, H; Jardak, N; Khayat, I; Keskes, H; Khabir, A; Rebai, T; El Feki, H; El Feki, A

    2013-07-01

    New synthetic biomaterials are constantly being developed for wound repair and regeneration. Bioactive glasses (BG) containing strontium have shown successful applications in tissue engineering account of their biocompatibility and the positive biological effects after implantation. This study aimed to assess whether BG-Sr was accepted by the host tissue and to characterize oxidative stress biomarker and antioxidant enzyme profiles during muscle and skin healing. Wistar rats were divided into five groups (six animals per group): the group (I) was used as negative control (T), after ovariectomy, groups II, III, IV and V were used respectively as positive control (OVX), implanted tissue with BG (OVX-BG), BG-Sr (OVX-BG-Sr) and presented empty defects (OVX-NI). Soft tissues surrounding biomaterials were used to estimate superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) concentration. Our results show that 60 days after operation, treatment of rats with BG-Sr significantly increased MDA concentration and caused an increase of SOD, CAT and GPx activities in both skin and muscular tissues. BG-Sr revealed maturation of myotubes followed a normal appearance of muscle regenerated with high density and mature capillary vessels. High wound recovery with complete re-epithelialization and regeneration of skin was observed. The results demonstrate that the protective action against reactive oxygen species (ROS) was clearly observed in soft tissue surrounding BG-Sr. Moreover, the potential use of BG-Sr rapidly restores the wound skin and muscle structural and functional properties. The BG advantages such as ion release might make BG-Sr an effective biomaterial choice for antioxidative activity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Jäkel, Oliver [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schlampp, Ingmar [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2014-04-01

    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 (TD{sub 5}) 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

  9. 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.

  10. CYTOKINES IN BREAST CANCER PATIENTS DURING RADIATION THERAPY: COMPLEMENTARY EFFECTS OF BIOLOGICALLY ACTIVE FOOD ADDITIVE CONTAINING SALMON SOFT ROE AND VITAMIN C

    Directory of Open Access Journals (Sweden)

    L. N. Fedyanina

    2007-01-01

    Full Text Available Abstract. We studied some effects of a biologically active food additive (BAFA «DNAaC» which contains DNA from salmon soft roe and vitamin C as active substances. This BAFA was investigated as a complementary remedy during radiation therapy of women with breast cancer (BrC, with respect to dynamics and levels blood serum cytokines, i.e., early hematopoietic factors (IL-3, GM-CSF, TNFa, and balance of marker cytokines for Th1- and Th2-response (IFNγ, IL-10. It was shown that «DNAaC» has modulating effect on secretion of all investigated cytokines. There was, however, a higher and statistically valid corrective effect upon GM-CSF, along with increase of initially low IFNγ and TNFa concentrations, and reduction of initially high IL-10 levels. Hence, «DNAaC» contributes to improvement of cell-mediated immune deficiency, stabilization of hematopoietic system, and brings about tolerance to basic treatment approaches in oncological diseases.

  11. Effects of temperature-dependent optical properties on the fluence rate and temperature of biological tissue during low-level laser therapy.

    Science.gov (United States)

    Kim, Soogeun; Jeong, Sungho

    2014-03-01

    The effects of temperature-dependent optical properties on the change of fluence rate and temperature distribution within biological tissues during low-level laser therapy (LLLT) were investigated by experimental and numerical methods. The fluence rate and temperature within a porcine skin were measured in vitro using an optical fiber sensor and a thermocouple, respectively, while irradiating the sample with a continuous wave laser (IPG Laser GmbH, Burbach, Germany, 1,064 nm, 3.14 W/cm(2)). The absorption and reduced scattering coefficients of porcine skin were estimated using an inverse adding-doubling algorithm from the total reflectance and transmittance measured with a double-integrating sphere. It was shown that the reduced scattering coefficient of porcine skin decreased significantly as the skin temperature increased within the range of 26-40 °C. To incorporate the temperature dependency of tissue optical properties in the simulation, a mathematical model that adopted coupled equations for fluence rate and bioheat transfer was developed. It was shown that the predicted fluence rate and temperature by the proposed mathematical model agreed closely with the measured values of porcine skin. The calculation of human skin temperature using the developed model revealed that the skin temperature could be significantly underestimated if the temperature dependency of optical properties of human skin were ignored during LLLT simulation.

  12. ESF-EMBO Symposium Molecular Biology and Innovative Therapies in Sarcomas of Childhood and AdolescenceSept 29 – Oct 4, Polonia Castle Pultusk, Poland

    Directory of Open Access Journals (Sweden)

    Beat W Schäfer

    2013-06-01

    Full Text Available Rhabdomyosarcoma (RMS and Ewing sarcoma (ES are among the most common pediatric sarcomas (Arndt et al., 2012. Despite sarcomas representing a highly heterogeneous group of tumors, ES and alveolar RMS (ARMS typically share one common genetic characteristic, namely a specific chromosomal translocation (Helman and Meltzer, 2003; Lessnick and Ladanyi, 2012. These translocations generate fusion proteins, which are composed of two transcription factors (TF. Typically, one TF is a developmentally regulated factor that is essential for proper specification of a given lineage and provides the DNA-binding domain, while the partner TF contributes a transactivation domain that drives aberrant expression of target genes. Based on these common genetic characteristics, the first ESF-EMBO research conference entitled "Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence" with special focus on RMS and ES was held at the Polonia Castle in Pultusk, Poland. The conference gathered 70 participants from more than 15 countries and several continents representing most research groups that are active in this field.

  13. ESF-EMBO Symposium “Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence” Sept 29–Oct 4, Polonia Castle Pultusk, Poland

    Science.gov (United States)

    Schäfer, Beat W.; Koscielniak, Ewa; Kovar, Heinrich; Fulda, Simone

    2013-01-01

    Rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are among the most common pediatric sarcomas (Arndt et al., 2012). Despite sarcomas representing a highly heterogeneous group of tumors, ES and alveolar RMS (ARMS) typically share one common genetic characteristic, namely a specific chromosomal translocation (Helman and Meltzer, 2003; Lessnick and Ladanyi, 2012). These translocations generate fusion proteins, which are composed of two transcription factors (TF). Typically, one TF is a developmentally regulated factor that is essential for proper specification of a given lineage and provides the DNA-binding domain, while the partner TF contributes a transactivation domain that drives aberrant expression of target genes. Based on these common genetic characteristics, the first ESF-EMBO research conference entitled “Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence” with special focus on RMS and ES was held at the Polonia Castle in Pultusk, Poland. The conference gathered 70 participants from more than 15 countries and several continents representing most research groups that are active in this field. PMID:23761860

  14. ESF-EMBO Symposium "Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence" Sept 29-Oct 4, Polonia Castle Pultusk, Poland.

    Science.gov (United States)

    Schäfer, Beat W; Koscielniak, Ewa; Kovar, Heinrich; Fulda, Simone

    2013-01-01

    Rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) are among the most common pediatric sarcomas (Arndt et al., 2012). Despite sarcomas representing a highly heterogeneous group of tumors, ES and alveolar RMS (ARMS) typically share one common genetic characteristic, namely a specific chromosomal translocation (Helman and Meltzer, 2003; Lessnick and Ladanyi, 2012). These translocations generate fusion proteins, which are composed of two transcription factors (TF). Typically, one TF is a developmentally regulated factor that is essential for proper specification of a given lineage and provides the DNA-binding domain, while the partner TF contributes a transactivation domain that drives aberrant expression of target genes. Based on these common genetic characteristics, the first ESF-EMBO research conference entitled "Molecular Biology and Innovative Therapies in Sarcomas of Childhood and Adolescence" with special focus on RMS and ES was held at the Polonia Castle in Pultusk, Poland. The conference gathered 70 participants from more than 15 countries and several continents representing most research groups that are active in this field.

  15. 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

  16. 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)

  17. 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.

  18. Gene expression profile in the muscles of patients with inflammatory myopathies: effect of therapy with IVIg and biological validation of clinically relevant genes.

    Science.gov (United States)

    Raju, Raghavan; Dalakas, Marinos C

    2005-08-01

    To explore the biological significance of gene expression in the pathogenesis of inflammatory myopathies, we performed microarray experiments followed by real-time PCR and immunohistochemistry on muscle biopsies obtained before and after therapy from patients with dermatomyositis (DM) who improved and patients with inclusion body myositis (sIBM) who did not improve after controlled trials with three monthly intravenous immunoglobulin (IVIg) infusions. The pretreatment biopsies showed high expression of immunoglobulin, adhesion molecules, chemokines and cytokine genes in both sIBM and DM (sIBM > DM). In the repeated biopsies of DM patients who clinically improved, 2206 genes were downregulated more than 1.5-fold; in contrast, 1700 of the same genes remained unchanged in sIBM patients who did not improve. Genes markedly downregulated in DM, but not sIBM, were interleukin 22, Kallmann syndrome 1 (KAL-1), an adhesion molecule shown for the first time in muscle, ICAM-1, complement C1q, and several structural protein genes. Because mRNA for KAL-1 was selectively upregulated in vitro by transforming growth factor (TGF) beta1, a fibrogenic cytokine immunolocalized in the endomysial connective tissue of pretreatment DM muscles, the downregulation of both TGF-beta and KAL-1 after IVIg only in DM suggests that these molecules have a functional role in connective tissue proliferation and fibrosis. The improved muscles of DM, but not sIBM, showed upregulation of chemokines CXCL9 (Mig) and CXCL11, and several immunoglobulin-related genes, suggesting an effect on muscle remodelling and regeneration. The results suggest that IVIg modulates several immunoregulatory or structural muscle genes, but only a subset of them associated with inflammatory mediators, fibrosis and muscle remodelling are connected with the clinical response. Gene arrays, when combined with clinical assessments, may provide important information in the pathogenesis of inflammatory myopathies.

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

    Science.gov (United States)

    Cometto, A; Russo, G; Bourhaleb, F; Milian, F M; Giordanengo, S; Marchetto, F; Cirio, R; Attili, A

    2014-12-07

    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.

  20. Psoriasis : implications of biologics

    NARCIS (Netherlands)

    Lecluse, L.L.A.

    2010-01-01

    Since the end of 2004 several specific immunomodulating therapies: ‘biologic response modifiers’ or ‘biologics’ have been registered for moderate to severe psoriasis in Europe. This thesis is considering the implications of the introduction of the biologics for psoriasis patients, focusing on safety

  1. Proton Therapy

    Science.gov (United States)

    Oelfke, Uwe

    Proton therapy is one of the most rapidly developing new treatment technologies in radiation oncology. This treatment approach has — after roughly 40 years of technical developments — reached a mature state that allows a widespread clinical application. We therefore review the basic physical and radio-biological properties of proton beams. The main physical aspect is the elemental dose distribution arising from an infinitely narrow proton pencil beam. This includes the physics of proton stopping powers and the concept of CSDA range. Furthermore, the process of multiple Coulomb scattering is discussed for the lateral dose distribution. Next, the basic terms for the description of radio-biological properties of proton beams like LET and RBE are briefly introduced. Finally, the main concepts of modern proton dose delivery concepts are introduced before the standard method of inverse treatment planning for hadron therapy is presented.

  2. Discovery of innovative therapies for rare immune-mediated inflammatory diseases via off-label prescription of biologics: the case of IL-6 receptor blockade in Castleman’s disease

    Directory of Open Access Journals (Sweden)

    Anne eMusters

    2015-12-01

    Full Text Available Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs such as rheumatoid arthritis, inflammatory bowel diseases, and various haematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be ilustrated using a case of multicentric Castleman’s disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

  3. 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....

  4. Research Prospect of the Application of Synthetic Biology in Medicine and Cancer Therapy%合成生物学在医学及肿瘤治疗应用的研究前景

    Institute of Scientific and Technical Information of China (English)

    庄成乐(综述); 黄卫人; 蔡志明(审校)

    2015-01-01

    In the 21st century,synthetic biology has become known by people as a comprehensive sub-ject with great potential.Synthetic biology can construct novel biomolecular networks ,pathways and compo-nents,and is playing a more and more important role in modern medicine due to its special features .Synthetic biology will play a very significant role in medicine and cancer therapy in future .It also has broad application opportunities out of field of medicine,while has to face problems of biological safety and ethic.%进入21世纪以来,合成生物学作为一门具有巨大潜力的综合性学科引起了人们的关注。合成生物学可以组装新的生物分子网络、路径和元件,在现代医学中扮演着越来越重要的角色。今后,合成生物学将在医药领域及肿瘤治疗应用方面发挥非常重要的作用。在医学外领域,合成生物学也具有广阔的应用前景,但是面临着生物安全和伦理等问题。

  5. Polythiophenes in biological applications.

    Science.gov (United States)

    Sista, Prakash; Ghosh, Koushik; Martinez, Jennifer S; Rocha, Reginaldo C

    2014-01-01

    Polythiophene and its derivatives have shown tremendous potential for interfacing electrically conducting polymers with biological applications. These semiconducting organic polymers are relatively soft, conduct electrons and ions, have low cytotoxicity, and can undergo facile chemical modifications. In addition, the reduction in electrical impedance of electrodes coated with polythiophenes may prove to be invaluable for a stable and permanent connection between devices and biological tissues. This review article focuses on the synthesis and some key applications of polythiophenes in multidisciplinary areas at the interface with biology. These polymers have shown tremendous potential in biological applications such as diagnostics, therapy, drug delivery, imaging, implant devices and artificial organs.

  6. Proton therapy

    Science.gov (United States)

    Proton beam therapy; Cancer - proton therapy; Radiation therapy - proton therapy; Prostate cancer - proton therapy ... that use x-rays to destroy cancer cells, proton therapy uses a beam of special particles called ...

  7. 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.

  8. Evidence-based guidelines of the spanish psoriasis group on the use of biologic therapy in patients with psoriasis in difficult-to-treat sites (nails, scalp, palms, and soles).

    Science.gov (United States)

    Sánchez-Regaña, M; Aldunce Soto, M J; Belinchón Romero, I; Ribera Pibernat, M; Lafuente-Urrez, R F; Carrascosa Carrillo, J M; Ferrándiz Foraster, C; Puig Sanz, L; Daudén Tello, E; Vidal Sarró, D; Ruiz-Villaverde, R; Fonseca Capdevila, E; Rodríguez Cerdeira, M C; Alsina Gibert, M M; Herrera Acosta, E; Marrón Moya, S E

    2014-12-01

    Psoriatic lesions affecting the scalp, nails, palms, and the soles of the feet are described as difficult-to-treat psoriasis and require specific management. Involvement of these sites often has a significant physical and emotional impact on the patient and the lesions are difficult to control with topical treatments owing to inadequate penetration of active ingredients and the poor cosmetic characteristics of the vehicles used. Consequently, when difficult-to-treat sites are involved, psoriasis can be considered severe even though the lesions are not extensive. Scant information is available about the use of biologic therapy in this setting, and published data generally comes from clinical trials of patients who also had moderate to severe extensive lesions or from small case series and isolated case reports. In this article we review the quality of the scientific evidence for the 4 biologic agents currently available in Spain (infliximab, etanercept, adalimumab, and ustekinumab) and report level i evidence for the use of biologics to treat nail psoriasis (level of recommendation A) and a somewhat lower level of evidence in the case of scalp involvement and palmoplantar psoriasis.

  9. Antiproton therapy

    CERN Document Server

    Knudsen, Helge V; Bassler, Niels; Alsner, Jan; Beyer, Gerd-Jürgen; DeMarco, John J; Doser, Michael; Hajdukovic, Dragan; Hartley, Oliver; Iwamoto, Keisuke S; Jäkel, Oliver; Kovacevic, Sandra; Møller, Søren Pape; Overgaard, Jens; Petersen, Jørgen B; Ratib, Osman; Solberg, Timothy D; Vranjes, Sanja; Wouters, Bradly G

    2008-01-01

    Radiotherapy is one of the most important means we have for the treatment of localised tumours. It is therefore essential to optimize the technique, and a lot of effort goes into this endeavour. Since the proposal by Wilson in 1946 [R.R. Wilson, Radiology use of fast protons, Radiology 47 (1946) 487.] that proton beams might be better than photon beams at inactivating cancer cells, hadron therapy has been developed in parallel with photon therapy and a substantial knowledge has been gained on the effects of pions, protons and heavy ions (mostly carbon ions). Here we discuss the recent measurements by the CERN ACE collaboration of the biological effects of antiprotons, and argue that these particles very likely are the optimal agents for radiotherapy.

  10. Curative Effect of Biological Sequence Therapy on 1665 Children with Autism%生物调序益智疗法治疗1665例孤独症儿童的疗效观察

    Institute of Scientific and Technical Information of China (English)

    蒋燕清; 李介珍; 许晓燕; 陈小霞; 陈飞龙; 史积善

    2013-01-01

    Objective To observe the curative effect of biological sequence therapy on treatment of children with autism. Methods 1665 children with autism treated in our hospital between January 2010 and December 2012 are randomly divided into treatment group and control group. In treatment group, implantation of biological proteins, traditional Chinese medicine and rehabilitation treatment are conducted;while in the control group, only implement traditional Chinese medicine and rehabilitation therapy. Results Effective rate, significant efficiency rate and invalid rate of the treatment group are 70.39%, 49.84%and 29.61%, while those in the control group are 31.7%, 15.85%and 68.3%, respectively. Through the chi-square test, effective rate of the treatment group is better than that of the control group (P<0.05). Conclusion With biological sequence therapy to treat children with autism, is economic and quick with distinct clinical curative effect and is worthy of promotion.%目的:应用生物调序益智疗法治疗孤独症儿童疗效观察。方法随机将我院2010年1月至2012年12月底收治的1665例孤独症分为治疗组和对照组,治疗组实施生物蛋白埋植、中药及康复训练治疗;对照组实施中药及康复训练治疗。结果治疗组有效率达70.39%,显效率49.84%,无效率29.61%。对照组有效率31.7%,显效率15.85%,无效率68.3%,经χ2检验,P<0.05,治疗组有效率优于对照组。结论运用生物调序益智疗法治疗孤独症儿童,经济、时间短、疗效显著,值得推广。

  11. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Martínez-Rovira, I., E-mail: immamartinez@gmail.com; Jouvie, C.; Jan, S. [Service Hospitalier Frédéric Joliot, Commissariat à l’énergie atomique et aux énergies alternatives (CEA/DSV/I2BM/SHFJ), 4 place du général Leclerc, 91401 Orsay Cedex (France)

    2015-04-15

    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{sup +} activity distributions in terms of absolute quantification and spatial distribution was studied. Methods: First, the irradiation of a human head phantom with a {sup 12}C beam, so that a homogeneous dose distribution was achieved in the tumor, was simulated. The generated {sup 11}C and {sup 15}O distribution maps were used as β{sup +} 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 (T{sub ini} = 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

  13. 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.

  14. 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...

  15. A Personalized Approach to Biological Therapy Using Prediction of Clinical Response Based on MRP8/14 Serum Complex Levels in Rheumatoid Arthritis Patients.

    Directory of Open Access Journals (Sweden)

    S C Nair

    Full Text Available Measurement of MRP8/14 serum levels has shown potential in predicting clinical response to different biological agents in rheumatoid arthritis (RA. We aimed to develop a treatment algorithm based on a prediction score using MRP8/14 measurements and clinical parameters predictive for response to different biological agents.Baseline serum levels of MRP8/14 were measured in 170 patients starting treatment with infliximab, adalimumab or rituximab. We used logistic regression analysis to develop a predictive score for clinical response at 16 weeks. MRP8/14 levels along with clinical variables at baseline were investigated. We also investigated how the predictive effect of MRP8/14 was modified by drug type. A treatment algorithm was developed based on categorizing the expected response per drug type as high, intermediate or low for each patient and optimal treatment was defined. Finally, we present the utility of using this treatment algorithm in clinical practice.The probability of response increased with higher baseline MRP8/14 complex levels (OR = 1.39, differentially between the TNF-blockers and rituximab (OR of interaction term = 0.78, and also increased with higher DAS28 at baseline (OR = 1.28. Rheumatoid factor positivity, functional disability (a higher HAQ, and previous use of a TNF-inhibitor decreased the probability of response. Based on the treatment algorithm 80 patients would have been recommended for anti-TNF treatment, 8 for rituximab, 13 for another biological treatment (other than TNFi or rituximab and for 69 no recommendation was made. The predicted response rates matched the observed response in the cohort well. On group level the predicted response based on the algorithm resulted in a modest 10% higher response rate in our cohort with much higher differences in response probability in individual patients treated contrary to treatment recommendation.Prediction of response using MRP8/14 levels along with clinical predictors has

  16. 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.

  17. 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.

  18. All biology is computational biology

    Science.gov (United States)

    2017-01-01

    Here, I argue that computational thinking and techniques are so central to the quest of understanding life that today all biology is computational biology. Computational biology brings order into our understanding of life, it makes biological concepts rigorous and testable, and it provides a reference map that holds together individual insights. The next modern synthesis in biology will be driven by mathematical, statistical, and computational methods being absorbed into mainstream biological training, turning biology into a quantitative science. PMID:28278152

  19. 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.

  20. [Biologics in SLE].

    Science.gov (United States)

    Karonitsch, Thomas; Aringer, Martin

    2015-01-01

    Biologics have become indispensable in the last decade in the treatment of the more common rheumatic diseases. For treating systemic lupus erythematodes (SLE), B-cell depletion, albeit off-label, has been a well-accepted strategy in severe and refractory disease. Unexpectedly, however, the results of the first randomized controlled rituximab trials in SLE were negative. New trials with improved study protocols are ongoing, which should resolve this issue. In 2012, with the approval of belimumab, SLE finally entered the era of approved biological therapies. The anti-Blys/BAFF antibody belimumab showed prevention of SLE flares, glucocorticoid sparing, and significant improvement in the quality of life of SLE patients, in part by drastically reducing immune complex mediated fatigue. Positive reports on further targeting approaches give hope that additional biological agents will be available for SLE therapy soon.

  1. 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.

  2. Progress Study on the biological and immune therapy for malignant melanoma%恶性黑色素瘤生物免疫治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    秦鹏; 高全立; 买玲

    2011-01-01

    Melanoma is the most serious type of skin cancer and hard to be cured by traditional therapy when metastasis occurs in the patients. Since the immunogenicity of the melanoma was discovered,the biological and immune therapy for this tumour became a hot spot of research. The clinical research on adoptive cell transfer has developed rapidly in recent years and the most remarkable effecs obtained were the infusing of autotumor infiltrating lymphocyte with over a 70% partial response. In the mean time,the research on monoclonal antibodies and signalling pathway inhibitor has been progressing quickly. These researchs have provided new approaches to the biological and immune therapy. The effects of various medicine with different mechanisms will be demonstrated in the near future,especially ipilimumab,the anti-CTLA-4 monoclonal antibody and PLX4032,an highly selective inhibitor of BRAF.%恶性黑色素瘤是一种恶性程度极高的皮肤肿瘤,病人发生转移后应用传统治疗方法很难达到有效治疗.自从恶性黑色素瘤的肿瘤抗原表位被发现后,恶性黑色素瘤的免疫治疗就开始成为研究热点.过继性细胞治疗临床应用研究在近几年内得到快速发展,其中疗效最好的当属肿瘤浸润淋巴细胞(TIL)回输治疗,其治疗有效率可以达到70%以上.同时,各种用于调节免疫系统的单克隆抗体药物以及信号传导阻滞剂的研究也在快速发展,这些研究为恶性黑色素瘤的免疫治疗提供了新思路.多种不同作用机制的药物疗效将在不久的将来得到证实,尤其是抗细胞毒性T细胞相关抗原4(CTLA-4)抗体的ipilimumab以及高选择性B型有丝分裂原激活的蛋白激酶依粘性激酶的激酶(BRAF)阻断剂PLX4032.

  3. Molecular clonality determination of ipsilateral recurrence of invasive breast carcinomas after breast-conserving therapy: comparison with clinical and biologic factors.

    Science.gov (United States)

    Goldstein, Neal S; Vicini, Frank A; Hunter, Susan; Odish, Eva; Forbes, Suzy; Kraus, Daniel; Kestin, Larry L

    2005-05-01

    We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Factors influencing the choice of first- and second-line biologic therapy for the treatment of rheumatoid arthritis: real-life data from the Italian LORHEN Registry.

    Science.gov (United States)

    Monti, Sara; Klersy, Catherine; Gorla, Roberto; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola; Pellerito, Raffaele; Fusaro, Enrico; Paolazzi, Giuseppe; Rocchetta, Pier Andrea; Favalli, Ennio Giulio; Marchesoni, Antonio; Caporali, Roberto

    2017-04-01

    According to international recommendations, the selection of the biologic disease modifying anti-rheumatic drug (bDMARD) for rheumatoid arthritis (RA) is mainly left to the clinician's preference. We analyzed the real-life factors influencing the first-line choice or the switching strategy, focusing on the prescription of abatacept (ABA) or tocilizumab (TCZ) compared to TNFα inhibitors (TNFi). Patients enrolled in the Lombardy Rheumatology Network (LORHEN) Registry after January 1, 2010, when all considered bDMARD agents were available, were included. The population was divided into "first-" and "second-line" bDMARD. We included 1910 patients (first line n = 1264, second line n = 646). Age was higher in ABA or TCZ vs TNFi treated patients (p second-line treatment, higher age, dyslipidemia, pulmonary disease, other comorbidities, and extra-articular RA manifestations were associated with ABA compared to TNFi. TCZ was associated with a second-line treatment, higher age, and more severe disease activity. Stopping the first bDMARD due to adverse events (AE) influenced the choice towards ABA. In real life, higher age and comorbidities influence the choice towards ABA and TCZ compared to TNFi. ABA was preferred in case of suspension of previous treatments due to AE. After failing a first-line TNFi, swapping to a different mechanism of action is more common.

  9. [New immunological weapons for medicine in the 21st Century: biological therapy based on the use of the latest generation monoclonal antibodies].

    Science.gov (United States)

    Aguillón, Juan C; Contreras, Juan; Dotte, Andrés; Cruzat, Andrea; Catalán, Diego; Salazar, Lorena; Molina, María Carmen; Guerrero, Julia; López, Mercedes; Soto, Lilian; Salazar-Onfray, Flavio; Cuchacovich, Miguel

    2003-12-01

    The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumah, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantation; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function.

  10. A prospective, randomized clinical study evaluating the effect of transdermal continuous oxygen therapy on biological processes and foot ulcer healing in persons with diabetes mellitus.

    Science.gov (United States)

    Driver, Vickie R; Yao, Min; Kantarci, Alpdogan; Gu, Guosheng; Park, Nanjin; Hasturk, Hatice

    2013-11-01

    Hypoxia is a major factor in delayed wound healing. The aim of this prospective, randomized, clinical trial was to compare outcomes of treatment in persons with chronic diabetic foot ulcers (DFUs) randomly assigned to transdermal continuous oxygen therapy (TCOT) for 4 weeks as an adjunct to standard care (debridement, offloading, and moisture). Nine patients (age 58.6±7.1, range 38-73 years) received TCOT (treatment group) and eight patients (age 59.9±12.6, range 35-76 years) received standard care alone (control group). Most patients (12) were male, and all had a Wagner I or II foot ulcer for an average of 14 (control group) or 20 months (treatment group). Weekly wound measurements and wound tissue biopsies were obtained and wound fluid collected. Levels of pro-inflammatory cytokines and proteases in wound fluid samples were analyzed using Luminex-based multiplex assays. Tissue-resident macrophages were quantified by immunohistochemistry. At week 4, average wound size reduction was 87% (range 55.7% to 100%) in the treatment group compared to 46% (15% to 99%) in the control group (P <0.05). Changes in cytokine levels (IL-6, IL-8) and proteinases (MMP-1,-2,-9, TIMP-1) at weeks 2 to 4 in wound fluid correlated with clinical findings. CD68+ macrophage counts showed statistically significant reduction in response to TCOT compared to the control group (P <0.01). The results of this study show that TCOT may facilitate healing of DFUs by reversing the inflammatory process through reduction in pro-inflammatory cytokines and tissue-degrading proteases. Additional research to elucidate the effects of this treatment on complete healing and increase understanding about the role of wound fluid analysis is needed.

  11. 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.

  12. Biological computation

    CERN Document Server

    Lamm, Ehud

    2011-01-01

    Introduction and Biological BackgroundBiological ComputationThe Influence of Biology on Mathematics-Historical ExamplesBiological IntroductionModels and Simulations Cellular Automata Biological BackgroundThe Game of Life General Definition of Cellular Automata One-Dimensional AutomataExamples of Cellular AutomataComparison with a Continuous Mathematical Model Computational UniversalitySelf-Replication Pseudo Code Evolutionary ComputationEvolutionary Biology and Evolutionary ComputationGenetic AlgorithmsExample ApplicationsAnalysis of the Behavior of Genetic AlgorithmsLamarckian Evolution Genet

  13. Structure of the LINGO-1-anti-LINGO-1 Li81 antibody complex provides insights into the biology of LINGO-1 and the mechanism of action of the antibody therapy.

    Science.gov (United States)

    Pepinsky, R Blake; Arndt, Joseph W; Quan, Chao; Gao, Yan; Quintero-Monzon, Omar; Lee, Xinhua; Mi, Sha

    2014-07-01

    Multiple sclerosis (MS) is an autoimmune-inflammatory disease of the central nervous system (CNS) with prominent demyelination and axonal injury. While most MS therapies target the immunologic response, there is a large unmet need for treatments that can promote CNS repair. LINGO-1 (leucine-rich repeat and Ig-containing Nogo receptor interacting protein-1) is a membrane protein selectively expressed in the CNS that suppresses myelination, preventing the repair of damaged axons. We are investigating LINGO-1 antagonist antibodies that lead to remyelination as a new paradigm for treatment of individuals with MS. The anti-LINGO-1 Li81 antibody,BIIB033, is currently in clinical trials and is the first MS treatment targeting CNS repair. Here, to elucidate the mechanism of action of the antibody, we solved the crystal structure of the LINGO-1-Li81 Fab complex and used biochemical and functional studies to investigate structure-function relationships. Li81 binds to the convex surface of the leucine-rich repeat domain of LINGO-1 within repeats 4-8. Fab binding blocks contact points used in the oligomerization of LINGO-1 and produces a stable complex containing two copies each of LINGO-1 and Fab that results from a rearrangement of contacts stabilizing the quaternary structure of LINGO-1. The formation of the LINGO-1-Li81 Fab complex masks functional epitopes within the Ig domain of LINGO-1 that are important for its biologic activity in oligodendrocyte differentiation. These studies provide new insights into the structure and biology of LINGO-1 and how Li81 monoclonal antibody can block its function.

  14. Method for photo-altering a biological system to improve biological effect

    Science.gov (United States)

    Hill, Richard A.; Doiron, Daniel R.; Crean, David H.

    2000-08-01

    Photodynamic therapy is a new adjunctive therapy for filtration surgery that does not use chemotherapy agents or radiation, but uses pharmacologically-active sensitizing compounds to produce a titratable, localized, transient, post operative avascular conjunctiva. A photosensitizing agent in a biological system is selectively activated by delivering the photosensitive agent to the biological system and laser activating only a spatially selected portion of the delivered photosensitive agent. The activated portion of the photosensitive agent reacts with the biological system to obtain a predetermined biological effect. As a result, an improved spatial disposition and effectuation of the biological effect by the photosensitive agent in the biological system is achieved.

  15. 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.

  16. Crohn's Disease: current state of biological therapy Doença de Crohn: estado atual da terapia biológica

    Directory of Open Access Journals (Sweden)

    Júlio César Monteiro Santos Júnior

    2011-12-01

    Full Text Available The inflammatory bowel diseases (IBD are defined as nonspecific chronic intestinal inflammations with possible systemic involvement. IBD have unknown etiology. The inflammatory process is complex and heterogeneous, both as to the characterization of the disease that affects the digestive tract, without an intelligible pattern of revelation and balance, and in its different systemic damages when including the extensive and severe extraintestinal symptoms. Aparently, the natural history of the disease is irregular in relation to the offending agent system and the attacked system, both in the intestinal and extraintestinal teguments. Isolated aspects showing irregularity in this balance gives us the notion that IBD, especially Crohn's disease, can be caused by the stimulation of an immune response caused by damaging agents (intestinal bacteria, but mediated by inadequate genetic factors, whose expressions determine different individual susceptibilities. These observations have been shown in genetic studies that emphasize the importance of pathological interaction between host and bacteria subsidized by a genomic region that contains genes producing proteins (NOD2 - nucleotide-binding oligomerization domain containing 2 participating in an enhanced defense response by the tissue. Increased numbers and the activation of these cells in the intestinal mucosa elevate local levels of tumor necrosis factor α (TNF-α, interleukin-1β, interferon-Γ, and cytokines of the interleukin-23-Th17 pathway. So, it can be assumed that the susceptibility, which is a result of genetic alterations, is connected to an exaggerated response in the pro-inflammatory phase because of a dysfunction in the intestinal immune system. The identification of tumor necrosis factor (TNF-α as the active element in the pro-inflammatory inadequate response gave rise to the heightened production of biological substances that could block TNF-α, at different levels, opening a large

  17. Synthetic biology for therapeutic applications.

    Science.gov (United States)

    Abil, Zhanar; Xiong, Xiong; Zhao, Huimin

    2015-02-02

    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 discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.

  18. Lefunomide in combination therapy

    NARCIS (Netherlands)

    Kalden, J.R.; Smolen, J.S.; Emery, P.; Riel, P.L.C.M. van; Dougados, M.; Strand, C.V.; Breedveld, F.C.

    2004-01-01

    In most studies of disease modifying antirheumatic drug therapy, in combination with either leflunomide or biological agents, patients are given an additional agent after they have failed treatment with methotrexate (MTX). This review of clinical studies shows that leflunomide is clinically efficaci

  19. [Biological weapons].

    Science.gov (United States)

    Kerwat, K; Becker, S; Wulf, H; Densow, D

    2010-08-01

    Biological weapons are weapons of mass destruction that use pathogens (bacteria, viruses) or the toxins produced by them to target living organisms or to contaminate non-living substances. In the past, biological warfare has been repeatedly used. Anthrax, plague and smallpox are regarded as the most dangerous biological weapons by various institutions. Nowadays it seems quite unlikely that biological warfare will be employed in any military campaigns. However, the possibility remains that biological weapons may be used in acts of bioterrorism. In addition all diseases caused by biological weapons may also occur naturally or as a result of a laboratory accident. Risk assessment with regard to biological danger often proves to be difficult. In this context, an early identification of a potentially dangerous situation through experts is essential to limit the degree of damage.

  20. Biological applications of nanobiotechnology.

    Science.gov (United States)

    de Morais, Michele Greque; Martins, Vilásia Guimarães; Steffens, Daniela; Pranke, Patricia; da Costa, Jorge Alberto Vieira

    2014-01-01

    Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices derived from engineering, physics, chemistry, and biology. Nanotechnology has opened up by rapid advances in science and technology, creating new opportunities for advances in the fields of medicine, electronics, foods, and the environment. Nanoscale structures and materials (nanoparticles, nanowires, nanofibers, nanotubes) have been explored in many biological applications (biosensing, biological separation, molecular imaging, anticancer therapy) because their novel properties and functions differ drastically from their bulk counterparts. Their high volume/surface ratio, improved solubility, and multifunctionality open many new possibilities. The objective of this review is to describe the potential benefits and impacts of the nanobiotechnology in different areas.

  1. 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.

  2. GLP-1 biology and GLP-1 based antidiabetic therapy%GLP-1生物学及基于GLP-1的抗糖尿病药物研究

    Institute of Scientific and Technical Information of China (English)

    易凡; 李栋; 马伟志; 杜权

    2013-01-01

    在过去的几十年中,环境和生活方式的改变使得2型糖尿病患者的数量急剧增加,其中一个重要的病理基础是胰岛素分泌缺陷.胰高血糖素样肽1(GLP-1)是一种由肠道细胞产生及分泌的多肽激素,该激素以葡萄糖浓度依赖性方式促进胰岛β细胞分泌胰岛素,调节血糖水平.研究表明GLP-1是糖尿病治疗中的一个有效靶点,药物研发目前主要集中于GLP-1受体激动剂和降解酶抑制剂两个方面.以其强大的生物学活性为基础,GLP-1药物在临床上表现出高效、低副作用的显著优势.在此,我们对GLP-1生物学和基于GLP-1的抗糖尿病药物研发进行综述.%Environmental and lifestyle factors together account for the dramatic increase of type 2 diabetes in the past decades,in which defective insulin secretion emerges as the major culprit.Glucagon-like peptide 1 (GLP-1) is a peptide secreted from the intestine in response to nutrient ingestion,and plays an essential role in the regulation of blood glucose level by stimulating glucoses-dependent insulin secretion.Recently,GLP-1 develops to be a viable therapeutic target for the treatment of type 2 diabetes,by means of GLP-1 receptor agonists and dipeptidyl peptidase-4 inhibitors.Stemmed from its potent physiological activities,GLP-l-based therapies are clinically efficient and safe for both early and late stages of the disease,with low risk of adverse events.In this review,a comprehensive understanding of GLP-1 biology and the recent development ofGLP-l-based antidiabetic therapy are summarized.

  3. p21cip1在肿瘤生物治疗中的地位与作用%Status and role of p21cip1 for cancer biological therapy

    Institute of Scientific and Technical Information of China (English)

    陈文虎; 毛伟敏

    2009-01-01

    肿瘤是一类细胞周期性疾病,将细胞周期调控因子导入肿瘤细胞可代替或补偿缺陷的基因以抑制肿瘤的异常增生或逆转基因型.p21cip1是一种重要的细胞周期负调控蛋白,它参与细胞的生长、分化、衰老及死亡过程,同时义与肿瘤发生密切相关.就p21在肿瘤发生、发展中的作用及在肿瘤生物治疗中的主要策略作一综述.%Cancer is frequently considered to be a disease of cell cycle. Recently, it is reported that the transfer of functional ceil cycle regulators into caneer cells via vectors has the potential to intervene tumorigenesis development. This therapeutic strategy might allow cancer cells to regain missing or dysfunctional gene expression due to inhibiting aberrant proliferation or restoring phenotypes defects. As an important negative effecter of cell cycle progression, p21cip1 not only plays central roles in cell proliferation,differentiation, senescence and apoptosis, but also associates with tumor regression. In this review, we will mainly focus on discussing some recent progress in novel strategies for cancer biological therapy, related with the functions of p21cip1 in cell proliferation and apoptosis during tumorigenesis.

  4. Is synthetic biology mechanical biology?

    Science.gov (United States)

    Holm, Sune

    2015-12-01

    A widespread and influential characterization of synthetic biology emphasizes that synthetic biology is the application of engineering principles to living systems. Furthermore, there is a strong tendency to express the engineering approach to organisms in terms of what seems to be an ontological claim: organisms are machines. In the paper I investigate the ontological and heuristic significance of the machine analogy in synthetic biology. I argue that the use of the machine analogy and the aim of producing rationally designed organisms does not necessarily imply a commitment to mechanical biology. The ideal of applying engineering principles to biology is best understood as expressing recognition of the machine-unlikeness of natural organisms and the limits of human cognition. The paper suggests an interpretation of the identification of organisms with machines in synthetic biology according to which it expresses a strategy for representing, understanding, and constructing living systems that are more machine-like than natural organisms.

  5. Computational biology

    DEFF Research Database (Denmark)

    Hartmann, Lars Røeboe; Jones, Neil; Simonsen, Jakob Grue

    2011-01-01

    Computation via biological devices has been the subject of close scrutiny since von Neumann’s early work some 60 years ago. In spite of the many relevant works in this field, the notion of programming biological devices seems to be, at best, ill-defined. While many devices are claimed or proved t...

  6. Biological Oceanography

    Science.gov (United States)

    Dyhrman, Sonya

    2004-10-01

    The ocean is arguably the largest habitat on the planet, and it houses an astounding array of life, from microbes to whales. As a testament to this diversity and its importance, the discipline of biological oceanography spans studies of all levels of biological organization, from that of single genes, to organisms, to their population dynamics. Biological oceanography also includes studies on how organisms interact with, and contribute to, essential global processes. Students of biological oceanography are often as comfortable looking at satellite images as they are electron micrographs. This diversity of perspective begins the textbook Biological Oceanography, with cover graphics including a Coastal Zone Color Scanner image representing chlorophyll concentration, an electron micrograph of a dinoflagellate, and a photograph of a copepod. These images instantly capture the reader's attention and illustrate some of the different scales on which budding oceanographers are required to think. Having taught a core graduate course in biological oceanography for many years, Charlie Miller has used his lecture notes as the genesis for this book. The text covers the subject of biological oceanography in a manner that is targeted to introductory graduate students, but it would also be appropriate for advanced undergraduates.

  7. 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.

  8. Foldit Biology

    Science.gov (United States)

    2015-07-31

    Report 8/1/2013-7/31/2015 4. TITLE AND SUBTITLE Sa. CONTRACT NUMBER Foldit Biology NOOO 14-13-C-0221 Sb. GRANT NUMBER N/A Sc. PROGRAM ELEMENT...Include area code) Unclassified Unclassified Unclassified (206) 616-2660 Zoran Popović Foldit Biology (Task 1, 2, 3, 4) Final Report...Period Covered by the Report August 1, 2013 – July 31, 2015 Date of Report: July 31, 2015 Project Title: Foldit Biology Contract Number: N00014-13

  9. Biotech drugs : biological therapeutic agents

    OpenAIRE

    Grech, Godfrey; Fenech, Anthony

    2009-01-01

    The recent years has seen significant growth in a new therapeutic approach to the management of disease. Biological therapeutic agents, constitute a broad category of drugs, usually generated by recombinant techniques from living organisms. These therapies revolutionise the traditional approaches to drug design and development, and regulatory agencies have been swift in developing the necessary structures to ensure their optimal use.

  10. The Clinical Efficacy Analysis of Biological Resonance Therapy System for Children with Cough Variant Asthma%生物共振治疗系统对儿童咳嗽变异性哮喘的临床疗效观察

    Institute of Scientific and Technical Information of China (English)

    王凡; 马秀丽; 段司凤

    2014-01-01

    目的:探讨生物共振治疗系统对儿童咳嗽变异性哮喘变应原检测的意义和临床疗效.方法:选取我院咳嗽变异性哮喘儿童92例,使用生物共振治疗仪进行变应原检测,随机分成3组,包括生物共振治疗组30例(生物共振组)、服用孟鲁司特钠组34例(白三烯组)、吸入丙酸氟替卡松组28例(吸入激素组).结果:生物共振仪检测变应原阳性依次为尘螨、花粉、环境化学物、动物皮毛、杀虫剂、霉菌、细菌、木材/植物纤维等.3组治疗后的症状评分及肺功能检测较治疗前均有显著改善,生物共振组与白三烯组比较,症状评分及肺功能改善差异无统计学意义(P>0.05);而吸入激素组优于生物共振组,症状评分及肺功能改善差异有统计学意义(P<0.05).结论:生物共振治疗系统可作为儿童咳嗽变异性哮喘变应原检测的一种参考方法,近期疗效与单用白三烯调节剂相当,无明显不良反应,是治疗这类疾病的一种选择,但与吸入激素比较有差异,吸入激素仍为儿童咳嗽变异性哮喘治疗的首选方案.%Objective:To investigate the meaning and clinical efficacy of biological resonance therapy system for children with cough variant asthma.Methods:Ninety-two children with cough variant asthma detected with biological resonance therapy instrument for allergen.All children were randomly divided into three groups,including biological resonance therapy group (n =30),montelukast sodium group (n =34),fluticasone propionate group (n =28).Results:Biological resonance instrument detecting allergens are dustmites,pollen,environmental chemicals,animal fur,pesticides,mycete,bacterial,wood/plant fiber etc.The symptom scores and pulmonary functions tests of 3 groups after treatment were significantly improved compared with before treatment.There were no significant difference between the biological resonance therapy group and montelukast sodium group in scores and pulmonary

  11. 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

    Energy Technology Data Exchange (ETDEWEB)

    Machtay, Mitchell, E-mail: Mitchell.machtay@uhhospitals.org [University Hospitals/Case Western Reserve University, Cleveland, OH (United States); Bae, Kyounghwa [Radiation Therapy Oncology Group (RTOG) Department of Statistics, Philadelphia, PA (United States); Movsas, Benjamin [Henry Ford Hospital, Detroit, MI (United States); Paulus, Rebecca [Radiation Therapy Oncology Group (RTOG) Department of Statistics, Philadelphia, PA (United States); Gore, Elizabeth M. [Medical College of Wisconsin, Milwaukee, WI (United States); Komaki, Ritsuko [M.D. Anderson Cancer Center, Houston, TX (United States); Albain, Kathy [Loyola University Chicago Stritch School of Medicine, Maywood, IL (United States); Sause, William T. [LDS Hospital, Salt Lake City, UT (United States); Curran, Walter J. [Emory University, Atlanta, GA (United States)

    2012-01-01

    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

  12. Hormone Therapy

    Science.gov (United States)

    ... types of estrogen therapy relieve vaginal dryness. • Systemic estrogen protects against the bone loss that occurs early in menopause and helps prevent hip and spine fractures. • Combined estrogen and progestin therapy may reduce the risk of ...

  13. Proton Therapy

    Science.gov (United States)

    ... IMRT) Brain Tumor Treatment Brain Tumors Prostate Cancer Lung Cancer Treatment Lung Cancer Head and Neck Cancer Images related to Proton Therapy Videos related to Proton Therapy Sponsored by Please ...

  14. Radiation Therapy

    Science.gov (United States)

    ... the area is stitched shut. Another treatment, called proton-beam radiation therapy , focuses the radiation on the ... after radiation treatment ends. Sore mouth and tooth decay. If you received radiation therapy to the head ...

  15. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  16. Marcadores tumorais no câncer de pulmão: um caminho para a terapia biológica Tumor markers in lung cancer: a pathway to biological therapy

    Directory of Open Access Journals (Sweden)

    FERNANDO AZEVEDO PACHECO

    2002-06-01

    Full Text Available Os avanços recentes na genética e na biologia molecular permitiram a identificação de genes e proteínas produzidos ou superexpressados pelos tumores. Tais produtos, os chamados marcadores tumorais, antes utilizados apenas como ferramentas de diagnóstico e prognóstico, vêm atualmente tomando papel importante no desenvolvimento de novas modalidades de tratamento, direcionadas a quebrar o ciclo biológico da progressão tumoral. Neste artigo, revisa-se o papel de alguns marcadores tumorais tradicionalmente conhecidos (CEA, p53, NSE, K-ras, e descrevem-se a prevalência e a função da superexpressão do receptor do fator de crescimento epidérmico (EGFR e do seu produto protéico (p185neu. Novos agentes têm sido desenvolvidos baseando-se no bloqueio da sinalização iniciada pelo EGFR. Destes, destaca-se o ZD1839 (Iressa, uma droga via oral que inibe de modo reversível e seletivo a atividade tirosina-quinase do EGFR, e que vem demonstrando bons resultados tanto isoladamente quanto em combinação com outros agentes quimioterápicos. Tais avanços devem contribuir de modo significativo no tratamento do câncer, principalmente no carcinoma de pulmão do tipo não-pequenas células.Recent advances in genetics and molecular biology lead to the identification of genes and protein products overexpressed by tumors. Such products, called tumor markers, were previously used only as diagnostic and prognostic tools, but are currently being the target of extensive research, with growing evidence that some of them may have an important role in the development of new treatment modalities, targeting the tumor cell biological cycle. In this article, the authors review the role of some of the traditionally known tumor markers (CEA, p53, NSE, K-ras, and describe the prevalence and the role of the epidermal growth factor receptor (EGFR overexpression and its protein product, p185neu. New drugs have been developed, aiming at the blockade of the signaling

  17. 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...

  18. Biological Warfare Agents

    Directory of Open Access Journals (Sweden)

    Dev Vrat Kamboj

    2006-10-01

    Full Text Available There is a long historic record of use of biological warfare (BW agents by warring countriesagainst their enemies. However, the frequency of their use has increased since the beginningof the twentieth century. World war I witnessed the use of anthrax agent against human beingsand animals by Germans, followed by large-scale field trials by Japanese against war prisonersand Chinese population during world war II. Ironically, research and development in biologicalwarfare agents increased tremendously after the Geneva Protocol, signed in 1925, because ofits drawbacks which were overcome by Biological and Toxin Weapons Convention (BTWC in1972. Biological warfare programme took back seat after the 1972 convention but biologicalagents regained their importance after the bioterrorist attacks of anthrax powder in 2001. In thelight of these attacks, many of which turned out to be hoax, general awareness is required aboutbiological warfare agents that can be used against them. This review has been written highlightingimportant biological warfare agents, diseases caused by them, possible therapies and otherprotection measures.

  19. [Particle therapy: carbon ions].

    Science.gov (United States)

    Pommier, Pascal; Hu, Yi; Baron, Marie-Hélène; Chapet, Olivier; Balosso, Jacques

    2010-07-01

    Carbon ion therapy is an innovative radiation therapy. It has been first proposed in the forties by Robert Wilson, however the first dedicated centres for human care have been build up only recently in Japan and Germany. The interest of carbon ion is twofold: 1) the very sharp targeting of the tumour with the so called spread out Bragg peak that delivers most of the beam energy in the tumour and nothing beyond it, sparing very efficiently the healthy tissues; 2) the higher relative biological efficiency compared to X rays or protons, able to kill radioresistant tumour cells. Both properties make carbon ions the elective therapy for non resectable radioresistant tumours loco-regionally threatening. The technical and clinical experience accumulated during the recent decades is summarized in this paper along with a detailed presentation of the elective indications. A short comparison between conventional radiotherapy and hadrontherapy is proposed for the indications which are considered as priority for carbon ions.

  20. 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.

  1. Biologic Agents in Inflammatory Eye Disease

    OpenAIRE

    Chiara Posarelli; Ilir Arapi; Michele Figus; Piergiorgio Neri

    2011-01-01

    Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly im...

  2. Biology Notes.

    Science.gov (United States)

    School Science Review, 1981

    1981-01-01

    Outlines a variety of laboratory procedures, techniques, and materials including construction of a survey frame for field biology, a simple tidal system, isolation and applications of plant protoplasts, tropisms, teaching lung structure, and a key to statistical methods for biologists. (DS)

  3. (Biological dosimetry)

    Energy Technology Data Exchange (ETDEWEB)

    Preston, R.J.

    1990-12-17

    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  4. 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)

  5. Scaffolded biology.

    Science.gov (United States)

    Minelli, Alessandro

    2016-09-01

    Descriptions and interpretations of the natural world are dominated by dichotomies such as organism vs. environment, nature vs. nurture, genetic vs. epigenetic, but in the last couple of decades strong dissatisfaction with those partitions has been repeatedly voiced and a number of alternative perspectives have been suggested, from perspectives such as Dawkins' extended phenotype, Turner's extended organism, Oyama's Developmental Systems Theory and Odling-Smee's niche construction theory. Last in time is the description of biological phenomena in terms of hybrids between an organism (scaffolded system) and a living or non-living scaffold, forming unit systems to study processes such as reproduction and development. As scaffold, eventually, we can define any resource used by the biological system, especially in development and reproduction, without incorporating it as happens in the case of resources fueling metabolism. Addressing biological systems as functionally scaffolded systems may help pointing to functional relationships that can impart temporal marking to the developmental process and thus explain its irreversibility; revisiting the boundary between development and metabolism and also regeneration phenomena, by suggesting a conceptual framework within which to investigate phenomena of regular hypermorphic regeneration such as characteristic of deer antlers; fixing a periodization of development in terms of the times at which a scaffolding relationship begins or is terminated; and promoting plant galls to legitimate study objects of developmental biology.

  6. Biology Notes.

    Science.gov (United States)

    School Science Review, 1984

    1984-01-01

    Presents information on the teaching of nutrition (including new information relating to many current O-level syllabi) and part 16 of a reading list for A- and S-level biology. Also includes a note on using earthworms as a source of material for teaching meiosis. (JN)

  7. Biologic Agents in Inflammatory Eye Disease

    Directory of Open Access Journals (Sweden)

    Chiara Posarelli

    2011-01-01

    Full Text Available Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy.

  8. Biologic agents in inflammatory eye disease.

    Science.gov (United States)

    Posarelli, Chiara; Arapi, Ilir; Figus, Michele; Neri, Piergiorgio

    2011-10-01

    Non-infectious uveitis is a potentially sight threatening disease. Along the years, several therapeutic strategies have been proposed as a means to its treatment, including local and systemic steroids, immunosuppressives and more recently, biologic agents. The introduction of biologics can be defined as a new era: biologic therapies provide new options for patients with refractory and sight threatening inflammatory disorders. The availability of such novel treatment modalities has markedly improved the therapy of uveitis and considerably increased the possibility of long-term remissions. This article provides a review of current literature on biologic agents, such as tumor necrosis factor blockers, anti-interleukins and other related biologics, such as interferon alpha, for the treatment of uveitis. Several reports describe the efficacy of biologics in controlling a large number of refractory uveitides, suggesting a central role in managing ocular inflammatory diseases. However, there is still lack of randomized controlled trials to validate most of their applications. Biologics are promising drugs for the treatment of uveitis, showing a favorable safety and efficacy profile. On the other hand, lack of evidence from randomized controlled studies limits our understanding as to when commence treatment, which agent to choose, and how long to continue therapy. In addition, high cost and the potential for serious and unpredictable complications have very often limited their use in uveitis refractory to traditional immunosuppressive therapy.

  9. [Laser radiations in medical therapy].

    Science.gov (United States)

    Richand, P; Boulnois, J L

    1983-06-30

    The therapeutic effects of various types of laser beams and the various techniques employed are studied. Clinical and experimental research has shown that Helio-Neon laser beams are most effective as biological stimulants and in reducing inflammation. For this reasons they are best used in dermatological surgery cases (varicose ulcers, decubital and surgical wounds, keloid scars, etc.). Infrared diode laser beams have been shown to be highly effective painkillers especially in painful pathologies like postherpetic neuritis. The various applications of laser therapy in acupuncture, the treatment of reflex dermatologia and optic fibre endocavital therapy are presented. The neurophysiological bases of this therapy are also briefly described.

  10. 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.

  11. 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.

  12. Sweat Therapy.

    Science.gov (United States)

    Colmant, Stephen A.; Merta, Rod J.

    2000-01-01

    A study combined group sweating and group counseling. Four adolescent boys with disruptive behavior disorders participated in 12 sweat therapy sessions. They reported the sessions useful for sharing personal concerns and receiving assistance with problem solving. Three boys showed improvement in self-esteem. Advantages of sweat therapy over other…

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

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    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)

  14. 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…

  15. Exploring targeted therapies in oncology

    NARCIS (Netherlands)

    Mom, Constantijne Helene

    2007-01-01

    Targeted therapy in oncology is treatment directed at specific biological pathways and processes that play a critical role in carcinogenesis. Increased knowledge regarding the molecular changes underlying tumor progression and metastatis has resulted in the development of agents that are designed to

  16. 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.

  17. Biological features of the choriocapillaries after hypocrellin B photodynamic therapy%竹红菌乙素-光动力疗法对脉络膜毛细血管影响的生物学特征

    Institute of Scientific and Technical Information of China (English)

    刘凡光; 韩丽娜; 顾瑛; 张丽; 陈红霞

    2005-01-01

    BACKGROUND:The authors' experiments of the earlier stage proved that the hypocrellin B photodynamic therapy(HB-PDT) can cause selective injuries to choriocapillaries. It is not known whether changing the therapeutic parameters would gain a different result regarding the choriocapillaries after the hypocrellin B photodynamic treatment for a month.OBJECTIVE: To observe the features of Chinchilla rabbit choriocapillaries after HB-PDT treatment and to probe into the research prospect of using HB-PDT to treat choroidal neovascularization (CNV) and of using green light as the light source for PDT.DESIGN: A single sample study.SETTING: Laser Department of the Chinese PLA General Hospital.MATERIALS: The trial was conducted at the Laser Department and the Department of Pathology of the Chinese PLA General Hospital as well as the Department of Photoelectric Engineering of Beijing University of Science and Engineering. The materials included photosensitizing agent hypocrellin B (HB), a green laser transmitter, fundus fluorescence camera and transmission electronic microscope.METHODS: The 532 nm green laser transmitter and slit-lamp microscope were connected by light fiber. Chinchilla rabbits of 2.5 to 3.5 kg was narcotized generally and HB(1. 0 mg/kg) was injected into the marginal ear vein. HB was excited with the green laser of 532 nm. The power density of the light spot on fundus was 300 mW/cm2, and the energy density 30 J/cm2. Laser was applied immediately after HB injection and the diameter of the light spot was 2 000 μm. Direct observation of retina, fluorescein fundus angiography and observation with light microscope and electronic microscope were conducted on the 1st, 7th and 28th days respectively after PDT to find the biological features of retina and the choroid.MAIN OUTCOME MEASURES: Non-selective injury of retina through direct observation of the fundus; obliteration of the choriocapillaries detected through fluorescein fundus angiography; the position and

  18. 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.

  19. Adjuvant Therapy: Melanoma

    Directory of Open Access Journals (Sweden)

    Diwakar Davar

    2011-01-01

    Full Text Available With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4 monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway.

  20. 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 ...

  1. Radiation Therapy

    Science.gov (United States)

    Radiation therapy is a cancer treatment. It uses high doses of radiation to kill cancer cells and stop them from ... half of all cancer patients receive it. The radiation may be external, from special machines, or internal, ...

  2. Targeted Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    David Cheng

    2011-10-01

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

  3. 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

  4. 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 ...

  5. 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.

  6. 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 ...

  7. Hyperbaric Oxygen Therapy

    Science.gov (United States)

    ... before your first hyperbaric oxygen therapy session. During hyperbaric oxygen therapy Hyperbaric oxygen therapy typically is performed ... and the therapy unit throughout your treatment. After hyperbaric oxygen therapy You may feel somewhat tired or ...

  8. 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…

  9. 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.

  10. Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression : A longitudinal pilot study

    NARCIS (Netherlands)

    Tendolkar, Indira; van Beek, Marleen; van Oostrom, Iris; Mulder, Marlies; Janzing, Joost; Voshaar, Richard Oude; van Eijndhoven, Philip

    2013-01-01

    Electroconvulsive therapy (ECT) is the most potent biological therapy in depression. Animal studies suggest that ECT acts via neuroplasticity effects on limbic structures involved in the pathophysiology of depression but in vivo evidence at the human system level is scarce. Therefore, the aim of the

  11. 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.

  12. [Testosterone therapy].

    Science.gov (United States)

    Diemer, T; Hauptmann, A; Wagenlehner, F M E

    2016-04-01

    Hormone replacement therapy with testosterone has become well-established over the course of time. The initial substantial concerns with respect to complications and potential adverse events, particularly in older patients, were proven to be unfounded over time. Testosterone therapy has therefore gradually become a regular treatment modality in urological practice. It has also been shown to represent a valuable tool as supportive treatment for patients with erectile dysfunction and hypogonadism. A variety of testosterone preparations are available for treatment. Recent pharmaceutical developments have greatly improved the practicability and ease of administration for patients. Several guidelines have been developed that provide clearly formulated standards and instructions for indications, contraindications, application, risk factors and monitoring of testosterone therapy. Adverse events affecting the cardiovascular system and especially diseases of the prostate gland are of great importance, thus making the urologist the primary partner in the treatment of patients with testosterone deficiency.

  13. 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....

  14. 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......, 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...... 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...

  15. Isolation and Characterization of Two Lytic Bacteriophages, φSt2 and φGrn1; Phage Therapy Application for Biological Control of Vibrio alginolyticus in Aquaculture Live Feeds.

    Science.gov (United States)

    Kalatzis, Panos G; Bastías, Roberto; Kokkari, Constantina; Katharios, Pantelis

    2016-01-01

    Bacterial infections are a serious problem in aquaculture since they can result in massive mortalities in farmed fish and invertebrates. Vibriosis is one of the most common diseases in marine aquaculture hatcheries and its causative agents are bacteria of the genus Vibrio mostly entering larval rearing water through live feeds, such as Artemia and rotifers. The pathogenic Vibrio alginolyticus strain V1, isolated during a vibriosis outbreak in cultured seabream, Sparus aurata, was used as host to isolate and characterize the two novel bacteriophages φSt2 and φGrn1 for phage therapy application. In vitro cell lysis experiments were performed against the bacterial host V. alginolyticus strain V1 but also against 12 presumptive Vibrio strains originating from live prey Artemia salina cultures indicating the strong lytic efficacy of the 2 phages. In vivo administration of the phage cocktail, φSt2 and φGrn1, at MOI = 100 directly on live prey A. salina cultures, led to a 93% decrease of presumptive Vibrio population after 4 h of treatment. Current study suggests that administration of φSt2 and φGrn1 to live preys could selectively reduce Vibrio load in fish hatcheries. Innovative and environmental friendly solutions against bacterial diseases are more than necessary and phage therapy is one of them.

  16. Isolation and Characterization of Two Lytic Bacteriophages, φSt2 and φGrn1; Phage Therapy Application for Biological Control of Vibrio alginolyticus in Aquaculture Live Feeds.

    Directory of Open Access Journals (Sweden)

    Panos G Kalatzis

    Full Text Available Bacterial infections are a serious problem in aquaculture since they can result in massive mortalities in farmed fish and invertebrates. Vibriosis is one of the most common diseases in marine aquaculture hatcheries and its causative agents are bacteria of the genus Vibrio mostly entering larval rearing water through live feeds, such as Artemia and rotifers. The pathogenic Vibrio alginolyticus strain V1, isolated during a vibriosis outbreak in cultured seabream, Sparus aurata, was used as host to isolate and characterize the two novel bacteriophages φSt2 and φGrn1 for phage therapy application. In vitro cell lysis experiments were performed against the bacterial host V. alginolyticus strain V1 but also against 12 presumptive Vibrio strains originating from live prey Artemia salina cultures indicating the strong lytic efficacy of the 2 phages. In vivo administration of the phage cocktail, φSt2 and φGrn1, at MOI = 100 directly on live prey A. salina cultures, led to a 93% decrease of presumptive Vibrio population after 4 h of treatment. Current study suggests that administration of φSt2 and φGrn1 to live preys could selectively reduce Vibrio load in fish hatcheries. Innovative and environmental friendly solutions against bacterial diseases are more than necessary and phage therapy is one of them.

  17. 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.

  18. Nuclear physics and particle therapy

    Directory of Open Access Journals (Sweden)

    Battistoni G.

    2016-01-01

    Full Text Available 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.

  19. Truth therapy/lie therapy.

    Science.gov (United States)

    Langs, R

    In this paper an attempt is made to conceptualize a basic dimension of various psychotherapeutic treatment modalities, especially psychoanalysis and psychoanalytically oriented psychotherapy. The central variable under consideration is the extent to which each endeavors to approach the truth within both patient and therapist as it exists dynamically in terms of their spiraling unconscious communicative interaction. That treatment modality which takes into account every possible dimension of such truths is termed truth therapy. Treatment modalities that make no attempt to arrive at these truths or that deliberately or inadvertently falsify their nature are termed lie or barrier therapies. Extensive consideration is given to truth therapy and the truth system on which it is based. The basis for the need for lie therapies is explored, and lie systems, which may arise from either patient or therapist, or both, are identified. A classification of common types of lie patients and lie therapists (and their main techniques) is offered. The implications of this delineation for our understanding of the dynamic therapies are discussed, and a number of new clinical issues arising from this perspective are addressed.

  20. Cell biology perspectives in phage biology.

    Science.gov (United States)

    Ansaldi, Mireille

    2012-01-01

    Cellular biology has long been restricted to large cellular organisms. However, as the resolution of microscopic methods increased, it became possible to study smaller cells, in particular bacterial cells. Bacteriophage biology is one aspect of bacterial cell biology that has recently gained insight from cell biology. Despite their small size, bacteriophages could be successfully labeled and their cycle studied in the host cells. This review aims to put together, although non-extensively, several cell biology studies that recently pushed the elucidation of key mechanisms in phage biology, such as the lysis-lysogeny decision in temperate phages or genome replication and transcription, one step further.

  1. 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)

  2. Pet Therapy.

    Science.gov (United States)

    Kavanagh, Kim

    1994-01-01

    This resource guide presents information on a variety of ways that animals can be used as a therapeutic modality with people having disabilities. Aspects addressed include: pet ownership and selection criteria; dogs (including service dogs, hearing/signal dogs, seeing leader dogs, and social/specialty dogs); horseriding for both therapy and fun;…

  3. 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

  4. 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...

  5. 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, cognitive, emotional, and social functioning. Music therapists work with children and adults with developmental ...

  6. 77 FR 71194 - Draft Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy...

    Science.gov (United States)

    2012-11-29

    ... Investigational Cellular and Gene Therapy Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION... for Biologics Research and Evaluation (CBER), Office of Cellular, Tissue, and Gene Therapies (OCTGT). The product areas covered by this guidance are cellular therapy, gene therapy, therapeutic...

  7. 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.

  8. Narrative therapy, family therapy and history

    OpenAIRE

    Harper, David J.

    2009-01-01

    This article was inspired by listening to the interesting plenary on the influence of narrative therapy on family therapy at the AFT annual conference in Manchester in September 2008. One of the issues raised concerned the historical connections between narrative therapy and the broader family therapy field. The contributors seemed keen to avoid a split between narrative therapy and the broader family therapy field and, instead, to find connections but this issue seemed difficult to negotiate...

  9. Molecular Biology and Prevention of Endometrial Cancer. Addendum

    Science.gov (United States)

    2008-07-01

    gain insight into the biologic mechanism underlying the chemopreventive effect of the oral contraceptive pill (OCP). Project 1: Objectives completed...oral contraceptive pill and hormone replacement therapy on reproductive organs. This objective has been completed and the results were submitted...protective effect of oral contraceptive (OC) therapy. Methods: 1) Oligonucleotide microarray analysis was performed on a panel of endometrial cancers

  10. 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.

  11. 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...

  12. 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...

  13. 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,

  14. Patient Adherence to Biologic Agents in Psoriasis

    DEFF Research Database (Denmark)

    Hsu, Der Yi; Gniadecki, Robert

    2016-01-01

    BACKGROUND: Low adherence to therapies in psoriasis decreases treatment outcomes and increases the total health care costs. In spite of the wide use of biologic agents, patients' adherence to these drugs has not been extensively investigated. OBJECTIVE: The aim of this study is to measure adherence...... adverse effects, and positive attitudes to the treatment. CONCLUSION: Adherence to biologic therapies is very high in patients with psoriasis, which is consistent with a positive attitude to the treatment....... to the biologic drugs in a population of patients treated for psoriasis vulgaris using the medication possession ratio (MPR) index and to survey patients' attitudes to the treatment. METHODS: This is a single-center study on 247 patients with psoriasis vulgaris treated with adalimumab (n = 113), etanercept (n...

  15. Radiation Therapy (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Radiation Therapy KidsHealth > For Parents > Radiation Therapy Print A ... have many questions and concerns about it. About Radiation Therapy In radiation therapy, high-energy radiation from ...

  16. Biological warfare agents.

    Science.gov (United States)

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  17. Medical physics aspects of particle therapy.

    Science.gov (United States)

    Jäkel, Oliver

    2009-11-01

    Charged particle beams offer an improved dose conformation to the target volume when compared with photon radiotherapy, with better sparing of normal tissue structures close to the target. In addition, beams of heavier ions exhibit a strong increase of the linear energy transfer in the Bragg peak when compared with the entrance region. These physical and biological properties make ion beams more favourable 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 summarises 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.

  18. 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...

  19. Chemical and Biological Terrorism: Current Updates for Nurse Educators.

    Science.gov (United States)

    Veenema, Tener Goodwin

    2002-01-01

    Describes eight topics related to chemical/biological terrorism for a standalone nursing course or integration into other courses: surveillance systems; identification, communication, and response; chemical agents; biological agents; recognition of covert exposure; patient decontamination and mass triage; availability and safety of therapies; and…

  20. 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

  1. Applications of ozone therapy in dentistry

    OpenAIRE

    Shiva Gupta; D Deepa

    2016-01-01

    Ozone is an allotropic form of oxygen, which is effectively used in the treatment of different diseases for more than 100 years. In the present era of increasing antibiotic resistance, ozone therapy is an alternative medical treatment that rationales to increase the amount of oxygen to the body through institution of ozone into the body. Owing to its beneficial biological properties including antimicrobial and immune-stimulating effects, ozone therapy has opened new vistas in treatment modali...

  2. Particle therapy and treatment of cancer.

    Science.gov (United States)

    Halperin, Edward C

    2006-08-01

    The desire of radiation oncologists and medical physicists to maximise the radiation dose to the tumour while minimising that to healthy tissues has led to attempts to improve the dose distributions and biological effects achievable with photons and electrons. Protons, neutrons, pions, boron-neutron capture therapy, and charged-nuclei therapy (with argon, carbon, helium [alpha particles], neon, nitrogen, and silicon) have been assessed for their physical, biological, and clinical effects. In the 90 years since protons and neutrons were discovered, investigations of particle therapy for cancer have helped to elucidate many fundamental radiobiological ideas, such as linear energy transfer, relative biological effectiveness, oxygen effect, and oxygen enhancement. Particle therapy has contributed to our understanding of medical ethics when neutron therapy became intertwined with the debate over standards of informed consent in radiation experiments in humans during the cold war era. Particle teletherapy and brachytherapy continue to show promise in some clinical situations. In the future, the insights of molecular biology might clarify the ideal particles for clinical situations.

  3. 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)

  4. Nutritional Therapy.

    Science.gov (United States)

    Schwartz, Julie

    2016-03-01

    This article provides the reader with steps needed to accurately assess patient nutrition behaviors that contribute to weight gain, inability to lose weight, or inability to sustain weight loss. Evidence-based approaches in nutrition therapy that can create the daily energy deficit needed to produce 1/2 to 2 pounds of weight loss per week, and the strategies to create the energy deficit, are presented. To optimize health, long-term weight loss maintenance is needed. The benefits of using a multidisciplinary team approach in treating obesity are highlighted.

  5. [Gestalt therapy.].

    Science.gov (United States)

    Corbeil, J; Poupard, D

    1978-01-01

    The authors describe Gestalt Therapy. They retrace its fundamental theoretical axes. These are psychoanalysis, character analysis, the german Gestalt theory of perception, existentialism, and the Orient. Some principal concepts are then elaborated more fully such as the cycle of awareness, desensitization, excitation anxiety and the five defense mechanisms: retroflection, introjection, projection, deflection, and confluence. The nature and goals of the therapeutic process are also described before the presentation of some techniques specific to this approach such as enactment and role playing. Finally, certain basic Gestalt rules, which aim at facilitating and intensifying the communication process among group members, are enunciated.

  6. 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.

  7. 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.

  8. 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

  9. Translational environmental biology: cell biology informing conservation.

    Science.gov (United States)

    Traylor-Knowles, Nikki; Palumbi, Stephen R

    2014-05-01

    Typically, findings from cell biology have been beneficial for preventing human disease. However, translational applications from cell biology can also be applied to conservation efforts, such as protecting coral reefs. Recent efforts to understand the cell biological mechanisms maintaining coral health such as innate immunity and acclimatization have prompted new developments in conservation. Similar to biomedicine, we urge that future efforts should focus on better frameworks for biomarker development to protect coral reefs.

  10. Laser therapy in cardiovascular disease

    Science.gov (United States)

    Rindge, David

    2009-02-01

    Cardiovascular disease is the number one cause of death worldwide. It is broadly defined to include anything which adversely affects the heart or blood vessels. One-third of Americans have one or more forms of it. By one estimate, average human life expectancy would increase by seven years if it were eliminated. The mainstream medical model seeks mostly to "manage" cardiovascular disease with pharmaceuticals or to surgically bypass or reopen blocked vessels via angioplasty. These methods have proven highly useful and saved countless lives. Yet drug therapy may be costly and ongoing, and it carries the risk of side effects while often doing little or nothing to improve underlying health concerns. Similarly, angioplasty or surgery are invasive methods which entail risk. Laser therapy1 regenerates tissue, stimulates biological function, reduces inflammation and alleviates pain. Its efficacy and safety have been increasingly well documented in cardiovascular disease of many kinds. In this article we will explore the effects of laser therapy in angina, atherosclerosis, coronary artery disease, hypertension, hyperlipidemia, myocardial infarction, stroke and other conditions. The clinical application of various methods of laser therapy, including laserpuncture and transcutaneous, supravascular and intravenous irradiation of blood will be discussed. Implementing laser therapy in the treatment of cardiovascular disease offers the possibility of increasing the health and wellbeing of patients while reducing the costs and enhancing safety of medical care.

  11. Targeted therapy in melanoma.

    Science.gov (United States)

    Kudchadkar, Ragini R; Smalley, Keiran S M; Glass, L Frank; Trimble, James S; Sondak, Vernon K

    2013-01-01

    Since the discovery of activating mutations in the BRAF oncogene in melanoma, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma. We review the latest developments in our understanding of the role of BRAF/MEK/ERK pathway signaling in melanoma, and the development of inhibitors of this pathway. We also explore alternative mutations seen in melanoma, such as NRAS, KIT, GNAQ, and GNA11, and the drug development that is ongoing based on this biology. Strategies for the management of the vexing clinical problem of BRAF inhibitor resistance, primarily via combination therapy, are outlined. With the recent approval of the BRAF inhibitor vemurafenib for stage IV metastatic melanoma, use of this agent is expanding in the United States. Thus, management of the skin toxicities of this agent, such as squamous cell carcinomas, "acneiform" eruptions, hand-foot syndrome, and panniculitis, will be a growing problem facing dermatologists today. We discuss the toxicities of targeted agents in use for melanoma, in particular the dermatologic effects and the management of these skin toxicities.

  12. Computational Systems Chemical Biology

    OpenAIRE

    Oprea, Tudor I.; Elebeoba E. May; 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).

  13. Psoriatic arthritis: immunologic mechanisms and biological therapy%银屑病性关节炎免疫机制及生物制剂治疗的进展

    Institute of Scientific and Technical Information of China (English)

    赵伟; 龚瑜; 史玉玲

    2015-01-01

    银屑病性关节炎是一种与银屑病相关的炎症性关节病,病程迁延反复,晚期可致关节强直甚至致残,严重影响患者的生活质量.因此,早期诊断,早期干预以及制定有效的治疗方案改善患者的关节症状,缓解其心身的双重压力是银屑病性关节炎面临的挑战.银屑病性关节炎的发病机制十分复杂,有多种免疫细胞和免疫分子参与,异常T细胞的活化、增殖、分化是发病的主要原因.此外,肿瘤坏死因子α和白细胞介素12、23、17等为主要的炎症介质靶点.针对发病机制中不同炎症因子的靶向治疗药物,为银屑病性关节炎的治疗带来了革命性的变化.目前,一些新型的生物靶向药物正在研究中,有希望成为银屑病性关节炎患者未来治疗的新选择.%Psoriatic arthritis (PsA),a psoriasis-associated inflammatory arthropathy with a chronic and recurrent clinical course,may lead to ankylosis and even disability at late stage,and seriously affects the quality of life in patients.It remains a challenge to improve joint symptoms and relieve physical and mental stress by early diagnosis,early intervention and effective therapeutic strategies.The pathogenesis of PsA is very complicated with the involvement of various immunocytes and immune molecules,in which the abnormal activation,proliferation and differentiation of T-lymphocytes may play a key role.Additionally,tumor necrosis factor alpha (TNF-α),interleukin 12 (IL-12),IL-23 and IL-17 are the main targets for inflammatory mediators.Aiming directly at different inflammatory cytokines in the pathogenesis of PsA,targeted drugs have brought revolutionary changes for the treatment of PsA.At present,some novel targeted biological drugs are under investigation,and may bring novel choices for the treatment of PsA.

  14. 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...

  15. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases

    Directory of Open Access Journals (Sweden)

    George E. Louridas

    2017-02-01

    Full Text Available Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction and emergence (upward biological direction could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  16. Conceptual Foundations of Systems Biology Explaining Complex Cardiac Diseases.

    Science.gov (United States)

    Louridas, George E; Lourida, Katerina G

    2017-02-21

    Systems biology is an important concept that connects molecular biology and genomics with computing science, mathematics and engineering. An endeavor is made in this paper to associate basic conceptual ideas of systems biology with clinical medicine. Complex cardiac diseases are clinical phenotypes generated by integration of genetic, molecular and environmental factors. Basic concepts of systems biology like network construction, modular thinking, biological constraints (downward biological direction) and emergence (upward biological direction) could be applied to clinical medicine. Especially, in the field of cardiology, these concepts can be used to explain complex clinical cardiac phenotypes like chronic heart failure and coronary artery disease. Cardiac diseases are biological complex entities which like other biological phenomena can be explained by a systems biology approach. The above powerful biological tools of systems biology can explain robustness growth and stability during disease process from modulation to phenotype. The purpose of the present review paper is to implement systems biology strategy and incorporate some conceptual issues raised by this approach into the clinical field of complex cardiac diseases. Cardiac disease process and progression can be addressed by the holistic realistic approach of systems biology in order to define in better terms earlier diagnosis and more effective therapy.

  17. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa; Freude, Kristine

    2016-01-01

    Recent breakthroughs in stem cell biology have accelerated research in the area of regenerative medicine. Over the past years, it has become possible to derive patient-specific stem cells which can be used to generate different cell populations for potential cell therapy. Systems biological...... modeling of stem cell pluripotency and differentiation have largely been based on prior knowledge of signaling pathways, gene regulatory networks, and epigenetic factors. However, there is a great need to extend the complexity of the modeling and to integrate different types of data, which would further...... improve systems biology and its uses in the field. In this chapter, we first give a general background on stem cell biology and regenerative medicine. Stem cell potency is introduced together with the hierarchy of stem cells ranging from pluripotent embryonic stem cells (ESCs) and induced pluripotent stem...

  18. Natural production of biological optical systems

    Science.gov (United States)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  19. 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.

  20. Lung cancer: Biology and treatment options.

    Science.gov (United States)

    Lemjabbar-Alaoui, Hassan; Hassan, Omer Ui; Yang, Yi-Wei; Buchanan, Petra

    2015-12-01

    Lung cancer remains the leading cause of cancer mortality in men and women in the U.S. and worldwide. About 90% of lung cancer cases are caused by smoking and the use of tobacco products. However, other factors such as radon gas, asbestos, air pollution exposures, and chronic infections can contribute to lung carcinogenesis. In addition, multiple inherited and acquired mechanisms of susceptibility to lung cancer have been proposed. Lung cancer is divided into two broad histologic classes, which grow and spread differently: small-cell lung carcinomas (SCLCs) and non-small cell lung carcinomas (NSCLCs). Treatment options for lung cancer include surgery, radiation therapy, chemotherapy, and targeted therapy. Therapeutic-modalities recommendations depend on several factors, including the type and stage of cancer. Despite the improvements in diagnosis and therapy made during the past 25 years, the prognosis for patients with lung cancer is still unsatisfactory. The responses to current standard therapies are poor except for the most localized cancers. However, a better understanding of the biology pertinent to these challenging malignancies, might lead to the development of more efficacious and perhaps more specific drugs. The purpose of this review is to summarize the recent developments in lung cancer biology and its therapeutic strategies, and discuss the latest treatment advances including therapies currently under clinical investigation.

  1. 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.

  2. Biologics in SLE: towards new approaches.

    Science.gov (United States)

    van Vollenhoven, Ronald F; Parodis, Ioannis; Levitsky, Adrian

    2013-06-01

    In recent years the use of biologic therapies in the management of systemic lupus erythematosus (SLE) has increased, and a number of clinical trials have highlighted both the potential and the pitfalls in the development of such agents. Many investigators reported that the off-label use of rituximab seemed promising in patients with refractory disease, but randomised trials with this agent failed. Likewise, the theoretical appeal of the co-stimulation blocker abatacept could not be confirmed in two clinical trials. Various considerations and post hoc analyses nonetheless suggest that these two biologics might have a role in the treatment of SLE. The anti-B-lymphocyte stimulator (anti-Blys) antibody belimumab demonstrated efficacy and safety in two large randomised trials and became the first approved biologic for lupus. Use in clinical practice has increased slowly, in part, due to uncertainty over which patients should be treated with this agent and in what stage of the disease. Finally, several other biologic agents are currently in advanced stages of clinical development for SLE. The overall picture that emerges is one of optimism that advances in SLE therapy will be realised through the targeted use of an increasing number of biologics.

  3. Osteoarthritis year in review 2013: biology.

    Science.gov (United States)

    Loeser, R F

    2013-10-01

    The purpose of this review was to present highlights from the published literature on the topic of the biology of osteoarthritis (OA). A PubMed search was conducted in order to locate original research manuscripts published since the last OARSI meeting in 2012. From review of the published literature, common themes emerged as active areas of research over the past year including studies in the areas of epigenetics, Wnt signaling, the role of inflammatory pathways in OA, lubricin, fibroblast growth factor signaling, and studies on OA biology in bone. Key findings in these areas were summarized and implications for future therapies were discussed.

  4. [Principles of management in biological infections].

    Science.gov (United States)

    Płusa, Tadeusz

    2012-11-01

    The effectiveness of the management in respiratory infection is depending on the nature of the biological pathogen and the immune status of the patient. For this reason, providing assistance to victims the organ function support, similarly as defining the pathogen and targeted antibiotic therapy should be applied. Available diagnostic tests provide rapid ability to identify the pathogen and antibiotics are able to control infection. Lack of efficacy of treatment may indicate the diversity of the pathogen than previously known and raises suspicion of biological warfare pathogen.

  5. Targeted Agents for Imaging and Therapy

    NARCIS (Netherlands)

    Grüll, H.; Robillard, M.S.

    2005-01-01

    Molecular Imaging allows the visualization of biological processesin vivo, offering new chances for healthcare with respect to early diagnosis and improved therapy. The new field of molecular imaging isboosted by more sensitive imaging systems and the emergence of targeted imaging agents that hom

  6. 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

  7. Digital Vasculitis Associated With Interferon Therapy

    Science.gov (United States)

    1992-06-01

    fin- fevers, arthralgias, myalgias, dysphagia , history of ger. frostbite, toxin exposure, or trauma. The DSA in our patient showed evidence of a...leukocyte A interferon: after discontinuation of the interferon therapy, in- pharmacokinetics, single-dose tolerance , and biologic effects in cancer

  8. Novel Therapies in Development for Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Michael S.; Kopetz, Scott

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer mortality in the United States. Despite advances in therapy, metastatic CRC remains lethal, and further improvements in therapy are needed. Growing understanding of cancer biology, particularly in growth factor signaling, angiogenesis, and cancer immunology, has translated into many novel therapies under investigation. Patients are increasingly selected for clinical trials rationally on the basis of integral biomarkers. This re...

  9. Adenovirus-Mediated Gene Therapy Against Viral Biothreat Agents

    Science.gov (United States)

    2016-04-12

    34--- I lr_ Transworld Research Network 37/661 (2), Fort P.O., Trivandrum-695 023, Kerala, India Recent Development in Gene Therapy , 2007: 77-94...ISBN: 81-7895-262-9 Editor: Jim Xiang Adenovirus-mediated gene therapy against viral biothreat agents Josh Q.H. Wu Chemical Biological Defence... therapy , which introduces therapeutic genes into mammalian cells to achieve therapeutic effective, hds a great potential for use as a defensive

  10. 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 ...

  11. Resetting Biological Clocks

    Science.gov (United States)

    Winfree, Arthur T.

    1975-01-01

    Reports on experiments conducted on two biological clocks, in organisms in the plant and animal kingdoms, which indicate that biological oscillation can be arrested by a single stimulus of a definite strength delivered at the proper time. (GS)

  12. Biology is simple.

    Science.gov (United States)

    Newman, Tim

    2015-12-30

    This paper explores the potential for simplicity to reveal new biological understanding. Borrowing selectively from physics thinking, and contrasting with Crick's reductionist philosophy, the author argues that greater emphasis on simplicity is necessary to advance biology and its applications.

  13. Biology of Blood

    Science.gov (United States)

    ... here for the Professional Version Home Blood Disorders Biology of Blood Overview of Blood Resources In This ... Version. DOCTORS: Click here for the Professional Version Biology of Blood Overview of Blood Components of Blood ...

  14. Mammalian synthetic biology: emerging medical applications.

    Science.gov (United States)

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

    2015-05-06

    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 toggle switches will be described. Several synthetic gene networks are further reviewed in the medical applications section, including cancer therapy gene circuits, immuno-regulatory networks, among others. The final sections focus on the applicability of synthetic gene networks to drug discovery, drug delivery, receptor-activating gene circuits and mammalian biomanufacturing processes.

  15. 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...

  16. [Physical therapy].

    Science.gov (United States)

    Chohnabayashi, Naohiko

    2008-01-01

    Recently, pulmonary rehabilitation program is widely considered one of the most effective and evidence-based treatment for not only chronic obstructive pulmonary disease (COPD) but many clinical situations including neuro-muscular disease, post-operative status and weaning period from the ventilator, etc. The essential components of a pulmonary rehabilitation program are team assessment, patient training, psycho-social intervention, exercise, and follow-up. In 2003, Japanese medical societies (J. Thoracic Society, J. Pul. Rehabilitation Society and J. Physiotherapist Society) made a new guideline for pulmonary rehabilitation, especially how to aproach the execise training. As for the duration after surgical operation, airway cleaning is the important technique to prevent post-operative complications including pneumonia. Postural dranage technique is well known for such condition, at the same time, several instruments (flutter vulve, positive expiratory mask, high frequecy oscillation, etc) were also used for the patient to expectrate airway mucus easier. Lung transplantation is a new method of treatment for the critically-ill patients with chronic respiratoy failure. Several techniques of physical therapy are must be needed before and after lung transplantation to prevent both pulmonary infection and osteoporosis.

  17. Portable Low-Volume Therapy for Severe Blood Loss

    Science.gov (United States)

    2014-06-01

    presented by Dr. Schwartz at the FASEB conference on "Melatonin Biology: Actions and Therapeutics" held July 7th-12th, 2013 in Niagara Falls , NY...therapy, BHB/M. FASEB Conference: Melatonin biology: Actions and therapeutics, July 7th-12th, 2013, Niagara Falls , NY.) In an effort to further

  18. Breast Cancer Therapy Using Antibody-Endostatin Fusion Proteins

    Science.gov (United States)

    2008-04-01

    psoriasis . N Engl J Med 2003;349(21):2014-22. 33. Weinberg JM. An overview of infliximab, etanercept, efalizumab, and alefacept as biologic therapy for... psoriasis . Clin Ther 2003;25(10):2487-505. 34. Foss FM, Bacha P, Osann KE, Demierre MF, Bell T, Kuzel T. Biological correlates of acute...

  19. Educating for social responsibility: changing the syllabus of developmental biology.

    Science.gov (United States)

    Gilbert, Scott F; Fausto-Sterling, Anne

    2003-01-01

    Developmental biology is deeply embedded in the social issues of our times. Such topics as cloning, stems cells, reproductive technologies, sex selection, environmental hormone mimics and gene therapy all converge on developmental biology. It is therefore critical that developmental biologists learn about the possible social consequences of their work and of the possible molding of their discipline by social forces. We present two models for integrating social issues into the developmental biology curriculum. One model seeks to place discussions of social issues into the laboratory portion of the curriculum; the other model seeks to restructure the course, such that developmental biology and its social contexts are synthesized directly.

  20. 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.

  1. BIOLOGICAL FOUNDATIONS OF LANGUAGE.

    Science.gov (United States)

    LENNEBERG, ERIC H.

    THE RELATIONSHIP BETWEEN BIOLOGY AND LANGUAGE IS EXPLORED IN THIS VOLUME. THE AUTHOR BELIEVES THAT "LANGUAGE IS THE MANIFESTATION OF SPECIES-SPECIFIC COGNITIVE PROPENSITIES. IT IS THE CONSEQUENCE OF THE BIOLOGICAL PECULIARITIES THAT MAKE A HUMAN TYPE OF COGNITION POSSIBLE." IN ATTEMPTING TO "REINSTATE THE CONCEPT OF THE BIOLOGICAL BASIS OF…

  2. 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…

  3. 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.

  4. Progestogens in menopausal hormone therapy

    Directory of Open Access Journals (Sweden)

    Małgorzata Bińkowska

    2015-06-01

    Full Text Available Progestogens share one common effect: the ability to convert proliferative endometrium to its secretory form. In contrast, their biological activity is varied, depending on the chemical structure, pharmacokinetics, receptor affinity and different potency of action. Progestogens are widely used in the treatment of menstrual cycle disturbances, various gynaecological conditions, contraception and menopausal hormone therapy. The administration of progestogen in menopausal hormone therapy is essential in women with an intact uterus to protect against endometrial hyperplasia and cancer. Progestogen selection should be based on the characteristics available for each progestogen type, relying on the assessment of relative potency of action in experimental models and animal models, and on the indirect knowledge brought by studies of the clinical use of different progestogen formulations. The choice of progestogen should involve the conscious use of knowledge of its benefits, with a focus on minimizing potential side effects. Unfortunately, there are no direct clinical studies comparing the metabolic effects of different progestogens.

  5. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial

    Science.gov (United States)

    Ritchlin, Christopher; Rahman, Proton; Kavanaugh, Arthur; McInnes, Iain B; Puig, Lluis; Li, Shu; Wang, Yuhua; Shen, Yaung-Kaung; Doyle, Mittie K; Mendelsohn, Alan M; Gottlieb, Alice B

    2014-01-01

    Objective Assess ustekinumab efficacy (week 24/week 52) and safety (week 16/week 24/week 60) in patients with active psoriatic arthritis (PsA) despite treatment with conventional and/or biological anti-tumour necrosis factor (TNF) agents. Methods In this phase 3, multicentre, placebo-controlled trial, 312 adults with active PsA were randomised (stratified by site, weight (≤100 kg/>100 kg), methotrexate use) to ustekinumab 45 mg or 90 mg at week 0, week 4, q12 weeks or placebo at week 0, week 4, week 16 and crossover to ustekinumab 45 mg at week 24, week 28 and week 40. At week 16, patients with <5% improvement in tender/swollen joint counts entered blinded early escape (placebo→45 mg, 45 mg→90 mg, 90 mg→90 mg). The primary endpoint was ≥20% improvement in American College of Rheumatology (ACR20) criteria at week 24. Secondary endpoints included week 24 Health Assessment Questionnaire-Disability Index (HAQ-DI) improvement, ACR50, ACR70 and ≥75% improvement in Psoriasis Area and Severity Index (PASI75). Efficacy was assessed in all patients, anti-TNF-naïve (n=132) patients and anti-TNF-experienced (n=180) patients. Results More ustekinumab-treated (43.8% combined) than placebo-treated (20.2%) patients achieved ACR20 at week 24 (p<0.001). Significant treatment differences were observed for week 24 HAQ-DI improvement (p<0.001), ACR50 (p≤0.05) and PASI75 (p<0.001); all benefits were sustained through week 52. Among patients previously treated with ≥1 TNF inhibitor, sustained ustekinumab efficacy was also observed (week 24 combined vs placebo: ACR20 35.6% vs 14.5%, PASI75 47.1% vs 2.0%, median HAQ-DI change −0.13 vs 0.0; week 52 ustekinumab-treated: ACR20 38.9%, PASI75 43.4%, median HAQ-DI change −0.13). No unexpected adverse events were observed through week 60. Conclusions The interleukin-12/23 inhibitor ustekinumab (45/90 mg q12 weeks) yielded significant and sustained improvements in PsA signs/symptoms in a diverse

  6. Interventional anoxia therapy; Interventionelle Therapie des Schlaganfalls

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, Olav [Universitaetsklinikum Schleswig-Holstein (UKSH), Kiel (Germany). Inst. fuer Neuroradiologie; Brueckmann, Hartmut (eds.) [Univ. Muenchen-Grosshadern Klinikum, Muenchen (Germany). Abt. fuer Neuroradiologie

    2011-07-01

    The book on interventional anoxia therapy covers the following issues: (1) Neuroradiologic diagnostics: Closure of the carotid artery; closure of the cerebral arteries, vertebrobasilary closure; dissections, sinus and brain vein thrombosis; (2) therapy of the acute ischemic anoxia: thrombolysis; intra-arterial thrombolysis, mechanical re-channelization materials; stroke-stent; therapy concepts and results; (3) therapy for acute venous obliterations; (4) therapy for extra and intra-cranial artery stenosis: stents, filters, balloons; extra-cranial carotid stenosis; intra-cranial stenosis; sub-clavian Steal syndrome; proximal vertebral artery stenosis; aortic arch stenosis.

  7. Computational systems chemical biology.

    Science.gov (United States)

    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) (Nat Chem Biol 3: 447-450, 2007).The overarching goal of computational SCB is to develop tools for integrated chemical-biological data acquisition, filtering and processing, by taking into account relevant information related to interactions between proteins and small molecules, possible metabolic transformations of small molecules, as well as associated information related to genes, networks, small molecules, and, where applicable, mutants and variants of those proteins. There is yet an unmet need to develop an integrated in silico pharmacology/systems biology continuum that embeds drug-target-clinical outcome (DTCO) triplets, a capability that is vital to the future of chemical biology, pharmacology, and systems biology. Through the development of the SCB approach, scientists will be able to start addressing, in an integrated simulation environment, questions that make the best use of our ever-growing chemical and biological data repositories at the system-wide level. This chapter reviews some of the major research concepts and describes key components that constitute the emerging area of computational systems chemical biology.

  8. Assessment of the biological effect of hypocrellin B in photodynamic therapy system for retina and choroid%竹红菌乙素对视网膜和脉络膜光动力学治疗系统生物学效应的评定作用

    Institute of Scientific and Technical Information of China (English)

    韩丽娜; 顾瑛; 刘凡光; 李晓松

    2004-01-01

    biological effect of domestic photosensitizer hypocrellin B (HB) PTD system on retina and choroid was accessed in our study, to explore the worthiness of further study on the prospect of HB in treating SMD.OBJECTIVE: To introduce an experimental system to perform PDT irradiation system, the determination of the photosensitivity of the photosensitizers in vitro and evaluation of the therapeutic effect of photosensitizers for the retina and choroids in vivo.DESIGN: An open trial.SETTING, MATERIALS and INTERVENTION: The trial was conducted in the Department of Laser Medicine, General Hospital of Chinese PLA. Establishment of irradiation system: a laser window was created at the slit lamp microscope, which connected with 532 nm-laser in order to make the laser and the irradiation light of the slit lamp microscope to arrive at the fundus oculi at the same time. The photosensitivity of the photosensitizer was determined primarily by Methyl-thialolyl-tetrasolium(MTT) and compared with that of BPD-MA. Using chinchilla rabbits as subjects, the system was testified by domestic photosensitizer hypocrellin B photodynamic therapy (HB-PDT), whose biological effects at the irradiated area of rabbit were evaluated by fundus observation, fluorescein angiography and light and electron microscopy examination to investigate the feasibility and reliability of our experimental system.MAIN OUTCOME MEASURES: The coupling efficiency between sbt lamp microscope and laser, in vitro photosensitivity of photosensitizer and their biological effects at the irradiated area.RESULTS: The output of the laser was stable and the coupling efficiency between the laser and laser window of the slit lamp microscope was about 60%. The photosensitivity of HB in vitro was similar to BPD-MA, and HB-PDT displayed selective therapeutic property presented by closure of the retinal and choroidal capillaries with less damage to surrounding normal retina.CONCLUSION: It is useful to decide if a new photosensitizer fit for

  9. 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...

  10. 77 FR 63840 - Cellular, Tissue and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2012-10-17

    ... 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..., Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, and...

  11. 78 FR 79699 - Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting

    Science.gov (United States)

    2013-12-31

    ... No. FDA-2013-N-0001] Cellular, Tissue, and Gene Therapies Advisory Committee; Notice of Meeting... the public. Name of Committee: Cellular, Tissue, and Gene Therapies Advisory Committee. General..., Tissue, and Gene Therapies, Center for Biologics Evaluation and Research (CBER), FDA. On February...

  12. 77 FR 65693 - Cellular, Tissue and Gene Therapies Advisory Committee; Amendment of Notice

    Science.gov (United States)

    2012-10-30

    ... HUMAN SERVICES Food and Drug Administration Cellular, Tissue and Gene Therapies Advisory Committee... Register of October 17, 2012, FDA announced that a meeting of the Cellular, Tissue and Gene Therapies..., Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, FDA. On...

  13. 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...

  14. Gene therapy oversight: lessons for nanobiotechnology.

    Science.gov (United States)

    Wolf, Susan M; Gupta, Rishi; Kohlhepp, Peter

    2009-01-01

    Oversight of human gene transfer research ("gene therapy") presents an important model with potential application to oversight of nanobiology research on human participants. Gene therapy oversight adds centralized federal review at the National Institutes of Health's Office of Biotechnology Activities and its Recombinant DNA Advisory Committee to standard oversight of human subjects research at the researcher's institution (by the Institutional Review Board and, for some research, the Institutional Biosafety Committee) and at the federal level by the Office for Human Research Protections. The Food and Drug Administration's Center for Biologics Evaluation and Research oversees human gene transfer research in parallel, including approval of protocols and regulation of products. This article traces the evolution of this dual oversight system; describes how the system is already addressing nanobiotechnology in gene transfer: evaluates gene therapy oversight based on public opinion, the literature, and preliminary expert elicitation; and offers lessons of the gene therapy oversight experience for oversight of nanobiotechnology.

  15. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  16. Silicon nanostructures for cancer diagnosis and therapy.

    Science.gov (United States)

    Peng, Fei; Cao, Zhaohui; Ji, Xiaoyuan; Chu, Binbin; Su, Yuanyuan; He, Yao

    2015-01-01

    The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

  17. 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.

  18. Basics of particle therapy: introduction to hadrons.

    Science.gov (United States)

    Welsh, James S

    2008-10-01

    With the arrival of 3-dimensional conformal radiation therapy and intensity modulated radiation therapy, radiation dose distributions in radiation oncology have improved dramatically over the past couple of decades. As part of a natural progression there recently has been a resurgence of interest in hadron therapy, specifically charged particle therapy, because of the even better dose distributions potentially achievable. In principle, using charged particle beams, radiation dose distributions can be achieved that surpass those possible with even the most sophisticated photon radiation delivery techniques. Certain charged particle beams might possess some biologic advantages in terms of tumor kill potential as well as this dosimetric advantage. The particles under consideration for such clinical applications all belong to the category of particles known as hadrons. This review introduces some of the elementary physics of the various hadron species previously used, currently used or being considered for future use in radiation oncology.

  19. Physical Therapy (For Parents)

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Physical Therapy KidsHealth > For Parents > Physical Therapy A A A en español Terapia física Physical Therapy Basics Doctors often recommend physical therapy (PT) for ...

  20. 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…

  1. Marriage or Family Therapy.

    Science.gov (United States)

    Haley, Jay

    1984-01-01

    Reviews the differences between family therapy and marriage counseling in terms of professional organization, theory, and practice. Suggests that training in marriage therapy does not appear adequate for family therapy. The goal of the therapy field should be more consensus in theory and a single profession of therapists. (JAC)

  2. Family Play Therapy.

    Science.gov (United States)

    Ariel, Shlomo

    This paper examines a case study of family play therapy in Israel. The unique contributions of play therapy are evaluated including the therapy's accessibility to young children, its richness and flexibility, its exposure of covert patterns, its wealth of therapeutic means, and its therapeutic economy. The systematization of the therapy attempts…

  3. Standard biological parts knowledgebase.

    Science.gov (United States)

    Galdzicki, Michal; Rodriguez, Cesar; Chandran, Deepak; Sauro, Herbert M; Gennari, John H

    2011-02-24

    We have created the Knowledgebase of Standard Biological Parts (SBPkb) as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org). The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org). SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL), a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  4. Standard biological parts knowledgebase.

    Directory of Open Access Journals (Sweden)

    Michal Galdzicki

    Full Text Available We have created the Knowledgebase of Standard Biological Parts (SBPkb as a publically accessible Semantic Web resource for synthetic biology (sbolstandard.org. The SBPkb allows researchers to query and retrieve standard biological parts for research and use in synthetic biology. Its initial version includes all of the information about parts stored in the Registry of Standard Biological Parts (partsregistry.org. SBPkb transforms this information so that it is computable, using our semantic framework for synthetic biology parts. This framework, known as SBOL-semantic, was built as part of the Synthetic Biology Open Language (SBOL, a project of the Synthetic Biology Data Exchange Group. SBOL-semantic represents commonly used synthetic biology entities, and its purpose is to improve the distribution and exchange of descriptions of biological parts. In this paper, we describe the data, our methods for transformation to SBPkb, and finally, we demonstrate the value of our knowledgebase with a set of sample queries. We use RDF technology and SPARQL queries to retrieve candidate "promoter" parts that are known to be both negatively and positively regulated. This method provides new web based data access to perform searches for parts that are not currently possible.

  5. 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.

  6. Development of Biologically Based Therapies for Basal-Like Tumors

    Science.gov (United States)

    2007-04-01

    5FU 72h 5FU -> 72h Cetux...72 Cetux+ 5FU 144h Cetux+ 5FU µM 5-Fluorouracil0 8040 120 160 0.1 1 10 100 1000 10000 0 0.2 0.4 0.6 0.8 1 Fraction Affected C om bi na tio n In de x...72h Cetux -> 72h 5FU 72h 5FU -> 72h Cetux 72 Cetux+ 5FU 144h Cetux+ 5FU 72h Cetux -> 72h DOX 72h DOX -> 72h Cetux 72h Cetux+DOX 144h Cetux+DOX 0.1 1

  7. Stem cell biology in thyroid cancer: Insights for novel therapies

    Science.gov (United States)

    Bhatia, Parisha; Tsumagari, Koji; Abd Elmageed, Zakaria Y; Friedlander, Paul; Buell, Joseph F; Kandil, Emad

    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. PMID:25426258

  8. 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...

  9. [Associated metabolic and nutritional side effects to biological cancer therapy].

    Science.gov (United States)

    Alonso Castellanos, Sara; Soto Célix, María; Alonso Galarreta, Judith; del Riego Valledor, Ana; Miján de la Torre, Alberto

    2014-02-01

    Introducción: Los diferentes tipos de cáncer constituyen una de las principales causas de morbi-mortalidad en el mundo. La terapia clásica antitumoral (cirugía, quimioterapia, radioterapia) ha incrementado notoriamente la supervivencia. Las terapias biológicas, con mecanismos de acción selectivos y frecuentemente específicos, constituyen una incorporación relativamente reciente al tratamiento oncológico; entre las más utilizadas se incluyen: citoquinas, anticuerpos monoclonales e inhibidores de tirosin kinasa y de mTOR. Si bien están adecuadamente documentados los efectos adversos nutricionales y metabólicos asociados a la terapia clásica, tanto en literatura como en guías clínicas, no ocurre igual con la terapia biológica. Objetivo: Revisar la literatura al respecto y detallar de modo organizado los resultados obtenidos. Métodos: Se revisó la literatura indizada así como todas las fichas técnicas de los fármacos incluidos en las distintas familias mediante la Agencia Española del Medicamento y Productos Sanitarios a Julio de 2013. Se registran los síntomas y signos clínicos con teórica acción sobre el estado nutricional o metabólico. Resultados: Se describe la acción específica de cada familia. Se agrupan los posibles efectos adversos de cada una sobre el estado nutricional y metabolismo, detallando y diferenciándolos en tablas para una más fácil y cómoda revisión y consulta. Se observan como posibles efectos secundarios más prevalentes los relacionados con el apetito, aparato digestivo y alteraciones electrolíticas. Conclusiones: Los posibles efectos secundarios asociados a terapias biológicas son múltiples y aparecen con diferente frecuencia y gravedad. Es importante al utilizarlas conocer el impacto nutricional y metabólico que pueden presentar, para su prevención y tratamiento.

  10. Ozone- A Biological Therapy in Dentistry- Reality or Myth?????

    OpenAIRE

    Saraswathi V Naik; K, Rajeshwari; Kohli, Shivani; Zohabhasan, Sayyad; Bhatia, Shekhar

    2016-01-01

    The usage of ozone in dentistry has been proposed because of its antimicrobial, disinfectant, biocompatibility and healing properties. In the last decade a number of therapeutic protocols with ozone have been developed to address common dental infections associated with periodontal disease, RCT and caries. Despite these advantages, therapeutic ozone’s application in dentistry is limited because of its possible side effects. Hence, dental practitioners need to know the proper usage of ozone th...

  11. Predoctoral Training in Breast Cancer Biology and Therapy.

    Science.gov (United States)

    1998-08-01

    apoptosis. /. Cell. Biochem. 67:399-408. 9. White E. (1996) Life, death and the pursuit of apoptosis. Genes Devop . 10:1-15. 10. Evan GL, Wyllie AH, Gilbert...Laquerre S, Goins WF, Moriuchi S, Oligino T, Krisky DM, Marconi P, Soares MK, Cohen JB, Fink DJ, Glorioso JC. (In Press) Gene transfer tool : herpes

  12. Proton therapy - Present and future.

    Science.gov (United States)

    Mohan, Radhe; Grosshans, David

    2017-01-15

    evaluation of PSPT and IMPT require special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of the energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of its true potential. Ongoing research is aimed at better understanding the consequences of the various uncertainties on proton therapy and reducing the uncertainties through image-guidance, adaptive radiotherapy, further study of biological properties of protons and the development of novel dose computation and optimization methods. However, residual uncertainties will remain in spite of the best efforts. To increase the resilience of dose distributions in the face of uncertainties and improve our confidence in dose distributions seen on treatment plans, robust optimization techniques are being developed and implemented. We assert that, with such research, proton therapy will be a commonly applied radiotherapy modality for most types of solid cancers in the near future.

  13. Nanoscale insights into ion-beam cancer therapy

    CERN Document Server

    2017-01-01

    This book provides a unique and comprehensive overview of state-of-the-art understanding of the molecular and nano-scale processes that play significant roles in ion-beam cancer therapy. It covers experimental design and methodology, and reviews the theoretical understanding of the processes involved. It offers the reader an opportunity to learn from a coherent approach about the physics, chemistry and biology relevant to ion-beam cancer therapy, a growing field of important medical application worldwide. The book describes phenomena occurring on different time and energy scales relevant to the radiation damage of biological targets and ion-beam cancer therapy from the molecular (nano) scale up to the macroscopic level. It illustrates how ion-beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal tissue whilst maximizing cell-killing within the tumour, offering a significant development in cancer therapy. The full potential ...

  14. Defining the optimal biological monotherapy in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Tarp, Simon; Furst, Daniel E; Dossing, Anna;

    2017-01-01

    OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources for rando......OBJECTIVES: To summarize and compare the benefits and harms of biological agents used as monotherapy for rheumatoid arthritis (RA) in order to inform decisions for patients who are intolerant to conventional DMARD therapy. METHODS: We searched MEDLINE, EMBASE, CENTRAL, and other sources...

  15. Plant synthetic biology.

    Science.gov (United States)

    Liu, Wusheng; Stewart, C Neal

    2015-05-01

    Plant synthetic biology is an emerging field that combines engineering principles with plant biology toward the design and production of new devices. This emerging field should play an important role in future agriculture for traditional crop improvement, but also in enabling novel bioproduction in plants. In this review we discuss the design cycles of synthetic biology as well as key engineering principles, genetic parts, and computational tools that can be utilized in plant synthetic biology. Some pioneering examples are offered as a demonstration of how synthetic biology can be used to modify plants for specific purposes. These include synthetic sensors, synthetic metabolic pathways, and synthetic genomes. We also speculate about the future of synthetic biology of plants.

  16. 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...

  17. Biologics for the treatment of pyoderma gangrenosum in ulcerative colitis

    Science.gov (United States)

    Arivarasan, K; Bhardwaj, Vaishali; Sud, Sukrit; Sachdeva, Sanjeev

    2016-01-01

    Pyoderma gangrenosum (PG) is an uncommon extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite limited published literature, biologics have caused a paradigm shift in the management of this difficult-to-treat skin condition. The clinical data and outcomes of three patients with active ulcerative colitis and concurrent PG treated with biologics (infliximab two and adalimumab one) are reviewed in this report. Biologics were added because of the sub-optimal response of the colonic symptoms and skin lesions to parenteral hydrocortisone therapy. All three patients showed a dramatic response to the addition of the biologics. In view of the rapid healing of the skin lesions, superior response rate, and the additional benefit of improvement in the underlying colonic disease following treatment, anti-tumor necrosis factor blockers should be considered as a first line therapy in the management of PG with underlying IBD. PMID:27799888

  18. Chemical Biology is.....

    OpenAIRE

    2007-01-01

    Chemical Biology is a relatively new field, and as such is not yet simply or succinctly defined. It includes such a wide range of fundamental problems that this commentary could only include just a few snapshots of potential areas of interest. Overarching themes and selected recent successes and ideas in chemical biology are described to illustrate broadly the scope of the field, but should not be taken as exhaustive. The Chemical Biology Section of Chemistry Central Journal is pleased to rec...

  19. 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.

  20. Biological detector and method

    Science.gov (United States)

    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.

  1. Biological Individuality of Man

    Science.gov (United States)

    1974-12-01

    RECIPIENT’S CAT * LOO NUMBER Biological Individuality of Man 5 TlrPE OF REPORT a PERIOD COVERED Technical « PERFORMING ORO REPORT...Variability 13 A. Background , 13 B. Slatistictl Approaches to Biological Variability 13 C. Genetic Aspects of Biological Variability . 14 III...ioiological determinants of individuality. Only recently, have genetic infaienccs been investigated and the potentialities for future control of bio

  2. 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.

  3. Stem Cell Therapy in Wound Healing and Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2016-08-01

    a novel approach to many diseases. SUMMARY: Wound healing therapies continue to rapidly evolve, with advances in basic science and engineering research heralding the development of new therapies, as well as ways to modify existing treatments. Stem cell-based therapy is one of the most promising therapeutic concepts for wound healing. Advances in stem cell biology have enabled researchers and clinicians alike with access to cells capable of actively modulating the healing response.  KEYWORDS: wound healing, tissue regeneration, stem cells therapy

  4. Horticultural therapy--the role gardening plays in healing.

    Science.gov (United States)

    Sullivan, M E

    1979-05-01

    Horticultural therapy is an adjunct therapy--to be used in addition to occupational and physical therapies, and combining means used by both. It is meant to increase the motivation of the physically and/or mentally handicapped, while at the same time stimulating the five senses and furnishing a means of self-gratification and self esteem. Now that neurologically orientated psychologists are identifying schizophrenia as being biologically based and capable of being reversed with exercise, it is time to study the many benefits of gardening as a therapy method.

  5. Chemical space and biology.

    Science.gov (United States)

    Dobson, Christopher M

    2004-12-16

    Chemical space--which encompasses all possible small organic molecules, including those present in biological systems--is vast. So vast, in fact, that so far only a tiny fraction of it has been explored. Nevertheless, these explorations have greatly enhanced our understanding of biology, and have led to the development of many of today's drugs. The discovery of new bioactive molecules, facilitated by a deeper understanding of the nature of the regions of chemical space that are relevant to biology, will advance our knowledge of biological processes and lead to new strategies to treat disease.

  6. Applications of ozone therapy in dentistry

    Directory of Open Access Journals (Sweden)

    Shiva Gupta

    2016-01-01

    Full Text Available Ozone is an allotropic form of oxygen, which is effectively used in the treatment of different diseases for more than 100 years. In the present era of increasing antibiotic resistance, ozone therapy is an alternative medical treatment that rationales to increase the amount of oxygen to the body through institution of ozone into the body. Owing to its beneficial biological properties including antimicrobial and immune-stimulating effects, ozone therapy has opened new vistas in treatment modalities of dental pathologies for patients of all ages. The objective of this article is to review the literature available on applications of ozone in dentistry.

  7. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  8. 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.

  9. 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)

  10. Biology Library Workbook.

    Science.gov (United States)

    Miller, Constance; And Others

    A library skills workbook provides college biology students with an introduction to biological library resources. Divided into two sections, the first contains explanations of the various steps in the library research process. The second consists of exercises keyed to the explanatory chapters of the first section. (RAA)

  11. Homosexuality, biology, and ideology.

    Science.gov (United States)

    Haumann, G

    1995-01-01

    This paper critically examines the complex relationships and interdependencies between biological theories on homosexuality and sociosexual ideologies. It challenges the privileged status of biology as the ultimate authority on homosexuality. This status is based on the belief that biology is a value-free science. On the contrary, this essay shows how unacknowledged assumptions and culturally bound patterns of thinking about sexuality taint biological research. Sociosexual ideologies are defined as principles that organize the ways we express our sexualities and the way we theorize about them in biology. The following ideologies are identified: (1) sexuality-as-heterosexuality, (2) sexuality-as-reproduction, (3) sexual dualism (male vs. female), and (4) the view the homosexuality is a sexual inversion. The process by which these ideologies are incorporated into biology is two-fold: (1) as a projective act from society onto nature and (2) as a reflective act from nature back into society. It is further argued that biological knowledge of homosexuality resulting from that process can be used for diverse political interests. Finally, it is proposed that since biological theories on homosexuality are inseparable from the context of their paradigmatic origin, it is possible that new theories could be derived from new ideologies.

  12. 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.

  13. 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…

  14. Introduction to systems biology

    NARCIS (Netherlands)

    Bruggeman, F.J.; Hornberg, J.J.; Boogerd, F.C.; Westerhoff, H.V.; Boogerd, F.C.; Bruggeman, F.J.; Hofmeyr, J.H.S.; Westerhoff, H.V.

    2007-01-01

    The developments in the molecular biosciences have made possible a shift to combined molecular and system-level approaches to biological research under the name of Systems Biology. It integrates many types of molecular knowledge, which can best be achieved by the synergistic use of models and experi

  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. 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...

  17. 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.

  18. Space biology research development

    Science.gov (United States)

    Bonting, Sjoerd L.

    1993-01-01

    The purpose of the Search for Extraterrestrial Intelligence (SETI) Institute is to conduct and promote research related activities regarding the search for extraterrestrial life, particularly intelligent life. Such research encompasses the broad discipline of 'Life in the Universe', including all scientific and technological aspects of astronomy and the planetary sciences, chemical evolution, the origin of life, biological evolution, and cultural evolution. The primary purpose was to provide funding for the Principal Investigator to collaborate with the personnel of the SETI Institute and the NASA-Ames Research center in order to plan and develop space biology research on and in connection with Space Station Freedom; to promote cooperation with the international partners in the space station; to conduct a study on the use of biosensors in space biology research and life support system operation; and to promote space biology research through the initiation of an annual publication 'Advances in Space Biology and Medicine'.

  19. 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.

  20. 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.

  1. 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.

  2. Initiatives in biological research in Indian psychiatry.

    Science.gov (United States)

    Shrivatava, Amresh

    2010-01-01

    Biological psychiatry is an exploratory science for mental health. These biological changes provide some explicit insight into the complex area of 'brain-mind and behavior'. One major achievement of research in biological field is the finding to explain how biological factors cause changes in behavior. In India, we have a clear history of initiatives in research from a biological perspective, which goes back to 1958. In the last 61 years, this field has seen significant evolution, precision and effective utilization of contemporary technological advances. It is a matter of great pride to see that in spite of difficult times in terms of challenges of practice and services, administration, resource, funding and manpower the zest for research was very forthcoming. There was neither dedicated time nor any funding for conducting research. It came from the intellectual insight of our fore fathers in the field of mental health to gradually grow to the state of strategic education in research, training in research, international research collaborations and setting up of internationally accredited centers. During difficult economic conditions in the past, the hypothesis tested and conclusions derived have not been so important. It is more important how it was done, how it was made possible and how robust traditions were established. Almost an entire spectrum of biological research has been touched upon by Indian researchers. Some of these are electroconvulsive therapy, biological markers, neurocognition, neuroimaging, neuroendocrine, neurochemistry, electrophysiology and genetics. A lot has been published given the limited space in the Indian Journal of Psychiatry and other medical journals published in India. A large body of biological research conducted on Indian patients has also been published in International literature (which I prefer to call non-Indian journals). Newer research questions in biological psychiatry, keeping with trend of international standards are

  3. Gene transfer therapy in vascular diseases.

    Science.gov (United States)

    McKay, M J; Gaballa, M A

    2001-01-01

    Somatic gene therapy of vascular diseases is a promising new field in modern medicine. Recent advancements in gene transfer technology have greatly evolved our understanding of the pathophysiologic role of candidate disease genes. With this knowledge, the expression of selective gene products provides the means to test the therapeutic use of gene therapy in a multitude of medical conditions. In addition, with the completion of genome sequencing programs, gene transfer can be used also to study the biologic function of novel genes in vivo. Novel genes are delivered to targeted tissue via several different vehicles. These vectors include adenoviruses, retroviruses, plasmids, plasmid/liposomes, and oligonucleotides. However, each one of these vectors has inherent limitations. Further investigations into developing delivery systems that not only allow for efficient, targeted gene transfer, but also are stable and nonimmunogenic, will optimize the clinical application of gene therapy in vascular diseases. This review further discusses the available mode of gene delivery and examines six major areas in vascular gene therapy, namely prevention of restenosis, thrombosis, hypertension, atherosclerosis, peripheral vascular disease in congestive heart failure, and ischemia. Although we highlight some of the recent advances in the use of gene therapy in treating vascular disease discovered primarily during the past two years, many excellent studies published during that period are not included in this review due to space limitations. The following is a selective review of practical uses of gene transfer therapy in vascular diseases. This review primarily covers work performed in the last 2 years. For earlier work, the reader may refer to several excellent review articles. For instance, Belalcazer et al. (6) reviewed general aspects of somatic gene therapy and the different vehicles used for the delivery of therapeutic genes. Gene therapy in restenosis and stimulation of

  4. 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.

  5. [Practical guide for the use of biological agents in rheumatoid arthritis - December 2011 update].

    Science.gov (United States)

    Mourão, Ana Filipa; Fonseca, João Eurico; Canhão, Helena; Santos, Maria José; Bernardo, Alexandra; Cordeiro, Ana; Cravo, Ana Rita; Ribeiro, Ana; Teixeira, Ana; Barcelos, Anabela; Malcata, Armando; Faustino, Augusto; Duarte, Cátia; Ribeiro, Célia; Nour, Dolores; Araújo, Domingos; Sousa, Elsa; Mariz, Eva; Ramos, Filipa; Vinagre, Filipe; Ventura, Francisco Simões; Sequeira, Graça; Santos, Helena; Branco, Jaime Cunha; Gomes, J A; Silva, J A; Ramos, João; Santo, Jorge Espírito; Costa, José António; Silva, J A; Ribeiro, José Saraiva; Inês, Luís; Miranda, Luís; Sampaio, Luzia; Costa, Maria Lúcia; Rodrigues, Mário; Afonso, Maria Carmo; Cunha, Maria Inês; Saavedra, Maria João; Queiroz, Mário Viana; Couto, Maura; Bernardes, Miguel; Bogas, Mónica; Pinto, Patrícia; Valente, Paula; Coelho, Paulo; Abreu, Pedro; Cortes, Sara; Pimenta, Sofia; Ramiro, Sofia; Figueira, Ricardo; Nóvoa, Teresa

    2011-01-01

    The authors review the practical aspects of biological therapy use for rheumatoid arthritis patients, commenting safety issues before and after treatment initiation and the best treatment strategies to optimize efficacy.

  6. Biologic Treatments for Sports Injuries II Think Tank-Current Concepts, Future Research, and Barriers to Advancement, Part 1: Biologics Overview, Ligament Injury, Tendinopathy.

    Science.gov (United States)

    LaPrade, Robert F; Geeslin, Andrew G; Murray, Iain R; Musahl, Volker; Zlotnicki, Jason P; Petrigliano, Frank; Mann, Barton J

    2016-12-01

    Biologic therapies, including stem cells, platelet-rich plasma, growth factors, and other biologically active adjuncts, have recently received increased attention in the basic science and clinical literature. At the 2015 AOSSM Biologics II Think Tank held in Colorado Springs, Colorado, a group of orthopaedic surgeons, basic scientists, veterinarians, and other investigators gathered to review the state of the science for biologics and barriers to implementation of biologics for the treatment of sports medicine injuries. This series of current concepts reviews reports the summary of the scientific presentations, roundtable discussions, and recommendations from this think tank.

  7. 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 ...

  8. 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, ...

  9. Home Oxygen Therapy

    Science.gov (United States)

    ... Teenagers Living With Lung Disease Articles written by Respiratory Experts Home Oxygen Therapy More and more people are using oxygen therapy ... April 12, 2012 Revised: © 2017 American Association for Respiratory Care

  10. Targeted Cancer Therapies

    Science.gov (United States)

    ... targeted therapies are directed against HER-2, including trastuzumab (Herceptin®), which is approved to treat certain breast and ... traditional chemotherapy drugs. For example, the targeted therapy trastuzumab (Herceptin®) has been used in combination with docetaxel , ...

  11. Therapy and Counseling

    Science.gov (United States)

    ... troubling feelings and behavior.Behavior therapy. Sometimes called behavior modification therapy, this treatment focuses on changing unwanted or unhealthy behaviors. You replace them with healthy ones. This treatment ...

  12. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... References Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387. [PubMed Abstract] Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; ...

  13. 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 ...

  14. 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

  15. What Is Music Therapy?

    Science.gov (United States)

    ... is the clinical and evidence-based use of music interventions to accomplish individualized goals within a therapeutic relationship by a credentialed professional who has completed an approved music therapy program. Music Therapy is an established health ...

  16. Complementary and Integrative Therapies

    Science.gov (United States)

    ... Art therapy and music therapy • Chiropractic medicine and massage • Guided imagery • Meditation and prayer • Qi gong • Reflexology • Reiki • Yoga Whole medical systems use many types ...

  17. Botulinum Toxin Therapy

    Science.gov (United States)

    ... care Kids’ zone Video library Find a dermatologist Botulinum toxin therapy Overview Before treatment: This woman disliked her deep frown lines. Botulinum toxin therapy: Overview Also called botulinum rejuvenation Brand names: ...

  18. Complementary Pancreatitis Therapies

    Science.gov (United States)

    ... medication, and improve quality of life.1,2 Massage Therapy Massage therapy involves touch and different techniques of stroking ... of the body or be a full-body massage. Massage can be performed through one’s clothing or ...

  19. Quantification of biological aging in young adults

    Science.gov (United States)

    Belsky, Daniel W.; Caspi, Avshalom; Houts, Renate; Cohen, Harvey J.; Corcoran, David L.; Danese, Andrea; Harrington, HonaLee; Israel, Salomon; Levine, Morgan E.; Schaefer, Jonathan D.; Sugden, Karen; Williams, Ben; Yashin, Anatoli I.; Poulton, Richie; Moffitt, Terrie E.

    2015-01-01

    Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies. PMID:26150497

  20. 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