WorldWideScience

Sample records for biologically based therapies

  1. EUD-based biological optimization for carbon ion therapy

    International Nuclear Information System (INIS)

    Brüningk, Sarah C.; Kamp, Florian; Wilkens, Jan J.

    2015-01-01

    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

  2. [Biologic therapy in idiopathic inflammatory myopathy].

    Science.gov (United States)

    Selva-O'Callaghan, Albert; Ramos Casals, Manel; Grau Junyent, Josep M

    2014-09-15

    The aim of this article is to study the evidence-based knowledge related to the use of biological therapies in patients diagnosed with idiopathic inflammatory myopathy (dermatomyositis, polymyositis and inclusion body myositis). In this review the leading published studies related to the use of biological therapy in patients with myositis are analysed; mainly those with high methodological standards, that means randomized and controlled studies. Methodological drawbacks due to the rarity and heterogeneity of these complex diseases are also addressed. Up to now is not possible to ascertain the biologics as a recommended therapy in patients with myositis, at least based in the current evidence-based knowledge, although it can not be neglected as a therapeutic option in some clinical situations, taking into account the scarce of effective treatments in those patients, especially in refractory myositis. Future studies probably will help to better define the role of biological therapies in patients with idiopathic inflammatory myopathy. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  3. Biological therapy in geriatric patients

    International Nuclear Information System (INIS)

    Mego, M.

    2012-01-01

    Targeted biological therapy, alone or in combination with conventional chemotherapy, make significant progress in the treatment of patients with malignancy. Its use as opposed to high-dose chemotherapy is not limited by age, nevertheless, we have relatively little knowledge of the toxicity and effectiveness in geriatric patients. Aim of this article is to give an overview of the biological effectiveness and toxicity of anticancer therapy in geriatric patients, based on published data. (author)

  4. 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...

  5. Biological-based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Diot, Quentin; Kavanagh, Brian; Timmerman, Robert; Miften, Moyed

    2012-01-01

    Purpose: To describe biological-based optimization and Monte Carlo (MC) dose calculation-based treatment planning for volumetric modulated arc therapy (VMAT) delivery of stereotactic body radiation therapy (SBRT) in lung, liver, and prostate patients. Methods: Optimization strategies and VMAT planning parameters using a biological-based optimization MC planning system were analyzed for 24 SBRT patients. Patients received a median dose of 45 Gy [range, 34-54 Gy] for lung tumors in 1-5 fxs and a median dose of 52 Gy [range, 48-60 Gy] for liver tumors in 3-6 fxs. Prostate patients received a fractional dose of 10 Gy in 5 fxs. Biological-cost functions were used for plan optimization, and its dosimetric quality was evaluated using the conformity index (CI), the conformation number (CN), the ratio of the volume receiving 50% of the prescription dose over the planning target volume (Rx/PTV50). The quality and efficiency of the delivery were assessed according to measured quality assurance (QA) passing rates and delivery times. For each disease site, one patient was replanned using physical cost function and compared to the corresponding biological plan. Results: Median CI, CN, and Rx/PTV50 for all 24 patients were 1.13 (1.02-1.28), 0.79 (0.70-0.88), and 5.3 (3.1-10.8), respectively. The median delivery rate for all patients was 410 MU/min with a maximum possible rate of 480 MU/min (85%). Median QA passing rate was 96.7%, and it did not significantly vary with the tumor site. Conclusions: VMAT delivery of SBRT plans optimized using biological-motivated cost-functions result in highly conformal dose distributions. Plans offer shorter treatment-time benefits and provide efficient dose delivery without compromising the plan conformity for tumors in the prostate, lung, and liver, thereby improving patient comfort and clinical throughput. The short delivery times minimize the risk of patient setup and intrafraction motion errors often associated with long SBRT treatment

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

    NARCIS (Netherlands)

    Paganetti, Harald; van Luijk, Peter

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

  7. [Side effects of biologic therapies in psoriasis].

    Science.gov (United States)

    Altenburg, A; Augustin, M; Zouboulis, C C

    2018-04-01

    The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

  8. Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

    Science.gov (United States)

    Sukhikh, E.; Sheino, I.; Vertinsky, A.

    2017-09-01

    Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

  9. Top-down approach to biological therapy of Crohn's disease.

    Science.gov (United States)

    Hirschmann, Simon; Neurath, Markus F

    2017-03-01

    Crohn's disease (CD) is a chronic, immune-mediated condition with a potentially disabling and destructive course. Despite growing data on when to use a therapeutic 'top-down' strategy, clinical management of this complex disorder is still challenging. Currently, the discussion of 'top-down' strategy in CD mostly includes biological therapy alone or in combination. Areas covered: This article is based on a review of existing literature regarding the use of biological therapy in a 'top-down' approach for the treatment of Crohn's disease. The authors reviewed all the major databases including MEDLINE as well as DDW and ECCO abstracts, respectively. Expert opinion: A 'top-down' therapeutic approach in Crohn's disease is strongly supported by existing data in patients with several risk factors for a severe course of disease. Moreover, there is an increasing amount of published data recommending a more individualised therapeutic strategy to identify candidates for 'top-down' treatment, based on enhanced diagnostics using biomarkers. Emerging therapeutic approaches besides existing therapy concepts using biologicals may possibly redefine the 'top-down' therapeutic strategy for Crohn's disease in the future.

  10. Radiation biology and radiation therapy

    International Nuclear Information System (INIS)

    Wideroee, R.

    1975-01-01

    Radiation biology and radiation therapy can be compared with investigations in different layers of earth. Radiation biology works upwards from the elementary foundations, therapy works downwards with roots to secure and improve the clinical 'surface work'. The Ellis formula (Strandquist), which is a collection of clinical experience, is suited to form connections with radiobiology in the middle layers, and cooperation can give impulses for research. The structure and conditions of tumours and the complicated problems met with are discussed, based on the Carmel symposium of 1969. The oxygen problem in anoxic tumours is not yet solved. Experimental investigations of the effect itself give partly contradictory results. From a clinical viewpoint reoxygenation is of the utmost significance for obtaining control over the primary tumour, and advanced irradiation programmes will here give better results than the traditional ones. New chemicals, e.g. R 0 -07-0582, appear to reduce the OER value to 1.5, thereby making neutron therapy superfluous. Finally a problem from fundamental research is dealt with, wherein two hypotheses explaining the β-effect are described. The repair hypothesis gives a simple explanation but leaves many questions unanswered. The other hypothesis explains the β-effect as two neighbouring single breaks of the DNA molecule. It still presents difficulties, and is scarcely the correct explanation. (JIW)

  11. Biological therapies for spondyloarthritis.

    Science.gov (United States)

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

    2014-06-01

    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 treat patients at an early stage of disease to reduce disease progression; moreover it is necessary to identify causes of therapy inefficacy in preventing joint damage in the axial subset.

  12. 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. 

  13. 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.

  14. Biologic Drugs: A New Target Therapy in COPD?

    Science.gov (United States)

    Yousuf, Ahmed; Brightling, Christopher E

    2018-04-23

    Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease associated with significant morbidity and mortality. Current diagnostic criteria based on the presence of fixed airflow obstruction and symptoms do not integrate the complex pathological changes occurring within the lung and they do not define different airway inflammatory patterns. The current management of COPD is based on 'one size fits all' approach and does not take the importance of heterogeneity in COPD population into account. The available treatments aim to alleviate symptoms and reduce exacerbation frequency but do not alter the course of the disease. Recent advances in molecular biology have furthered our understanding of inflammatory pathways in pathogenesis of COPD and have led to development of targeted therapies (biologics and small molecules) based on predefined biomarkers. Herein we shall review the trials of biologics in COPD and potential future drug developments in the field.

  15. One-appointment endodontic therapy: biological considerations.

    Science.gov (United States)

    Lin, Louis M; Lin, Jarshen; Rosenberg, Paul A

    2007-11-01

    The authors conducted a literature review to present the best available biological evidence concerning one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. Because of recent advances in technology, such as rotary engines and nickel-titanium instruments, some practitioners are performing one-appointment endodontic therapy for asymptomatic teeth with apical periodontitis. The authors reviewed the literature, which revealed only a small number of randomized, controlled clinical trials that have been conducted on one-appointment versus multiple-appointment endodontic therapy. As the apical canal preparation is enlarged, a greater percentage of bacteria is eradicated from infected root canals. In addition, sufficiently large apical root canal enlargement facilitates the delivery of antimicrobial irrigant to the apical portion of the canal. However, an association between positive or negative preobturation root canal culture results and the outcome of endodontic treatment has not been well-established. The best available evidence, based on a systematic literature review, indicates that one-appointment endodontic therapy may be feasible in selected cases of apical periodontitis in asymptomatic teeth. However, additional randomized, controlled clinical trials are required.

  16. 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.

  17. Discussion: DMARDs and biologic therapies in the management of inflammatory joint diseases.

    Science.gov (United States)

    Vaz, Austin; Lisse, Jeffrey; Rizzo, Warren; Albani, Salvatore

    2009-05-01

    Therapy for inflammatory joint diseases, such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis, includes various conventional disease-modifying antirheumatic drugs (DMARDs). These therapeutic agents are termed DMARDs because they have the potential to reduce or prevent joint damage and preserve joint integrity and function. Conventional DMARDs are used as monotherapy or in combination and include methotrexate, leflunomide, azathioprine, ciclosporin, hydroxychloroquine, sulfasalazine, gold and minocycline. Biologic response modifiers, which are based on proteins made by living cells, are newer agents available for the treatment of various inflammatory joint diseases. Biologic therapies now approved for use in inflammatory joint diseases are TNF inhibitors, T-cell modulators and B-cell depleters. They have all been shown to have clinical efficacy and are able to retard structural damage. However, all current immune-modulating therapies also have potential side effects, and the decision to use a particular agent for treatment should be based on a thorough discussion of the benefits and risks with the patient. Newer biologic response modifiers and other immunologic therapies are currently being developed for the treatment of inflammatory joint diseases and are discussed in this review.

  18. Clinically Applicable Monte Carlo–based Biological Dose Optimization for the Treatment of Head and Neck Cancers With Spot-Scanning Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.; Ma, Daniel J.; Beltran, Chris

    2016-08-01

    Purpose: Our aim is 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 and Materials: 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 intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of this novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 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 intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for

  19. Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.

    Science.gov (United States)

    Qin, Nan; Shen, Chenyang; Tsai, Min-Yu; Pinto, Marco; Tian, Zhen; Dedes, Georgios; Pompos, Arnold; Jiang, Steve B; Parodi, Katia; Jia, Xun

    2018-01-01

    One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

    2011-01-01

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

  1. The future of cytotoxic therapy: selective cytotoxicity based on biology is the key

    International Nuclear Information System (INIS)

    Bono, Johann S de; Tolcher, Anthony W; Rowinsky, Eric K

    2003-01-01

    Although mortality from breast cancer is decreasing, 15% or more of all patients ultimately develop incurable metastatic disease. It is hoped that new classes of target-based cytotoxic therapeutics will significantly improve the outcome for these patients. Many of these novel agents have displayed cytotoxic activity in preclinical and clinical evaluations, with little toxicity. Such preferential cytotoxicity against malignant tissues will remain tantamount to the Holy Grail in oncologic therapeutics because this portends improved patient tolerance and overall quality of life, and the capacity to deliver combination therapy. Combinations of such rationally designed target-based therapies are likely to be increasingly important in treating patients with breast carcinoma. The anticancer efficacy of these agents will, however, remain dependent on the involvement of the targets of these agents in the biology of the individual patient's disease. Results of DNA microarray analyses have raised high hopes that the analyses of RNA expression levels can successfully predict patient prognosis, and indicate that the ability to rapidly 'fingerprint' the oncogenic profile of a patient's tumor is now possible. It is hoped that these studies will support the identification of the molecules driving a tumor's growth, and the selection of the appropriate combination of targeted agents in the near future

  2. WE-FG-BRB-03: Challenges and Opportunities for Implementing Biological Optimization in Particle Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, D. [Yale University School of Medicine (United States)

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  3. Travel and biologic therapy: travel-related infection risk, vaccine response and recommendations.

    Science.gov (United States)

    Hall, Victoria; Johnson, Douglas; Torresi, Joseph

    2018-01-01

    Biologic therapy has revolutionized the management of refractory chronic autoimmune and auto-inflammatory disease, as well as several malignancies, providing rapid symptomatic relief and/or disease remission. Patients receiving biologic therapies have an improved quality of life, facilitating travel to exotic destinations and potentially placing them at risk of a range of infections. For each biologic agent, we review associated travel-related infection risk and expected travel vaccine response and effectiveness. A PUBMED search [vaccination OR vaccine] AND/OR ['specific vaccine'] AND/OR [immunology OR immune response OR response] AND [biologic OR biological OR biologic agent] was performed. A review of the literature was performed in order to develop recommendations on vaccination for patients in receipt of biologic therapy travelling to high-risk travel destinations. There is a paucity of literature in this area, however, it is apparent that travel-related infection risk is increased in patients on biologic therapy and when illness occurs they are at a higher risk of complication and hospitalization. Patients in receipt of biologic agents are deemed as having a high level of immunosuppression-live vaccines, including the yellow fever vaccine, are contraindicated. Inactivated vaccines are considered safe; however, vaccine response can be attenuated by the patient's biologic therapy, thereby resulting in reduced vaccine effectiveness and protection. Best practice requires a collaborative approach between the patient's primary healthcare physician, relevant specialist and travel medicine expert, who should all be familiar with the immunosuppressive and immunomodulatory effects resulting from the biologic therapies. Timing of vaccines should be carefully planned, and if possible, vaccination provided well before established immunosuppression.

  4. Portuguese recommendations for the use of biological therapies in patients with axial spondyloarthritis – 2016 update

    Directory of Open Access Journals (Sweden)

    Pedro Machado

    2017-07-01

    Full Text Available Objective: To update the recommendations for the treatment of axial spondyloarthritis (axSpA with biological therapies, endorsed by the Portuguese Society of Rheumatology. Methods: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting, the 7 recommendations included in this document were discussed and updated. A draft of the full text of the recommendations was then circulated and suggestions were incorporated. A final version was again circulated before publication and the level of agreement among Portuguese Rheumatologists was anonymously assessed using an online survey. Results: A consensus was achieved regarding the initiation, assessment of response and switching of biological therapies in patients with axSpA. In total, seven recommendations were produced. The first recommendation is a general statement indicating that biological therapy is not a first-line drug treatment option and should only be used after conventional treatment has failed. The second recommendation is also a general statement about the broad concept of axSpA adopted by these recommendations that includes both non-radiographic and radiographic axSpA. Recommendations 3 to 7 deal with the definition of active disease (including the recommended threshold of 2.1 for the Ankylosing Spondylitis Disease Activity Score [ASDAS] or the threshold of 4 [0-10 scale] for the Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], conventional treatment failure (nonsteroidal anti-inflammatory drugs being the first-line drug treatment, assessment of response to treatment (based on an ASDAS improvement  of at least 1.1 units or a BASDAI improvement of at least 2 units [0-10 scale] or at least 50%, and strategy in the presence of an inadequate response (where switching is recommended or in the presence of long-term remission (where a process of biological therapy optimization can be

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

    International Nuclear Information System (INIS)

    Teng Gaojun; Lu Qin

    2007-01-01

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

  6. Clinical impact of concomitant immunomodulators on biologic therapy: Pharmacokinetics, immunogenicity, efficacy and safety.

    Science.gov (United States)

    Xu, Zhenhua; Davis, Hugh M; Zhou, Honghui

    2015-03-01

    Immune-mediated inflammatory diseases encompass a variety of different clinical syndromes, manifesting as either common diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis, or rare diseases such as cryopyrin-associated periodic syndromes. The therapy for these diseases often involves the use of a wide range of drugs including nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, immunomodulators, and biologic therapies. Due to the abundance of relevant clinical data, this article provides a general overview on the clinical impact of the concomitant use of immunomodulators and biologic therapies, with a focus on anti-tumor necrosis factor-α agents (anti-TNFα), for the treatment of RA and Crohn's disease (CD). Compared to biologic monotherapy, concomitant use of immunomodulators (methotrexate, azathioprine, and 6-mercaptopurine) often increases the systemic exposure of the anti-TNFα agent and decreases the formation of antibodies to the anti-TNFα agent, consequently enhancing clinical efficacy. Nevertheless, long-term combination therapy with immunomodulators and anti-TNFα agents may be associated with increased risks of serious infections and malignancies. Therefore, the determination whether combination therapy is suitable for a patient should always be based on an individualized benefit-risk evaluation. More research should be undertaken to identify and validate prognostic markers for predicting patients who would benefit the most and those who are at greater risk from combination therapy with immunomodulators and anti-TNFα agents. © 2015, The American College of Clinical Pharmacology.

  7. New perspectives on biological HDL-targeted therapies

    OpenAIRE

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

    2017-01-01

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

  8. SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Taleei, R; Qin, N; Jiang, S [UT Southwestern Medical Center, Dallas, TX (United States); Peeler, C [UT MD Anderson Cancer Center, Houston, TX (United States); Jia, X [The University of Texas Southwestern Medical Ctr, Dallas, TX (United States)

    2016-06-15

    Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relative Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.

  9. Evaluation of a commercial biologically based IMRT treatment planning system

    International Nuclear Information System (INIS)

    Semenenko, Vladimir A.; Reitz, Bodo; Day, Ellen; Qi, X. Sharon; Miften, Moyed; Li, X. Allen

    2008-01-01

    A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose

  10. 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.

  11. 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.

  12. Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution

    International Nuclear Information System (INIS)

    Yang Yong; Xing Lei

    2005-01-01

    It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT

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

    Science.gov (United States)

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

    2011-11-15

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

  14. Value-Based Medicine and Integration of Tumor Biology.

    Science.gov (United States)

    Brooks, Gabriel A; Bosserman, Linda D; Mambetsariev, Isa; Salgia, Ravi

    2017-01-01

    Clinical oncology is in the midst of a genomic revolution, as molecular insights redefine our understanding of cancer biology. Greater awareness of the distinct aberrations that drive carcinogenesis is also contributing to a growing armamentarium of genomically targeted therapies. Although much work remains to better understand how to combine and sequence these therapies, improved outcomes for patients are becoming manifest. As we welcome this genomic revolution in cancer care, oncologists also must grapple with a number of practical problems. Costs of cancer care continue to grow, with targeted therapies responsible for an increasing proportion of spending. Rising costs are bringing the concept of value into sharper focus and challenging the oncology community with implementation of value-based cancer care. This article explores the ways that the genomic revolution is transforming cancer care, describes various frameworks for considering the value of genomically targeted therapies, and outlines key challenges for delivering on the promise of personalized cancer care. It highlights practical solutions for the implementation of value-based care, including investment in biomarker development and clinical trials to improve the efficacy of targeted therapy, the use of evidence-based clinical pathways, team-based care, computerized clinical decision support, and value-based payment approaches.

  15. Biological basis of heavy ion beams for cancer therapy

    International Nuclear Information System (INIS)

    Sakamoto, Kiyohiko

    1985-01-01

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

  16. Phage Therapy in the Era of Synthetic Biology.

    Science.gov (United States)

    Barbu, E Magda; Cady, Kyle C; Hubby, Bolyn

    2016-10-03

    For more than a century, bacteriophage (or phage) research has enabled some of the most important discoveries in biological sciences and has equipped scientists with many of the molecular biology tools that have advanced our understanding of replication, maintenance, and expression of genetic material. Phages have also been recognized and exploited as natural antimicrobial agents and nanovectors for gene therapy, but their potential as therapeutics has not been fully exploited in Western medicine because of challenges such as narrow host range, bacterial resistance, and unique pharmacokinetics. However, increasing concern related to the emergence of bacteria resistant to multiple antibiotics has heightened interest in phage therapy and the development of strategies to overcome hurdles associated with bacteriophage therapeutics. Recent progress in sequencing technologies, DNA manipulation, and synthetic biology allowed scientists to refactor the entire bacterial genome of Mycoplasma mycoides, thereby creating the first synthetic cell. These new strategies for engineering genomes may have the potential to accelerate the construction of designer phage genomes with superior therapeutic potential. Here, we discuss the use of phage as therapeutics, as well as how synthetic biology can create bacteriophage with desirable attributes. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

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

    International Nuclear Information System (INIS)

    Orton, C; Borras, C; Carlson, D

    2014-01-01

    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

  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. Biologic agents therapy for Saudi children with rheumatic diseases: indications and safety.

    Science.gov (United States)

    Al-Mayouf, Sulaiman M; Alenazi, Abdullatif; AlJasser, Hind

    2016-06-01

    To report the indications and safety of biologic agents in childhood rheumatic diseases at a tertiary hospital. Children with rheumatic diseases treated with biologic agents at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, from January 2001 to December 2011 were included. All patients were reviewed for: demographic characteristics, diagnosis, concomitant treatment and indications of using biologic agents, age at start of therapy and side effects during the treatment period. In all, 134 children (89 female) with various rheumatic diseases were treated with biologic agents. Mean age at starting biologic treatment was 9.3 (4.25-14) years and mean therapy duration was 14.7 (3-88) months. Juvenile idiopathic arthritis (JIA) was the most frequent diagnosis (70.1%) followed by systemic lupus erythematosus (12.7%) and vasculitis (4.5%). All patients received concomitant therapy (corticosteroids and disease-modifying antirheumatic drugs). In total, 273 treatments with biologic agents were used, (95 etanercept, 52 rituximab, 47 adalimumab, 37 infliximab, 23 anakinra, 10 tocilizumab and nine abatacept). Therapy was switched to another agent in 57 (42.5%) patients, mainly because of inefficacy (89.4%) or adverse event (10.6%). A total of 95 (34.8%) adverse events were notified; of these, the most frequent were infusion-related reactions (33.7%) followed by infections (24.2%) and autoantibody positivity (10.6%). One patient developed macrophage activation syndrome. Biologic agents were used in children with a range of rheumatic diseases. Of these, the most frequent was JIA. Off-label use of biologic agents in our cohort is common. These agents seem safe. However, they may associated with various adverse events. Sequential therapy seems well tolerated. However, this should be carefully balanced and considered on an individual basis. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  20. Radiation biology as a basis for multidisciplinary cancer therapy

    International Nuclear Information System (INIS)

    Hosoya, N.

    2017-01-01

    The research field of radiation biology has progressed greatly thanks to the advances in molecular biology. DNA in the cell nucleus is the principal target of radiation. The biological effect of radiation can be determined by how the DNA damage is processed in the cell. In order to prevent deleterious biological effects due to DNA damage, the cells possess a system termed 'DNA damage response'. The DNA damage response finally induces cell cycle arrest, activation of DNA repair pathways, or cell death. If accurately repaired, DNA damage will result in survival of cells with no biological effects. If inaccurately repaired, DNA damage may result in survival of cells exhibiting genetic alterations, which can lead to the development of various diseases including cancer. If unrepaired, fatal DNA damage such as the DNA double-strand break will result in cell depth. Since radiation therapy and chemotherapy are designed to specifically kill cancer cells by inducing DNA double-strand breaks, it is important to take advantage of cancer-specific abnormalities in DNA damage response. In this review, I describe the impact of targeting DNA damage response in cancer therapy and show how progress in radiation biology has contributed to the development of novel therapeutic strategies. (author)

  1. 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

  2. Building for Biology: A Gene Therapy Trial Infrastructure

    Directory of Open Access Journals (Sweden)

    Samuel Taylor-Alexander

    2017-06-01

    Full Text Available In this article, we examine the construction of the infrastructure for a Phase II gene therapy trial for Cystic Fibrosis (CF. Tracing the development of the material technologies and physical spaces used in the trial, we show how the trial infrastructure took form at the uncertain intersection of scientific norms, built environments, regulatory negotiations, patienthood, and the biologies of both disease and therapy. We define infrastructures as material and immaterial (including symbols and affect composites that serve a selective distributive purpose and facilitate projects of making and doing. There is a politics to this distributive action, which is itself twofold, because whilst infrastructures enable and delimit the movement of matter, they also mediate the very activity for which they provide the grounds. An infrastructural focus allows us to show how purposeful connections are made in a context of epistemic and regulatory uncertainty. The gene therapy researchers were working in a context of multiple uncertainties, regarding not only how to do gene therapy, but also how to anticipate and enact ambiguous regulatory requirements in a context of limited resources (technical, spatial, and financial. At the same time, the trial infrastructure had to accommodate Cystic Fibrosis biology by bridging the gap between pathology and therapy. The consortium’s approach to treating CF required that they address concerns about contamination and safety while finding a way of getting a modified gene product into the lungs of the trial participants.

  3. 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.

  4. 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.

  5. Tumor biology and cancer therapy – an evolving relationship

    Directory of Open Access Journals (Sweden)

    Lother Ulrike

    2009-08-01

    Full Text Available Abstract The aim of palliative chemotherapy is to increase survival whilst maintaining maximum quality of life for the individual concerned. Although we are still continuing to explore the optimum use of traditional chemotherapy agents, the introduction of targeted therapies has significantly broadened the therapeutic options. Interestingly, the results from current trials put the underlying biological concept often into a new, less favorable perspective. Recent data suggested that altered pathways underlie cancer, and not just altered genes. Thus, an effective therapeutic agent will sometimes have to target downstream parts of a signaling pathway or physiological effects rather than individual genes. In addition, over the past few years increasing evidence has suggested that solid tumors represent a very heterogeneous group of cells with different susceptibility to cancer therapy. Thus, since therapeutic concepts and pathophysiological understanding are continuously evolving a combination of current concepts in tumor therapy and tumor biology is needed. This review aims to present current problems of cancer therapy by highlighting exemplary results from recent clinical trials with colorectal and pancreatic cancer patients and to discuss the current understanding of the underlying reasons.

  6. 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.

  7. Biological basis of combination therapy with radiation and bleomycin

    International Nuclear Information System (INIS)

    Fukuda, Hiroshi; Matsuzawa, Taiju; Yokoyama, Kumiko; Okuyama, Shinichi; Yamaura, Hiroshi

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C 2 W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C 2 W cells were irradiated, incubated at 37 0 C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising. (J.P.N.)

  8. Biological basis of combination therapy with radiation and bleomycin

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, H; Matsuzawa, T; Yokoyama, K; Okuyama, S; Yamaura, H [Tohoku Univ., Sendai (Japan). Research Inst. for Tuberculosis, Leprosy and Cancer

    1976-01-01

    The biological basis for combination therapy with radiation and bleomycin (BLM) was studied on C/sub 2/W cells growing in vitro. When BLM was added to the medium before or after irradiation, a potentiating effect was observed. The potentiation remained for 4-6 hours after irradiation. To make clear the mechanism, both type of repair from radiation damage (Elkind type and PLD) by BLM were examined. BLM didn't inhibit the Elkind type recovery but it did inhibit the repair of potentially lethal damage (PLD repair). Plateau phase C/sub 2/W cells were irradiated, incubated at 37/sup 0/C for a various number of hours, then trypsinized for colony formation. PLD repair was inhibited when BLM was added immediately after irradiation. Based on such experimental results, we treated lung cancer with combination of radiation and BLM. BLM was injected intravenously within 30 minutes after irradiation. Although it seems too early to discuss the result of the combination therapy, it is very promising.

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

    Energy Technology Data Exchange (ETDEWEB)

    Nestle, Ursula; Hentschel, Michael; Grosu, Anca-Ligia [Departments of Radiation Oncology, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany); Weber, Wolfgang [Nuclear Medicine, University of Freiburg, Robert Koch Str. 3, 79106 Freiburg (Germany)], E-mail: ursula.nestle@uniklinik-freiburg.de

    2009-01-07

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

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

    Science.gov (United States)

    Nestle, Ursula; Weber, Wolfgang; Hentschel, Michael; Grosu, Anca-Ligia

    2009-01-07

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

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

    Science.gov (United States)

    Hoffmann, Aswin L; den Hertog, Dick; Siem, Alex Y D; Kaanders, Johannes H A M; Huizenga, Henk

    2008-11-21

    Finding fluence maps for intensity-modulated radiation therapy (IMRT) can be formulated as a multi-criteria optimization problem for which Pareto optimal treatment plans exist. To account for the dose-per-fraction effect of fractionated IMRT, it is desirable to exploit radiobiological treatment plan evaluation criteria based on the linear-quadratic (LQ) cell survival model as a means to balance the radiation benefits and risks in terms of biologic response. Unfortunately, the LQ-model-based radiobiological criteria are nonconvex functions, which make the optimization problem hard to solve. We apply the framework proposed by Romeijn et al (2004 Phys. Med. Biol. 49 1991-2013) to find transformations of LQ-model-based radiobiological functions and establish conditions under which transformed functions result in equivalent convex criteria that do not change the set of Pareto optimal treatment plans. The functions analysed are: the LQ-Poisson-based model for tumour control probability (TCP) with and without inter-patient heterogeneity in radiation sensitivity, the LQ-Poisson-based relative seriality s-model for normal tissue complication probability (NTCP), the equivalent uniform dose (EUD) under the LQ-Poisson model and the fractionation-corrected Probit-based model for NTCP according to Lyman, Kutcher and Burman. These functions differ from those analysed before in that they cannot be decomposed into elementary EUD or generalized-EUD functions. In addition, we show that applying increasing and concave transformations to the convexified functions is beneficial for the piecewise approximation of the Pareto efficient frontier.

  12. Bacteriophage-based synthetic biology for the study of infectious diseases

    Science.gov (United States)

    Lu, Timothy K.

    2014-01-01

    Since their discovery, bacteriophages have contributed enormously to our understanding of molecular biology as model systems. Furthermore, bacteriophages have provided many tools that have advanced the fields of genetic engineering and synthetic biology. Here, we discuss bacteriophage-based technologies and their application to the study of infectious diseases. New strategies for engineering genomes have the potential to accelerate the design of novel phages as therapies, diagnostics, and tools. Though almost a century has elapsed since their discovery, bacteriophages continue to have a major impact on modern biological sciences, especially with the growth of multidrug-resistant bacteria and interest in the microbiome. PMID:24997401

  13. Challenges of biological therapy in patients with pustular psoriasis coexisting with psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Joanna Narbutt

    2017-04-01

    Full Text Available Introduction . Psoriasis is a chronic inflammatory skin disease affecting approximately 2–3% of the general population. It is a condition with immunological and genetic background, coexisting with psoriatic arthritis in about 25% of cases. Biologic drugs have brought a significant improvement in managing the disease, however they are not approved for the treatment of pustular psoriasis. An increasing number of reports indicate the efficacy of biological drugs in pustular psoriasis. In some patients there are factors responsible for a worse clinical response to biologic therapy. Objective . Presentation of therapeutic difficulties identified in a patient with pustular psoriasis and psoriatic arthritis. Case report . We report a case of a 48-year-old man with generalized pustular psoriasis coexisting with psoriatic arthritis in whom therapy with multiple biologic drugs (adalimumab, infliximab, golimumab, ustekinumab has failed to bring a satisfactory improvement. Conclusions . Further studies are needed to verify the efficacy and pos­sibly approve biological drugs for the treatment of pustular psoriasis. Also, attempts should be made to identify predictors of poorer response to treatment in order to individualize therapy and prevent the loss of efficacy of biologic drugs during prolonged use.

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

    Science.gov (United States)

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

    2016-07-01

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

  15. Biological Therapy for Pyoderma Gangrenosum

    Directory of Open Access Journals (Sweden)

    Naw Ally Krüger

    2013-10-01

    Full Text Available Introduction: pyoderma gangrenosum (PG is a rare and severe neutrophilic dermatosis asso- ciated with inflammatory bowel disease (IBD and other systemic diseases such as rheu- matoid arthritis and hematological malignancies. Diagnosis is based on clinical criteria and exclusion of other skin disorders. There is no gold standard for the treatment of PG; traditionally intravenous corticosteroids are used, but recently the use of drugs that in- hibit tumor necrosis factor alpha (TNF-alpha has changed the management of PG, showing great effectiveness.Case report: female patient, 23 years old, diagnosed with severe nonspecific ulcerative colitis (UC three years ago, undergoing treatment with oral mesalamine and azathioprine. She developed PG fourteen days after hospital discharge; hospitalization was due to worsening of intestinal disease symptoms. She was successfully treated using biological therapy after unfavorable evolution with corticosteroid therapy.Conclusion: PG, a rare extraintestinal manifestation of IBD of difficult resolution that has significant impact on patient quality of life. The use of biological therapy for PG has higher efficacy in the treatment of patients decreasing wound healing time and return to daily activities. Resumo: Introdução: pioderma gangrenoso (PG é uma rara e grave dermatose neutrofílica associada a doença inflamatória intestinal (DII e a outras doenças sistêmicas como a artrite reumatoi- de e neoplasias hematológicas. O diagnóstico é baseado em critérios clínicos e exclusão de outras desordens da pele. Ainda não há padrão ouro para o tratamento do PG, tradicional- mente usa-se corticoides endovenosos, porém recentemente o uso de fármacos inibidores do fator de necrose tumoral alfa (TNF-alfa tem mudado o manejo do PG mostrando grande efetividade.Relato do caso: paciente feminina, 23 anos, com diagnóstico de retocolite ulcerativa inespe- cífica (RCUI severa há três anos, em tratamento com

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

    Science.gov (United States)

    D'Angelo, Salvatore; Tramontano, Giuseppina; Gilio, Michele; Leccese, Pietro; Olivieri, Ignazio

    2017-01-01

    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.

  17. Graphene-based nanovehicles for photodynamic medical therapy

    Directory of Open Access Journals (Sweden)

    Li Y

    2015-03-01

    Full Text Available Yan Li,1 Haiqing Dong,1 Yongyong Li,1 Donglu Shi1,2 1Shanghai East Hospital, The Institute for Biomedical Engineering and Nano Science (iNANO, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2The Materials Science and Engineering Program, Department of Mechanical and Materials Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH, USA Abstract: Graphene and its derivatives such as graphene oxide (GO have been widely explored as promising drug delivery vehicles for improved cancer treatment. In this review, we focus on their applications in photodynamic therapy. The large specific surface area of GO facilitates efficient loading of the photosensitizers and biological molecules via various surface functional groups. By incorporation of targeting ligands or activatable agents responsive to specific biological stimulations, smart nanovehicles are established, enabling tumor-triggering release or tumor-selective accumulation of photosensitizer for effective therapy with minimum side effects. Graphene-based nanosystems have been shown to improve the stability, bioavailability, and photodynamic efficiency of organic photosensitizer molecules. They have also been shown to behave as electron sinks for enhanced visible-light photodynamic activities. Owing to its intrinsic near infrared absorption properties, GO can be designed to combine both photodynamic and photothermal hyperthermia for optimum therapeutic efficiency. Critical issues and future aspects of photodynamic therapy research are addressed in this review. Keywords: graphene, nanovehicle, photodynamic therapy, photosensitizer, hyperthermia

  18. em>In vivoem> 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...

  19. 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

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

    International Nuclear Information System (INIS)

    Swanson, K; Corwin, D; Rockne, R

    2014-01-01

    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

  1. Physics fundamentals and biological effects of synchrotron radiation therapy

    International Nuclear Information System (INIS)

    Prezado, Y.

    2010-01-01

    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 (SRT). In this work the three new radiation therapy techniques under development at the European Synchrotron Radiation Facility (ESRF), in Grenoble (France) will be described, namely: synchrotron stereotactic radiation therapy (SSRT), microbeam radiation therapy (MRT) and minibeam 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).

  2. METHODS OF ASSESSMENT OF THE RELATIVE BIOLOGICAL EFFECTIVENESS OF NEUTRONS IN NEUTRON THERAPY

    Directory of Open Access Journals (Sweden)

    V. A. Lisin

    2017-01-01

    Full Text Available The relative biological effectiveness (RBE of fast neutrons is an important factor influencing the quality of neutron therapy therefore, the assessment of RBE is of great importance. Experimental and clinical studies as well as different mathematical and radiobiological models are used for assessing RBE. Research is conducted for neutron sources differing in the method of producing particles, energy and energy spectrum. Purpose: to find and analyze the dose-dependence of fast neutron RBE in neutron therapy using the U-120 cyclotron and NG-12I generator. Material and methods: The optimal method for assessing the relative biological effectiveness of neutrons for neutron therapy was described. To analyze the dependence of the RBE on neutron dose, the multi-target model of cell survival was applied. Results: The dependence of the RBE of neutrons produced from the U-120 cyclotron and NG-120 generator on the dose level was found for a single irradiation of biological objects. It was shown that the function of neutron dose was consistent with similar dependencies found by other authors in the experimental and clinical studies.

  3. 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.

  4. Light-based therapy on wound healing : a review

    International Nuclear Information System (INIS)

    Suan, Lau Pik; Bidin, Noriah; Cherng, Chong Jia; Hamid, Asmah

    2014-01-01

    Wound healing is a complex matrix and overlapping process. In order to accelerate the healing process and minimize bacterial infection, light-based therapy was applied to stimulate bio-reaction to improve healing. The aim of this paper is to review the effects induced by light source (laser and incoherent light like LED) on different biological targets. The light-based therapy techniques were categorized according to the wavelength, energy density, type of irradiance and activity of tissues in the healing process. Out of 80 cases, 77% were animal studies, 5% were human studies and 18% were cell studies. Around 75% of light-based therapy has an advantage on tissue interaction and 25% has no effect or inhibition on the healing process. The appropriate dose appears to be between 1 and 5 J cm −2 . At shorter wavelength, photobiostimulation would be effective with a high frequently administrated low-energy dose. On the other hand, for longer wavelength it is the reverse, i.e., more effective with a low frequent treated schedule and a high-energy dose. (topical reviews)

  5. A prospective observational study of pigmented naevi changes in psoriasis patients on biologic therapy.

    Science.gov (United States)

    Choi, Seohee Deanne; D'Souza, Mario I; Menzies, Scott W; Weninger, Wolfgang

    2018-05-23

    Patients on biologic therapy are thought to be at increased risk of developing non-melanoma skin cancers and melanomas. It is unknown whether biologic therapy alters the natural history of melanocytic naevi. Therefore, a prospective observational study was conducted to determine whether psoriasis patients on biologic therapy develop changes in naevi. Clinical and dermoscopic assessment of all melanocytic naevi was performed in 45 psoriasis patients on biologic therapy versus a control cohort of 43 subjects, using sequential digital dermoscopic imaging and total body photography. The mean follow-up period was 1.5 years. The study and control patients had comparable age, gender, previous and family history of non-melanoma skin cancers and melanomas, as well as previous sun exposure and total number of naevi. The number of naevi with major dermoscopic changes was 3% in the study and 1.9% in the control group, with an adjusted incidence rate ratio of 1.45 (95% confidence interval 0.90-2.33; P = 0.125). The rate of minor changes was 15.9% in the study group versus 19.4% in the control (adjusted incidence rate ratio 0.77, 95% confidence interval 0.57-1.08; P = 0.14). There were six new dysplastic naevi in 4/45 biologic patients and four in 4/43 controls; however, the difference was not significant (relative risk 0.96, 95% confidence interval -0.12 to 0.12; P = 0.95). There were no melanomas in either group. Over a mean follow-up period of 1.5 years there was no evidence of significantly different changes in naevi or development of new dysplastic naevi in psoriasis patients on biologic treatment compared to controls. © 2018 The Australasian College of Dermatologists.

  6. 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

  7. Preoperative biological therapy and short-term outcomes of abdominal surgery in patients with inflammatory bowel disease.

    Science.gov (United States)

    Waterman, Matti; Xu, Wei; Dinani, Amreen; Steinhart, A Hillary; Croitoru, Kenneth; Nguyen, Geoffrey C; McLeod, Robin S; Greenberg, Gordon R; Cohen, Zane; Silverberg, Mark S

    2013-03-01

    Previous investigations of short-term outcomes after preoperative exposure to biological therapy in inflammatory bowel disease (IBD) were conflicting. The authors aimed to assess postoperative outcomes in patients who underwent abdominal surgery with recent exposure to anti-tumour necrosis factor therapy. A retrospective case-control study with detailed matching was performed for subjects with IBD with and without exposure to biologics within 180 days of abdominal surgery. Postoperative outcomes were compared between the groups. 473 procedures were reviewed consisting of 195 patients with exposure to biologics and 278 matched controls. There were no significant differences in most postoperative outcomes such as: length of stay, fever (≥ 38.5°C), urinary tract infection, pneumonia, bacteraemia, readmission, reoperations and mortality. On univariate analysis, procedures on biologics had more wound infections compared with controls (19% vs 11%; p=0.008), but this was not significant in multivariate analysis. Concomitant therapy with biologics and thiopurines was associated with increased frequencies of urinary tract infections (p=0.0007) and wound infections (p=0.0045). Operations performed ≤ 14 days from last biologic dose had similar rates of infections and other outcomes when compared with those performed within 15-30 days or 31-180 days. Patients with detectable preoperative infliximab levels had similar rates of wound infection compared with those with undetectable levels (3/10 vs 0/9; p=0.21). Preoperative treatment with TNF-α antagonists in patients with IBD is not associated with most early postoperative complications. A shorter time interval from last biological dose is not associated with increased postoperative complications. In most cases, surgery should not be delayed, and appropriate biological therapy may be continued perioperatively.

  8. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Joanna Świdrowska

    2015-04-01

    Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

  9. Cost-utility Analysis: Thiopurines Plus Endoscopy-guided Biological Step-up Therapy is the Optimal Management of Postoperative Crohn's Disease.

    Science.gov (United States)

    Candia, Roberto; Naimark, David; Sander, Beate; Nguyen, Geoffrey C

    2017-11-01

    Postoperative recurrence of Crohn's disease is common. This study sought to assess whether the postoperative management should be based on biological therapy alone or combined with thiopurines and whether the therapy should be started immediately after surgery or guided by either endoscopic or clinical recurrence. A Markov model was developed to estimate expected health outcomes in quality-adjusted life years (QALYs) and costs in Canadian dollars (CAD$) accrued by hypothetical patients with high recurrence risk after ileocolic resection. Eight strategies of postoperative management were evaluated. A lifetime time horizon, an annual discount rate of 5%, a societal perspective, and a cost-effectiveness threshold of 50,000 CAD$/QALY were assumed. Deterministic and probabilistic sensitivity analyses were conducted. The model was validated against randomized trials and historical cohorts. Three strategies dominated the others: endoscopy-guided full step-up therapy (14.80 QALYs, CAD$ 462,180), thiopurines immediately post-surgery plus endoscopy-guided biological step-up therapy (14.89 QALYs, CAD$ 464,099) and combination therapy immediately post-surgery (14.94 QALYs, CAD$ 483,685). The second strategy was the most cost-effective, assuming a cost-effectiveness threshold of 50,000 CAD$/QALY. Probabilistic sensitivity analysis showed that the second strategy has the highest probability of being the optimal alternative in all comparisons at cost-effectiveness thresholds from 30,000 to 100,000 CAD$/QALY. The strategies guided only by clinical recurrence and those using biologics alone were dominated. According to this decision analysis, thiopurines immediately after surgery and addition of biologics guided by endoscopic recurrence is the optimal strategy of postoperative management in patients with Crohn's disease with high risk of recurrence (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B654).

  10. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Science.gov (United States)

    Veleri, Shobi; Lazar, Csilla H.; Chang, Bo; Sieving, Paul A.; Banin, Eyal; Swaroop, Anand

    2015-01-01

    Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases. PMID:25650393

  11. Epithelioid Sarcoma: Opportunities for Biology-Driven Targeted Therapy.

    Science.gov (United States)

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

    2015-01-01

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

  12. Experiences of mobility for people living with rheumatoid arthritis who are receiving biologic drug therapy: implications for podiatry services.

    Science.gov (United States)

    Sanders, Lucy; Donovan-Hall, Margaret; Borthwick, Alan; Bowen, Catherine J

    2017-01-01

    Despite significant advancements in new treatment modalities for rheumatoid arthritis with biological therapies, foot complications remain a disabling and common feature of the disease . In this study the aim was to explore and describe the personal experiences of people with rheumatoid arthritis in receipt of biologic treatments in a bid to understand the impact of this form of medication on their mobility. An interpretative phenomenological analysis (IPA) was undertaken to explore in depth the individual experience of rheumatoid disease through personal accounts of the patient journey spanning both 'before' and 'after' the instigation of biologic therapy. A purposive sampling strategy was adopted and in-depth semi structured interviews used to facilitate rich, detailed interview data exploring the lived experiences of individuals undertaking biological therapy and the changes to mobility experienced as a result. Thematic analysis was employed with an IPA framework to identify key meanings, and report patterns within the data. Five people with rheumatoid arthritis participated in the study. The mean disease duration was 20.2 years (range: 6 -32) and all were being treated with biologic therapies. Four key themes emerged from the data: 1) Life before biologic treatment, depicted in accounts as a negative experience characterised by painful and disabling symptoms and feelings of hopelessness. 2) Life with biologic treatment, often experienced as a life changing transition, restoring function and mobility and offering renewed hope. 3) Sense of self, in which the impact of rheumatoid disease and the subsequent changes arising from biologic therapy reveal a profound impact on feelings of personal identity both pre and post biologic therapy; an effect of footwear on self-image emerges as a dominant sub theme; 4) Unmet footcare needs were evident in the patient narrative, where the unrelenting if diminished impact of foot pain on mobility was viewed in the context of

  13. Platinum-Based Therapy in Adenosquamous Pancreatic Cancer: Experience at Two Institutions

    OpenAIRE

    Andre Luiz De Souza; Muhammad Wasif Saif

    2014-01-01

    Adenosquamous carcinoma of the pancreas is a rare type of pancreatic cancer. Although its molecular biology profile hasbeen shown to be similar to pancreatic ductal adenocarcinoma tumors, it has different prognostic features. There is noconsensus or guidelines to treat this tumor differently from pancreatic adenocarcinoma, but therapies based on gemcitabineand platinum chemotherapeutics such as cisplatin and oxaliplatin have been used based on results of a few case reports. Wediscuss the Abst...

  14. Recent insights in nanotechnology-based drugs and formulations designed for effective anti-cancer therapy.

    Science.gov (United States)

    Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert

    2016-05-26

    The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.

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

    Directory of Open Access Journals (Sweden)

    A. S. Mikhaylova

    2018-01-01

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

  16. 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.

  17. 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

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

    Science.gov (United States)

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

    2010-08-10

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

  19. Nanoparticle-based delivery of small interfering RNA: challenges for cancer therapy

    Directory of Open Access Journals (Sweden)

    Miele E

    2012-07-01

    Full Text Available Evelina Miele,1,* Gian Paolo Spinelli,2,* Ermanno Miele,3 Enzo Di Fabrizio,3,6 Elisabetta Ferretti,4 Silverio Tomao,2 Alberto Gulino,1,5 1Department of Molecular Medicine, 2Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, 3Nanostructures, Istituto Italiano di Tecnologia, via Morego, 30, 16163 Genova, 4Department of Experimental Medicine, Sapienza University of Rome, Rome, 5Center for Life Nanoscience, Istituto Italiano di Tecnologia, Rome, Italy, 6BIONEM lab, University of Magna Graecia, Campus S. Venuta, Viale Europa 88100 Catanzaro, Italy *These authors contributed equally to this workAbstract: During recent decades there have been remarkable advances and profound changes in cancer therapy. Many therapeutic strategies learned at the bench, including monoclonal antibodies and small molecule inhibitors, have been used at the bedside, leading to important successes. One of the most important advances in biology has been the discovery that small interfering RNA (siRNA is able to regulate the expression of genes, by a phenomenon known as RNA interference (RNAi. RNAi is one of the most rapidly growing fields of research in biology and therapeutics. Much research effort has gone into the application of this new discovery in the treatment of various diseases, including cancer. However, even though these molecules may have potential and strong utility, some limitations make their clinical application difficult, including delivery problems, side effects due to off-target actions, disturbance of physiological functions of the cellular machinery involved in gene silencing, and induction of the innate immune response. Many researchers have attempted to overcome these limitations and to improve the safety of potential RNAi-based therapeutics. Nanoparticles, which are nanostructured entities with tunable size, shape, and surface, as well as biological behavior, provide an ideal opportunity to modify current

  20. Biology and therapy of inherited retinal degenerative disease: insights from mouse models

    Directory of Open Access Journals (Sweden)

    Shobi Veleri

    2015-02-01

    Full Text Available Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.

  1. Commissioning of accelerator based boron neutron capture therapy system

    International Nuclear Information System (INIS)

    Nakamura, S.; Wakita, A.; Okamoto, H.; Igaki, H.; Itami, J.; Ito, M.; Abe, Y.; Imahori, Y.

    2017-01-01

    Boron neutron capture therapy (BNCT) is a treatment method using a nuclear reaction of 10 B(n, α) 7 Li. BNCT can be deposited the energy to a tumor since the 10 B which has a higher cross-section to a neutron is high is concentrated on the tumor. It is different from conventional radiation therapies that BNCT expects higher treatment effect to radiation resistant tumors since the generated alpha and lithium particles have higher radiological biological effectiveness. In general, BNCT has been performed in research nuclear reactor. Thus, BNCT is not widely applied in a clinical use. According to recent development of accelerator-based boron neutron capture therapy system, the system has an adequate flux of neutrons. Therefore, National Cancer Canter Hospital, Tokyo, Japan is planning to install accelerator based BNCT system. Protons with 2.5 MeV are irradiated to a lithium target system to generate neutrons. As a result, thermal load of the target is 50 kW since current of the protons is 20.0 mA. Additionally, when the accelerator-based BNCT system is installed in a hospital, the facility size is disadvantage in term of neutron measurements. Therefore, the commissioning of the BNCT system is being performed carefully. In this article, we report about the commissioning. (author)

  2. Patient Understanding of the Risks and Benefits of Biologic Therapies in Inflammatory Bowel Disease: Insights from a Large-scale Analysis of Social Media Platforms.

    Science.gov (United States)

    Martinez, Bibiana; Dailey, Francis; Almario, Christopher V; Keller, Michelle S; Desai, Mansee; Dupuy, Taylor; Mosadeghi, Sasan; Whitman, Cynthia; Lasch, Karen; Ursos, Lyann; Spiegel, Brennan M R

    2017-07-01

    Few studies have examined inflammatory bowel disease (IBD) patients' knowledge and understanding of biologic therapies outside traditional surveys. Here, we used social media data to examine IBD patients' understanding of the risks and benefits associated with biologic therapies and how this affects decision-making. We collected posts from Twitter and e-forum discussions from >3000 social media sites posted between June 27, 2012 and June 27, 2015. Guided by natural language processing, we identified posts with specific IBD keywords that discussed the risks and/or benefits of biologics. We then manually coded the resulting posts and performed qualitative analysis using ATLAS.ti software. A hierarchical coding structure was developed based on the keyword list and relevant themes were identified through manual coding. We examined 1598 IBD-related posts, of which 452 (28.3%) centered on the risks and/or benefits of biologics. There were 5 main themes: negative experiences and concerns with biologics (n = 247; 54.6%), decision-making surrounding biologic use (n = 169; 37.4%), positive experiences with biologics (n = 168; 37.2%), information seeking from peers (n = 125; 27.7%), and cost (n = 38; 8.4%). Posts describing negative experiences primarily commented on side effects from biologics, concerns about potential side effects and increased cancer risk, and pregnancy safety concerns. Posts on decision-making focused on nonbiologic treatment options, hesitation to initiate biologics, and concerns about changing or discontinuing regimens. Social media reveals a wide range of themes governing patients' experience and choice with IBD biologics. The complexity of navigating their risk-benefit profiles suggests merit in creating online tailored decision tools to support IBD patients' decision-making with biologic therapies.

  3. Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

    International Nuclear Information System (INIS)

    Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

    2009-01-01

    High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

  4. A Monte Carlo-based treatment-planning tool for ion beam therapy

    CERN Document Server

    Böhlen, T T; Dosanjh, M; Ferrari, A; Haberer, T; Parodi, K; Patera, V; Mairan, A

    2013-01-01

    Ion beam therapy, as an emerging radiation therapy modality, requires continuous efforts to develop and improve tools for patient treatment planning (TP) and research applications. Dose and fluence computation algorithms using the Monte Carlo (MC) technique have served for decades as reference tools for accurate dose computations for radiotherapy. In this work, a novel MC-based treatment-planning (MCTP) tool for ion beam therapy using the pencil beam scanning technique is presented. It allows single-field and simultaneous multiple-fields optimization for realistic patient treatment conditions and for dosimetric quality assurance for irradiation conditions at state-of-the-art ion beam therapy facilities. It employs iterative procedures that allow for the optimization of absorbed dose and relative biological effectiveness (RBE)-weighted dose using radiobiological input tables generated by external RBE models. Using a re-implementation of the local effect model (LEM), theMCTP tool is able to perform TP studies u...

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

    DEFF Research Database (Denmark)

    Rask Lage-Hansen, Philip; Chrysidis, S; Lage-Hansen, M

    2016-01-01

    identified. No group differences were found regarding disease duration, age, gender, and serological status. Of the RA patients with concomitant FM, 64% were treated with biological therapy vs. 32% of RA patients without concomitant FM (p = 0.002). The mean DAS28 in the FM group was 4.4 compared to 2......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...... applied to investigate group differences in the use of biological therapy, baseline characteristics, patient-reported outcomes, and DAS28 between groups when appropriate. RESULTS: Questionnaires were completed by 162 out of 264 (61%) patients. Twenty-five patients (15.4%) with concomitant FM were...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  8. Biologically based therapies are commonly self-prescribed by Brazilian women for the treatment of advanced breast cancer or its symptoms.

    Science.gov (United States)

    Alfano, Ana Camila Callado; Paiva, Carlos Eduardo; Rugno, Fernanda Capella; da Silva, Raquel Haas; Paiva, Bianca Sakamoto Ribeiro

    2014-05-01

    Breast cancer (BC) might be associated with loss of function in affected patients, with a direct impact on their quality of life (QOL). Many women with metastatic BC seek relief of symptoms, including the use of complementary and alternative medicine (CAM) to cure cancer. The present study aimed to identify the pattern of CAM used by patients with metastatic BC and to assess the correlation between CAM use and scores on anxiety, depression, and QOL scales. A total of 126 women with metastatic BC were interviewed using four instruments: (1) a questionnaire containing socioeconomic, clinical, and demographic data and CAM use; (2) European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ)-C30; (3) EORTC QLQ-BR23; and (4) the Hospital Anxiety and Depression Scale. Fifty percent of the participants reported the use of at least one CAM modality. Biologically based practices were the most frequently used to treat BC and/or its symptoms, the most commonly discussed with the oncologists, and one of the CAM categories in which more patients reported a desire to learn more about. The overall use of CAM was not correlated with the scores on the anxiety, depression, and QOL scales. However, analysis of the association of the QOL scores with specific CAM modalities revealed some potential associations (especially for food supplements, art therapy, psychotherapy, and prayer). Women with metastatic BC frequently make use of CAM to treat the cancer and/or its symptoms. Biologically based practices seem to be particularly important in Brazil. An association between specific CAM modalities and some QOL domains was suggested, but it needs further confirmation.

  9. 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

  10. Vitamin D deficiency in patients with either rheumatic diseases or inflammatory bowel diseases on biologic therapy.

    Science.gov (United States)

    Bruzzese, Vincenzo; Zullo, Angelo; Picchianti Diamanti, Andrea; Ridola, Lorenzo; Lorenzetti, Roberto; Marrese, Cinzia; Scolieri, Palma; De Francesco, Vincenzo; Hassan, Cesare; Migliore, Alberto; Laganà, Bruno

    2016-09-01

    Vitamin D deficiency has been reported in patients with chronic inflammatory conditions, such as rheumatic and inflammatory bowel diseases (IBD). We evaluated the role of biologic therapy on vitamin D, calcium and parathormone (PTH) levels. This cross-sectional study enrolled consecutive patients with either rheumatic diseases or IBD who underwent an ambulatory visit. Patients receiving vitamin D/calcium supplementation were excluded. Vitamin D deficiency or insufficiency was diagnosed when values were rheumatic disease (M/F 37/99; mean age 60.7 ± 12.9 years) and 64 with IBD (M/F 41/23; Mean age 49.6 ± 13.1 years) were enrolled. Vitamin D deficiency/insufficiency was detected in as many as 63.5 % patients, being 61.8 and 67.2 % in patients with either rheumatic diseases or IBD, respectively. The prevalence of vitamin D deficiency/insufficiency was higher in those receiving biologics than other therapies (78.3 vs 43.2 %; p rheumatic diseases (78.7 vs 41 %; p rheumatic diseases or IBD receiving a biologic therapy.

  11. Effectiveness of Biology-Based Methods for Inhibiting Orthodontic Tooth Movement. A Systematic Review.

    Science.gov (United States)

    Cadenas de Llano-Pérula, M; Yañez-Vico, R M; Solano-Reina, E; Palma-Fernandez, J C; Iglesias-Linares, A

    Several experimental studies in the literature have tested different biology-based methods for inhibiting or decreasing orthodontic tooth movement (OTM) in humans. This systematic review investigated the effects of these interventions on the rate of tooth movement. Electronic [MedLine; SCOPUS; Cochrane Library; OpenGrey;Web of Science] and manual searches were conducted up to January 26th, 2016 in order to identify publications of clinical trials that compared the decreasing or inhibiting effects of different biology-based methods over OTM in humans. A primary outcome (rate of OTM deceleration/inhibition) and a number of secondary outcomes were examined (clinical applicability, orthodontic force used, possible side effects). Two reviewers selected the studies complying with the eligibility criteria (PICO format) and assessed risk of bias [Cochrane Collaboration's tool]. Data collection and analysis were performed following the Cochrane recommendations. From the initial electronic search, 3726 articles were retrieved and 5 studies were finally included. Two types of biology-based techniques used to reduce the rate of OTM in humans were described: pharmacological and low-level laser therapy. In the first group, human Relaxin was compared to a placebo and administered orally. It was described as having no effect on the inhibition of OTM in humans after 32 days, while the drug tenoxicam, injected locally, inhibited the rate of OTM by up to 10% in humans after 42 days. In the second group, no statistically significant differences were reported, compared to placebo, for the rate of inhibition of OTM in humans after 90 days of observation when a 860 nm continuous wave GaAlA slow-level laser was used. The currently available data do not allow us to draw definitive conclusions about the use of various pharmacological substances and biology-based therapies in humans able to inhibit or decrease the OTM rate. There is an urgent need for more sound well-designed randomized

  12. Understanding positional cues in salamander limb regeneration: implications for optimizing cell-based regenerative therapies

    Directory of Open Access Journals (Sweden)

    Catherine D. McCusker

    2014-06-01

    Full Text Available Regenerative medicine has reached the point where we are performing clinical trials with stem-cell-derived cell populations in an effort to treat numerous human pathologies. However, many of these efforts have been challenged by the inability of the engrafted populations to properly integrate into the host environment to make a functional biological unit. It is apparent that we must understand the basic biology of tissue integration in order to apply these principles to the development of regenerative therapies in humans. Studying tissue integration in model organisms, where the process of integration between the newly regenerated tissues and the ‘old’ existing structures can be observed and manipulated, can provide valuable insights. Embryonic and adult cells have a memory of their original position, and this positional information can modify surrounding tissues and drive the formation of new structures. In this Review, we discuss the positional interactions that control the ability of grafted cells to integrate into existing tissues during the process of salamander limb regeneration, and discuss how these insights could explain the integration defects observed in current cell-based regenerative therapies. Additionally, we describe potential molecular tools that can be used to manipulate the positional information in grafted cell populations, and to promote the communication of positional cues in the host environment to facilitate the integration of engrafted cells. Lastly, we explain how studying positional information in current cell-based therapies and in regenerating limbs could provide key insights to improve the integration of cell-based regenerative therapies in the future.

  13. Automated radiofrequency-based US measurement of common carotid intima-media thickness in RA patients treated with synthetic vs synthetic and biologic DMARDs.

    Science.gov (United States)

    Naredo, Esperanza; Möller, Ingrid; Corrales, Alfonso; Bong, David A; Cobo-Ibáñez, Tatiana; Corominas, Hector; Garcia-Vivar, Ma Luz; Macarrón, Pilar; Navio, Teresa; Richi, Patricia; Iagnocco, Annamaria; Garrido, Jesús; Martínez-Hernández, David

    2013-02-01

    To compare the carotid intima-media thickness (IMT) assessed with automated radiofrequency-based US in RA patients treated with synthetic vs synthetic and biologic DMARDs and controls. Ninety-four RA patients and 94 sex- and age-matched controls were prospectively recruited at seven centres. Cardiovascular (CV) risk factors and co-morbidities, RA characteristics and therapy were recorded. Common carotid artery (CCA)-IMT was assessed in RA patients and controls with automated radiofrequency-based US by the same investigator at each centre. Forty-five (47.9%) RA patients had been treated with synthetic DMARDs and 49 (52.1%) with synthetic and biologic DMARDs. There were no significant differences between the RA patients and controls in demographics, CV co-morbidities and CV disease. There were significantly more smokers among RA patients treated with synthetic and biologic DMARDs (P = 0.036). Disease duration and duration of CS and synthetic DMARD therapy was significantly longer in RA patients treated with synthetic and biologic DMARDs (P radiofrequency-based measurement of CCA-IMT can discriminate between RA patients treated with synthetic DMARDs vs RA patients treated with synthetic and biologic DMARDs.

  14. Advances in Viral Vector-Based TRAIL Gene Therapy for Cancer

    International Nuclear Information System (INIS)

    Norian, Lyse A.; James, Britnie R.; Griffith, Thomas S.

    2011-01-01

    Numerous biologic approaches are being investigated as anti-cancer therapies in an attempt to induce tumor regression while circumventing the toxic side effects associated with standard chemo- or radiotherapies. Among these, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has shown particular promise in pre-clinical and early clinical trials, due to its preferential ability to induce apoptotic cell death in cancer cells and its minimal toxicity. One limitation of TRAIL use is the fact that many tumor types display an inherent resistance to TRAIL-induced apoptosis. To circumvent this problem, researchers have explored a number of strategies to optimize TRAIL delivery and to improve its efficacy via co-administration with other anti-cancer agents. In this review, we will focus on TRAIL-based gene therapy approaches for the treatment of malignancies. We will discuss the main viral vectors that are being used for TRAIL gene therapy and the strategies that are currently being attempted to improve the efficacy of TRAIL as an anti-cancer therapeutic

  15. Depressive symptoms, depression, and the effect of biologic therapy among patients in Psoriasis Longitudinal Assessment and Registry (PSOLAR).

    Science.gov (United States)

    Strober, Bruce; Gooderham, Melinda; de Jong, Elke M G J; Kimball, Alexa B; Langley, Richard G; Lakdawala, Nikita; Goyal, Kavitha; Lawson, Fabio; Langholff, Wayne; Hopkins, Lori; Fakharzadeh, Steve; Srivastava, Bhaskar; Menter, Alan

    2018-01-01

    Patients with psoriasis are at an increased risk for depression. However, the impact of treatment on this risk is unclear. Evaluate the incidence and impact of treatment on depression among patients with moderate-to-severe psoriasis. We defined a study population within the Psoriasis Longitudinal Assessment and Registry and measured the incidence of depressive symptoms (Hospital Anxiety and Depression Scale-Depression score ≥8) and adverse events (AEs) of depression within cohorts receiving biologics, conventional systemic therapies, or phototherapy. Patients were evaluated at approximately 6-month intervals. Multivariate modeling determined the impact of treatment on risk. The incidence rates of depressive symptoms were 3.01 per 100 patient-years (PYs) (95% confidence interval [CI], 2.73-3.32), 5.85 per 100 PYs (95% CI, 4.29-7.97), and 5.70 per 100 PYs (95% CI, 4.58-7.10) for biologics, phototherapy, and conventional therapy, respectively. Compared with conventional therapy, biologics reduced the risk for depressive symptoms (hazard ratio, 0.76; 95% CI, 0.59-0.98), whereas phototherapy did not (hazard ratio, 1.05; 95% CI, 0.71-1.54). The incidence rates for AEs of depression were 0.21 per 100 PYs (95% CI, 0.15-0.31) for biologics, 0.55 per 100 PYs (95% CI, 0.21-1.47) for phototherapy, and 0.14 per 100 PYs (95% CI, 0.03-0.55) for conventional therapy; the fact that there were too few events (37 AEs) precluded modeling. Incomplete capture of depression and confounders in the patients on registry. Compared with conventional therapy, biologics appear to be associated with a lower incidence of depressive symptoms among patients with psoriasis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Bower, Julienne E; Irwin, Michael R

    2016-01-01

    The use of mind-body therapies, including Tai Chi, Qigong, yoga, and meditation, has grown steadily in recent years. These approaches have been shown to be effective in reducing symptoms and improving quality of life, and research has begun to examine the impact of these therapies on biological processes, including inflammation. A review of 26 randomized controlled trials was conducted to describe the effects of mind-body therapies (MBTs) on circulating, cellular, and genomic markers of inflammation. This qualitative evaluation showed mixed effects of MBTs on circulating inflammatory markers, including CRP and IL-6, and on measures of stimulated cytokine production. More consistent findings were seen for genomic markers, with trials showing decreased expression of inflammation-related genes and reduced signaling through the proinflammatory transcription factor NF-κB. Potential mechanisms for these effects are discussed, including alterations in neuroendocrine, neural, and psychological and behavioral processes. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

    Science.gov (United States)

    Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

    2017-06-01

    The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were

  18. [Cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of rheumatoid arthritis].

    Science.gov (United States)

    Salinas-Escudero, Guillermo; Vargas-Valencia, Juan; García-García, Erika Gabriela; Munciño-Ortega, Emilio; Galindo-Suárez, Rosa María

    2013-01-01

    to conduct cost-effectiveness analysis of etanercept compared with other biologic therapies in the treatment of moderate or severe rheumatoid arthritis in patients with previous unresponse to immune selective anti-inflammatory derivatives failure. a pharmacoeconomic model based on decision analysis to assess the clinical outcome after giving etanercept, infliximab, adalimumab or tocilizumab to treat moderate or severe rheumatoid arthritis was employed. Effectiveness of medications was assessed with improvement rates of 20 % or 70 % of the parameters established by the American College of Rheumatology (ACR 20 and ACR 70). the model showed that etanercept had the most effective therapeutic response rate: 79.7 % for ACR 20 and 31.4 % for ACR 70, compared with the response to other treatments. Also, etanercept had the lowest cost ($149,629.10 per patient) and had the most cost-effective average ($187,740.40 for clinical success for ACR 20 and $476,525.80 for clinical success for ACR 70) than the other biologic therapies. we demonstrated that treatment with etanercept is more effective and less expensive compared to the other drugs, thus making it more efficient therapeutic option both in terms of means and incremental cost-effectiveness ratios for the treatment of rheumatoid arthritis.

  19. Targeted alpha therapy using Radium-223: From physics to biological effects.

    Science.gov (United States)

    Marques, I A; Neves, A R; Abrantes, A M; Pires, A S; Tavares-da-Silva, E; Figueiredo, A; Botelho, M F

    2018-05-25

    With the advance of the use of ionizing radiation in therapy, targeted alpha therapy (TAT) has assumed an important role around the world. This kind of therapy can potentially reduce side effects caused by radiation in normal tissues and increased destructive radiobiological effects in tumor cells. However, in many countries, the use of this therapy is still in a pioneering phase. Radium-223 ( 223 Ra), an alpha-emitting radionuclide, has been the first of its kind to be approved for the treatment of bone metastasis in metastatic castration-resistant prostate cancer. Nevertheless, the interaction mechanism and the direct effects of this radiopharmaceutical in tumor cells are not fully understood neither characterized at a molecular level. In fact, the ways how TAT is linked to radiobiological effects in cancer is not yet revised. Therefore, this review introduces some physical properties of TAT that leads to biological effects and links this information to the hallmarks of cancer. The authors also collected the studies developed with 223 Ra to correlate with the three categories reviewed - properties of TAT, 5 R's of radiobiology and hallmarks of cancer- and with the promising future to this radiopharmaceutical. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Frequency and prognostic role of mucosal healing in patients with Crohn’s disease and ulcerative colitis after one-year of biological therapy

    Science.gov (United States)

    Farkas, Klaudia; Lakatos, Péter László; Szűcs, Mónika; Pallagi-Kunstár, Éva; Bálint, Anita; Nagy, Ferenc; Szepes, Zoltán; Vass, Noémi; Kiss, Lajos S; Wittmann, Tibor; Molnár, Tamás

    2014-01-01

    AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn’s disease (CD) and ulcerative colitis (UC). METHODS: The data from 41 patients with CD and 22 patients with UC were assessed. Twenty-four CD patients received infliximab, and 17 received adalimumab. The endoscopic severity of CD was quantified with the simplified endoscopic activity score for Crohn’s disease in CD and with the Mayo endoscopic subscore in UC. RESULTS: Mucosal healing was achieved in 23 CD and 7 UC patients. Biological therapy had to be restarted in 78% of patients achieving complete mucosal healing with CD and in 100% of patients with UC. Neither clinical remission nor mucosal healing was associated with the time to restarting the biological therapy in either CD or UC. CONCLUSION: Mucosal healing did not predict sustained clinical remission in patients in whom the biological therapies had been stopped. PMID:24659890

  1. Denosumab for bone diseases: translating bone biology into targeted therapy.

    Science.gov (United States)

    Tsourdi, Elena; Rachner, Tilman D; Rauner, Martina; Hamann, Christine; Hofbauer, Lorenz C

    2011-12-01

    Signalling of receptor activator of nuclear factor-κB (RANK) ligand (RANKL) through RANK is a critical pathway to regulate the differentiation and activity of osteoclasts and, hence, a master regulator of bone resorption. Increased RANKL activity has been demonstrated in diseases characterised by excessive bone loss such as osteoporosis, rheumatoid arthritis and osteolytic bone metastases. The development and approval of denosumab, a fully MAB against RANKL, has heralded a new era in the treatment of bone diseases by providing a potent, targeted and reversible inhibitor of bone resorption. This article summarises the molecular and cellular biology of the RANKL/RANK system and critically reviews preclinical and clinical studies that have established denosumab as a promising novel therapy for metabolic and malignant bone diseases. We will discuss the potential indications for denosumab along with a critical review of safety and analyse its potential within the concert of established therapies.

  2. 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.

  3. Effectiveness of CAM therapy: understanding the evidence.

    Science.gov (United States)

    Staud, Roland

    2011-02-01

    By definition, complementary and alternative medicine (CAM) attempts to diagnose and treat illnesses in unconventional ways. CAM has been classified as: (1) alternative medical systems (eg, traditional Chinese medicine [including acupuncture], naturopathic medicine, ayurvedic medicine, and homeopathy); (2) biologic-based therapies (eg, herbal, special dietary, and individual biologic treatments); (3) energy therapies (eg, Reiki, therapeutic touch, magnet therapy, Qi Gong, and intercessory prayer); (4) manipulative and body-based systems (eg, chiropractic, osteopathy, and massage); and (5) mind-body interventions (eg, meditation, biofeedback, hypnotherapy, and the relaxation response). This review focuses on how to assess the effectiveness of CAM therapies for chronic musculoskeletal pains, emphasizing the role of specific and nonspecific analgesic mechanisms, including placebo. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. 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

    2015-01-01

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

  5. Nanoparticle-Based Drug Delivery for Therapy of Lung Cancer: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2013-01-01

    Full Text Available The last decade has witnessed enormous advances in the development and application of nanotechnology in cancer detection, diagnosis, and therapy culminating in the development of the nascent field of “cancer nanomedicine.” A nanoparticle as per the National Institutes of Health (NIH guidelines is any material that is used in the formulation of a drug resulting in a final product smaller than 1 micron in size. Nanoparticle-based therapeutic systems have gained immense popularity due to their ability to overcome biological barriers, effectively deliver hydrophobic therapies, and preferentially target disease sites. Currently, many formulations of nanocarriers are utilized including lipid-based, polymeric and branched polymeric, metal-based, magnetic, and mesoporous silica. Innovative strategies have been employed to exploit the multicomponent, three-dimensional constructs imparting multifunctional capabilities. Engineering such designs allows simultaneous drug delivery of chemotherapeutics and anticancer gene therapies to site-specific targets. In lung cancer, nanoparticle-based therapeutics is paving the way in the diagnosis, imaging, screening, and treatment of primary and metastatic tumors. However, translating such advances from the bench to the bedside has been severely hampered by challenges encountered in the areas of pharmacology, toxicology, immunology, large-scale manufacturing, and regulatory issues. This review summarizes current progress and challenges in nanoparticle-based drug delivery systems, citing recent examples targeted at lung cancer treatment.

  6. Biosimilars: A new scenario in biologic therapies.

    Science.gov (United States)

    Serra López-Matencio, José M; Morell Baladrón, Alberto; Castañeda, Santos

    There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. Population-based differences in treatment outcome following anticancer drug therapies.

    Science.gov (United States)

    Ma, Brigette By; Hui, Edwin P; Mok, Tony Sk

    2010-01-01

    Population-based differences in toxicity and clinical outcome following treatment with anticancer drugs have an important effect on oncology practice and drug development. These differences arise from complex interactions between biological and environmental factors, which include genetic diversity affecting drug metabolism and the expression of drug targets, variations in tumour biology and host physiology, socioeconomic disparities, and regional preferences in treatment standards. Some well-known examples include the high prevalence of activating epidermal growth factor receptor (EGFR) mutations in pulmonary adenocarcinoma among northeast (China, Japan, Korea) and parts of southeast Asia (excluding India) non-smokers, which predict sensitivity to EGFR kinase inhibitors, and the sharp contrast between Japan and the west in the management and survival outcome of gastric cancer. This review is a critical overview of population-based differences in the four most prevalent cancers in the world: lung, breast, colorectal, and stomach cancer. Particular attention is given to the clinical relevance of such knowledge in terms of the individualisation of drug therapy and in the design of clinical trials. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  8. Predicting response to incretin-based therapy

    Directory of Open Access Journals (Sweden)

    Agrawal N

    2011-04-01

    Full Text Available Sanjay Kalra1, Bharti Kalra2, Rakesh Sahay3, Navneet Agrawal41Department of Endocrinology, 2Department of Diabetology, Bharti Hospital, Karnal, India; 3Department of Endocrinology, Osmania Medical College, Hyderabad, India; 4Department of Medicine, GR Medical College, Gwalior, IndiaAbstract: There are two important incretin hormones, glucose-dependent insulin tropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1. The biological activities of GLP-1 include stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. GLP-1 appears to have a number of additional effects in the gastrointestinal tract and central nervous system. Incretin based therapy includes GLP-1 receptor agonists like human GLP-1 analogs (liraglutide and exendin-4 based molecules (exenatide, as well as DPP-4 inhibitors like sitagliptin, vildagliptin and saxagliptin. Most of the published studies showed a significant reduction in HbA1c using these drugs. A critical analysis of reported data shows that the response rate in terms of target achievers of these drugs is average. One of the first actions identified for GLP-1 was the glucose-dependent stimulation of insulin secretion from islet cell lines. Following the detection of GLP-1 receptors on islet beta cells, a large body of evidence has accumulated illustrating that GLP-1 exerts multiple actions on various signaling pathways and gene products in the ß cell. GLP-1 controls glucose homeostasis through well-defined actions on the islet ß cell via stimulation of insulin secretion and preservation and expansion of ß cell mass. In summary, there are several factors determining the response rate to incretin therapy. Currently minimal clinical data is available to make a conclusion. Key factors appear to be duration of diabetes, obesity, presence of autonomic neuropathy, resting energy expenditure, plasma glucagon levels and

  9. [Dr. Sklenar's Kombucha mushroom infusion--a biological cancer therapy. Documentation No. 18].

    Science.gov (United States)

    Hauser, S P

    1990-02-27

    Kombucha, a fungal infusion, is a 'symbiotic mixture' of bacteria, yeasts, tea and sugar. A number of components are listed, but exact analyses are not published. On the basis of 'thorough detoxification', Kombucha is claimed to be a prophylactic and therapeutic agent in countless diseases, such as rheumatism, intestinal disorders, ageing and cancer. All 'stages of the Sklenar blood picture' have to be treated with Kombucha Drink, Kombucha Drops, coli preparations and Gelum oral-rd for a period of months. A litre-bottle costs 13 DM, the blood analysis 150 Sfr. In the 1960's Dr. R. Sklenar developed a 'biological cancer therapy with Kombucha as the main agent' and his own system of diagnosing cancer. Sklenar's diagnosis of cancer is based on iris diagnosis and demonstration of the causative organism by means of a 'Blood picture according to Dr. Sklenar'. He claims, on one hand, that cancer is only one of the many metabolic diseases and, on the other, that viruses, in his view parasitic microorganisms in general, are responsible for the pathogenesis of cancer. No preclinical and nor investigations are available, as 'success has proved him (Dr. Sklenar) to be right'. The seven 'case histories' described have no solid medical data. There is so far no evidence to support the claim that Kombucha offers 'effective biological treatment of cancer'.

  10. New therapies versus first-generation biologic drugs in psoriasis: a review of adverse events and their management.

    Science.gov (United States)

    Carrascosa, J M; Del-Alcazar, E

    2018-04-01

    Biologic drugs have revolutionized the treatment of moderate to severe psoriasis in recent years because of their high efficacy and low risk of toxicity. However, even within the group of biologic therapies, there are differences related to the different mechanisms of action. Areas covered: We review the main adverse events associated with the biologic agents currently available for the treatment of psoriasis and the new inhibitors targeting the p19 subunit of interleukin (IL) 23 and the IL-17A receptor. This review covers injection site reactions, infections, cardiovascular events, demyelinating disorders, tumours, class effects secondary adverse events, immunogenicity, safety in pregnancy and vaccines efficacy. Expert commentary: More than a decade after the first approval of biologic drugs for use in psoriasis, the good safety profile of these drugs is one of the main justifications and incentives for their long-term use. The emergence of new pharmacological groups has made it possible to avoid some of the class effects of first-generation biologic agents and the new therapies appear to pose less risk of reactivation of latent infections, such as hepatitis B virus and tuberculosis. However, they are associated with new adverse effects related to their mechanism of action, including candidiasis and the risk of exacerbation or onset of inflammatory bowel disease.

  11. Exploring the TRAILs less travelled: TRAIL in cancer biology and therapy.

    Science.gov (United States)

    von Karstedt, Silvia; Montinaro, Antonella; Walczak, Henning

    2017-05-24

    The discovery that the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis of cancer cells without causing toxicity in mice has led to the in-depth study of pro-apoptotic TRAIL receptor (TRAIL-R) signalling and the development of biotherapeutic drug candidates that activate TRAIL-Rs. The outcome of clinical trials with these TRAIL-R agonists has, however, been disappointing so far. Recent evidence indicates that many cancers, in addition to being TRAIL resistant, use the endogenous TRAIL-TRAIL-R system to their own advantage. However, novel insight on two fronts - how resistance of cancer cells to TRAIL-based pro-apoptotic therapies might be overcome, and how the pro-tumorigenic effects of endogenous TRAIL might be countered - gives reasonable hope that the TRAIL system can be harnessed to treat cancer. In this Review we assess the status quo of our understanding of the biology of the TRAIL-TRAIL-R system - as well as the gaps therein - and discuss the opportunities and challenges in effectively targeting this pathway.

  12. Evidence-based music therapy practice: an integral understanding.

    Science.gov (United States)

    Abrams, Brian

    2010-01-01

    The American Music Therapy Association has recently put into action a plan called its Research Strategic Priority, with one of its central purposes to advance the music therapy field through research promoting Evidence-Based Practice of music therapy. The extant literature on music therapy practice, theory, and research conveys a range of very different perspectives on what may count as the "evidence" upon which practice is based. There is therefore a need to conceptualize evidence-based music therapy practice in a multifaceted, yet coherent and balanced way. The purpose of this paper is to illustrate a framework based upon four distinct epistemological perspectives on evidence-based music therapy practice that together represent an integral understanding.

  13. Agent-based modelling in synthetic biology.

    Science.gov (United States)

    Gorochowski, Thomas E

    2016-11-30

    Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

  14. Should over-treatment of axial spondyloarthritis with biologics remain a concern after the issue of the new ASAS criteria? Data from REGISPONSERBIO (Spanish Register of Biological Therapy in Spondyloarthritides).

    Science.gov (United States)

    Moreno, Mireia; Gratacós, Jordi; Navarro-Compán, Victoria; de Miguel, Eugenio; Font, Pilar; Clavaguera, Teresa; Linares, Luis Francisco; Joven, Beatriz; Juanola, Xavier

    2018-05-08

    To study whether disease status at treatment initiation has changed after the issue of the ASAS classification criteria. REGISPONSERBIO registers patients with axial spondyloarthritis (axSpA) on biological treatment since 2013. It includes patients starting biological treatment (incident) or already on biological therapies (prevalent). Patients in both groups were compared in terms of: age at disease onset and at treatment start, disease duration, gender, HLA-B27, body mass index (BMI), BASDAI, BASFI, C-reactive protein, ESR, metrological data, ASQoL, WAPAI, extra-articular manifestations, comorbidities, radiological study, type of biological treatment and concomitant treatments. 256 patients were included, of whom 174 (65%) were already on biologic therapy. Compared to incident patients, prevalent patients started treatment with longer disease duration (15 vs. 8.6 years; p<0.001), a higher proportion of them were men (83% vs. 67%; p=0.01), a smaller proportion of them showed non-radiographic axial spondylarthritis (nr-axSpA)(17% vs. 32%; p<0.01), and a higher proportion had HLAB27 (85% vs. 73%; p=0.02). There were no statistically significant differences in terms of disease activity, degree of disability, quality of life, or prevalence of extra-articular manifestations. Data suggest that, after the issue of the new classification criteria for SpA, biological therapy is being administered earlier than previously in SpA patients and in a higher proportion of patients with nr-axSpA. However, this change in prescribing profile, apparently, has not caused an over-treatment, as patients do not seem to have a lower disease burden than prior to the issue of the criteria.

  15. FDA 101: Regulating Biological Products

    Science.gov (United States)

    ... based and cellular biologics, at the forefront of biomedical research today, may make it possible to treat a ... transplantation vaccines The Center for Drug Evaluation and Research ... as targeted therapies in cancer and other diseases cytokines (types of ...

  16. Biological effectiveness and application of heavy ions in radiation therapy described by a physical and biological model

    International Nuclear Information System (INIS)

    Olsen, K.J.; Hansen, J.W.

    1982-12-01

    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 is inadequately described by an RBE-factor, whereas the complete formulation of the probability of survival must be used, as survival depends on both radiation quality and dose. The theoretical model of track structure can be used in dose-effect calculations for neutron-, high-LET, and low-LET radiation applied simultaneously in therapy. (author)

  17. Synthetic biology in mammalian cells: Next generation research tools and therapeutics

    Science.gov (United States)

    Lienert, Florian; Lohmueller, Jason J; Garg, Abhishek; Silver, Pamela A

    2014-01-01

    Recent progress in DNA manipulation and gene circuit engineering has greatly improved our ability to programme and probe mammalian cell behaviour. These advances have led to a new generation of synthetic biology research tools and potential therapeutic applications. Programmable DNA-binding domains and RNA regulators are leading to unprecedented control of gene expression and elucidation of gene function. Rebuilding complex biological circuits such as T cell receptor signalling in isolation from their natural context has deepened our understanding of network motifs and signalling pathways. Synthetic biology is also leading to innovative therapeutic interventions based on cell-based therapies, protein drugs, vaccines and gene therapies. PMID:24434884

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

    International Nuclear Information System (INIS)

    Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

    2010-01-01

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

  19. Synthesis and Biological Assessment of Racemic Benzochromenopyrimidinimines as Antioxidant, Cholinesterase, and Aβ1-42 Aggregation Inhibitors for Alzheimer's Disease Therapy.

    Science.gov (United States)

    Dgachi, Youssef; Ismaili, Lhassane; Knez, Damijan; Benchekroun, Mohamed; Martin, Hélène; Szałaj, Natalia; Wehle, Sarah; Bautista-Aguilera, Oscar M; Luzet, Vincent; Bonnet, Alexandre; Malawska, Barbara; Gobec, Stanislav; Chioua, Mourad; Decker, Michael; Chabchoub, Fakher; Marco-Contelles, José

    2016-06-20

    Given the complex nature of Alzheimer's disease (AD), compounds that are able to simultaneously address two or more AD-associated targets show greater promise for development into drugs for AD therapy. Herein we report an efficient two-step synthesis and biological evaluation of new racemic benzochromene derivatives as antioxidants, inhibitors of cholinesterase and β-amyloid (Aβ1-42 ) aggregation. Based on the results of the primary screening, we identified 15-(3-methoxyphenyl)-9,11,12,15-tetrahydro-10H,14H-benzo[5,6]chromeno[2,3-d]pyrido[1,2-a]pyrimidin-14-imine (3 e) and 16-(3-methoxyphenyl)-9,10,11,12,13,16-hexahydro-15H-benzo[5',6']chromeno[2',3':4,5]pyrimido[1,2-a]azepin-15-imine (3 f) as new potential multitarget-directed ligands for AD therapy. Further in-depth biological analysis showed that compound 3 f is a good human acetylcholinesterase inhibitor [IC50 =(0.36±0.02) μm], has strong antioxidant activity (3.61 μmol Trolox equivalents), and moderate Aβ1-42 antiaggregating power (40.3 %). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. WE-FG-BRB-00: The Challenges of Predicting RBE Effects in Particle Therapy and Opportunities for Improving Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  1. Adjuvant Biological Therapies in Chronic Leg Ulcers

    Directory of Open Access Journals (Sweden)

    Natalia Burgos-Alonso

    2017-11-01

    Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

  2. Models for synthetic biology.

    Science.gov (United States)

    Kaznessis, Yiannis N

    2007-11-06

    Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.

  3. Stem cells engineering for cell-based therapy.

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  4. [Acceptance and mindfulness-based cognitive-behavioral therapies].

    Science.gov (United States)

    Ngô, Thanh-Lan

    2013-01-01

    Cognitive behavioral therapy (CBT) is one of the main approaches in psychotherapy. It teaches the patient to examine the link between dysfunctional thoughts and maladaptive behaviors and to re- evaluate the cognitive biases involved in the maintenance of symptoms by using strategies such as guided discovery. CBT is constantly evolving in part to improve its' effectiveness and accessibility. Thus in the last decade, increasingly popular approaches based on mindfulness and acceptance have emerged. These therapies do not attempt to modify cognitions even when they are biased and dysfunctional but rather seek a change in the relationship between the individual and the symptoms. This article aims to present the historical context that has allowed the emergence of this trend, the points of convergence and divergence with traditional CBT as well as a brief presentation of the different therapies based on mindfulness meditation and acceptance. Hayes (2004) described three successive waves in behavior therapy, each characterized by "dominant assumptions, methods and goals": traditional behavior therapy, cognitive therapy and therapies based on mindfulness meditation and acceptance. The latter consider that human suffering occurs when the individual lives a restricted life in order avoid pain and immediate discomfort to the detriment of his global wellbeing. These therapies combine mindfulness, experiential, acceptance strategies with traditional behavior principles in order to attain lasting results. There are significant points of convergence between traditional CBT and therapies based on mindfulness meditation and acceptance. They are both empirically validated, based upon a theoretical model postulating that avoidance is key in the maintenance of psychopathology and they recommend an approach strategy in order to overcome the identified problem. They both use behavioral techniques in the context of a collaborative relationship in order to identify precise problems and to

  5. Moving from Virtual Reality Exposure-Based Therapy to Augmented Reality Exposure-Based Therapy: A Review

    OpenAIRE

    Baus, Oliver; Bouchard, Stéphane

    2014-01-01

    This paper reviews the move from virtual reality exposure-based therapy to augmented reality exposure-based therapy (ARET). Unlike virtual reality (VR), which entails a complete virtual environment (VE), augmented reality (AR) limits itself to producing certain virtual elements to then merge them into the view of the physical world. Although, the general public may only have become aware of AR in the last few years, AR type applications have been around since beginning of the twentieth centur...

  6. Mindfulness-Based Cognitive Therapy for severe Functional Disorders

    DEFF Research Database (Denmark)

    Fjorback, Lone Overby

    MINDFULNESS-BASED COGNITIVE THERAPY FOR FUNCTIONAL DISORDERS- A RANDOMISED CONTROLLED TRIAL   Background: Mindfulness-Based Stress Reduction (MBSR) is a group skills-training program developed by Kabat-Zinn. It is designed to teach patients to become more aware of and relate differently...... to their thoughts, feelings, and bodily sensations. Randomised controlled studies of MBSR have shown mitigation of stress, anxiety, and dysphoria in general population and reduction in total mood disturbance and stress symptoms in a medical population. In Mindfulness Based Cognitive Therapy MBSR is recombined...... with cognitive therapy. Aim: To examine the efficacy of Mindfulness-Based Cognitive Therapy in severe Functional disorders, defined as severe Bodily Distress Disorder. Method: 120 patients are randomised to either Mindfulness Based Cognitive Therapy: a manualized programme with eight weekly 3 ½ hour group...

  7. Mindfulness-Based Cognitive Therapy for severe Functional Disorders

    DEFF Research Database (Denmark)

    Fjorback, Lone Overby

    with cognitive therapy. Aim: To examine the efficacy of Mindfulness-Based Cognitive Therapy in severe Functional disorders, defined as severe Bodily Distress Disorder. Method: 120 patients are randomised to either Mindfulness Based Cognitive Therapy: a manualized programme with eight weekly 3 ½ hour group......MINDFULNESS-BASED COGNITIVE THERAPY FOR FUNCTIONAL DISORDERS- A RANDOMISED CONTROLLED TRIAL   Background: Mindfulness-Based Stress Reduction (MBSR) is a group skills-training program developed by Kabat-Zinn. It is designed to teach patients to become more aware of and relate differently...... to their thoughts, feelings, and bodily sensations. Randomised controlled studies of MBSR have shown mitigation of stress, anxiety, and dysphoria in general population and reduction in total mood disturbance and stress symptoms in a medical population. In Mindfulness Based Cognitive Therapy MBSR is recombined...

  8. Technical Stability and Biological Variability in MicroRNAs from Dried Blood Spots: A Lung Cancer Therapy-Monitoring Showcase.

    Science.gov (United States)

    Kahraman, Mustafa; Laufer, Thomas; Backes, Christina; Schrörs, Hannah; Fehlmann, Tobias; Ludwig, Nicole; Kohlhaas, Jochen; Meese, Eckart; Wehler, Thomas; Bals, Robert; Keller, Andreas

    2017-09-01

    Different work flows have been proposed to use miRNAs as blood-borne biomarkers. In particular, the method used for collecting blood from patients can considerably influence the diagnostic results. We explored whether dried blood spots (DBSs) facilitate stable miRNA measurements and compared its technical stability with biological variability. First, we tested the stability of DBS samples by generating from 1 person 18 whole-genome-wide miRNA profiles of DBS samples that were exposed to different temperature and humidity conditions. Second, we investigated technical reproducibility by performing 7 replicates of DBS again from 1 person. Third, we investigated DBS samples from 53 patients with lung cancer undergoing different therapies. Across these 3 stages, 108 genome-wide miRNA profiles from DBS were generated and evaluated biostatistically. In the stability analysis, we observed that temperature and humidity had an overall limited influence on the miRNomes (average correlation between the different conditions of 0.993). Usage of a silica gel slightly diminished DBS' technical reproducibility. The 7 technical replicates had an average correlation of 0.996. The correlation with whole-blood PAXGene miRNomes of the same individual was remarkable (correlation of 0.88). Finally, evaluation of the samples from the 53 patients with lung cancer exposed to different therapies showed that the biological variations exceeded the technical variability significantly ( P work flow for profiling of whole miRNomes on the basis of samples collected from DBS. Biological variations exceeded technical variations significantly. DBS-based miRNA profiles will potentially further the translational character of miRNA biomarker studies. © 2017 American Association for Clinical Chemistry.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mairani, A [University of Pavia, Department of Nuclear and Theoretical Physics, and INFN, via Bassi 6, 27100 Pavia (Italy); Brons, S; Parodi, K [Heidelberg Ion Beam Therapy Center and Department of Radiation Oncology, Im Neuenheimer Feld 450, 69120 Heidelberg (Germany); Cerutti, F; Ferrari, A; Sommerer, F [CERN, 1211 Geneva 23 (Switzerland); Fasso, A [SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025 (United States); Kraemer, M; Scholz, M, E-mail: Andrea.Mairani@mi.infn.i [GSI Biophysik, Planck-Str. 1, D-64291 Darmstadt (Germany)

    2010-08-07

    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 fuer 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 {sup 12}C 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-dose distributions in water used as input basic data in TRiP98 and the FLUKA recalculated ones. On the other hand, taking into account the differences in the physical beam modeling, the FLUKA-based biological calculations of the CHO cell survival profiles are found in good agreement with the experimental data as well with the TRiP98 predictions. The developed approach that combines the MC transport/interaction capability with the same biological model as in the treatment planning system (TPS) will be used at HIT to support validation/improvement of both dose and RBE-weighted dose calculations performed by the analytical TPS.

  10. Biologic targets identified from dynamic 18FDG-PET and implications for image-guided therapy

    International Nuclear Information System (INIS)

    Rusten, Espen; Malinen, Eirik; Roedal, Jan; Bruland, Oeyvind S.

    2013-01-01

    Purpose: The outcome of biologic image-guided radiotherapy depends on the definition of the biologic target. The purpose of the current work was to extract hyper perfused and hypermetabolic regions from dynamic positron emission tomography (D-PET) images, to dose escalate either region and to discuss implications of such image guided strategies. Methods: Eleven patients with soft tissue sarcomas were investigated with D-PET. The images were analyzed using a two-compartment model producing parametric maps of perfusion and metabolic rate. The two image series were segmented and exported to a treatment planning system, and biological target volumes BTV per and BTV met (perfusion and metabolism, respectively) were generated. Dice's similarity coefficient was used to compare the two biologic targets. Intensity-modulated radiation therapy (IMRT) plans were generated for a dose painting by contours regime, where planning target volume (PTV) was planned to 60 Gy and BTV to 70 Gy. Thus, two separate plans were created for each patient with dose escalation of either BTV per or BTV met . Results: BTV per was somewhat smaller than BTV met (209 ±170 cm 3 against 243 ±143 cm 3 , respectively; population-based mean and s.d.). Dice's coefficient depended on the applied margin, and was 0.72 ±0.10 for a margin of 10 mm. Boosting BTV per resulted in mean dose of 69 ±1.0 Gy to this region, while BTV met received 67 ±3.2 Gy. Boosting BTV met gave smaller dose differences between the respective non-boost DVHs (such as D 98 ). Conclusions: Dose escalation of one of the BTVs results in a partial dose escalation of the other BTV as well. If tumor aggressiveness is equally pronounced in hyper perfused and hypermetabolic regions, this should be taken into account in the treatment planning

  11. Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy.

    Science.gov (United States)

    Ryoma, Yoshiki; Moriya, Yoichiro; Okamoto, Masato; Kanaya, Isao; Saito, Motoo; Sato, Mitsunobu

    2004-01-01

    OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975. In the ensuing 30 years, since then, a significant amount of data, including clinical as well as experimental studies, has been accumulated. OK-432 has been reported to induce various cytokines, activate immunological cells and thus augment anticancer immunity. Recently, the interrelation between innate immunity and adaptive immunity has become clear and it was reported that OK-432 acts, at least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway. In addition, dendritic cells (DCs) are considered to play a pivotal role in immunological response and it is reported that OK-432 induced maturation of DCs both in vitro and in vivo. These results suggest that OK-432 is a useful adjuvant in DC-based anticancer immunotherapy. Clinical studies of DC therapy with OK-432 are under way.

  12. NK cell-based cancer immunotherapy: from basic biology to clinical application.

    Science.gov (United States)

    Li, Yang; Yin, Jie; Li, Ting; Huang, Shan; Yan, Han; Leavenworth, JianMei; Wang, Xi

    2015-12-01

    Natural killer (NK) cells, which recognize and kill target cells independent of antigen specificity and major histocompatibility complex (MHC) matching, play pivotal roles in immune defence against tumors. However, tumor cells often acquire the ability to escape NK cell-mediated immune surveillance. Thus, understanding mechanisms underlying regulation of NK cell phenotype and function within the tumor environment is instrumental for designing new approaches to improve the current cell-based immunotherapy. In this review, we elaborate the main biological features and molecular mechanisms of NK cells that pertain to regulation of NK cell-mediated anti-tumor activity. We further overview current clinical approaches regarding NK cell-based cancer therapy, including cytokine infusion, adoptive transfer of autologous or allogeneic NK cells, applications of chimeric antigen receptor (CAR)-expressing NK cells and adoptive transfer of memory-like NK cells. With these promising clinical outcomes and fuller understanding the basic questions raised in this review, we foresee that NK cell-based approaches may hold great potential for future cancer immunotherapy.

  13. A balanced review of the status T cell-based therapy against cancer

    Directory of Open Access Journals (Sweden)

    Marincola Francesco M

    2005-04-01

    Full Text Available Abstract A recent commentary stirred intense controversy over the status of anti-cancer immunotherapy. The commentary suggested moving beyond current anti-cancer vaccines since active-specific immunization failed to match expectations toward a more aggressive approach involving the adoptive transfer of in vitro expanded tumor antigen-specific T cells. Although the same authors clarified their position in response to others' rebuttal more discussion needs to be devoted to the current status of T cell-based anti-cancer therapy. The accompanying publications review the status of adoptive transfer of cancer vaccines on one hand and active-specific immunization on the other. Hopefully, reading these articles will offer a balanced view of the current status of antigen-specific ant-cancer therapies and suggest future strategies to foster unified efforts to complement either approach with the other according to specific biological principles.

  14. PENERAPAN BLENDED-PROBLEM BASED LEARNING DALAM PEMBELAJARAN BIOLOGI

    Directory of Open Access Journals (Sweden)

    Samuel Agus Triyanto

    2016-07-01

    Biologi abad 21 merupakan integrasi dan mengintegrasikan kembali sub disiplin ilmu biologi, serta integrasi biologi dengan disiplin ilmu lain untuk mengatasi permasalahan sosial. Penelitian ini bertujuan untuk mengetahui penerapan Blended-Problem Based Learning, aktivitas belajar, dan respon siswa dalam pembelajaran biologi. Penelitian ini merupakan penelitian survei dengan pendekatan deskriptif kualitatif. Data hasil penelitian menunjukkan bahwa aktivitas positif siswa dalam pembelajaran memuaskan, sedangkan respon siswa baik terhadap pembelajaran. Berdasarkan hasil penelitian, disimpulkan bahwa Blended-Problem Based Learning dapat diterapkan dan diterima sebagai model dalam pembelajaran.

  15. [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.

  16. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    Science.gov (United States)

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  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. A conceptual design of neutron tumor therapy reactor facility with a YAYOI based fast neutron source reactor

    International Nuclear Information System (INIS)

    Wakabayashi, Hiroaki; An, Shigehiro.

    1983-01-01

    Fast neutron is known as one of useful radiations for radiation therapy of tumors. Boron neutron capture therapy (BNCT) of tumors which makes use of 10 B(n, α) 7 Li reaction of 10 B compounds selectively attached to tumor cells with thermal and intermediate neutrons is another way of neutron based radiation therapy which is, above all, attractive enough to kill tumor cells selectively sparing normal tissue. In Japan, BNCT has already been applied and leaned to be effective. After more than a decade operational experiences and the specific experiments designed for therapeutical purposes, in this paper, a conceptual design of a special neutron therapy reactor facility based on YAYOI - fast neutron source reactor of Nuclear Engineering Research Laboratory, Faculty of Engineering, the University of Tokyo - modified to provide an upward beam of fast and intermediate neutrons is presented. Emphasis is placed on the in-house nature of facility and on the coordinating capability of biological and physical researches as well as maintenances of the facility. (author)

  19. Biomaterials-based electronics: polymers and interfaces for biology and medicine.

    Science.gov (United States)

    Muskovich, Meredith; Bettinger, Christopher J

    2012-05-01

    Advanced polymeric biomaterials continue to serve as a cornerstone for new medical technologies and therapies. The vast majority of these materials, both natural and synthetic, interact with biological matter in the absence of direct electronic communication. However, biological systems have evolved to synthesize and utilize naturally-derived materials for the generation and modulation of electrical potentials, voltage gradients, and ion flows. Bioelectric phenomena can be translated into potent signaling cues for intra- and inter-cellular communication. These cues can serve as a gateway to link synthetic devices with biological systems. This progress report will provide an update on advances in the application of electronically active biomaterials for use in organic electronics and bio-interfaces. Specific focus will be granted to covering technologies where natural and synthetic biological materials serve as integral components such as thin film electronics, in vitro cell culture models, and implantable medical devices. Future perspectives and emerging challenges will also be highlighted. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. The Quest for Evidence for Proton Therapy: Model-Based Approach and Precision Medicine

    Energy Technology Data Exchange (ETDEWEB)

    Widder, Joachim, E-mail: j.widder@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Schaaf, Arjen van der [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Lambin, Philippe [Department of Radiation Oncology, School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht (Netherlands); Marijnen, Corrie A.M. [Department of Radiation Oncology, Leiden University Medical Center, Leiden (Netherlands); Pignol, Jean-Philippe [Department of Radiation Oncology, Erasmus Medical Center Cancer Institute, Rotterdam (Netherlands); Rasch, Coen R. [Department of Radiation Oncology, Academic Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU Medical Center, Amsterdam (Netherlands); Verheij, Marcel [Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2016-05-01

    Purpose: Reducing dose to normal tissues is the advantage of protons versus photons. We aimed to describe a method for translating this reduction into a clinically relevant benefit. Methods and Materials: Dutch scientific and health care governance bodies have recently issued landmark reports regarding generation of relevant evidence for new technologies in health care including proton therapy. An approach based on normal tissue complication probability (NTCP) models has been adopted to select patients who are most likely to experience fewer (serious) adverse events achievable by state-of-the-art proton treatment. Results: By analogy with biologically targeted therapies, the technology needs to be tested in enriched cohorts of patients exhibiting the decisive predictive marker: difference in normal tissue dosimetric signatures between proton and photon treatment plans. Expected clinical benefit is then estimated by virtue of multifactorial NTCP models. In this sense, high-tech radiation therapy falls under precision medicine. As a consequence, randomizing nonenriched populations between photons and protons is predictably inefficient and likely to produce confusing results. Conclusions: Validating NTCP models in appropriately composed cohorts treated with protons should be the primary research agenda leading to urgently needed evidence for proton therapy.

  1. Molecular and cell-based therapies for muscle degenerations: a road under construction.

    Science.gov (United States)

    Berardi, Emanuele; Annibali, Daniela; Cassano, Marco; Crippa, Stefania; Sampaolesi, Maurilio

    2014-01-01

    Despite the advances achieved in understanding the molecular biology of muscle cells in the past decades, there is still need for effective treatments of muscular degeneration caused by muscular dystrophies and for counteracting the muscle wasting caused by cachexia or sarcopenia. The corticosteroid medications currently in use for dystrophic patients merely help to control the inflammatory state and only slightly delay the progression of the disease. Unfortunately, walkers and wheel chairs are the only options for such patients to maintain independence and walking capabilities until the respiratory muscles become weak and the mechanical ventilation is needed. On the other hand, myostatin inhibition, IL-6 antagonism and synthetic ghrelin administration are examples of promising treatments in cachexia animal models. In both dystrophies and cachectic syndrome the muscular degeneration is extremely relevant and the translational therapeutic attempts to find a possible cure are well defined. In particular, molecular-based therapies are common options to be explored in order to exploit beneficial treatments for cachexia, while gene/cell therapies are mostly used in the attempt to induce a substantial improvement of the dystrophic muscular phenotype. This review focuses on the description of the use of molecular administrations and gene/stem cell therapy to treat muscular degenerations. It reviews previous trials using cell delivery protocols in mice and patients starting with the use of donor myoblasts, outlining the likely causes for their poor results and briefly focusing on satellite cell studies that raise new hope. Then it proceeds to describe recently identified stem/progenitor cells, including pluripotent stem cells and in relationship to their ability to home within a dystrophic muscle and to differentiate into skeletal muscle cells. Different known features of various stem cells are compared in this perspective, and the few available examples of their use in

  2. Ultraviolet-based therapy for vitiligo: What′s new?

    Directory of Open Access Journals (Sweden)

    Iltefat H Hamzavi

    2012-01-01

    Full Text Available Vitiligo is an ancient disease in which depigmented and hypopigmented macules appear on the skin. It is a disfiguring condition that may lead to severe psychological trauma. Among the many treatment modalities available for use in vitiligo, those using light therapy, and in particular ultraviolet (UV light, are some of the most effective treatments. UV-based therapy includes phototherapy (narrowband UVB, photochemotherapy (psoralens with UVA, and targeted phototherapy (excimer laser and excimer lamp. It is important for any practitioner of UV-based therapy to understand the efficacy of each treatment type, as well as their respective adverse effects. In order to take full advantage of UV-based therapy, location, dosing, and photoadaptation must also be taken into account. This review discusses the various UV-based therapeutic options, adjuvant therapies, optimal dosing guidelines, appropriate patient selection, future treatment options, and recommendations based upon the current evidence and the authors′ experience with vitiligo.

  3. 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 randomi...... treatment with biological monotherapy. However, given our limited confidence in the estimates including possibility of bias, it is appropriate to strongly weight patients׳ preferences and values in the final treatment choice.......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 randomised trials that compared biological monotherapy with methotrexate, placebo, or other biological monotherapies. Primary outcomes were ACR50 and the number of patients who discontinued due to adverse events. Our network meta-analysis was based on mixed-effects logistic regression, including both direct...

  4. Biologic Therapy and Asthma.

    Science.gov (United States)

    Viswanathan, Ravi K; Busse, William W

    2018-02-01

    Although airway inflammation is an intrinsic and key feature of asthma, this response varies in its intensity and translation to clinical characteristics and responsiveness to treatment. The observations that clinical heterogeneity is an important aspect of asthma and a feature that likely dictates and determines responses to treatment in severe asthma, patient responsiveness to medication is incomplete, and risks for exacerbation are increased. The development of biologics, which target selected and specific components of inflammation, has been a promising advance to achieve asthma control in patients with severe disease. This article reviews the current biologics available and under development and how their use has affected asthma and which subpopulations appear to benefit the greatest. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

    International Nuclear Information System (INIS)

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

    2008-01-01

    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 α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial

  6. Nanotechnology-based combinational drug delivery: an emerging approach for cancer therapy.

    Science.gov (United States)

    Parhi, Priyambada; Mohanty, Chandana; Sahoo, Sanjeeb Kumar

    2012-09-01

    Combination therapy for the treatment of cancer is becoming more popular because it generates synergistic anticancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. In recent years, nanotechnology-based combination drug delivery to tumor tissues has emerged as an effective strategy by overcoming many biological, biophysical and biomedical barriers that the body stages against successful delivery of anticancer drugs. The sustained, controlled and targeted delivery of chemotherapeutic drugs in a combination approach enhanced therapeutic anticancer effects with reduced drug-associated side effects. In this article, we have reviewed the scope of various nanotechnology-based combination drug delivery approaches and also summarized the current perspective and challenges facing the successful treatment of cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Synthetic biology platform technologies for antimicrobial applications.

    Science.gov (United States)

    Braff, Dana; Shis, David; Collins, James J

    2016-10-01

    The growing prevalence of antibiotic resistance calls for new approaches in the development of antimicrobial therapeutics. Likewise, improved diagnostic measures are essential in guiding the application of targeted therapies and preventing the evolution of therapeutic resistance. Discovery platforms are also needed to form new treatment strategies and identify novel antimicrobial agents. By applying engineering principles to molecular biology, synthetic biologists have developed platforms that improve upon, supplement, and will perhaps supplant traditional broad-spectrum antibiotics. Efforts in engineering bacteriophages and synthetic probiotics demonstrate targeted antimicrobial approaches that can be fine-tuned using synthetic biology-derived principles. Further, the development of paper-based, cell-free expression systems holds promise in promoting the clinical translation of molecular biology tools for diagnostic purposes. In this review, we highlight emerging synthetic biology platform technologies that are geared toward the generation of new antimicrobial therapies, diagnostics, and discovery channels. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Microdosimetry for Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Maughan, R.L.; Kota, C.

    2000-01-01

    The specific aims of the research proposal were as follows: (1) To design and construct small volume tissue equivalent proportional counters for the dosimetry and microdosimetry of high intensity thermal and epithermal neutron beams used in BNCT, and of modified fast neutron beams designed for boron neutron capture enhanced fast neutron therapy (BNCEFNT). (2) To develop analytical methods for estimating the biological effectiveness of the absorbed dose in BNCT and BNCEFNT based on the measured microdosimetric spectra. (3) To develop an analytical framework for comparing the biological effectiveness of different epithermal neutron beams used in BNCT and BNCEFNT, based on correlated sets of measured microdosimetric spectra and radiobiological data. Specific aims (1) and (2) were achieved in their entirety and are comprehensively documented in Jay Burmeister's Ph.D. dissertation entitled ''Specification of physical and biologically effective absorbed dose in radiation therapies utilizing the boron neutron capture reaction'' (Wayne State University, 1999). Specific aim (3) proved difficult to accomplish because of a lack of sufficient radiobiological data

  9. Current concepts in F18 FDG PET/CT-based Radiation Therapy planning for Lung Cancer

    Directory of Open Access Journals (Sweden)

    Percy eLee

    2012-07-01

    Full Text Available Radiation therapy is an important component of cancer therapy for early stage as well as locally advanced lung cancer. The use of F18 FDG PET/CT has come to the forefront of lung cancer staging and overall treatment decision-making. FDG PET/CT parameters such as standard uptake value and metabolic tumor volume provide important prognostic and predictive information in lung cancer. Importantly, FDG PET/CT for radiation planning has added biological information in defining the gross tumor volume as well as involved nodal disease. For example, accurate target delineation between tumor and atelectasis is facilitated by utilizing PET and CT imaging. Furthermore, there has been meaningful progress in incorporating metabolic information from FDG PET/CT imaging in radiation treatment planning strategies such as radiation dose escalation based on standard uptake value thresholds as well as using respiratory gated PET and CT planning for improved target delineation of moving targets. In addition, PET/CT based follow-up after radiation therapy has provided the possibility of early detection of local as well as distant recurrences after treatment. More research is needed to incorporate other biomarkers such as proliferative and hypoxia biomarkers in PET as well as integrating metabolic information in adaptive, patient-centered, tailored radiation therapy.

  10. 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.

    Science.gov (United States)

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

    2009-07-28

    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). 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. 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. 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.

  11. 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.

  12. Correlation of microdosimetric measurements with relative biological effectiveness from clinical experience for two neutron therapy beams

    International Nuclear Information System (INIS)

    Stinchcomb, T.G.; Kuchnir, F.T.; Myrianthopoulos, L.C.; Horton, J.L. Jr.; Roberts, W.K.

    1986-01-01

    Microdosimetric measurements were made for the neutron therapy beams at the University of Chicago and at the Cleveland Clinic with the same geometry and phantom material using the same tissue-equivalent spherical proportional counter and standard techniques. The energy deposition spectra (dose distributions in lineal energy) are compared for these beams and for their scattered components (direct beam blocked). The model of dual radiation action (DRA) of Kellerer and Rossi is employed to interpret these data in terms of biological effectiveness over this limited range of radiation qualities. The site-diameter parameter of the DRA theory is determined for the Cleveland beam by setting the biological effectiveness (relative to 60 Co gamma radiation) equal to the relative biological effectiveness value deduced from radiobiology experiments and clinical experience. The resulting value of this site-diameter parameter is then used to predict the biological effectiveness of the Chicago beam. The prediction agrees with the value deduced from radiobiology and clinical experience. The biological effectiveness of the scattered components of both beams is also estimated using the model

  13. Biological effects of radiation

    International Nuclear Information System (INIS)

    2013-01-01

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

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

    International Nuclear Information System (INIS)

    Bonan, Paulo Rogerio Ferreti; Lopes, Marcio Ajudarte; Almeida, Oslei Paes de; Alves, Fabio de Abreu

    2005-01-01

    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)

  15. Systems biology in critical-care nursing.

    Science.gov (United States)

    Schallom, Lynn; Thimmesch, Amanda R; Pierce, Janet D

    2011-01-01

    Systems biology applies advances in technology and new fields of study including genomics, transcriptomics, proteomics, and metabolomics to the development of new treatments and approaches of care for the critically ill and injured patient. An understanding of systems biology enhances a nurse's ability to implement evidence-based practice and to educate patients and families on novel testing and therapies. Systems biology is an integrated and holistic view of humans in relationship with the environment. Biomarkers are used to measure the presence and severity of disease and are rapidly expanding in systems biology endeavors. A systems biology approach using predictive, preventive, and participatory involvement is being utilized in a plethora of conditions of critical illness and injury including sepsis, cancer, pulmonary disease, and traumatic injuries.

  16. Spinal cordd biological safety comparison of intensity modulated radiotherapy and conventional radiation therapy

    International Nuclear Information System (INIS)

    Xilinbaoleri; Xu Wanlong; Chen Gang; Liu Hao; Wang Ruozheng; Bai Jingping

    2010-01-01

    Objective: To compare the spine intensity modulated radiation therapy (IMRT) and the conventional radiation therapy on the beagle spinal cord neurons, in order to prove the biological safety of IMRT of the spinal cord. Methods: Twelve selected purebred beagles were randomly divided into 2 groups. A beagle clinical model of tumor was mimiced in the ninth and tenth thoracic vertebrae. Then the beagles were irradiated by 2 different models of intensity modulated radiotherapy and conventional radiation therapy, with the total irradiation doses of 50 and 70 Gy. The samples of spinal cord were taken out from the same position of the nine and tenth thoracic vertebrae at the third month after radiation.All the samples were observed by the electron microscope, and the Fas and HSP70 expression in spinal cord neurons were evaluated by immunohistochemistry method. Terminal deoxynucleatidyl transferase mediated dUTP nick and labeling (TUNEL) technique was used to examine the apoptotic cells in the spinal cord. Results: The neurons in the spinal cord of IMRT group were mainly reversible injury, and those in the conventional radiation therapy were mainly apoptosis. Compared with the conventional radiation therapy group [50 Gy group, (7.3 ± 1.1)%; 70 Gy group, (11.3 ± 1.4)%], the apoptosis rate of the spinal cord neurons of the intensity modulated radiotherapy group [50 Gy group, (1.2 ± 0.7)%; 70 Gy group (2.5 ± 0.8)%] was much lower[(50 Gy group, t=0.022, P<0.05; 70 Gy group, t=0.017, P<0.05)]. The expression levels of Fas in the IMPT group (50 Gy group, 4.6 ± 0.8; 70 Gy group, 7.4 ± 1.1) were also much lowerthan those in the other group (50 Gy group, 15.1 ± 6.4; 70 Gy group, 19.3 ± 7.6. 50 Gy group, t=0.231, P<0.05; 70 Gy group, t=0.457, P<0.05), while the expression levels of HSP70 in the IMPT group (50 Gy group, 9.1 ± 0.8; 70 Gy group, 7.3 ± 1.4)were much higher than those in the conventional radiation therapy group (50 Gy group, 2.1 ± 0.9; 70 Gy group, 1.7 ± 0

  17. Noise and poise: Enhancement of postural complexity in the elderly with a stochastic-resonance based therapy

    Science.gov (United States)

    Costa, M.; Priplata, A. A.; Lipsitz, L. A.; Wu, Z.; Huang, N. E.; Goldberger, A. L.; Peng, C.-K.

    2007-03-01

    Pathologic states are associated with a loss of dynamical complexity. Therefore, therapeutic interventions that increase physiologic complexity may enhance health status. Using multiscale entropy analysis, we show that the postural sway dynamics of healthy young and healthy elderly subjects are more complex than that of elderly subjects with a history of falls. Application of subsensory noise to the feet has been demonstrated to improve postural stability in the elderly. We next show that this therapy significantly increases the multiscale complexity of sway fluctuations in healthy elderly subjects. Quantification of changes in dynamical complexity of biologic variability may be the basis of a new approach to assessing risk and to predicting the efficacy of clinical interventions, including noise-based therapies.

  18. Supporting Treatment Decisions in Patients with Differentiated Thyroid Carcinoma (DTC) under Radioiodine-131 Therapy: Role of Biological Dosimetry Assessment

    International Nuclear Information System (INIS)

    Fadel, A.M.; Chebel, G.M.; Di Giorgio, M.; Vallerga, M.B.; Taja, M.R.; Radl, A.; Bubniak, R.V.; Oneto, A.

    2010-01-01

    Radioiodine-131 therapy is applied in patients with differentiated thyroid carcinoma (DTC), within the therapeutic scheme following thyroidectomy, for the ablation of thyroid remnants and treatment of metastatic disease. Several approaches for the selection of a therapeutic dose were applied. The aim of this therapy is to achieve a lethal dose in the tumor tissue, without exceeding the dose of tolerance in healthy tissues (doses greater than 2 Gy in bone marrow could lead to myelotoxicity). In this work, the treatment protocol used incorporates the assessment by biological dosimetry (BD) for estimating doses to whole body and bone marrow, to tailor patient's treatment. Biological Dosimetry prospective studies conducted on samples from patients with cumulative activities, before and after each therapeutic administration, allows to evaluate DNA damage and repair capacity in peripheral blood lymphocytes. (authors)

  19. Fast Biological Modeling for Voxel-based Heavy Ion Treatment Planning Using the Mechanistic Repair-Misrepair-Fixation Model and Nuclear Fragment Spectra

    Energy Technology Data Exchange (ETDEWEB)

    Kamp, Florian [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States); Department of Radiation Oncology, Technische Universität München, Klinikum Rechts der Isar, München (Germany); Physik-Department, Technische Universität München, Garching (Germany); Cabal, Gonzalo [Experimental Physics–Medical Physics, Ludwig Maximilians University Munich, Garching (Germany); Mairani, Andrea [Medical Physics Unit, Centro Nazionale Adroterapia Oncologica (CNAO), Pavia (Italy); Heidelberg Ion-Beam Therapy Center, Heidelberg (Germany); Parodi, Katia [Experimental Physics–Medical Physics, Ludwig Maximilians University Munich, Garching (Germany); Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum Rechts der Isar, München (Germany); Physik-Department, Technische Universität München, Garching (Germany); Carlson, David J., E-mail: david.j.carlson@yale.edu [Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut (United States)

    2015-11-01

    Purpose: The physical and biological differences between heavy ions and photons have not been fully exploited and could improve treatment outcomes. In carbon ion therapy, treatment planning must account for physical properties, such as the absorbed dose and nuclear fragmentation, and for differences in the relative biological effectiveness (RBE) of ions compared with photons. We combined the mechanistic repair-misrepair-fixation (RMF) model with Monte Carlo-generated fragmentation spectra for biological optimization of carbon ion treatment plans. Methods and Materials: Relative changes in double-strand break yields and radiosensitivity parameters with particle type and energy were determined using the independently benchmarked Monte Carlo damage simulation and the RMF model to estimate the RBE values for primary carbon ions and secondary fragments. Depth-dependent energy spectra were generated with the Monte Carlo code FLUKA for clinically relevant initial carbon ion energies. The predicted trends in RBE were compared with the published experimental data. Biological optimization for carbon ions was implemented in a 3-dimensional research treatment planning tool. Results: We compared the RBE and RBE-weighted dose (RWD) distributions of different carbon ion treatment scenarios with and without nuclear fragments. The inclusion of fragments in the simulations led to smaller RBE predictions. A validation of RMF against measured cell survival data reported in published studies showed reasonable agreement. We calculated and optimized the RWD distributions on patient data and compared the RMF predictions with those from other biological models. The RBE values in an astrocytoma tumor ranged from 2.2 to 4.9 (mean 2.8) for a RWD of 3 Gy(RBE) assuming (α/β){sub X} = 2 Gy. Conclusions: These studies provide new information to quantify and assess uncertainties in the clinically relevant RBE values for carbon ion therapy based on biophysical mechanisms. We present results from

  20. Ethnographic Observational Study of the Biologic Initiation Conversation Between Rheumatologists and Biologic-Naive Rheumatoid Arthritis Patients.

    Science.gov (United States)

    Kottak, Nicholas; Tesser, John; Leibowitz, Evan; Rosenberg, Melissa; Parenti, Dennis; DeHoratius, Raphael

    2018-01-30

    This ethnographic market research study investigated the biologic initiation conversation between rheumatologists and biologic-naive patients with rheumatoid arthritis to assess how therapy options, particularly mode of administration, were discussed. Consenting rheumatologists (n = 16) and patients (n = 48) were videotaped during medical visits and interviewed by a trained ethnographer. The content, structure, and timing of conversations regarding biologic initiation were analyzed. The mean duration of physician-patient visits was approximately 15 minutes; biologic therapies were discussed for a mean of 5.6 minutes. Subcutaneous (SC) and intravenous (IV) therapy options were mentioned in 45 and 35 visits, respectively, out of a total of 48 visits. All patients had some familiarity with SC administration, but nearly half of patients (22 of 48) were unfamiliar with IV therapy going into the visit. IV administration was not defined or described by rheumatologists in 77% of visits (27 of 35) mentioning IV therapy. Thus, 19 of 22 patients who were initially unfamiliar with IV therapy remained unfamiliar after the visit. Disparities in physician-patient perceptions were revealed, as all rheumatologists (16 of 16) believed IV therapy would be less convenient than SC therapy for patients, while 46% of patients (22 of 48) felt this way. In post-visit interviews, some patients seemed confused and overwhelmed, particularly when presented with many treatment choices in a visit. Some patients stated they would benefit from visual aids or summary sheets of key points. This study revealed significant educational opportunities to improve the biologic initiation conversation and indicated a disparity between patients' and rheumatologists' perception of IV therapy. © 2018 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.

  1. Reconstruction of biological networks based on life science data integration.

    Science.gov (United States)

    Kormeier, Benjamin; Hippe, Klaus; Arrigo, Patrizio; Töpel, Thoralf; Janowski, Sebastian; Hofestädt, Ralf

    2010-10-27

    For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH--an integration toolkit for building life science data warehouses, CardioVINEdb--a information system for biological data in cardiovascular-disease and VANESA--a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  2. Ankylosing Spondylitis Patients Commencing Biologic Therapy Have High Baseline Levels of Comorbidity: A Report from the Australian Rheumatology Association Database

    Directory of Open Access Journals (Sweden)

    John Oldroyd

    2009-01-01

    Full Text Available Aims. To compare the baseline characteristics of a population-based cohort of patients with ankylosing spondylitis (AS commencing biological therapy to the reported characteristics of bDMARD randomised controlled trials (RCTs participants. Methods. Descriptive analysis of AS participants in the Australian Rheumatology Association Database (ARAD who were commencing bDMARD therapy. Results. Up to December 2008, 389 patients with AS were enrolled in ARAD. 354 (91.0% had taken bDMARDs at some time, and 198 (55.9% completed their entry questionnaire prior to or within 6 months of commencing bDMARDs. 131 (66.1% had at least one comorbid condition, and 24 (6.8% had a previous malignancy (15 nonmelanoma skin, 4 melanoma, 2 prostate, 1 breast, cervix, and bowel. Compared with RCT participants, ARAD participants were older, had longer disease duration and higher baseline disease activity. Conclusions. AS patients commencing bDMARDs in routine care are significantly different to RCT participants and have significant baseline comorbidities.

  3. Engineering toxins for 21st century therapies.

    Science.gov (United States)

    Chaddock, John A; Acharya, K Ravi

    2011-04-01

    'Engineering Toxins for 21st Century Therapies' (9-10 September 2010) was part of the Royal Society International Seminar series held at the Kavli International Centre, UK. Participants were assembled from a range of disciplines (academic, industry, regulatory, public health) to discuss the future potential of toxin-based therapies. The meeting explored how the current structural and mechanistic knowledge of toxins could be used to engineer future toxin-based therapies. To date, significant progress has been made in the design of novel recombinant biologics based on domains of natural toxins, engineered to exhibit advantageous properties. The meeting concluded, firstly that future product development vitally required the appropriate combination of creativity and innovation that can come from the academic, biotechnology and pharma sectors. Second, that continued investigation into understanding the basic science of the toxins and their targets was essential in order to develop new opportunities for the existing products and to create new products with enhanced properties. Finally, it was concluded that the clinical potential for development of novel biologics based on toxin domains was evident. © 2011 The Authors Journal compilation © 2011 FEBS.

  4. Investigating the experiences in a school-based occupational therapy program to inform community-based paediatric occupational therapy practice.

    Science.gov (United States)

    Rens, Lezahn; Joosten, Annette

    2014-06-01

    A collaborative approach with teachers is required when providing community-based occupational therapy to educationally at risk children. Collaborators share common goals and interact and support each other but challenges arise in providing collaborative occupational therapy in settings outside the school environment. The aim of this study was to capture experiences of teachers and occupational therapists working within a school-based occupational therapy program to determine if their experiences could inform collaborative practice. In this pilot study, participant responses to questionnaires (n = 32) about their experiences formed the basis for focus groups and individual interviews. Two focus group were conducted, one with teachers (n = 11) and one with occupational therapy participants (n = 6). Individual interviews were conducted with the supervising occupational therapist, school principal and two leading teachers. Descriptive statistics were used to analyse the data from closed questions, and thematic analysis using a constant comparison approach was used to analyse open ended questions, focus groups and interviews. Three main themes emerged: (i) the need for occupational therapists to spend time in the school, to explain their role, build relationships, understand classroom routines and the teacher role; (ii) occupational therapists need to not see themselves as the expert but develop equal partnerships to set collaborative goals and (iii) occupational therapists advocating for all parties to be informed throughout the occupational therapy process. The pilot study findings identified teacher and therapist experiences within the school setting that could inform improved collaborative practice with teachers and community-based occupational therapists and these findings warrant further investigation. © 2013 Occupational Therapy Australia.

  5. Reconstruction of biological networks based on life science data integration

    Directory of Open Access Journals (Sweden)

    Kormeier Benjamin

    2010-06-01

    Full Text Available For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH - an integration toolkit for building life science data warehouses, CardioVINEdb - a information system for biological data in cardiovascular-disease and VANESA- a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  6. 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.

  7. 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.

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

    Science.gov (United States)

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

    2018-05-30

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

  9. 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

    Science.gov (United States)

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

    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. PMID:19630105

  10. Hadron Therapy for Cancer Treatment

    International Nuclear Information System (INIS)

    Lennox, Arlene

    2003-01-01

    The biological and physical rationale for hadron therapy is well understood by the research community, but hadron therapy is not well established in mainstream medicine. This talk will describe the biological advantage of neutron therapy and the dose distribution advantage of proton therapy, followed by a discussion of the challenges to be met before hadron therapy can play a significant role in treating cancer. A proposal for a new research-oriented hadron clinic will be presented.

  11. Therapy Decision Support Based on Recommender System Methods.

    Science.gov (United States)

    Gräßer, Felix; Beckert, Stefanie; Küster, Denise; Schmitt, Jochen; Abraham, Susanne; Malberg, Hagen; Zaunseder, Sebastian

    2017-01-01

    We present a system for data-driven therapy decision support based on techniques from the field of recommender systems. Two methods for therapy recommendation, namely, Collaborative Recommender and Demographic-based Recommender , are proposed. Both algorithms aim to predict the individual response to different therapy options using diverse patient data and recommend the therapy which is assumed to provide the best outcome for a specific patient and time, that is, consultation. The proposed methods are evaluated using a clinical database incorporating patients suffering from the autoimmune skin disease psoriasis. The Collaborative Recommender proves to generate both better outcome predictions and recommendation quality. However, due to sparsity in the data, this approach cannot provide recommendations for the entire database. In contrast, the Demographic-based Recommender performs worse on average but covers more consultations. Consequently, both methods profit from a combination into an overall recommender system.

  12. TOPICAL REVIEW: Stem cells engineering for cell-based therapy

    Science.gov (United States)

    Taupin, Philippe

    2007-09-01

    Stem cells carry the promise to cure a broad range of diseases and injuries, from diabetes, heart and muscular diseases, to neurological diseases, disorders and injuries. Significant progresses have been made in stem cell research over the past decade; the derivation of embryonic stem cells (ESCs) from human tissues, the development of cloning technology by somatic cell nuclear transfer (SCNT) and the confirmation that neurogenesis occurs in the adult mammalian brain and that neural stem cells (NSCs) reside in the adult central nervous system (CNS), including that of humans. Despite these advances, there may be decades before stem cell research will translate into therapy. Stem cell research is also subject to ethical and political debates, controversies and legislation, which slow its progress. Cell engineering has proven successful in bringing genetic research to therapy. In this review, I will review, in two examples, how investigators are applying cell engineering to stem cell biology to circumvent stem cells' ethical and political constraints and bolster stem cell research and therapy.

  13. Epidemiology, biology and therapy of Merkel cell carcinoma: conclusions from the EU project IMMOMEC

    DEFF Research Database (Denmark)

    Becker, Juergen C.; Stang, Andreas; zur Hausen, Axel

    2018-01-01

    Merkel cell carcinoma (MCC) is a highly aggressive, often lethal neuroendocrine cancer. Its carcinogenesis may be either caused by the clonal integration of the Merkel cell polyomavirus into the host genome or by UV-induced mutations. Notably, virally-encoded oncoproteins and UV-induced mutations...... knowledge on epidemiology, biology and therapy of MCC as conclusion of the project 'Immune Modulating strategies for treatment of Merkel Cell Carcinoma', which was funded over a 5-year period by the European Commission to investigate innovative immunotherapies for MCC....

  14. Nanobody-based cancer therapy of solid tumors

    NARCIS (Netherlands)

    Kijanka, Marta|info:eu-repo/dai/nl/328212792; Dorresteijn, Bram|info:eu-repo/dai/nl/31401635X; Oliveira, Sabrina; van Bergen en Henegouwen, Paul M P|info:eu-repo/dai/nl/071919481

    The development of tumor-targeted therapies using monoclonal antibodies has been successful during the last 30 years. Nevertheless, the efficacy of antibody-based therapy is still limited and further improvements are eagerly awaited. One of the promising novel developments that may overcome the

  15. Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry.

    Science.gov (United States)

    Strand, Vibeke; Miller, Paul; Williams, Setareh A; Saunders, Katherine; Grant, Shannon; Kremer, Joel

    2017-12-01

    Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation. Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002-2011); age of RA onset: ≥16 years; ≥6 months' follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire. Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007-2010 versus 2002-2003, and Clinical Disease Activity Index scores. Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy. Corrona LLC and MedImmune.

  16. Genomancy: predicting tumour response to cancer therapy based on the oracle of genetics.

    Science.gov (United States)

    Williams, P D; Lee, J K; Theodorescu, D

    2009-01-01

    Cells are complex systems that regulate a multitude of biologic pathways involving a diverse array of molecules. Cancer can develop when these pathways become deregulated as a result of mutations in the genes coding for these proteins or of epigenetic changes that affect gene expression, or both1,2. The diversity and interconnectedness of these pathways and their molecular components implies that a variety of mutations may lead to tumorigenic cellular deregulation3-6. This variety, combined with the requirement to overcome multiple anticancer defence mechanisms7, contributes to the heterogeneous nature of cancer. Consequently, tumours with similar histology may vary in their underlying molecular circuitry8-10, with resultant differences in biologic behaviour, manifested in proliferation rate, invasiveness, metastatic potential, and unfortunately, response to cytotoxic therapy. Thus, cancer can be thought of as a family of related tumour subtypes, highlighting the need for individualized prediction both of disease progression and of treatment response, based on the molecular characteristics of the tumour.

  17. Use of polyclonal/monoclonal antibody therapies in transplantation.

    Science.gov (United States)

    Yeung, Melissa Y; Gabardi, Steven; Sayegh, Mohamed H

    2017-03-01

    For over thirty years, antibody (mAb)-based therapies have been a standard component of transplant immunosuppression, and yet much remains to be learned in order for us to truly harness their therapeutic capabilities. Current mAbs used in transplant directly target and destroy graft-destructive immune cells, interrupt cytokine and costimulation-dependent T and B cell activation, and prevent down-stream complement activation. Areas covered: This review summarizes our current approaches to using antibody-based therapies to prevent and treat allograft rejection. It also provides examples of promising novel mAb therapies, and discusses the potential for future mAb development in transplantation. Expert opinion: The broad capability of antibodies, in parallel with our growing ability to synthetically modulate them, offers exciting opportunities to develop better biologic therapeutics. In order to do so, we must further our understanding about the basic biology underlying allograft rejection, and gain better appreciation of how characteristics of therapeutic antibodies affect their efficacy.

  18. 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.

  19. 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.

  20. Reoptimization of Intensity Modulated Proton Therapy Plans Based on Linear Energy Transfer

    Energy Technology Data Exchange (ETDEWEB)

    Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Botas, Pablo [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg (Germany); Giantsoudi, Drosoula; Gorissen, Bram L.; Paganetti, Harald [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2016-12-01

    Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dose objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.

  1. Therapy Decision Support Based on Recommender System Methods

    Directory of Open Access Journals (Sweden)

    Felix Gräßer

    2017-01-01

    Full Text Available We present a system for data-driven therapy decision support based on techniques from the field of recommender systems. Two methods for therapy recommendation, namely, Collaborative Recommender and Demographic-based Recommender, are proposed. Both algorithms aim to predict the individual response to different therapy options using diverse patient data and recommend the therapy which is assumed to provide the best outcome for a specific patient and time, that is, consultation. The proposed methods are evaluated using a clinical database incorporating patients suffering from the autoimmune skin disease psoriasis. The Collaborative Recommender proves to generate both better outcome predictions and recommendation quality. However, due to sparsity in the data, this approach cannot provide recommendations for the entire database. In contrast, the Demographic-based Recommender performs worse on average but covers more consultations. Consequently, both methods profit from a combination into an overall recommender system.

  2. [The safety of biologics : a risk-benefit assessment of treating rheumatoid arthritis with biologics based on registry data on mortality].

    Science.gov (United States)

    Sander, O

    2010-11-01

    The aim of this study is a risk-benefit assessment of treating rheumatoid arthritis with biologics based on registry data on mortality.UK, Sweden and Spain have published evaluable data on mortality. A parallel control group was conducted in the UK. Sweden and Spain used an historical cohort for comparison.Central registries supported British and Swedish research by sending details on all deaths. The variety of possible confounders prevents direct comparisons of the registers and safe predictions for individual patients.The death rate in TNF-inhibitor-treated patients is higher than in the general population but lower than in the control groups with RA. Thus comorbidities are not balanced, the weighted mortality rate scaled down the difference between exposed patients and controls. When TNF-inhibitors are given for the usual indication, mortality is reduced compared to conventional therapy.

  3. Cell-based therapies for chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, A.N.

    2013-01-01

    Chronic kidney disease (CKD) may lead to end-stage renal failure, requiring renal replacement strategies. Development of new therapies to reduce progression of CKD is therefore a major global public health target. The aim of this thesis was to investigate whether cell-based therapies have the

  4. Home-based Constraint Induced Movement Therapy Poststroke

    OpenAIRE

    Stephen Isbel HScD; Christine Chapparo PhD; David McConnell PhD; Judy Ranka PhD

    2014-01-01

    Background: This study examined the efficacy of a home-based Constraint Induced Movement Therapy (CI Therapy) protocol with eight poststroke survivors. Method: Eight ABA, single case experiments were conducted in the homes of poststroke survivors. The intervention comprised restraint of the intact upper limb in a mitt for 21 days combined with a home-based and self-directed daily activity regime. Motor changes were measured using The Wolf Motor Function Test (WMFT) and the Motor Activity L...

  5. Biological therapy and development of neoplastic disease in patients with juvenile rheumatic disease: a systematic review

    Directory of Open Access Journals (Sweden)

    Vanessa Patricia L. Pereira

    Full Text Available Abstract Juvenile rheumatic diseases affect the musculoskeletal system and begin before the age of 18. These conditions have varied, identifiable or unknown etiologies, but those of an autoimmune inflammatory nature have been associated with an increased risk of development of cancer, regardless of treatment. This study aims to assess, through a systematic review of the literature according to Prisma (Preferred Reporting Items for Systematic Reviews and Meta-Analyses quality criteria, the risk of cancer in patients with juvenile rheumatic disease, and its association with biological agents. The criteria described by the Strengthening the Reporting of Observational Studies in Epidemiology initiative were used in order to assess the methodological quality of those individual items selected in this study. We analyzed nine publications, from a total of 251 papers initially selected. There was an increase in cancer risk in the population with juvenile rheumatic disease versus the general population. Most specified cancers were of a lymphoproliferative nature. Seven studies did not specify the treatment or not defined an association between treatment and cancer risk. Only one study has suggested this association; in it, their authors observed high risk in patients diagnosed in the last 20 years, a period of the advent of new therapies. One study found an increased risk in a population not treated with biological agents, suggesting a disease in its natural course, and not an adverse effect of therapy. Studies have shown an increased risk of malignancy associated with juvenile rheumatic disease, and this may be related to disease activity and not specifically to the treatment with biological agents.

  6. Nanotechnology for Cancer Therapy Based on Chemotherapy

    Directory of Open Access Journals (Sweden)

    Chen-Yang Zhao

    2018-04-01

    Full Text Available Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover, to achieve the accurate pre-diagnosis and real-time monitoring for tumor, the research of nano-theranostics, which integrates diagnosis with treatment process, is a promising field in cancer treatment. In this review, the recent studies on combinational therapy based on chemotherapy will be systematically discussed. Furthermore, as a current trend in cancer treatment, advance in theranostic nanoparticles based on chemotherapy will be exemplified briefly. Finally, the present challenges and improvement tips will be presented in combination therapy and nano-theranostics.

  7. The Implementation of Research-based Learning on Biology Seminar Course in Biology Education Study Program of FKIP UMRAH

    Science.gov (United States)

    Amelia, T.

    2018-04-01

    Biology Seminar is a course in Biology Education Study Program of Faculty of Teacher Training and Education University of Maritim Raja Ali Haji (FKIP UMRAH) that requires students to have the ability to apply scientific attitudes, perform scientific writing and undertake scientific publications on a small scale. One of the learning strategies that can drive the achievement of learning outcomes in this course is Research-Based Learning. Research-Based Learning principles are considered in accordance with learning outcomes in Biology Seminar courses and generally in accordance with the purpose of higher education. On this basis, this article which is derived from a qualitative research aims at describing Research-based Learning on Biology Seminar course. Based on a case study research, it was known that Research-Based Learning on Biology Seminar courses is applied through: designing learning activities around contemporary research issues; teaching research methods, techniques and skills explicitly within program; drawing on personal research in designing and teaching courses; building small-scale research activities into undergraduate assignment; and infusing teaching with the values of researchers.

  8. 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.

  9. Switching of biologics in psoriasis: Reasons and results.

    Science.gov (United States)

    Honda, Hiromi; Umezawa, Yoshinori; Kikuchi, Sota; Yanaba, Koichi; Fukuchi, Osamu; Ito, Toshihiro; Nobeyama, Yoshimasa; Asahina, Akihiko; Nakagawa, Hidemi

    2017-09-01

    Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis. © 2017 Japanese Dermatological Association.

  10. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response

    NARCIS (Netherlands)

    D'Haens, Geert R.; Panaccione, Remo; Higgins, Peter D. R.; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B.; Herfarth, Hans; Hommes, Daan W.; Kamm, Michael; Löfberg, Robert; Quary, A.; Sands, Bruce; Sood, A.; Watermayer, G.; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M.; Feagan, Brian; Sandborn, William J.; Colombel, Jean Frédéric; Travis, Simon

    2011-01-01

    The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability,

  11. WE-FG-BRB-01: Clinical Significance of RBE Variations in Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Paganetti, H. [Massachusetts General Hospital (United States)

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  12. Comparison of dose-volume histograms for Tomo therapy, linear accelerator-based 3D conformal radiation therapy, and intensity-modulated radiation therapy

    International Nuclear Information System (INIS)

    Ji, Youn-Sang; Dong, Kyung-Rae; Kim, Chang-Bok; Choi, Seong-Kwan; Chung, Woon-Kwan; Lee, Jong-Woong

    2011-01-01

    Highlights: → Evaluation of DVH from 3D CRT, IMRT and Tomo therapy was conducted for tumor therapy. → The doses of GTV and CTV were compared using DVHs from 3D CRT, IMRT and Tomo therapy. → The GTV was higher when Tomo therapy was used, while the doses of critical organ were low. → They said that Tomo therapy satisfied the goal of radiation therapy more than the others. - Abstract: Evaluation of dose-volume histograms from three-dimensional conformal radiation therapy (3D CRT), intensity-modulated radiation therapy (IMRT), and Tomo therapy was conducted. These three modalities are among the diverse treatment systems available for tumor therapy. Three patients who received tumor therapy for a malignant oligodendroglioma in the cranium, nasopharyngeal carcinoma in the cervical neck, and prostate cancer in the pelvis were selected as study subjects. Therapy plans were made for the three patients before dose-volume histograms were obtained. The doses of the gross tumor volume (GTV) and the clinical target volume (CTV) were compared using the dose-volume histograms obtained from the LINAC-based 3D CRT, IMRT planning station (Varian Eclipse-Varian, version 8.1), and Tomo therapy planning station. In addition, the doses of critical organs in the cranium, cervix, and pelvis that should be protected were compared. The GTV was higher when Tomo therapy was used compared to 3D CRT and the LINAC-based IMRT, while the doses of critical organ tissues that required protection were low. These results demonstrated that Tomo therapy satisfied the ultimate goal of radiation therapy more than the other therapies.

  13. Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies

    DEFF Research Database (Denmark)

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Navarese, Eliano P

    2016-01-01

    In contrast to multiple publication-based meta-analyses involving clinical cardiac regeneration therapy in patients with recent myocardial infarction, a recently published meta-analysis based on individual patient data reported no effect of cell therapy on left ventricular function or clinical...

  14. Histological image classification using biologically interpretable shape-based features

    International Nuclear Information System (INIS)

    Kothari, Sonal; Phan, John H; Young, Andrew N; Wang, May D

    2013-01-01

    Automatic cancer diagnostic systems based on histological image classification are important for improving therapeutic decisions. Previous studies propose textural and morphological features for such systems. These features capture patterns in histological images that are useful for both cancer grading and subtyping. However, because many of these features lack a clear biological interpretation, pathologists may be reluctant to adopt these features for clinical diagnosis. We examine the utility of biologically interpretable shape-based features for classification of histological renal tumor images. Using Fourier shape descriptors, we extract shape-based features that capture the distribution of stain-enhanced cellular and tissue structures in each image and evaluate these features using a multi-class prediction model. We compare the predictive performance of the shape-based diagnostic model to that of traditional models, i.e., using textural, morphological and topological features. The shape-based model, with an average accuracy of 77%, outperforms or complements traditional models. We identify the most informative shapes for each renal tumor subtype from the top-selected features. Results suggest that these shapes are not only accurate diagnostic features, but also correlate with known biological characteristics of renal tumors. Shape-based analysis of histological renal tumor images accurately classifies disease subtypes and reveals biologically insightful discriminatory features. This method for shape-based analysis can be extended to other histological datasets to aid pathologists in diagnostic and therapeutic decisions

  15. The use of biologically based cancer risk models in radiation epidemiology

    International Nuclear Information System (INIS)

    Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

    2003-01-01

    Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

  16. Cell-Based Therapies Used to Treat Lumbar Degenerative Disc Disease: A Systematic Review of Animal Studies and Human Clinical Trials

    Directory of Open Access Journals (Sweden)

    David Oehme

    2015-01-01

    Full Text Available Low back pain and degenerative disc disease are a significant cause of pain and disability worldwide. Advances in regenerative medicine and cell-based therapies, particularly the transplantation of mesenchymal stem cells and intervertebral disc chondrocytes, have led to the publication of numerous studies and clinical trials utilising these biological therapies to treat degenerative spinal conditions, often reporting favourable outcomes. Stem cell mediated disc regeneration may bridge the gap between the two current alternatives for patients with low back pain, often inadequate pain management at one end and invasive surgery at the other. Through cartilage formation and disc regeneration or via modification of pain pathways stem cells are well suited to enhance spinal surgery practice. This paper will systematically review the current status of basic science studies, preclinical and clinical trials utilising cell-based therapies to repair the degenerate intervertebral disc. The mechanism of action of transplanted cells, as well as the limitations of published studies, will be discussed.

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

    Science.gov (United States)

    Nishio, Kazuto

    2004-07-01

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

  18. 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

  19. Home-based Constraint Induced Movement Therapy Poststroke

    Directory of Open Access Journals (Sweden)

    Stephen Isbel HScD

    2014-10-01

    Full Text Available Background: This study examined the efficacy of a home-based Constraint Induced Movement Therapy (CI Therapy protocol with eight poststroke survivors. Method: Eight ABA, single case experiments were conducted in the homes of poststroke survivors. The intervention comprised restraint of the intact upper limb in a mitt for 21 days combined with a home-based and self-directed daily activity regime. Motor changes were measured using The Wolf Motor Function Test (WMFT and the Motor Activity Log (MAL. Results: Grouped results showed statistically and clinically significant differences on the WMFT (WMFT [timed items]: Mean 7.28 seconds, SEM 1.41, 95% CI 4.40 – 10.18, p = 0.000; WMFT (Functional Ability: z = -4.63, p = 0.000. Seven out of the eight participants exceeded the minimal detectable change on both subscales of the MAL. Conclusion: This study offers positive preliminary data regarding the feasibility of a home-based CI Therapy protocol. This requires further study through an appropriately powered control trial.

  20. TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y [Tsinghua University, Beijing, Beijing (China); UT Southwestern Medical Center, Dallas, TX (United States); Tian, Z; Jiang, S; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States); Song, T [Southern Medical University, Guangzhou, Guangdong (China); UT Southwestern Medical Center, Dallas, TX (United States); Wu, Z; Liu, Y [Tsinghua University, Beijing, Beijing (China)

    2015-06-15

    Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC into IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical

  1. TU-EF-304-07: Monte Carlo-Based Inverse Treatment Plan Optimization for Intensity Modulated Proton Therapy

    International Nuclear Information System (INIS)

    Li, Y; Tian, Z; Jiang, S; Jia, X; Song, T; Wu, Z; Liu, Y

    2015-01-01

    Purpose: Intensity-modulated proton therapy (IMPT) is increasingly used in proton therapy. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of its high accuracy, especially in cases with a high level of heterogeneity. It is also preferred in biological optimization problems due to the capability of computing quantities related to biological effects. However, MC simulation is typically too slow to be used for this purpose. Although GPU-based MC engines have become available, the achieved efficiency is still not ideal. The purpose of this work is to develop a new optimization scheme to include GPU-based MC into IMPT. Methods: A conventional approach using MC in IMPT simply calls the MC dose engine repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on some spots that turned out to have very small weights after solving the optimization problem. GPU-memory writing conflict occurring at a small beam size also reduces computational efficiency. To solve these problems, we developed a new framework that iteratively performs MC dose calculations and plan optimizations. At each dose calculation step, the particles were sampled from different spots altogether with Metropolis algorithm, such that the particle number is proportional to the latest optimized spot intensity. Simultaneously transporting particles from multiple spots also mitigated the memory writing conflict problem. Results: We have validated the proposed MC-based optimization schemes in one prostate case. The total computation time of our method was ∼5–6 min on one NVIDIA GPU card, including both spot dose calculation and plan optimization, whereas a conventional method naively using the same GPU-based MC engine were ∼3 times slower. Conclusion: A fast GPU-based MC dose calculation method along with a novel optimization workflow is developed. The high efficiency makes it attractive for clinical

  2. Comparison of the efficacy of biologics versus conventional systemic therapies in the treatment of psoriasis at a comprehensive psoriasis care center.

    Science.gov (United States)

    Au, Shiu-Chung; Madani, Abdulaziz; Alhaddad, Marwan; Alkofide, Maha; Gottlieb, Alice B

    2013-08-01

    The efficacy of biologic treatment for psoriasis has not been compared to that of conventional systemic therapies and phototherapy outside of clinical trial settings. Retrospective, cross-sectional. All patient visits with a code for psoriasis (ICD-9 696.1) in the clinical practice of two dermatologists with a high percentage (over 70% of chief complaints) of psoriasis patients from Jan 1, 2008 to Jan 4, 2012 inclusive were included in this retrospective data analysis. Patients were excluded if the baseline Physician's Global Assessment (PGA) at start of treatment was unknown, or less than 3 (moderate). The practice is a comprehensive psoriasis care center in the Northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type (biologic, conventional systemic or both) and history of previous treatments. Patients were evaluated by Body Surface Area (BSA), PGA, Simple-Measure for Assessing Psoriasis Activity (S-MAPA, calculated by BSA multiplied by PGA). Patients were evaluated at baseline, 8, 12, 16, and 24 weeks after start of treatment. Patients must have completed at least 8 weeks on a single treatment in order to be included. 46 courses of biologics, 12 courses of conventional systemic therapies, and 18 courses of both together were identified with PGA 3 or greater at baseline. Baseline S-MAPA for biologics was 74, for non-biologic systemics was 62.25. At week 24, S-MAPA improved 70.2% over baseline in patients treated with biologics, patients treated with non-biologic systemics improved by only 40.4% (PMAPA (PGA multiplied by BSA) at week 24. These results were observed despite the fact that patients on biologics had a greater baseline severity and had a greater number of previous treatments.

  3. Vitiligo-like lesions occurring in patients receiving anti-programmed cell death-1 therapies are clinically and biologically distinct from vitiligo.

    Science.gov (United States)

    Larsabal, Maiana; Marti, Aurélie; Jacquemin, Clément; Rambert, Jérôme; Thiolat, Denis; Dousset, Léa; Taieb, Alain; Dutriaux, Caroline; Prey, Sorilla; Boniface, Katia; Seneschal, Julien

    2017-05-01

    The use of anti-programmed cell death (PD)-1 therapies in metastatic tumors is associated with cutaneous side effects including vitiligo-like lesions. We sought to characterize clinically and biologically vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies by studying a case series of 8 patients with metastatic tumors and 30 control subjects with vitiligo. Eight patients receiving anti-PD-1 therapies with features of vitiligo-like lesions seen in our department were recruited. Clinical features and photographs were analyzed. For some patients, skin and blood samples were obtained. Results were compared with the vitiligo group. All patients developed lesions localized on photoexposed areas with a specific depigmentation pattern consisting of multiple flecked lesions without Koebner phenomenon. In contrast to vitiligo, patients receiving anti-PD-1 therapies who developed vitiligo-like lesions did not report any personal or family histories of vitiligo, thyroiditis, or other autoimmune disorders. Analysis of blood and skin samples revealed increased C-X-C motif ligand 10 levels in serum of patients developing vitiligo-like lesions, associated with skin infiltration of CD8 T-cells expressing C-X-C motif receptor 3 and producing elevated levels of interferon-γ and tumor necrosis factor-alfa. This cross-sectional study concerned a single center. Clinical and biological patterns of vitiligo-like lesions occurring in patients receiving anti-PD-1 therapies differ from vitiligo, suggesting a different mechanism. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  4. Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

    Science.gov (United States)

    Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network. PMID:20810955

  5. Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

  6. Biological treatments in Behçet's disease: beyond anti-TNF therapy.

    Science.gov (United States)

    Caso, Francesco; Costa, Luisa; Rigante, Donato; Lucherini, Orso Maria; Caso, Paolo; Bascherini, Vittoria; Frediani, Bruno; Cimaz, Rolando; Marrani, Edoardo; Nieves-Martín, Laura; Atteno, Mariangela; Raffaele, Carmela G L; Tarantino, Giusyda; Galeazzi, Mauro; Punzi, Leonardo; Cantarini, Luca

    2014-01-01

    Behçet's disease (BD) is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

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

    Directory of Open Access Journals (Sweden)

    Lindsay Hannah

    2010-01-01

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

  8. Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.

    Science.gov (United States)

    Laffey, John G; Matthay, Michael A

    2017-08-01

    On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

  9. 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

  10. Abatacept as a successful therapy for myositis—a case-based review.

    Science.gov (United States)

    Kerola, Anne M; Kauppi, Markku J

    2015-03-01

    Only limited evidence exists on the therapeutic potential of biologic agents in the treatment of myositis. We present a brief review of the literature on off-label experiences of biologic agents in myositis, with a special interest in abatacept. Rituximab has been indicated to be beneficial and well tolerated in one large randomized controlled trial and many smaller studies. Initial data on tumour necrosis factor (TNF) inhibitors are conflicting. There are only a few case reports and mechanistic studies on the treatment of myositis with other biologics, including alemtuzumab, anakinra, tocilizumab and abatacept. We report a patient with severe myositis overlap syndrome, manifesting also as rheumatoid arthritis, peripheral vasculitis and interstitial lung disease. Her myositis was refractory to many conventional and biologic therapies but was well controlled with abatacept. This suggests that abatacept might be a beneficial option for the treatment of refractory myositis and that clinical trials are needed to further investigate its efficacy.

  11. Nano-scale processes behind ion-beam cancer therapy

    Science.gov (United States)

    Surdutovich, Eugene; Garcia, Gustavo; Mason, Nigel; Solov'yov, Andrey V.

    2016-04-01

    This topical issue collates a series of papers based on new data reported at the third Nano-IBCT Conference of the COST Action MP1002: Nanoscale Insights into Ion Beam Cancer Therapy, held in Boppard, Germany, from October 27th to October 31st, 2014. The Nano-IBCT COST Action was launched in December 2010 and brought together more than 300 experts from different disciplines (physics, chemistry, biology) with specialists in radiation damage of biological matter from hadron-therapy centres, and medical institutions. This meeting followed the first and the second conferences of the Action held in October 2011 in Caen, France and in May 2013 in Sopot, Poland respectively. This conference series provided a focus for the European research community and has highlighted the pioneering research into the fundamental processes underpinning ion beam cancer therapy. Contribution to the Topical Issue "COST Action Nano-IBCT: Nano-scale Processes Behind Ion-Beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Gustavo Garcia and Eugene Surdutovich.

  12. Knowledge base and functionality of concepts of some Filipino biology teachers in five biology topics

    Science.gov (United States)

    Barquilla, Manuel B.

    2018-01-01

    This mixed research, is a snapshot of some Filipino Biology teachers' knowledge structure and how their concepts of the five topics in Biology (Photosynthesis, Cellular Respiration, human reproductive system, Mendelian genetics and NonMendelian genetics) functions and develops inside a biology classroom. The study focuses on the six biology teachers and a total of 222 students in their respective classes. Of the Six (6) teachers, three (3) are under the Science curriculum and the other three (3) are under regular curriculum in both public and private schools in Iligan city and Lanao del Norte, Philippines. The study utilized classroom discourses, concept maps, interpretative case-study method, bracketing method, and concept analysis for qualitative part; the quantitative part uses a nonparametric statistical tool, Kendall's tau Coefficient for determining relationship and congruency while measures of central tendencies and dispersion (mean, and standard deviation) for concept maps scores interpretation. Knowledge Base of Biology teachers were evaluated by experts in field of specialization having a doctorate program (e.g. PhD in Genetics) and PhD Biology candidates. The data collection entailed seven (7) months immersion: one (1) month for preliminary phase for the researcher to gain teachers' and students' confidence and the succeeding six (6) months for main observation and data collection. The evaluation of teachers' knowledge base by experts indicated that teachers' knowledge of (65%) is lower than the minimum (75%) recommended by ABD-el-Khalick and Boujaoude (1997). Thus, the experts believe that content knowledge of the teachers is hardly adequate for their teaching assignment. Moreover, the teachers in this study do not systematically use reallife situation to apply the concepts they teach. They can identify concepts too abstract for their student; however, they seldom use innovative ways to bring the discussion to their students' level of readiness and

  13. Biomedicines—Moving Biologic Agents into Approved Treatment Options

    Directory of Open Access Journals (Sweden)

    Kenneth Cornetta

    2013-03-01

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

  14. Quality of life, treatment satisfaction and efficacy of non-biological systemic therapies in patients with plaque psoriasis: study protocol for a prospective observational study.

    Science.gov (United States)

    Fink, Christine; Schank, Timo E; Trenkler, Nina; Uhlmann, Lorenz; Schäkel, Knut

    2017-06-30

    Psoriasis vulgaris often leads to a significant impaired quality of life and dissatisfaction with the existing therapeutic approaches. However, patients' quality of life and treatment satisfaction are of utmost importance, since it is positively related to therapy adherence and encourages patient's compliance. The study described herein evaluates the quality of life, treatment satisfaction and efficacy during the initial 6 months of treatment with a non-biological systemic agent in a real-life clinical setting. This observational study compares quality of life, treatment satisfaction and the efficacy of non-biological systemic therapy between 60 patients suffering from plaque psoriasis receiving the non-biological systemic therapies with apremilast, methotrexate and fumaric acid esters. Ethics approval was provided by the ethics committee of the medical faculty of the University of Heidelberg. Ethics approval number is S-298/2015. The design and the final results of the study will be published and made available to the public. German Clinical Trial Register (DRKS): DRKS00008721 (https://www.germanctr.de/). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  15. RNA-based therapies for genodermatoses

    NARCIS (Netherlands)

    Bornert, Olivier; Peking, Patricia; Bremer, Jeroen; Koller, Ulrich; van den Akker, Peter C.; Aartsma-Rus, Annemieke; Pasmooij, Anna M. G.; Murauer, Eva M.; Nystroem, Alexander

    Genetic disorders affecting the skin, genodermatoses, constitute a large and heterogeneous group of diseases, for which treatment is generally limited to management of symptoms. RNA-based therapies are emerging as a powerful tool to treat genodermatoses. In this review, we discuss in detail RNA

  16. HIV Therapy Simulator: a graphical user interface for comparing the effectiveness of novel therapy regimens.

    Science.gov (United States)

    Lim, Huat Chye; Curlin, Marcel E; Mittler, John E

    2011-11-01

    Computer simulation models can be useful in exploring the efficacy of HIV therapy regimens in preventing the evolution of drug-resistant viruses. Current modeling programs, however, were designed by researchers with expertise in computational biology, limiting their accessibility to those who might lack such a background. We have developed a user-friendly graphical program, HIV Therapy Simulator (HIVSIM), that is accessible to non-technical users. The program allows clinicians and researchers to explore the effectiveness of various therapeutic strategies, such as structured treatment interruptions, booster therapies and induction-maintenance therapies. We anticipate that HIVSIM will be useful for evaluating novel drug-based treatment concepts in clinical research, and as an educational tool. HIV Therapy Simulator is freely available for Mac OS and Windows at http://sites.google.com/site/hivsimulator/. jmittler@uw.edu. Supplementary data are available at Bioinformatics online.

  17. 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

  18. Systems Biology and Stem Cell Pluripotency

    DEFF Research Database (Denmark)

    Mashayekhi, Kaveh; Hall, Vanessa Jane; 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...

  19. Molecular methods in nuclear medicine therapy

    International Nuclear Information System (INIS)

    Lee, Kyung Han

    2001-01-01

    Nuclear medicine has traditionally contributed to molecular oncology by allowing noninvasive monitoring of tumor metabolism, growth and genetic changes, thereby providing a basis for appropriate biology-based treatment planning. However, NM techniques are now being applied as an active therapeutic tool in novel molecular approaches for cancer treatment. Such areas include research on cancer therapy with radiolabeled ligands or oligonucleotides, and utilization of synergism between NM radiotherapy and gene transfer techniques. Here we will focus on novel aspects of nuclear medicine therapy

  20. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K

    2011-01-01

    for the treatment of type 2 diabetes. In contrast to other antidiabetic treatments, these agents have a positive outcome profile on body weight. Worldwide there are 500 million obese people, and 3 million are dying every year from obesity-related diseases. Recently, incretin-based therapy was proposed...... for the treatment of obesity. Currently two different incretin therapies are widely used in the treatment of type 2 diabetes: 1) the GLP-1 receptor agonists which cause significant and sustained weight loss in overweight patients, and 2) dipeptidyl peptidase 4 (DPP-4) inhibitors being weight neutral. These findings...... have led to a greater interest in the physiology of intestinal peptides with potential weight-reducing properties. This review discusses the effects of the incretin-based therapies in obesity, and provides an overview of intestinal peptides with promising effects as potential new treatments for obesity....

  1. Antibody-drug conjugates for cancer therapy: The technological and regulatory challenges of developing drug-biologic hybrids.

    Science.gov (United States)

    Hamilton, Gregory S

    2015-09-01

    Antibody-drug conjugates (ADCs) are a new class of therapeutic agents that combine the targeting ability of monoclonal antibodies (mAbs) with small molecule drugs. The combination of a mAb targeting a cancer-specific antigen with a cytotoxin has tremendous promise as a new type of targeted cancer therapy. Two ADCs have been approved and many more are in clinical development, suggesting that this new class of drugs is coming to the forefront. Because of their unique nature as biologic-small drug hybrids, ADCs are challenging to develop, from both the scientific and regulatory perspectives. This review discusses both these aspects in current practice, and surveys the current state of the art of ADC drug development. Copyright © 2015 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  2. Moving from virtual reality exposure-based therapy to augmented reality exposure-based therapy: a review.

    Science.gov (United States)

    Baus, Oliver; Bouchard, Stéphane

    2014-01-01

    This paper reviews the move from virtual reality exposure-based therapy to augmented reality exposure-based therapy (ARET). Unlike virtual reality (VR), which entails a complete virtual environment (VE), augmented reality (AR) limits itself to producing certain virtual elements to then merge them into the view of the physical world. Although, the general public may only have become aware of AR in the last few years, AR type applications have been around since beginning of the twentieth century. Since, then, technological developments have enabled an ever increasing level of seamless integration of virtual and physical elements into one view. Like VR, AR allows the exposure to stimuli which, due to various reasons, may not be suitable for real-life scenarios. As such, AR has proven itself to be a medium through which individuals suffering from specific phobia can be exposed "safely" to the object(s) of their fear, without the costs associated with programing complete VEs. Thus, ARET can offer an efficacious alternative to some less advantageous exposure-based therapies. Above and beyond presenting what has been accomplished in ARET, this paper covers some less well-known aspects of the history of AR, raises some ARET related issues, and proposes potential avenues to be followed. These include the type of measures to be used to qualify the user's experience in an augmented reality environment, the exclusion of certain AR-type functionalities from the definition of AR, as well as the potential use of ARET to treat non-small animal phobias, such as social phobia.

  3. Moving from Virtual Reality Exposure-Based Therapy to Augmented Reality Exposure-Based Therapy: A Review

    Science.gov (United States)

    Baus, Oliver; Bouchard, Stéphane

    2014-01-01

    This paper reviews the move from virtual reality exposure-based therapy to augmented reality exposure-based therapy (ARET). Unlike virtual reality (VR), which entails a complete virtual environment (VE), augmented reality (AR) limits itself to producing certain virtual elements to then merge them into the view of the physical world. Although, the general public may only have become aware of AR in the last few years, AR type applications have been around since beginning of the twentieth century. Since, then, technological developments have enabled an ever increasing level of seamless integration of virtual and physical elements into one view. Like VR, AR allows the exposure to stimuli which, due to various reasons, may not be suitable for real-life scenarios. As such, AR has proven itself to be a medium through which individuals suffering from specific phobia can be exposed “safely” to the object(s) of their fear, without the costs associated with programing complete VEs. Thus, ARET can offer an efficacious alternative to some less advantageous exposure-based therapies. Above and beyond presenting what has been accomplished in ARET, this paper covers some less well-known aspects of the history of AR, raises some ARET related issues, and proposes potential avenues to be followed. These include the type of measures to be used to qualify the user’s experience in an augmented reality environment, the exclusion of certain AR-type functionalities from the definition of AR, as well as the potential use of ARET to treat non-small animal phobias, such as social phobia. PMID:24624073

  4. Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

    Science.gov (United States)

    Wright, Robin; Boggs, James

    2002-01-01

    To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…

  5. A biological network-based regularized artificial neural network model for robust phenotype prediction from gene expression data.

    Science.gov (United States)

    Kang, Tianyu; Ding, Wei; Zhang, Luoyan; Ziemek, Daniel; Zarringhalam, Kourosh

    2017-12-19

    Stratification of patient subpopulations that respond favorably to treatment or experience and adverse reaction is an essential step toward development of new personalized therapies and diagnostics. It is currently feasible to generate omic-scale biological measurements for all patients in a study, providing an opportunity for machine learning models to identify molecular markers for disease diagnosis and progression. However, the high variability of genetic background in human populations hampers the reproducibility of omic-scale markers. In this paper, we develop a biological network-based regularized artificial neural network model for prediction of phenotype from transcriptomic measurements in clinical trials. To improve model sparsity and the overall reproducibility of the model, we incorporate regularization for simultaneous shrinkage of gene sets based on active upstream regulatory mechanisms into the model. We benchmark our method against various regression, support vector machines and artificial neural network models and demonstrate the ability of our method in predicting the clinical outcomes using clinical trial data on acute rejection in kidney transplantation and response to Infliximab in ulcerative colitis. We show that integration of prior biological knowledge into the classification as developed in this paper, significantly improves the robustness and generalizability of predictions to independent datasets. We provide a Java code of our algorithm along with a parsed version of the STRING DB database. In summary, we present a method for prediction of clinical phenotypes using baseline genome-wide expression data that makes use of prior biological knowledge on gene-regulatory interactions in order to increase robustness and reproducibility of omic-scale markers. The integrated group-wise regularization methods increases the interpretability of biological signatures and gives stable performance estimates across independent test sets.

  6. Pancreatic cancer stromal biology and therapy

    Science.gov (United States)

    Xie, Dacheng; Xie, Keping

    2015-01-01

    Pancreatic cancer is one of the most lethal malignancies. Significant progresses have been made in understanding of pancreatic cancer pathogenesis, including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia (PanINs), description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior. However, the currently used therapeutic strategies targeting tumor epithelial cells, which are potent in cell culture and animal models, have not been successful in the clinic. Presumably, therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis, which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression. Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies. This review focuses on the origination, evolution and disruption of stromal molecular and cellular components in pancreatic cancer, and their biological effects on pancreatic cancer pathogenesis. PMID:26114155

  7. Computer models for optimizing radiation therapy

    International Nuclear Information System (INIS)

    Duechting, W.

    1998-01-01

    The aim of this contribution is to outline how methods of system analysis, control therapy and modelling can be applied to simulate normal and malignant cell growth and to optimize cancer treatment as for instance radiation therapy. Based on biological observations and cell kinetic data, several types of models have been developed describing the growth of tumor spheroids and the cell renewal of normal tissue. The irradiation model is represented by the so-called linear-quadratic model describing the survival fraction as a function of the dose. Based thereon, numerous simulation runs for different treatment schemes can be performed. Thus, it is possible to study the radiation effect on tumor and normal tissue separately. Finally, this method enables a computer-assisted recommendation for an optimal patient-specific treatment schedule prior to clinical therapy. (orig.) [de

  8. Impact of biological therapy on body composition of patients with Chron's disease

    Directory of Open Access Journals (Sweden)

    Julianne Campos dos Santos

    Full Text Available Summary Introduction: Protein-energy malnutrition in Crohn's disease (CD has been reported in 20 to 92% of patients, and is associated with increased morbidity and mortality and higher costs for the health system. Anti-TNF drugs are a landmark in the clinical management, promoting prolonged remission in patients with CD. It is believed that the remission of this disease leads to nutritional recovery. The effect of biological therapy on body composition and nutritional status is unclear. Method: Prospective study of body assessment by bioelectrical impedance method in patients with moderate to severe CD undergoing treatment with infliximab. The main outcome was the body composition before and after 6 months of anti-TNF therapy. Results: There was a predominance of females (52% with a mean age of 42±12 years. Most patients were eutrophic at baseline and remained so. There was an increase in all parameters of body composition after anti-TNF treatment: BMI (22.9±3.2 versus 25±3.8; p=0.005, waist circumference (88.1±6.7 versus 93.9±7.7; p=0.002, lean mass index (17.5±2.2 versus 18.2±2.3; p=0.000 and fat mass index (5.5±2.3 versus 6.8±2.3; p=0.000. Phase angle remained unchanged (6.2 versus 6.8; p=0.94. Conclusion: After therapy with IFX, all components of body composition increased, except for phase angle. The substantial increase in fat mass index and waist circumference led to concern regarding cardiovascular risk and, thus, to the need for further studies.

  9. Biology of radiation therapy

    International Nuclear Information System (INIS)

    Peters, L.J.

    1987-01-01

    A working knowledge of the biologic principles underlying radiotherapy for head and neck tumors is desirable for all the disciplines involved in the management of patients with these cancers. Clinical practice is certainly possible without this basic understanding, and historically most clinical advances have been made empirically. However, an understanding of the basic concepts permits a better appreciation of the strengths and weaknesses of various treatment strategies and offers a rational approach for future modifications of techniques so as to improve the outcome of treatment

  10. A problem-based learning curriculum for occupational therapy education.

    Science.gov (United States)

    Royeen, C B

    1995-04-01

    To prepare practitioners and researchers who are well equipped to deal with the inevitable myriad changes in health care and in society coming in the 21st century, a new focus is needed in occupational therapy education. In addition to proficiency in clinical skills and technical knowledge, occupational therapy graduates will need outcome competencies underlying the skills of critical reflection. In this article, the author presents (a) the rationale for the need for change in occupational therapy education, (b) key concepts of clinical reasoning and critical reflection pertaining to the outcome such change in occupational therapy education should address, (c) problem-based learning as a process and educational method to prepare occupational therapists in these competencies, and (d) the experience of the Program in Occupational Therapy at Shenandoah University in Winchester, Virginia, in implementing a problem-based learning curriculum.

  11. 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.

  12. Conventional and novel stem cell based therapies for androgenic alopecia

    Directory of Open Access Journals (Sweden)

    Talavera-Adame D

    2017-08-01

    Full Text Available Dodanim Talavera-Adame,1 Daniella Newman,2 Nathan Newman1 1American Advanced Medical Corp. (Private Practice, Beverly Hills, CA, 2Western University of Health Sciences, Pomona, CA, USA Abstract: The prevalence of androgenic alopecia (AGA increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine. Keywords: stem cells, stem cell therapies, hair follicle, dermal papilla, androgenic alopecia, laser, hair regeneration

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

    International Nuclear Information System (INIS)

    Kreimann, Erica L.; Dagrosa, Maria A.; Schwint, Amanda E.; Itoiz, Maria E.; Pisarev, Mario A.; Farias, Silvia S.; Garavaglia, Ricardo N.; Batistoni, Daniel A.

    1999-01-01

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

  14. Challenges and Opportunities for Learning Biology in Distance-Based Settings

    Science.gov (United States)

    Hallyburton, Chad L.; Lunsford, Eddie

    2013-01-01

    The history of learning biology through distance education is documented. A review of terminology and unique problems associated with biology instruction is presented. Using published research and their own teaching experience, the authors present recommendations and best practices for managing biology in distance-based formats. They offer ideas…

  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. 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

  17. A New Player in the Development of TRAIL Based Therapies for Hepatocarcinoma Treatment: ATM Kinase

    International Nuclear Information System (INIS)

    Stagni, Venturina; Santini, Simonetta; Barilà, Daniela

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. HCCs are genetically and phenotypically heterogeneous tumors characterized by very poor prognosis, mainly due to the lack, at present, of effective therapeutic options, as these tumors are rarely suitable for radiotherapy and often resistant to chemotherapy protocols. In the last years, agonists targeting the Tumor Necrosis Factor Related Apoptosis Inducing Ligand (TRAIL) death receptor, has been investigated as a valuable promise for cancer therapy, based on their selectivity for malignant cells and low toxicity for healthy cells. However, many cancer models display resistance to death receptor induced apoptosis, pointing to the requirement for the development of combined therapeutic approaches aimed to selectively sensitize cancer cells to TRAIL. Recently, we identified ATM kinase as a novel modulator of the ability of chemotherapeutic agents to enhance TRAIL sensitivity. Here, we review the biological determinants of HCC responsiveness to TRAIL and provide an exhaustive and updated analysis of the molecular mechanisms exploited for combined therapy in this context. The role of ATM kinase as potential novel predictive biomarker for combined therapeutic approaches based on TRAIL and chemotherapeutic drugs will be closely discussed

  18. Radon therapy; Radon in der Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Spruck, Kaija [Technische Hochschule Mittelhessen, Giessen (Germany). Inst. fuer Medizinische Physik und Strahlenschutz

    2017-04-01

    Radon therapies are used since more than 100 years in human medicine. Today this method is controversially discussed due to the possible increase of ionizing radiation induced tumor risk. Although the exact mode of biological radiation effect on the cell level is still not known new studies show the efficiency of the radon therapy without side effect for instance for rheumatic/inflammatory or respiratory disorders.

  19. Combined tumor therapy

    International Nuclear Information System (INIS)

    Wrba, H.

    1990-01-01

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

  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. Performative, Arts-Based, or Arts-Informed? Reflections on the Development of Arts-Based Research in Music Therapy.

    Science.gov (United States)

    Ledger, Alison; McCaffrey, Tríona

    2015-01-01

    Arts-based research (ABR) has emerged in music therapy in diverse ways, employing a range of interpretive paradigms and artistic media. It is notable that no consensus exists as to when and where the arts are included in the research process, or which music therapy topics are most suited to arts-based study. This diversity may pose challenges for music therapists who are developing, reading, and evaluating arts-based research. This paper provides an updated review of arts-based research literature in music therapy, along with four questions for researchers who are developing arts-based research. These questions are 1) When should the arts be introduced? 2) Which artistic medium is appropriate? 3) How should the art be understood? and 4) What is the role of the audience? We argue that these questions are key to understanding arts-based research, justifying methods, and evaluating claims arising from arts-based research. Rather than defining arts-based research in music therapy, we suggest that arts-based research should be understood as a flexible research strategy appropriate for exploring the complexities of music therapy practice. © the American Music Therapy Association 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study

    International Nuclear Information System (INIS)

    Nikoghosyan, Anna V; Rauch, Geraldine; Münter, Marc W; Jensen, Alexandra D; Combs, Stephanie E; Kieser, Meinhard; Debus, Jürgen

    2010-01-01

    Low and intermediate grade chondrosarcomas are relative rare bone tumours. About 5-12% of all chondrosarcomas are localized in base of skull region. Low grade chondrosarcoma has a low incidence of distant metastasis but is potentially lethal disease. Therefore, local therapy is of crucial importance in the treatment of skull base chondrosarcomas. Surgical resection is the primary treatment standard. Unfortunately the late diagnosis and diagnosis at the extensive stage are common due to the slow and asymptomatic growth of the lesions. Consequently, complete resection is hindered due to close proximity to critical and hence dose limiting organs such as optic nerves, chiasm and brainstem. Adjuvant or additional radiation therapy is very important for the improvement of local control rates in the primary treatment. Proton therapy is the gold standard in the treatment of skull base chondrosarcomas. However, high-LET (linear energy transfer) beams such as carbon ions theoretically offer advantages by enhanced biologic effectiveness in slow-growing tumours. The study is a prospective randomised active-controlled clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial. Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV (planning target volume) in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Up to now it was impossible to compare two different

  3. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

    Science.gov (United States)

    D'Haens, Geert R; Panaccione, Remo; Higgins, Peter D R; Vermeire, Severine; Gassull, Miquel; Chowers, Yehuda; Hanauer, Stephen B; Herfarth, Hans; Hommes, Daan W; Kamm, Michael; Löfberg, Robert; Quary, A; Sands, Bruce; Sood, A; Watermeyer, G; Watermayer, G; Lashner, Bret; Lémann, Marc; Plevy, Scott; Reinisch, Walter; Schreiber, Stefan; Siegel, Corey; Targan, Stephen; Watanabe, M; Feagan, Brian; Sandborn, William J; Colombel, Jean Frédéric; Travis, Simon

    2011-02-01

    The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn's disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for >1 year, without signs of active inflammation can remain in remission after stopping treatment.

  4. Animal experiments to investigate biological-chemical radiation protection and the therapy of radiolesions

    International Nuclear Information System (INIS)

    Brueckner, V.

    1974-01-01

    The influence of a combined therapy of radiation protection agents and erythropoetin on the radiation-induced suppression of erythropoiesis in mice is studied with the aid of the radioiron utilization test. After whole-body irradiation with 500 R, the erythropoietic system is so severely affected that erythropoetin application alone does not yield any results. AET (significant) and Cysteamin (insignificant), on the other hand, protect the bone marrow to a certain degree. The protected bone marrow provides a better base for erythropoetin therapy than the bone marrow of the irradiated and unprotected animals. Compared to the application of radiation protection agents alone, the combined therapy with AET and erythropoetin increases the radioiron incorporation in the erythrocytes by 7.5% while the therapy with Cysteamin and erythropoetin results in a 19.3% increase. In spite of these methods, however, the radioiron incorporation rate of the control animals was not reached. (BSC/AK) [de

  5. 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. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.

  6. Biological Treatments in Behçet’s Disease: Beyond Anti-TNF Therapy

    Directory of Open Access Journals (Sweden)

    Francesco Caso

    2014-01-01

    Full Text Available Behçet’s disease (BD is universally recognized as a multisystemic inflammatory disease of unknown etiology with chronic course and unpredictable exacerbations: its clinical spectrum varies from pure vasculitic manifestations with thrombotic complications to protean inflammatory involvement of multiple organs and tissues. Treatment has been revolutionized by the progressed knowledge in the pathogenetic mechanisms of BD, involving dysfunction and oversecretion of multiple proinflammatory molecules, chiefly tumor necrosis factor- (TNF- α, interleukin- (IL- 1β, and IL-6. However, although biological treatment with anti-TNF-α agents has been largely demonstrated to be effective in BD, not all patients are definite responders, and this beneficial response might drop off over time. Therefore, additional therapies for a subset of refractory patients with BD are inevitably needed. Different agents targeting various cytokines and their receptors or cell surface molecules have been studied: the IL-1 receptor has been targeted by anakinra, the IL-1 by canakinumab and gevokizumab, the IL-6 receptor by tocilizumab, the IL12/23 receptor by ustekinumab, and the B-lymphocyte antigen CD-20 by rituximab. The aim of this review is to summarize all current experiences and the most recent evidence regarding these novel approaches with biological drugs other than TNF-α blockers in BD, providing a valuable addition to the actually available therapeutic armamentarium.

  7. Adapting Animal-Assisted Therapy Trials to Prison-Based Animal Programs.

    Science.gov (United States)

    Allison, Molly; Ramaswamy, Megha

    2016-09-01

    Prison-based animal programs have shown promise when it comes to increased sociability, responsibility, and levels of patience for inmates who participate in these programs. Yet there remains a dearth of scientific research that demonstrates the impact of prison-based animal programs on inmates' physical and mental health. Trials of animal-assisted therapy interventions, a form of human-animal interaction therapy most often used with populations affected by depression/anxiety, mental illness, and trauma, may provide models of how prison-based animal program research can have widespread implementation in jail and prison settings, whose populations have high rates of mental health problems. This paper reviews the components of prison-based animal programs most commonly practiced in prisons today, presents five animal-assisted therapy case studies, evaluates them based on their adaptability to prison-based animal programs, and discusses the institutional constraints that act as barriers for rigorous prison-based animal program research implementation. This paper can serve to inform the development of a research approach to animal-assisted therapy that nurses and other public health researchers can use in working with correctional populations. © 2016 Wiley Periodicals, Inc.

  8. A Biologically Based Chemo-Sensing UAV for Humanitarian Demining

    Directory of Open Access Journals (Sweden)

    Paul F.M.J. Verschure

    2008-11-01

    Full Text Available Antipersonnel mines, weapons of cheap manufacture but lethal effect, have a high impact on the population even decades after the conflicts have finished. Here we investigate the use of a chemo-sensing Unmanned Aerial Vehicle (cUAV for demining tasks. We developed a blimp based UAV that is equipped with a broadly tuned metal-thin oxide chemo-sensor. A number of chemical mapping strategies were investigated including two biologically based localization strategies derived from the moth chemical search that can optimize the efficiency of the detection and localization of explosives and therefore be used in the demining process. Additionally, we developed a control layer that allows for both fully autonomous and manual controlled flight, as well as for the scheduling of a fleet of cUAVs. Our results confirm the feasibility of this technology for demining in real-world scenarios and give further support to a biologically based approach where the understanding of biological systems is used to solve difficult engineering problems.

  9. A Biologically Based Chemo-Sensing UAV for Humanitarian Demining

    Directory of Open Access Journals (Sweden)

    Sergi Bermúdez i Badia

    2007-06-01

    Full Text Available Antipersonnel mines, weapons of cheap manufacture but lethal effect, have a high impact on the population even decades after the conflicts have finished. Here we investigate the use of a chemo-sensing Unmanned Aerial Vehicle (cUAV for demining tasks. We developed a blimp based UAV that is equipped with a broadly tuned metal-thin oxide chemo-sensor. A number of chemical mapping strategies were investigated including two biologically based localization strategies derived from the moth chemical search that can optimize the efficiency of the detection and localization of explosives and therefore be used in the demining process. Additionally, we developed a control layer that allows for both fully autonomous and manual controlled flight, as well as for the scheduling of a fleet of cUAVs. Our results confirm the feasibility of this technology for demining in real-world scenarios and give further support to a biologically based approach where the understanding of biological systems is used to solve difficult engineering problems.

  10. Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study

    Energy Technology Data Exchange (ETDEWEB)

    Feuvret, Loïc, E-mail: loic.feuvret@psl.aphp.fr [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bracci, Stefano [Institute of Radiation Oncology, Sapienza University, Sant' Andrea Hospital, Rome (Italy); Calugaru, Valentin [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bolle, Stéphanie [Department of Radiation Oncology, Gustave Roussy, Villejuif (France); Mammar, Hamid; De Marzi, Ludovic [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); Bresson, Damien [Department of Neurosurgery, Hôpital Lariboisière (Assistance Publique–Hôpitaux de Paris), Paris (France); Habrand, Jean-Louis [Department of Radiation Oncology, Centre François Baclesse, Caen (France); Mazeron, Jean-Jacques [Department of Radiation Oncology, Groupe Hospitalier La Pitié-Salpêtrière–Charles Foix (Assistance Publique–Hôpitaux de Paris), Paris (France); Dendale, Rémi [Department of Radiation Oncology, Institut Curie–Centre de protonthérapie d' Orsay (CPO), Orsay (France); and others

    2016-05-01

    Purpose: Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). Methods and Materials: From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. Results: With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age <40 years and primary disease status were independent favorable prognostic factors for progression-free survival and OS, and local tumor control was an independent favorable predictor of OS. In contrast, the extent of surgery, dosimetric parameters, and adjacent organs at risk were not prognostic factors for LC or OS. Conclusions: Systematic high-dose postoperative proton therapy for skull base chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended.

  11. Severe and acute complications of biologics in psoriasis.

    Science.gov (United States)

    Oussedik, Elias; Patel, Nupur U; Cash, Devin R; Gupta, Angela S; Feldman, Steven R

    2017-12-01

    Biologic therapies have revolutionized the approach to immune-mediated diseases such as psoriasis. Due to their favorable safety profiles and excellent efficacy, biologic agents are considered the gold standard for moderate-to-severe psoriasis. The aim of this paper is to saliently review the severe and acute complications of the Food and Drug Administration (FDA) approved biologic agents for psoriasis. Reviewed agents include tumor necrosis factor alpha inhibitors (etanercept, infliximab, and adalimumab), interleukin 12/23 inhibitors (ustekinumab), and interleukin 17 (IL-17) inhibitors (secukinumab and ixekizumab). While malignancies, serious infections, and major adverse cardiovascular events have been reported, their association with biologic therapy are not hypothesized as causal. However, IL-17 inhibitors appear to cause exacerbations and new cases of inflammatory bowel disease. While more long-term studies are warranted in understanding the biologic's long-term side effect profile, short-term studies have confirmed that the biologics are some of the safest treatment options for psoriasis. Nevertheless, certain populations yield higher risk to acute complications with the biologics than others - physicians must use their judgement and vigilance when monitoring and treating patients undergoing therapy with biological agents.

  12. Emerging technologies for enabling proangiogenic therapy

    International Nuclear Information System (INIS)

    Roy, Rituparna Sinha; Roy, Bhaskar; Sengupta, Shiladitya

    2011-01-01

    Ischemic disease causes a large number of deaths and significant clinical problems worldwide. Therapeutic angiogenesis, strengthened by advances in growth-factor-based therapies, is a promising solution to ischemic pathologies. Major challenges in therapeutic angiogenesis are the lack of stability of native angiogenic proteins and also providing sustained delivery of biologically active proteins at the ischemic sites. This paper will discuss various protein engineering strategies to develop stabilized proangiogenic proteins and several biomaterial technologies used to amplify the angiogenic outcome by delivering biologically active growth factors in a sustained manner.

  13. Emerging technologies for enabling proangiogenic therapy

    Science.gov (United States)

    Sinha Roy, Rituparna; Roy, Bhaskar; Sengupta, Shiladitya

    2011-12-01

    Ischemic disease causes a large number of deaths and significant clinical problems worldwide. Therapeutic angiogenesis, strengthened by advances in growth-factor-based therapies, is a promising solution to ischemic pathologies. Major challenges in therapeutic angiogenesis are the lack of stability of native angiogenic proteins and also providing sustained delivery of biologically active proteins at the ischemic sites. This paper will discuss various protein engineering strategies to develop stabilized proangiogenic proteins and several biomaterial technologies used to amplify the angiogenic outcome by delivering biologically active growth factors in a sustained manner.

  14. [Smart therapeutics based on synthetic gene circuits].

    Science.gov (United States)

    Peng, Shuguang; Xie, Zhen

    2017-03-25

    Synthetic biology has an important impact on biology research since its birth. Applying the thought and methods that reference from electrical engineering, synthetic biology uncovers many regulatory mechanisms of life systems, transforms and expands a series of biological components. Therefore, it brings a wide range of biomedical applications, including providing new ideas for disease diagnosis and treatment. This review describes the latest advances in the field of disease diagnosis and therapy based on mammalian cell or bacterial synthetic gene circuits, and provides new ideas for future smart therapy design.

  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. Biomedicines?Moving Biologic Agents into Approved Treatment Options

    OpenAIRE

    Cornetta, Kenneth

    2013-01-01

    The development of biologic agents for therapeutic purposes, or biomedicines, has seen an active area of research both at the bench and in clinical trials. There is mounting evidence that biologic products can provide effective therapy for diseases that have been unresponsive to traditional pharmacologic approaches. Monoclonal antibody therapy for cancer and rheumatologic diseases has become a well accepted part of disease treatment plans. Gene therapy products have been approved in China and...

  17. Can We Advance Proton Therapy for Prostate? Considering Alternative Beam Angles and Relative Biological Effectiveness Variations When Comparing Against Intensity Modulated Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Underwood, Tracy, E-mail: tunderwood@mgh.harvard.edu [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States); Department of Medical Physics and Bioengineering, University College London, London (United Kingdom); Giantsoudi, Drosoula; Moteabbed, Maryam; Zietman, Anthony; Efstathiou, Jason; Paganetti, Harald; Lu, Hsiao-Ming [Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts (United States)

    2016-05-01

    Purpose: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. Methods and Materials: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions were simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. Results: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. Conclusion: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.

  18. Developing Home-Based Virtual Reality Therapy Interventions.

    Science.gov (United States)

    Lin, Janice; Kelleher, Caitlin L; Engsberg, Jack R

    2013-02-01

    Stroke is one of the leading causes of serious long-term disability. However, home exercise programs given at rehabilitation often lack in motivational aspects. The purposes of this pilot study were (1) create individualized virtual reality (VR) games and (2) determine the effectiveness of VR games for improving movement in upper extremities in a 6-week home therapy intervention for persons with stroke. Participants were two individuals with upper extremity hemiparesis following a stroke. VR games were created using the Looking Glass programming language and modified based on personal interests, goals, and abilities. Participants were asked to play 1 hour each day for 6 weeks. Assessments measured upper extremity movement (range of motion and Action Research Arm Test [ARAT]) and performance in functional skills (Canadian Occupational Performance Measure [COPM] and Motor Activity Log [MAL]). Three VR games were created by a supervised occupational therapist student. The participants played approximately four to six times a week and performed over 100 repetitions of movements each day. Participants showed improvement in upper extremity movement and participation in functional tasks based on results from the COPM, ARAT, and MAL. Further development in the programming environment is needed to be plausible in a rehabilitation setting. Suggestions include graded-level support and continuation of creating a natural programming language, which will increase the ability to use the program in a rehabilitation setting. However, the VR games were shown to be effective as a home therapy intervention for persons with stroke. VR has the potential to advance therapy services by creating a more motivating home-based therapy service.

  19. Compliance with biologic therapies for rheumatoid arthritis: do patient out-of-pocket payments matter?

    Science.gov (United States)

    Curkendall, S; Patel, V; Gleeson, M; Campbell, R S; Zagari, M; Dubois, R

    2008-10-15

    To assess the impact of patient out-of-pocket (OOP) expenditures on adherence and persistence with biologics in patients with rheumatoid arthritis (RA). An inception cohort of RA patients with pharmacy claims for etanercept or adalimumab during 2002-2004 was selected from an insurance claims database of self-insured employer health plans (n=2,285) in the US. Adherence was defined as medication possession ratio (MPR): the proportion of the 365 followup days covered by days supply. Persistence was determined using a survival analysis of therapy discontinuation during followup. Patient OOP cost was measured as the patient's coinsurance and copayments per week of therapy, and as the proportion of the total medication charges paid by the patient. Multivariate linear regression models of MPR and proportional hazards models of persistence were used to estimate the impact of cost, adjusting for insurance type and demographic and clinical variables. Mean +/- SD OOP expenditures averaged $7.84+/-$14.15 per week. Most patients (92%) paid less than $20 OOP for therapy/week. The mean +/- SD MPR was 0.52+/-0.31. Adherence significantly decreased with increased weekly OOP (coeff= -0.0035, Pcosts paid by patients (coeff= -0.8794, Pcost exceeded $50 were more likely to discontinue than patients with lower costs (hazard ratio 1.58, Pcompliance. The adverse impact of high OOP costs on adherence, persistence, and outcomes must be considered when making decisions about increasing copayments.

  20. Validation of GPU based TomoTherapy dose calculation engine.

    Science.gov (United States)

    Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

    2012-04-01

    The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

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

    International Nuclear Information System (INIS)

    Gruen, Rebecca Antonia

    2014-01-01

    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

  2. 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.

  3. Next generation of biologics for the treatment of Crohn’s disease: an evidence-based review on ustekinumab

    Directory of Open Access Journals (Sweden)

    Jauregui-Amezaga A

    2017-11-01

    Full Text Available Aranzazu Jauregui-Amezaga, Michael Somers, Heiko De Schepper, Elisabeth Macken Department of Gastroenterology, Universitair Ziekenhuis Antwerpen, University of Antwerp, Antwerp, Belgium Abstract: The limited efficacy of the currently available medical therapies in a proportion of patients with Crohn’s disease has led to the research and development of molecules that can block new inflammatory pathways. Ustekinumab is a fully human IgG1 monoclonal antibody which targets the common p40 subunit of the cytokines interleukin-12 as well as interleukin-23. Consequently, the Th1 and Th17 inflammatory responses are inhibited. Ustekinumab has been recently approved for its use in patients with Crohn’s disease. Its efficacy and safety was initially proved in patients with psoriasis and psoriatic arthritis. More recently, three Phase III trials have confirmed its efficacy in patients with Crohn’s disease refractory to anti-tumor necrosis factor therapy. This biologic agent appears safe, with no increased risk of infectious or malignant complications, and a low immunogenic profile. Keywords: ustekinumab, interleukin-12, interleukin-23, biologic therapy, inflammatory bowel disease, Crohn’s disease

  4. Proton Therapy for Skull Base Chordomas: An Outcome Study from the University of Florida Proton Therapy Institute

    OpenAIRE

    Deraniyagala, Rohan L.; Yeung, Daniel; Mendenhall, William M.; Li, Zuofeng; Morris, Christopher G.; Mendenhall, Nancy P.; Okunieff, Paul; Malyapa, Robert S.

    2013-01-01

    Objectives Skull base chordoma is a rare, locally aggressive tumor located adjacent to critical structures. Gross total resection is difficult to achieve, and proton therapy has the conformal advantage of delivering a high postoperative dose to the tumor bed. We present our experience using proton therapy to treat 33 patients with skull base chordomas.

  5. Efficacy and Safety of Adjuvant Proton Therapy Combined With Surgery for Chondrosarcoma of the Skull Base: A Retrospective, Population-Based Study.

    Science.gov (United States)

    Feuvret, Loïc; Bracci, Stefano; Calugaru, Valentin; Bolle, Stéphanie; Mammar, Hamid; De Marzi, Ludovic; Bresson, Damien; Habrand, Jean-Louis; Mazeron, Jean-Jacques; Dendale, Rémi; Noël, Georges

    2016-05-01

    Chondrosarcoma is a rare malignant tumor of the cartilage affecting young adults. Surgery, followed by charged-particle irradiation, is considered the reference standard for the treatment of patients with grade I to II skull base chondrosarcoma. The present study was conducted to assess the effect of the quality of surgery and radiation therapy parameters on local control (LC) and overall survival (OS). From 1996 to 2013, 159 patients (median age 40 years, range 12-83) were treated with either protons alone or a combination of protons and photons. The median total dose delivered was 70.2 Gy (relative biologic effectiveness [RBE]; range 67-71). Debulking and biopsy were performed in 133 and 13 patients, respectively. With a median follow-up of 77 months (range 2-214), 5 tumors relapsed based on the initial gross tumor volume. The 5- and 10-year LC rates were 96.4% and 93.5%, respectively, and the 5- and 10-year OS rates were 94.9% and 87%, respectively. A total of 16 patients died (13 of intercurrent disease, 3 of disease progression). On multivariate analysis, age chondrosarcoma can achieve a high LC rate with a low toxicity profile. Maximal safe surgery, followed by high-dose conformal proton therapy, is therefore recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Prototype Biology-Based Radiation Risk Module Project

    Science.gov (United States)

    Terrier, Douglas; Clayton, Ronald G.; Patel, Zarana; Hu, Shaowen; Huff, Janice

    2015-01-01

    Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis.

  7. 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

  8. Molecular biology of gastric cancer.

    Science.gov (United States)

    Cervantes, A; Rodríguez Braun, E; Pérez Fidalgo, A; Chirivella González, I

    2007-04-01

    Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications.

  9. Model-based sensor-augmented pump therapy.

    Science.gov (United States)

    Grosman, Benyamin; Voskanyan, Gayane; Loutseiko, Mikhail; Roy, Anirban; Mehta, Aloke; Kurtz, Natalie; Parikh, Neha; Kaufman, Francine R; Mastrototaro, John J; Keenan, Barry

    2013-03-01

    In insulin pump therapy, optimization of bolus and basal insulin dose settings is a challenge. We introduce a new algorithm that provides individualized basal rates and new carbohydrate ratio and correction factor recommendations. The algorithm utilizes a mathematical model of blood glucose (BG) as a function of carbohydrate intake and delivered insulin, which includes individualized parameters derived from sensor BG and insulin delivery data downloaded from a patient's pump. A mathematical model of BG as a function of carbohydrate intake and delivered insulin was developed. The model includes fixed parameters and several individualized parameters derived from the subject's BG measurements and pump data. Performance of the new algorithm was assessed using n = 4 diabetic canine experiments over a 32 h duration. In addition, 10 in silico adults from the University of Virginia/Padova type 1 diabetes mellitus metabolic simulator were tested. The percentage of time in glucose range 80-180 mg/dl was 86%, 85%, 61%, and 30% using model-based therapy and [78%, 100%] (brackets denote multiple experiments conducted under the same therapy and animal model), [75%, 67%], 47%, and 86% for the control experiments for dogs 1 to 4, respectively. The BG measurements obtained in the simulation using our individualized algorithm were in 61-231 mg/dl min-max envelope, whereas use of the simulator's default treatment resulted in BG measurements 90-210 mg/dl min-max envelope. The study results demonstrate the potential of this method, which could serve as a platform for improving, facilitating, and standardizing insulin pump therapy based on a single download of data. © 2013 Diabetes Technology Society.

  10. Accelerator based neutron source for neutron capture therapy

    International Nuclear Information System (INIS)

    Salimov, R.; Bayanov, B.; Belchenko, Yu.; Belov, V.; Davydenko, V.; Donin, A.; Dranichnikov, A.; Ivanov, A.; Kandaurov, I; Kraynov, G.; Krivenko, A.; Kudryavtsev, A.; Kursanov, N.; Savkin, V.; Shirokov, V.; Sorokin, I.; Taskaev, S.; Tiunov, M.

    2004-01-01

    Full text: The Budker Institute of Nuclear Physics (Novosibirsk) and the Institute of Physics and Power Engineering (Obninsk) have proposed an accelerator based neutron source for neutron capture and fast neutron therapy for hospital. Innovative approach is based upon vacuum insulation tandem accelerator (VITA) and near threshold 7 Li(p,n) 7 Be neutron generation. Pilot accelerator based neutron source for neutron capture therapy is under construction now at the Budker Institute of Nuclear Physics, Novosibirsk, Russia. In the present report, the pilot facility design is presented and discussed. Design features of facility components are discussed. Results of experiments and simulations are presented. Complete experimental tests are planned by the end of the year 2005

  11. A Study of the Literature on Lab-Based Instruction in Biology

    Science.gov (United States)

    Puttick, Gillian; Drayton, Brian; Cohen, Eliza

    2015-01-01

    We analyzed the practitioner literature on lab-based instruction in biology in "The American Biology Teacher" between 2007 and 2012. We investigated what laboratory learning looks like in biology classrooms, what topics are addressed, what instructional methods and activities are described, and what is being learned about student…

  12. Carbon nanostructure-based field-effect transistors for label-free chemical/biological sensors.

    Science.gov (United States)

    Hu, PingAn; Zhang, Jia; Li, Le; Wang, Zhenlong; O'Neill, William; Estrela, Pedro

    2010-01-01

    Over the past decade, electrical detection of chemical and biological species using novel nanostructure-based devices has attracted significant attention for chemical, genomics, biomedical diagnostics, and drug discovery applications. The use of nanostructured devices in chemical/biological sensors in place of conventional sensing technologies has advantages of high sensitivity, low decreased energy consumption and potentially highly miniaturized integration. Owing to their particular structure, excellent electrical properties and high chemical stability, carbon nanotube and graphene based electrical devices have been widely developed for high performance label-free chemical/biological sensors. Here, we review the latest developments of carbon nanostructure-based transistor sensors in ultrasensitive detection of chemical/biological entities, such as poisonous gases, nucleic acids, proteins and cells.

  13. Emerging biologic therapies for hypercholesterolaemia.

    Science.gov (United States)

    Pucci, Giacomo; Cicero, Arrigo F; Borghi, Claudio; Schillaci, Giuseppe

    2017-09-01

    LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions. The discontinuation in the development of bococizumab due to efficacy and safety concerns, and the initial promising data about inclisiran, a long-acting small inhibiting RNA molecule against PCSK9 synthesis, is also discussed. Expert opinion: Initial data about cardiovascular (CV) outcomes in large scale, long-term studies suggest a possible further therapeutic pathway for LDL-C reduction, and currently support the notion that further LDL-C reduction, obtained with PCSK9 inhibition on top of best available therapy, provides increased CV protection in subjects at very high CV risk. The development and marketing of mAbs against PCSK9 could help to redefine current therapeutic strategies aimed at reducing cardiovascular (CV) morbidity and risk, through the reduction of LDL-C concentrations. The cost-effectiveness of these emerging drugs is yet to be established.

  14. [Molecular Biology for Surgical Treatment of Lung Cancer].

    Science.gov (United States)

    Suda, Kenichi; Mitsudomi, Tetsuya

    2017-01-01

    Progress in lung cancer research achieved during the last 10 years was summarized. These include identification of novel driver mutations and application of targeted therapies, resistance mechanisms to targeted therapies, and immunotherapy with immune checkpoint inhibitors. Molecular biology also affects the field of surgical treatment. Several molecular markers have been reported to predict benign/ malignant or stable/growing tumors, although far from clinical application. In perioperative period, there is a possibility of atrial natriuretic peptide to prevent cancer metastasis. As adjuvant settings, although biomarker-based cytotoxic therapies failed to show clinical efficacy, several trials are ongoing employing molecular targeted agents (EGFR-TKI or ALK-TKI) or immune checkpoint inhibitors. In clinical practice, mutational information is sometimes used to distinguish 2nd primary tumors from pulmonary metastases of previous cancers. Surgery also has important role for oligo-progressive disease during molecular targeted therapies.

  15. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy.

    Science.gov (United States)

    Sharma, Anjali; Kakkar, Ashok

    2015-09-17

    To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional "only one function" to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  16. Performing Art-Based Research: Innovation in Graduate Art Therapy Education

    Science.gov (United States)

    Moon, Bruce L.; Hoffman, Nadia

    2014-01-01

    This article presents an innovation in art therapy research and education in which art-based performance is used to generate, embody, and creatively synthesize knowledge. An art therapy graduate student's art-based process of inquiry serves to demonstrate how art and performance may be used to identify the research question, to conduct a process…

  17. 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...... 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...... = 39), and ustekinumab (n = 95). MPR calculation was calculated monthly based on the hospital records documenting the dispensing of biologics to the patients. Clinical data [Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), presence of psoriatic arthritis, concomitant...

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

    Science.gov (United States)

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

    2012-01-01

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

  19. Nanoparticle-based strategy for personalized B-cell lymphoma therapy

    Science.gov (United States)

    Martucci, Nicola M; Migliaccio, Nunzia; Ruggiero, Immacolata; Albano, Francesco; Calì, Gaetano; Romano, Simona; Terracciano, Monica; Rea, Ilaria; Arcari, Paolo; Lamberti, Annalisa

    2016-01-01

    B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite) were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2) with small interfering RNA (siRNA). An idiotype-specific peptide (Id-peptide) specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing observed is of significant biological importance and opens new possibilities for the personalized treatment of lymphomas. PMID:27895482

  20. Care of the patient receiving radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Yasko, J.M.

    1982-12-01

    External radiation therapy, or teletherapy, is the use of ionizing radiation to destroy cancer cells. Clinical use of ionizing radiation as treatment for cancer began with the discovery of x-rays in 1895, the identification of natural radioactivity (radium) in 1896, and the first reported cure of cancer, a basal cell epithelioma, induced by radiation in 1899. Initially, radiation was administered as a single large dose and produced severe, life-threatening side effects. The basis for the use of ionizing radiation in daily increments for a period of weeks was provided by Regaud in 1922; ten years later, Coutard clinically developed the method of dose fractionation, which remains in use today. Although the use of ionizing radiation as a treatment is over eighty years old, only in recent years have advancements in its clinical application been based on research related to the biologic effect of radiation on human cells. To effectively care for the patient prior to, during, and at the completion of external radiation therapy, the nurse must know the physical and biologic basis of external radiation therapy and its clinical application.

  1. Care of the patient receiving radiation therapy

    International Nuclear Information System (INIS)

    Yasko, J.M.

    1982-01-01

    External radiation therapy, or teletherapy, is the use of ionizing radiation to destroy cancer cells. Clinical use of ionizing radiation as treatment for cancer began with the discovery of x-rays in 1895, the identification of natural radioactivity (radium) in 1896, and the first reported cure of cancer, a basal cell epithelioma, induced by radiation in 1899. Initially, radiation was administered as a single large dose and produced severe, life-threatening side effects. The basis for the use of ionizing radiation in daily increments for a period of weeks was provided by Regaud in 1922; ten years later, Coutard clinically developed the method of dose fractionation, which remains in use today. Although the use of ionizing radiation as a treatment is over eighty years old, only in recent years have advancements in its clinical application been based on research related to the biologic effect of radiation on human cells. To effectively care for the patient prior to, during, and at the completion of external radiation therapy, the nurse must know the physical and biologic basis of external radiation therapy and its clinical application

  2. Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy

    International Nuclear Information System (INIS)

    Wiebe, L. I.

    1997-01-01

    The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of 'biologicals', in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified

  3. Radiopharmaceuticals to monitor the expression of transferred genes in gene transfer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, L I [University of Alberta, Edmonton (Canada). Noujaim Institute for Pharmaceutical Oncology Research

    1997-10-01

    The development and application of radiopharmaceuticals has, in many instances, been based on the pharmacological properties of therapeutic agents. The molecular biology-biotechnology revolution has had an important impact on treatment of diseases, in part through the reduced toxicity of `biologicals`, in part because of their specificity for interaction at unique molecular sites and in part because of their selective delivery to the target site. Immunotherapeutic approaches include the use of monoclonal antibodies (MABs), MAB-fragments and chemotactic peptides. Such agents currently form the basis of both diagnostic and immunotherapeutic radiopharmaceuticals. More recently, gene transfer techniques have been advanced to the point that a new molecular approach, gene therapy, has become a reality. Gene therapy offers an opportunity to attack disease at its most fundamental level. The therapeutic mechanism is based on the expression of a specific gene or genes, the product of which will invoke immunological, receptor-based or enzyme-based therapeutic modalities. Several approaches to gene therapy of cancer have been envisioned, the most clinically-advanced concepts involving the introduction of genes that will encode for molecular targets nor normally found in healthy mammalian cells. A number of gene therapy clinical trials are based on the introduction of the Herpes simplex virus type-1 (HSV-1) gene that encodes for viral thymidine kinase (tk+). Once HSV-1 tk+ is expressed in the target (cancer) cell, therapy can be effected by the administration of a highly molecularly-targeted and systemically non-toxic antiviral drug such as ganciclovir. The development of radiodiagnostic imaging in gene therapy will be reviewed, using HSV-1 tk+ and radioiodinated IVFRU as a basis for development of the theme. Molecular targets that could be exploited in gene therapy, other than tk+, will be identified

  4. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Magnetic resonance imaging and cell-based neurorestorative therapy after brain injury

    Directory of Open Access Journals (Sweden)

    Quan Jiang

    2016-01-01

    Full Text Available Restorative cell-based therapies for experimental brain injury, such as stroke and traumatic brain injury, substantially improve functional outcome. We discuss and review state of the art magnetic resonance imaging methodologies and their applications related to cell-based treatment after brain injury. We focus on the potential of magnetic resonance imaging technique and its associated challenges to obtain useful new information related to cell migration, distribution, and quantitation, as well as vascular and neuronal remodeling in response to cell-based therapy after brain injury. The noninvasive nature of imaging might more readily help with translation of cell-based therapy from the laboratory to the clinic.

  6. Nanoparticle-based strategy for personalized B-cell lymphoma therapy

    Directory of Open Access Journals (Sweden)

    Martucci NM

    2016-11-01

    Full Text Available Nicola M Martucci,1,* Nunzia Migliaccio,1,* Immacolata Ruggiero,1,* Francesco Albano,2 Gaetano Calì,3 Simona Romano,1 Monica Terracciano,4 Ilaria Rea,4 Paolo Arcari,1 Annalisa Lamberti1 1Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, 2Department of Experimental and Clinical Medicine, University of Catanzaro “Magna Graecia”, Catanzaro, 3Institute of Endocrinology and Molecular Oncology, 4Institute for Microelectronics and Microsystems, National Research Council, Naples, Italy *These authors contributed equally to this work Abstract: B-cell lymphoma is associated with incomplete response to treatment, and the development of effective strategies targeting this disease remains challenging. A new personalized B-cell lymphoma therapy, based on a site-specific receptor-mediated drug delivery system, was developed in this study. Specifically, natural silica-based nanoparticles (diatomite were modified to actively target the antiapoptotic factor B-cell lymphoma/leukemia 2 (Bcl2 with small interfering RNA (siRNA. An idiotype-specific peptide (Id-peptide specifically recognized by the hypervariable region of surface immunoglobulin B-cell receptor was exploited as a homing device to ensure specific targeting of lymphoma cells. Specific nanoparticle uptake, driven by the Id-peptide, was evaluated by flow cytometry and confocal microscopy and was increased by approximately threefold in target cells compared with nonspecific myeloma cells and when a random control peptide was used instead of Id-peptide. The specific internalization efficiency was increased by fourfold when siRNA was also added to the modified nanoparticles. The modified diatomite particles were not cytotoxic and their effectiveness in downregulation of gene expression was explored using siRNA targeting Bcl2 and evaluated by quantitative real-time polymerase chain reaction and Western blot analyses. The resulting gene silencing

  7. Examining portfolio-based assessment in an upper-level biology course

    Science.gov (United States)

    Ziegler, Brittany Ann

    Historically, students have been viewed as empty vessels and passive participants in the learning process but students actually are active forming their own conceptions. One way student learning is impacted is through assessment. Alternative assessment, which contrasts traditional assessment methods, takes into account how students learn by promoting engagement and construction of knowledge This dissertation explores portfolio-based assessment, a method of alternative assessment, which requires students to compose a purposeful collection of work demonstrating their knowledge in an upper-level biology course. The research objectives include characterizing and contributing to the understanding of portfolio-based assessment in higher education, examining reflection and inquiry portfolio components, determining student knowledge of biological concepts, and investigating student integrative thinking through the transformation of reflections into concept webs One main finding includes the majority of reflections categorized as naive or novice in quality. There was no difference in quality of reflections among biological topic. There was a relatively equal amount of high and low cognitive level questions. Students' knowledge of biological concepts significantly increased from the beginning to end of the course. Student written reflections were transformed into concept webs to allow for examination of student integrative thinking. Concepts, relationships, and interconnections in concept webs showed variation but declined by the end of the semester This study is one of the first examining portfolio-based assessment in an upper-level biology course We do not contend that this method of assessment is the only way to promote student learning but portfolio-based assessment may be a tool that can transform science education but currently the role of portfolio-based assessment in science education remains unclear. Additional research needs to be conducted before we will fully

  8. Conventional and novel stem cell based therapies for androgenic alopecia.

    Science.gov (United States)

    Talavera-Adame, Dodanim; Newman, Daniella; Newman, Nathan

    2017-01-01

    The prevalence of androgenic alopecia (AGA) increases with age and it affects both men and women. Patients diagnosed with AGA may experience decreased quality of life, depression, and feel self-conscious. There are a variety of therapeutic options ranging from prescription drugs to non-prescription medications. Currently, AGA involves an annual global market revenue of US$4 billion and a growth rate of 1.8%, indicating a growing consumer market. Although natural and synthetic ingredients can promote hair growth and, therefore, be useful to treat AGA, some of them have important adverse effects and unknown mechanisms of action that limit their use and benefits. Biologic factors that include signaling from stem cells, dermal papilla cells, and platelet-rich plasma are some of the current therapeutic agents being studied for hair restoration with milder side effects. However, most of the mechanisms exerted by these factors in hair restoration are still being researched. In this review, we analyze the therapeutic agents that have been used for AGA and emphasize the potential of new therapies based on advances in stem cell technologies and regenerative medicine.

  9. Improving creative thinking skills and scientific attitude through inquiry-based learning in basic biology lecture toward student of biology education

    Directory of Open Access Journals (Sweden)

    Bayu Sandika

    2018-03-01

    Full Text Available Inquiry-based learning is one of the learning methods which can provide an active and authentic scientific learning process in order students are able to improve the creative thinking skills and scientific attitude. This study aims at improving creative thinking skills and scientific attitude through inquiry-based learning in basic biology lecture toward students of biology education at the Institut Agama Islam Negeri (IAIN Jember, Indonesia. This study is included in a descriptive quantitative research. The research focused on the topic of cell transport which was taught toward 25 students of Biology 2 class from 2017 academic year of Biology Education Department at the IAIN Jember. The learning process was conducted in two meetings in November 2017. The enhancement of students' creative thinking skills was determined by one group pre-test and post-test research design using test instrument meanwhile the scientific attitude focused on curiosity and objectivity were observed using the non-test instrument. Research result showed that students' creative thinking skills enhanced highly and students' scientific attitude improved excellently through inquiry-based learning in basic biology lecture.

  10. A Randomized Controlled Trial of Acceptance-Based Behavior Therapy and Cognitive Therapy for Test Anxiety: A Pilot Study

    Science.gov (United States)

    Brown, Lily A.; Forman, Evan M.; Herbert, James D.; Hoffman, Kimberly L.; Yuen, Erica K.; Goetter, Elizabeth M.

    2011-01-01

    Many university students suffer from test anxiety that is severe enough to impair performance. Given mixed efficacy results of previous cognitive-behavior therapy (CBT) trials and a theoretically driven rationale, an acceptance-based behavior therapy (ABBT) approach was compared to traditional CBT (i.e., Beckian cognitive therapy; CT) for the…

  11. Mobile-based biology edutainment application for secondary schools

    Science.gov (United States)

    AL-Modwahi, Ashraf Abbas M.; Kaisara, Onalenna; Parkizkar, Behrang; Habibi Lashkari, Arash

    2013-03-01

    The high increase of mobile technology is leading to mobilized learning environment, thus making traditional learning to diminish slowly and become inactive and unproductive. Learners worldwide are being attracted to mobile environment more so that it promotes anytime, anywhere learning. Biology as a secondary school subject will be applicable for mobile learning for such a time and generation as this. This paper is therefore an attempt to mobile based biology edutainment system for the students who normally range from the ages of thirteen to sixteen.

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

    Science.gov (United States)

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

    2014-10-01

    Screening for opportunistic infections prior to starting biological therapy in patients with inflammatory bowel disease is recommended. To assess adherence to screening for opportunistic infections prior to starting biological therapy in Crohn's disease patients and its yield. A multicentre retrospective study was conducted in Crohn's disease patients in whom infliximab or adalimumab was started between 2000 and 2010. Screening included tuberculin skin test, interferon-gamma release assay or chest X-ray for tuberculosis. Extended screening included screening for tuberculosis and viral infections. Patients were followed until three months after ending treatment. Primary endpoints were opportunistic and serious infections. 611 patients were included, 91% on infliximab. 463 (76%) patients were screened for tuberculosis, of whom 113 (24%) underwent extended screening. Screening for tuberculosis and hepatitis B increased to, respectively, 90-97% and 36-49% in the last two years. During a median follow-up of two years, 64/611 (9%, 3.4/100 patient-years) opportunistic infections and 26/611 (4%, 1.6/100 patient-years) serious infections were detected. Comorbidity was significantly associated with serious infections (hazard ratio 3.94). Although screening rates for tuberculosis and hepatitis B increased, screening for hepatitis B was still suboptimal. More caution is required when prescribing biologicals in patients with comorbid conditions. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  13. Regenerative Therapy for Retinal Disorders

    Directory of Open Access Journals (Sweden)

    Narsis Daftarian

    2010-01-01

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

  14. 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. Evidence - based medicine/practice in sports physical therapy.

    Science.gov (United States)

    Manske, Robert C; Lehecka, B J

    2012-10-01

    A push for the use of evidence-based medicine and evidence-based practice patterns has permeated most health care disciplines. The use of evidence-based practice in sports physical therapy may improve health care quality, reduce medical errors, help balance known benefits and risks, challenge views based on beliefs rather than evidence, and help to integrate patient preferences into decision-making. In this era of health care utilization sports physical therapists are expected to integrate clinical experience with conscientious, explicit, and judicious use of research evidence in order to make clearly informed decisions in order to help maximize and optimize patient well-being. One of the more common reasons for not using evidence in clinical practice is the perceived lack of skills and knowledge when searching for or appraising research. This clinical commentary was developed to educate the readership on what constitutes evidence-based practice, and strategies used to seek evidence in the daily clinical practice of sports physical therapy.

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

    Science.gov (United States)

    Balwit, James M; Kalinski, Pawel; Sondak, Vernon K; Coulie, Pierre G; Jaffee, Elizabeth M; Gajewski, Thomas F; Marincola, Francesco M

    2011-05-12

    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.

  17. New Approaches in Cancer Biology Can Inform the Biology Curriculum.

    Science.gov (United States)

    Jones, Lynda; Gordon, Diana; Zelinski, Mary

    2018-03-01

    Students tend to be very interested in medical issues that affect them and their friends and family. Using cancer as a hook, the ART of Reproductive Medicine: Oncofertility curriculum (free, online, and NIH sponsored) has been developed to supplement the teaching of basic biological concepts and to connect biology and biomedical research. This approach allows integration of up-to-date information on cancer and cancer treatment, cell division, male and female reproductive anatomy and physiology, cryopreservation, fertility preservation, stem cells, ethics, and epigenetics into an existing biology curriculum. Many of the topics covered in the curriculum relate to other scientific disciplines, such as the latest developments in stem cell research including tissue bioengineering and gene therapy for inherited mitochondrial disease, how epigenetics occurs chemically to affect gene expression or suppression and how it can be passed down through the generations, and the variety of biomedical careers students could pursue. The labs are designed to be open-ended and inquiry-based, and extensions to the experiments are provided so that students can explore questions further. Case studies and ethical dilemmas are provided to encourage thoughtful discussion. In addition, each chapter of the curriculum includes links to scientific papers, additional resources on each topic, and NGSS alignment.

  18. Nanomedicine for cancer therapy from chemotherapeutic to hyperthermia-based therapy

    CERN Document Server

    Kumar, Piyush

    2017-01-01

    This Brief focuses on the cancer therapy available till date, from conventional drug delivery to nanomedicine in clinical trial. In addition, it reports on future generation based nanotherapeutics and cancer theranostic agent for effective therapeutic diagnosis and treatment. Breast cancer was chosen as the model system in this review. The authors give emphasis to multiple drug resistance (MDR) and its mechanism and how to overcome it using the nanoparticle approach. .

  19. A Project-Based Biologically-Inspired Robotics Module

    Science.gov (United States)

    Crowder, R. M.; Zauner, K.-P.

    2013-01-01

    The design of any robotic system requires input from engineers from a variety of technical fields. This paper describes a project-based module, "Biologically-Inspired Robotics," that is offered to Electronics and Computer Science students at the University of Southampton, U.K. The overall objective of the module is for student groups to…

  20. Designing Dendrimer and Miktoarm Polymer Based Multi-Tasking Nanocarriers for Efficient Medical Therapy

    Directory of Open Access Journals (Sweden)

    Anjali Sharma

    2015-09-01

    Full Text Available To address current complex health problems, there has been an increasing demand for smart nanocarriers that could perform multiple complimentary biological tasks with high efficacy. This has provoked the design of tailor made nanocarriers, and the scientific community has made tremendous effort in meeting daunting challenges associated with synthetically articulating multiple functions into a single scaffold. Branched and hyper-branched macromolecular architectures have offered opportunities in enabling carriers with capabilities including location, delivery, imaging etc. Development of simple and versatile synthetic methodologies for these nanomaterials has been the key in diversifying macromolecule based medical therapy and treatment. This review highlights the advancement from conventional “only one function” to multifunctional nanomedicine. It is achieved by synthetic elaboration of multivalent platforms in miktoarm polymers and dendrimers by physical encapsulation, covalent linking and combinations thereof.

  1. The radiation biology of Boron Neutron Capture Therapy

    International Nuclear Information System (INIS)

    Coderre, J.A.

    2003-01-01

    Boron Neutron Capture Therapy (BNCT) produces a complex mixture of high and low-LET radiations in tissue. Using data on the biological effectiveness of these various dose components, derived primarily in small animals irradiated with thermal neutrons, it has been possible to express clinical BNCT doses in photon-equivalent units. The accuracy of these calculated doses in normal tissue and tumor will be reviewed. Clinical trials are underway at a number of centers. There are differences in the neutron beams at these centers, and differences in the details of the clinical protocols. Ideally, data from all centers using similar boron compounds and treatment protocols should be compared and combined, if appropriate, in a multi-institutional study in order to strengthen statistical analysis. An international dosimetry exchange is underway that will allow the physical doses from the various treatment centers to be quantitatively compared. As a first step towards the comparison of the clinical data, the normal brain tolerance data from the patients treated in the initial Brookhaven National Laboratory and the Harvard/MIT BNCT clinical trials have been compared. The data provide a good estimate of the normal brain tolerance for a somnolence syndrome endpoint, and provide guidance for setting normal brain tolerance limits in ongoing and future clinical trials. Escalation of the dose in BNCT can be accomplished by increasing the amount of the boron compound administered, increasing the duration of the neutron exposure, or both. The dose escalations that have been carried out to date at the various treatment centers will be compared and contrasted. Possible future clinical trials using BNCT in combination with other modalities will be discussed

  2. Computer-based Programs in Speech Therapy of Dyslalia and Dyslexia- Dysgraphia

    Directory of Open Access Journals (Sweden)

    Mirela Danubianu

    2010-04-01

    Full Text Available During the last years, the researchers and therapists in speech therapy have been more and more concerned with the elaboration and use of computer programs in speech disorders therapy. The main objective of this study was to evaluate the therapeutic effectiveness of computer-based programs for the Romanian language in speech therapy. Along the study, we will present the experimental research through assessing the effectiveness of computer programs in the speech therapy for speech disorders: dyslalia, dyslexia and dysgraphia. Methodologically, the use of the computer in the therapeutic phases was carried out with the help of some computer-based programs (Logomon, Dislex-Test etc. that we elaborated and we experimented with during several years of therapeutic activity. The sample used in our experiments was composed of 120 subjects; two groups of 60 children with speech disorders were selected for both speech disorders: 30 for the experimental ('computer-based' group and 30 for the control ('classical method' group. The study hypotheses verified whether the results, obtained by the subjects within the experimental group, improved significantly after using the computer-based program, compared to the subjects within the control group, who did not use this program but got a classical therapy. The hypotheses were confirmed for the speech disorders included in this research; the conclusions of the study confirm the advantages of using computer-based programs within speech therapy by correcting these disorders, as well as due to the positive influence these programs have on the development of children’s personality.

  3. Gene Therapy in Cardiac Arrhythmias

    OpenAIRE

    Praveen, S.V; Francis, Johnson; Venugopal, K

    2006-01-01

    Gene therapy has progressed from a dream to a bedside reality in quite a few human diseases. From its first application in adenosine deaminase deficiency, through the years, its application has evolved to vascular angiogenesis and cardiac arrhythmias. Gene based biological pacemakers using viral vectors or mesenchymal cells tested in animal models hold much promise. Induction of pacemaker activity within the left bundle branch can provide stable heart rates. Genetic modification of the AV...

  4. Cell therapy medicinal product regulatory framework in Europe and its application for MSC based therapy development

    Directory of Open Access Journals (Sweden)

    Janis eAncans

    2012-08-01

    Full Text Available Advanced therapy medicinal products (ATMPs, including cell therapy products, form a new class of medicines in the European Union. Since ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT has been established at European Medicines Agency (EMA for centralized classification, certification and evaluation procedures, and other ATMP related tasks. Guidance documents, initiatives and interaction platforms are available to make the new framework more accessible for small and medium-sized enterprises, academia, hospitals and foundations. Good understanding of centralised and national components of the regulatory system is required to plan product development. It is in the best interests of cell therapy developers to utilise provided resources starting with the preclinical stage. Whilst there have not been mesenchymal stem cell (MSC based medicine authorisations in the EU, three MSC products have received marketing approval in other regions since 2011. Information provided on regulatory requirements, procedures and initiatives is aimed to facilitate MSC based medicinal product development and authorisation in the EU.

  5. Optical sensor for heat conduction measurement in biological tissue

    International Nuclear Information System (INIS)

    Gutierrez-Arroyo, A; Sanchez-Perez, C; Aleman-Garcia, N

    2013-01-01

    This paper presents the design of a heat flux sensor using an optical fiber system to measure heat conduction in biological tissues. This optoelectronic device is based on the photothermal beam deflection of a laser beam travelling in an acrylic slab this deflection is measured with a fiber optic angle sensor. We measure heat conduction in biological samples with high repeatability and sensitivity enough to detect differences in tissues from three chicken organs. This technique could provide important information of vital organ function as well as the detect modifications due to degenerative diseases or physical damage caused by medications or therapies.

  6. Biology-based combined-modality radiotherapy: workshop report

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Komaki, Ritsuko; Cox, James D.; Milas, Luka

    2001-01-01

    Purpose: The purpose of this workshop summary is to provide an overview of preclinical and clinical data on combined-modality radiotherapy. Methods and Materials: The 8th Annual Radiation Workshop at Round Top was held April 13-16, 2000 at the International Festival Institute (Round Top, TX). Results: Presentations by 30 speakers (from Germany, Netherlands, Australia, England, and France along with U.S. participants and M. D. Anderson Cancer Center faculty) formed the framework for discussions on the current status and future perspectives of biology-based combined-modality radiotherapy. Conclusion: Cellular and molecular pathways available for radiation modification by chemical and biologic agents are numerous, providing new opportunities for translational research in radiation oncology and for more effective combined-modality treatment of cancer

  7. Moving from Virtual Reality Exposure-Based Therapy (VRET to Augmented Reality Exposure-Based Therapy (ARET: A review.

    Directory of Open Access Journals (Sweden)

    Oliver eBaus

    2014-03-01

    Full Text Available This paper reviews the move from virtual reality exposure-based therapy (VRET to augmented reality exposure-based therapy (ARET. Unlike virtual reality (VR, which entails a complete virtual environment (VE, augmented reality (AR limits itself to producing certain virtual elements to then merge them into the view of the physical world. Although the general public may only have become aware of AR in the last few years, AR type applications have been around since beginning of the 20th century. Since, then, technological developments have enabled an ever increasing level of seamless integration of virtual and physical elements into one view. Like VR, AR allows the exposure to stimuli which, due to various reasons, may not be suitable for real-life scenarios. As such, AR has proven itself to be a medium through which individuals suffering from specific phobia can be exposed safely to the object(s of their fear, without the costs associated with programming complete virtual environments. Thus, ARET can offer an efficacious alternative to some less advantageous exposure-based therapies. Above and beyond presenting what has been accomplished in ARET, this paper also raises some ARET related issues, and proposes potential avenues to be followed. These include the definition of an AR related term, the type of measures to be used to qualify the user’s experience in an augmented reality environment (ARE, the development of alternative geospatial referencing systems, as well as the potential use of ARET to treat social phobia. Overall, it may be said that the use of ARET, although promising, is still in its infancy but that, given a continued cooperation between clinical and technical teams, ARET has the potential of going well beyond the treatment of small animal phobia.

  8. In vivo 808 nm image-guided photodynamic therapy based on an upconversion theranostic nanoplatform

    Science.gov (United States)

    Liu, Xiaomin; Que, Ivo; Kong, Xianggui; Zhang, Youlin; Tu, Langping; Chang, Yulei; Wang, Tong Tong; Chan, Alan; Löwik, Clemens W. G. M.; Zhang, Hong

    2015-09-01

    A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii) realizing in vivo NIR 808 nm image-guided PDT with both excitation (980 nm) and emission (808 nm) light falling in the biological window of tissues, which minimized auto-fluorescence, reduced light scatting and improved the imaging contrast and depth, and thus guaranteed noninvasive diagnostic accuracy. In vivo and ex vivo tests demonstrated its favorable bio-distribution, tumor-selectivity and high therapeutic efficacy. Owing to the effective ligand exchange strategy and the excellent intrinsic photophysical properties of C60, 1O2 production yield was improved, suggesting that a low 980 nm irradiation dosage (351 J cm-2) and a short treatment time (15 min) were sufficient to perform NIR (980 nm) to NIR (808 nm) image-guided PDT. Our work enriches the understanding of UCNP-based PDT nanophotosensitizers and highlights their potential use in future NIR image-guided noninvasive deep cancer therapy.A new strategy for efficient in vivo image-guided photodynamic therapy (PDT) has been demonstrated utilizing a ligand-exchange constructed upconversion-C60 nanophotosensitizer. This theranostic platform is superior to the currently reported nanophotosensitizers in (i) directly bonding photosensitizer C60 to the surface of upconversion nanoparticles (UCNPs) by a smart ligand-exchange strategy, which greatly shortened the energy transfer distance and enhanced the 1O2 production, resulting in the improvement of the therapeutic effect; (ii

  9. Biological interactions of carbon-based nanomaterials: From coronation to degradation.

    Science.gov (United States)

    Bhattacharya, Kunal; Mukherjee, Sourav P; Gallud, Audrey; Burkert, Seth C; Bistarelli, Silvia; Bellucci, Stefano; Bottini, Massimo; Star, Alexander; Fadeel, Bengt

    2016-02-01

    Carbon-based nanomaterials including carbon nanotubes, graphene oxide, fullerenes and nanodiamonds are potential candidates for various applications in medicine such as drug delivery and imaging. However, the successful translation of nanomaterials for biomedical applications is predicated on a detailed understanding of the biological interactions of these materials. Indeed, the potential impact of the so-called bio-corona of proteins, lipids, and other biomolecules on the fate of nanomaterials in the body should not be ignored. Enzymatic degradation of carbon-based nanomaterials by immune-competent cells serves as a special case of bio-corona interactions with important implications for the medical use of such nanomaterials. In the present review, we highlight emerging biomedical applications of carbon-based nanomaterials. We also discuss recent studies on nanomaterial 'coronation' and how this impacts on biodistribution and targeting along with studies on the enzymatic degradation of carbon-based nanomaterials, and the role of surface modification of nanomaterials for these biological interactions. Advances in technology have produced many carbon-based nanomaterials. These are increasingly being investigated for the use in diagnostics and therapeutics. Nonetheless, there remains a knowledge gap in terms of the understanding of the biological interactions of these materials. In this paper, the authors provided a comprehensive review on the recent biomedical applications and the interactions of various carbon-based nanomaterials. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  10. BicPAMS: software for biological data analysis with pattern-based biclustering.

    Science.gov (United States)

    Henriques, Rui; Ferreira, Francisco L; Madeira, Sara C

    2017-02-02

    Biclustering has been largely applied for the unsupervised analysis of biological data, being recognised today as a key technique to discover putative modules in both expression data (subsets of genes correlated in subsets of conditions) and network data (groups of coherently interconnected biological entities). However, given its computational complexity, only recent breakthroughs on pattern-based biclustering enabled efficient searches without the restrictions that state-of-the-art biclustering algorithms place on the structure and homogeneity of biclusters. As a result, pattern-based biclustering provides the unprecedented opportunity to discover non-trivial yet meaningful biological modules with putative functions, whose coherency and tolerance to noise can be tuned and made problem-specific. To enable the effective use of pattern-based biclustering by the scientific community, we developed BicPAMS (Biclustering based on PAttern Mining Software), a software that: 1) makes available state-of-the-art pattern-based biclustering algorithms (BicPAM (Henriques and Madeira, Alg Mol Biol 9:27, 2014), BicNET (Henriques and Madeira, Alg Mol Biol 11:23, 2016), BicSPAM (Henriques and Madeira, BMC Bioinforma 15:130, 2014), BiC2PAM (Henriques and Madeira, Alg Mol Biol 11:1-30, 2016), BiP (Henriques and Madeira, IEEE/ACM Trans Comput Biol Bioinforma, 2015), DeBi (Serin and Vingron, AMB 6:1-12, 2011) and BiModule (Okada et al., IPSJ Trans Bioinf 48(SIG5):39-48, 2007)); 2) consistently integrates their dispersed contributions; 3) further explores additional accuracy and efficiency gains; and 4) makes available graphical and application programming interfaces. Results on both synthetic and real data confirm the relevance of BicPAMS for biological data analysis, highlighting its essential role for the discovery of putative modules with non-trivial yet biologically significant functions from expression and network data. BicPAMS is the first biclustering tool offering the

  11. Practical Radiobiology for Proton Therapy Planning

    Science.gov (United States)

    Jones, Bleddyn

    2017-12-01

    Practical Radiobiology for Proton Therapy Planning covers the principles, advantages and potential pitfalls that occur in proton therapy, especially its radiobiological modelling applications. This book is intended to educate, inform and to stimulate further research questions. Additionally, it will help proton therapy centres when designing new treatments or when unintended errors or delays occur. The clear descriptions of useful equations for high LET particle beam applications, worked examples of many important clinical situations, and discussion of how proton therapy may be optimized are all important features of the text. This important book blends the relevant physics, biology and medical aspects of this multidisciplinary subject. Part of Series in Physics and Engineering in Medicine and Biology.

  12. Biological information systems: Evolution as cognition-based information management.

    Science.gov (United States)

    Miller, William B

    2018-05-01

    An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-01

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

  14. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... et al. Photodynamic therapy. Journal of the National Cancer Institute 1998; 90(12):889–905. [PubMed Abstract] Gudgin Dickson EF, Goyan RL, Pottier RH. New directions in photodynamic therapy. Cellular and Molecular Biology 2002; 48(8):939–954. [PubMed Abstract] Capella ...

  15. Therapy for obesity based on gastrointestinal hormones

    DEFF Research Database (Denmark)

    Bagger, Jonatan I; Christensen, Mikkel; Knop, Filip K

    2011-01-01

    It has long been known that peptide hormones from the gastrointestinal tract have significant impact on the regulation of nutrient metabolism. Among these hormones, incretins have been found to increase insulin secretion, and thus incretin-based therapies have emerged as new modalities...

  16. Biological impact of music and software-based auditory training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition. Learning outcomes The reader will (1) understand that the auditory system is malleable to experience and training, (2) learn the ingredients necessary for auditory learning to successfully be applied to communication, (3) learn that the auditory brainstem response to complex sounds (cABR) is a window into the integrated auditory system, and (4) see examples of how cABR can be used to track the outcome of experience and training. PMID:22789822

  17. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia

    Science.gov (United States)

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics. This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups. After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID:26871827

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

    International Nuclear Information System (INIS)

    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)

  19. [The molecular biology of epithelial ovarian cancer].

    Science.gov (United States)

    Leary, Alexandra; Pautier, Patricia; Tazi, Youssef; Morice, Philippe; Duvillard, Pierre; Gouy, Sébastien; Uzan, Catherine; Gauthier, Hélène; Balleyguier, Corinne; Lhommé, Catherine

    2012-12-01

    Epithelial ovarian cancer frequently presents at an advanced stage where the cornerstone of management remains surgery and platinum-based chemotherapy. Unfortunately, despite sometimes dramatic initial responses, advanced ovarian cancer almost invariably relapses. Little progress has been made in the identification of effective targeted-therapies for ovarian cancer. The majority of clinical trials investigating novel agents have been negative and the only approved targeted-therapy is bevacizumab, for which reliable predictive biomarkers still elude us. Ovarian cancer is treated as a uniform disease. Yet, biological studies have highlighted the heterogeneity of this malignancy with marked differences in histology, oncogenesis, prognosis, chemo-responsiveness, and molecular profile. Recent high throughput molecular analyses have identified a huge number of genomic/phenotypic alterations. Broadly speaking, high grade serous carcinomas (type II) display significant genomic instability and numerous amplifications and losses; low grade (type I) tumors are genomically stable but display frequent mutations. Importantly, many of these genomic alterations relate to known oncogenes for which targeted-therapies are available or in development. There is today a real potential for personalized medicine in ovarian cancer. We will review the current literature regarding the molecular characterization of epithelial ovarian cancer and discuss the biological rationale for a number of targeted strategies. In order to translate these biological advances into meaningful clinical improvements for our patients, it is imperative to incorporate translational research in ovarian cancer trials, a number of strategies will be proposed such as the acquisition of quality tumor samples, including sequential pre- and post-treatment biopsies, the potential of liquid biopsies, and novel trial designs more adapted to the molecular era of ovarian cancer research.

  20. Mindfulness-based cognitive therapy for multiple chemical sensitivity

    DEFF Research Database (Denmark)

    Hauge, Christian R; Bonde, Jens Peter E; Rasmussen, Alice

    2012-01-01

    no evidence-based treatments for MCS. Nevertheless, there is a substantial need for a treatment, because the condition can be severely disabling and can greatly reduce the quality of life (QOL) for those affected.In this study, we aim to assess the effects of a mindfulness-based cognitive therapy (MBCT...

  1. Perspective on future therapy of vasculitis.

    Science.gov (United States)

    Boumpas, D T; Kritikos, H D; Daskalakis, N G

    2000-10-01

    This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

  2. Bio-heat transfer model of electroconvulsive therapy: Effect of biological properties on induced temperature variation.

    Science.gov (United States)

    de Oliveira, Marilia M; Wen, Paul; Ahfock, Tony

    2016-08-01

    A realistic human head model consisting of six tissue layers was modelled to investigate the behavior of temperature profile and magnitude when applying electroconvulsive therapy stimulation and different biological properties. The thermo-electrical model was constructed with the use of bio-heat transfer equation and Laplace equation. Three different electrode montages were analyzed as well as the influence of blood perfusion, metabolic heat and electric and thermal conductivity in the scalp. Also, the effect of including the fat layer was investigated. The results showed that temperature increase is inversely proportional to electrical and thermal conductivity increase. Furthermore, the inclusion of blood perfusion slightly drops the peak temperature. Finally, the inclusion of fat is highly recommended in order to acquire more realistic results from the thermo-electrical models.

  3. 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.

  4. Cell therapy medicinal product regulatory framework in Europe and its application for MSC-based therapy development

    Science.gov (United States)

    Ancans, Janis

    2012-01-01

    Advanced therapy medicinal products (ATMPs), including cell therapy products, form a new class of medicines in the European Union. Since the ATMPs are at the forefront of scientific innovation in medicine, specific regulatory framework has been developed for these medicines and implemented from 2009. The Committee for Advanced Therapies (CAT) has been established at the European Medicines Agency (EMA) for centralized classification, certification and evaluation procedures, and other ATMP-related tasks. Guidance documents, initiatives, and interaction platforms are available to make the new framework more accessible for small- and medium-sized enterprises, academia, hospitals, and foundations. Good understanding of the centralized and national components of the regulatory system is required to plan product development. It is in the best interests of the cell therapy developers to utilize the resources provided starting with the pre-clinical stage. Whilst there have been no mesenchymal stem cell (MSC)-based medicine authorizations in the EU, three MSC products have received marketing approval in other regions since 2011. The information provided on the regulatory requirements, procedures, and initiatives is aimed at facilitating MSC-based medicinal product development and authorization in the EU. PMID:22912639

  5. Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

    Science.gov (United States)

    He, Lijie; Wang, Jing; Chang, Dandan; Lv, Dandan; Li, Haina; Zhang, Heping

    2018-02-01

    The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3 + , CD4 + , CD8 + and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8 + T lymphocytes and Treg populations were decreased, and that CD3 + and CD4 + T lymphocytes as well as the CD4 + /CD8 + ratio were increased after therapy; in SCLC patients, CD3 + , CD4 + and CD8 + T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination

  6. 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.

  7. Empirically Based Psychosocial Therapies for Schizophrenia: The Disconnection between Science and Practice

    Directory of Open Access Journals (Sweden)

    Glenn D. Shean

    2013-01-01

    Full Text Available Empirically validated psychosocial therapies for individuals diagnosed with schizophrenia were described in the report of the Schizophrenia Patient Outcomes Research Team (PORT, 2009. The PORT team identified eight psychosocial treatments: assertive community treatment, supported employment, cognitive behavioral therapy, family-based services, token economy, skills training, psychosocial interventions for alcohol and substance use disorders, and psychosocial interventions for weight management. PORT listings of empirically validated psychosocial therapies provide a useful template for the design of effective recovery-oriented mental health care systems. Unfortunately, surveys indicate that PORT listings have not been implemented in clinical settings. Obstacles to the implementation of PORT psychosocial therapy listings and suggestions for changes needed to foster implementation are discussed. Limitations of PORT therapy listings that are based on therapy outcome efficacy studies are discussed, and cross-cultural and course and outcome studies of correlates of recovery are summarized.

  8. Cell therapy-processing economics: small-scale microfactories as a stepping stone toward large-scale macrofactories.

    Science.gov (United States)

    Harrison, Richard P; Medcalf, Nicholas; Rafiq, Qasim A

    2018-03-01

    Manufacturing methods for cell-based therapies differ markedly from those established for noncellular pharmaceuticals and biologics. Attempts to 'shoehorn' these into existing frameworks have yielded poor outcomes. Some excellent clinical results have been realized, yet emergence of a 'blockbuster' cell-based therapy has so far proved elusive.  The pressure to provide these innovative therapies, even at a smaller scale, remains. In this process, economics research paper, we utilize cell expansion research data combined with operational cost modeling in a case study to demonstrate the alternative ways in which a novel mesenchymal stem cell-based therapy could be provided at small scale. This research outlines the feasibility of cell microfactories but highlighted that there is a strong pressure to automate processes and split the quality control cost-burden over larger production batches. The study explores one potential paradigm of cell-based therapy provisioning as a potential exemplar on which to base manufacturing strategy.

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

  10. DNA nanostructure-based drug delivery nanosystems in cancer therapy.

    Science.gov (United States)

    Wu, Dandan; Wang, Lei; Li, Wei; Xu, Xiaowen; Jiang, Wei

    2017-11-25

    DNA as a novel biomaterial can be used to fabricate different kinds of DNA nanostructures based on its principle of GC/AT complementary base pairing. Studies have shown that DNA nanostructure is a nice drug carrier to overcome big obstacles existing in cancer therapy such as systemic toxicity and unsatisfied drug efficacy. Thus, different types of DNA nanostructure-based drug delivery nanosystems have been designed in cancer therapy. To improve treating efficacy, they are also developed into more functional drug delivery nanosystems. In recent years, some important progresses have been made. The objective of this review is to make a retrospect and summary about these different kinds of DNA nanostructure-based drug delivery nanosystems and their latest progresses: (1) active targeting; (2) mutidrug co-delivery; (3) construction of stimuli-responsive/intelligent nanosystems. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

    International Nuclear Information System (INIS)

    Oesten, H; Loeck, S; Wohlfahrt, P; Helmbrecht, S; Tillner, F; Schuemann, J; Luehr, A

    2016-01-01

    Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

  12. SU-F-T-682: In-Vivo Simulation of the Relative Biological Effectiveness in Proton Therapy Using a Monte Carlo Method

    Energy Technology Data Exchange (ETDEWEB)

    Oesten, H [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Massachusetts General Hospital, Boston, MA (Germany); Loeck, S; Wohlfahrt, P [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Helmbrecht, S [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Institute of Radiation Physics, Helmholtz-Zentrum Dresden-Rossendorf (Germany); Tillner, F [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); Schuemann, J [Massachusetts General Hospital, Boston, MA (United States); Luehr, A [OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitaet Dresden (Germany); German Cancer Consortium (DKTK), Dresden (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2016-06-15

    Purpose: In proton therapy, the relative biological effectiveness (RBE) – compared with conventional photon therapy – is routinely set to 1.1. However, experimental in vitro studies indicate evidence for the variability of the RBE. To clarify the impact on patient treatment, investigation of the RBE in a preclinical case study should be performed. Methods: The Monte Carlo software TOPAS was used to simulate the radiation field of an irradiation setup at the experimental beamline of the proton therapy facility (OncoRay) in Dresden, Germany. Simulations were performed on cone beam CT-data (CBCT) of a xenogeneous mouse with an orthotopic lung carcinoma obtained by an in-house developed small animal image-guided radiotherapy device. A homogeneous physical fraction dose of 1.8Gy was prescribed for the contoured tumor volume. Simulated dose and linear energy transfer distributions were used to estimate RBE values in the mouse based on an RBE model by Wedenberg et al. To characterize radiation sensitivity of normal and tumor tissue, α/β-ratios were taken from the literature for NB1RGB (10.1Gy) and human squamous lung cancer (6.2Gy) cell lines, respectively. Results: Good dose coverage of the target volume was achieved with a spread-out Bragg peak (SOBP). The contra-lateral lung was completely spared from receiving radiation. An increase in RBE towards the distal end of the SOBP from 1.07 to 1.35 and from 1.05 to 1.3 was observed when considering normal tissue and tumor, respectively, with the highest RBE values located distal to the target volume. Conclusion: Modeled RBE values simulated on CBCT for experimental preclinical proton therapy varied with tissue type and depth in a mouse and differed therefore from a constant value of 1.1. Further translational work will include, first, conducting preclinical experiments and, second, analogous RBE studies in patients using experimentally verified simulation settings for our clinically used patient-specific beam

  13. Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

    Directory of Open Access Journals (Sweden)

    Mikel Sánchez

    2017-01-01

    Full Text Available Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI, focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

  14. Clinical oncology based upon radiation biology

    International Nuclear Information System (INIS)

    Hirata, Hideki

    2016-01-01

    This paper discussed the biological effects of radiation as physical energy, especially those of X-ray as electromagnetic radiation, by associating the position of clinical oncology with classical radiation cell biology as well as recent molecular biology. First, it described the physical and biological effects of radiation, cell death due to radiation and recovery, radiation effects at tissue level, and location information and dosage information in the radiotherapy of cancer. It also described the territories unresolved through radiation biology, such as low-dose high-sensitivity, bystander effects, etc. (A.O.)

  15. Rethinking biology instruction: The application of DNR-based instruction to the learning and teaching of biology

    Science.gov (United States)

    Maskiewicz, April Lee

    Educational studies report that secondary and college level students have developed only limited understandings of the most basic biological processes and their interrelationships from typical classroom experiences. Furthermore, students have developed undesirable reasoning schemes and beliefs that directly affect how they make sense of and account for biological phenomena. For these reasons, there exists a need to rethink instructional practices in biology. This dissertation discusses how the principles of Harel's (1998, 2001) DNR-based instruction in mathematics could be applied to the teaching and learning of biology. DNR is an acronym for the three foundational principles of the system: Duality, Necessity, and Repeated-reasoning. This study examines the application of these three principles to ecology instruction. Through clinical and teaching interviews, I developed models of students' existing ways of understanding in ecology and inferred their ways of thinking. From these models a hypothetical learning trajectory was developed for 16 college level freshmen enrolled in a 10-week ecology teaching experiment. Through cyclical, interpretive analysis I documented and analyzed the evolution of the participants' progress. The results provide empirical evidence to support the claim that the DNR principles are applicable to ecology instruction. With respect to the Duality Principle, helping students develop specific ways of understanding led to the development of model-based reasoning---a way of thinking and the cognitive objective guiding instruction. Through carefully structured problem solving tasks, the students developed a biological understanding of the relationship between matter cycling, energy flow, and cellular processes such as photosynthesis and respiration, and used this understanding to account for observable phenomena in nature. In the case of intellectual necessity, the results illuminate how problem situations can be developed for biology learners

  16. Biological therapies (immunomodulatory drugs), worsening of psoriasis and rebound effect: new evidence of similitude.

    Science.gov (United States)

    Teixeira, Marcus Zulian

    2016-11-01

    Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright © 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  17. Simulation and virtual reality in medical education and therapy: a protocol.

    Science.gov (United States)

    Roy, Michael J; Sticha, Deborah L; Kraus, Patricia L; Olsen, Dale E

    2006-04-01

    Continuing medical education has historically been provided primarily by didactic lectures, though adult learners prefer experiential or self-directed learning. Young physicians have extensive experience with computer-based or "video" games, priming them for medical education--and treating their patients--via new technologies. We report our use of standardized patients (SPs) to educate physicians on the diagnosis and treatment of biological and chemical warfare agent exposure. We trained professional actors to serve as SPs representing exposure to biological agents such as anthrax and smallpox. We rotated workshop participants through teaching stations to interview, examine, diagnose and treat SPs. We also trained SPs to simulate a chemical mass casualty (MASCAL) incident. Workshop participants worked together to treat MASCAL victims, followed by discussion of key teaching points. More recently, we developed computer-based simulation (CBS) modules of patients exposed to biological agents. We compare the strengths and weaknesses of CBS vs. live SPs. Finally, we detail plans for a randomized controlled trial to assess the efficacy of virtual reality (VR) exposure therapy compared to pharmacotherapy for post-traumatic stress disorder (PTSD). PTSD is associated with significant disability and healthcare costs, which may be ameliorated by the identification of more effective therapy.

  18. Third-wave cognitive therapy versus mentalisation-based treatment for major depressive disorder

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Kongerslev, Mickey

    2014-01-01

    OBJECTIVE: To compare the benefits and harms of third-wave cognitive therapy versus mentalisation-based therapy in a small sample of depressed participants. SETTING: The trial was conducted at an outpatient psychiatric clinic for non-psychotic patients in Roskilde, Denmark. PARTICIPANTS: 44...... consecutive adult participants diagnosed with major depressive disorder. INTERVENTIONS: 18 weeks of third-wave cognitive therapy (n=22) versus 18 weeks of mentalisation-based treatment (n=22). OUTCOMES: The primary outcome was the Hamilton Rating Scale for Depression (HDRS) at end of treatment (18 weeks...... for baseline HDRS score, the difference was favouring third-wave cognitive therapy (p=0.039). At 18 weeks, five of the third-wave participants (22.7%) were in remission versus none of the mentalisation-based participants (p=0.049). We recorded no suicide attempts or suicides during the intervention period...

  19. 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...

  20. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  1. WORKSHOP ON APPLICATION OF STATISTICAL METHODS TO BIOLOGICALLY-BASED PHARMACOKINETIC MODELING FOR RISK ASSESSMENT

    Science.gov (United States)

    Biologically-based pharmacokinetic models are being increasingly used in the risk assessment of environmental chemicals. These models are based on biological, mathematical, statistical and engineering principles. Their potential uses in risk assessment include extrapolation betwe...

  2. Diketopyrrolopyrrole-based carbon dots for photodynamic therapy.

    Science.gov (United States)

    He, Haozhe; Zheng, Xiaohua; Liu, Shi; Zheng, Min; Xie, Zhigang; Wang, Yong; Yu, Meng; Shuai, Xintao

    2018-06-01

    The development of a simple and straightforward strategy to synthesize multifunctional carbon dots for photodynamic therapy (PDT) has been an emerging focus. In this work, diketopyrrolopyrrole-based fluorescent carbon dots (DPP CDs) were designed and synthesized through a facile one-pot hydrothermal method by using diketopyrrolopyrrole (DPP) and chitosan (CTS) as raw materials. DPP CDs not only maintained the ability of DPP to generate singlet oxygen (1O2) but also have excellent hydrophilic properties and outstanding biocompatibility. In vitro and in vivo experiments demonstrated that DPP CDs greatly inhibited the growth of tumor cells under laser irradiation (540 nm). This study highlights the potential of the rational design of CDs for efficient cancer therapy.

  3. Silicon nanomaterials platform for bioimaging, biosensing, and cancer therapy.

    Science.gov (United States)

    Peng, Fei; Su, Yuanyuan; Zhong, Yiling; Fan, Chunhai; Lee, Shuit-Tong; He, Yao

    2014-02-18

    Silicon nanomaterials are an important class of nanomaterials with great potential for technologies including energy, catalysis, and biotechnology, because of their many unique properties, including biocompatibility, abundance, and unique electronic, optical, and mechanical properties, among others. Silicon nanomaterials are known to have little or no toxicity due to favorable biocompatibility of silicon, which is an important precondition for biological and biomedical applications. In addition, huge surface-to-volume ratios of silicon nanomaterials are responsible for their unique optical, mechanical, or electronic properties, which offer exciting opportunities for design of high-performance silicon-based functional nanoprobes, nanosensors, and nanoagents for biological analysis and detection and disease treatment. Moreover, silicon is the second most abundant element (after oxygen) on earth, providing plentiful and inexpensive resources for large-scale and low-cost preparation of silicon nanomaterials for practical applications. Because of these attractive traits, and in parallel with a growing interest in their design and synthesis, silicon nanomaterials are extensively investigated for wide-ranging applications, including energy, catalysis, optoelectronics, and biology. Among them, bioapplications of silicon nanomaterials are of particular interest. In the past decade, scientists have made an extensive effort to construct a silicon nanomaterials platform for various biological and biomedical applications, such as biosensors, bioimaging, and cancer treatment, as new and powerful tools for disease diagnosis and therapy. Nonetheless, there are few review articles covering these important and promising achievements to promote the awareness of development of silicon nanobiotechnology. In this Account, we summarize recent representative works to highlight the recent developments of silicon functional nanomaterials for a new, powerful platform for biological and

  4. 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.

  5. Topical therapies in the management of chronic rhinosinusitis: an evidence-based review with recommendations.

    Science.gov (United States)

    Rudmik, Luke; Hoy, Monica; Schlosser, Rodney J; Harvey, Richard J; Welch, Kevin C; Lund, Valerie; Smith, Timothy L

    2013-04-01

    Topical therapies have become an integral component in the management plan for chronic rhinosinusitis (CRS). Several topical therapy strategies have been evaluated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the utilization of topical therapies in the management of CRS. A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria were: adult population >18 years old; chronic rhinosinusitis (CRS) based on published diagnostic criteria; and clearly defined primary clinical end-point. We focused on reporting higher-quality studies (level 2b or higher), but reported on lower-level studies if the topic contained insufficient evidence. We excluded drug-eluting spacer and stent therapy from this review. This review identified and evaluated the literature on 5 topical therapy strategies for CRS: saline irrigation, topical steroid, topical antibiotic, topical antifungal, and topical alternatives (surfactant, manuka honey, and xylitol irrigations). Based on the available evidence, sinonasal saline irrigation and standard topical nasal steroid therapy are recommended in the topical treatment of CRS. Nonstandard (off-label) topical sinonasal steroid therapies can be an option for managing CRS. The evidence recommends against the use of topical antifungal therapy and topical antibiotic therapy delivered using nebulized and spray techniques in routine cases of CRS. There is insufficient clinical research to provide recommendations for alternative therapies or topical antibiotic therapy delivered using other delivery methods (eg, irrigations). © 2013 ARS-AAOA, LLC.

  6. Celiac Disease and Drug-Based Therapies: Inquiry into Patients Demands.

    Science.gov (United States)

    Branchi, Federica; Tomba, Carolina; Ferretti, Francesca; Norsa, Lorenzo; Roncoroni, Leda; Bardella, Maria Teresa; Conte, Dario; Elli, Luca

    2016-01-01

    Medical research is looking for alternative drug-based options to the gluten-free diet (GFD) for celiac disease. We aimed at evaluating the need for alternative therapies perceived by celiac patients. During the 2013 meeting of the Lombardy section of the Italian Celiac Patients Association, adult subjects were invited to fill in a questionnaire investigating their clinical profile in relation to compliance to the diet, quality of life (QOL) as well as their opinion on alternative therapies. Three hundred and seventy two patients (76 m, mean age 41.7 ± 13.9 years) completed the questionnaire. Patients reported a significant improvement in health status (HS) and QOL after the diet was started (p < 0.001). The GFD was accepted by 88% patients, but the need for alternative therapies was reported by 65%. Subjects expressing the need for a drug-based therapy showed a lower increase in QOL (p = 0.003) and HS (p = 0.005) on GFD. The preferred option for an alternative therapy was the use of enzymes (145 subjects), followed by a vaccine (111 subjects). The GFD is favorably accepted by most celiac patients. Nevertheless, a proportion of patients pronounce themselves in favor of the development of alternative drugs. © 2016 S. Karger AG, Basel.

  7. Temoporfin-loaded 1-tetradecanol-based thermoresponsive solid lipid nanoparticles for photodynamic therapy

    Czech Academy of Sciences Publication Activity Database

    Brezaniova, I.; Hrubý, Martin; Králová, Jarmila; Král, V.; Černochová, Zulfiya; Černoch, Peter; Šlouf, Miroslav; Kredatusová, Jana; Štěpánek, Petr

    2016-01-01

    Roč. 241, 10 November (2016), s. 34-44 ISSN 0168-3659 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109; GA TA ČR(CZ) TE01020118; GA MŠk(CZ) LO1507; GA MŠk(CZ) 7F14009 Institutional support: RVO:61389013 ; RVO:68378050 Keywords : photodynamic therapy * nanomedicine * drug delivery Subject RIV: CD - Macromolecular Chemistry; EB - Genetics ; Molecular Biology (UMG-J) Impact factor: 7.786, year: 2016

  8. Effectiveness of Mindfulness-based Therapy for Reducing Anxiety and Depression in Patients With Cancer

    Science.gov (United States)

    Zhang, Mei-Fen; Wen, Yong-Shan; Liu, Wei-Yan; Peng, Li-Fen; Wu, Xiao-Dan; Liu, Qian-Wen

    2015-01-01

    Abstract Anxiety and depression are common among patients with cancer, and are often treated with psychological interventions including mindfulness-based therapy. The aim of the study was to perform a meta-analysis of the effectiveness of mindfulness-based interventions for improving anxiety and depression in patients with cancer. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched. The randomized controlled trials designed for patients diagnosed with cancer were included. Mindfulness-based interventions were provided. The outcomes assessed were the changes in anxiety and depression scores from before to after the intervention. The treatment response was determined by calculating the standardized mean difference (SMD) for individual studies and for pooled study results. Subgroup analyses by cancer type, type of therapy, and length of follow-up were performed. Seven studies, involving 469 participants who received mindfulness-based interventions and 419 participants in a control group, were included in the meta-analysis. Mindfulness-based stress reduction and art therapy were the most common interventions (5/7 studies). All studies reported anxiety and depression scores. The pooled SMD of the change in anxiety significantly favored mindfulness-based therapy over control treatment (−0.75, 95% confidence interval −1.28, −0.22, P = 0.005). Likewise, the pooled SMD of the change in depression also significantly favored mindfulness-based therapy over control (−0.90, 95% confidence interval −1.53, −0.26, P = 0.006). During the length of follow-ups less than 12 weeks, mindfulness-based therapy significantly improved anxiety for follow-up ≤12 weeks after the start of therapy, but not >12 weeks after the start of therapy. There was a lack of consistency between the studies in the type of mindfulness-based/control intervention implemented. Patients had different forms of cancer. Subgroup analyses included a relatively small number of

  9. Reporter gene imaging: potential impact on therapy

    International Nuclear Information System (INIS)

    Serganova, Inna; Blasberg, Ronald

    2005-01-01

    Positron emission tomography (PET)-based molecular-genetic imaging in living organisms has enjoyed exceptional growth over the past 5 years; this is particularly striking since it has been identified as a new discipline only within the past decade. Positron emission tomography is one of three imaging technologies (nuclear, magnetic resonance and optical) that has begun to incorporate methods that are established in molecular and cell biology research. The convergence of these disciplines and the wider application of multi-modality imaging are at the heart of this success story. Most current molecular-genetic imaging strategies are 'indirect,' coupling a 'reporter gene' with a complimentary 'reporter probe.' Reporter gene constructs can be driven by constitutive promoter elements and used to monitor gene therapy vectors and the efficacy of trans gene targeting and transduction, as well as to monitor adoptive cell-based therapies. Inducible promoters can be used as 'sensors' to regulate the magnitude of reporter gene expression and can be used to provide information about endogenous cell processes. Reporter systems can also be constructed to monitor mRNA stabilization and specific protein-protein interactions. Promoters can be cell specific and restrict transgene expression to certain tissue and organs. The translation of reporter gene imaging to specific clinical applications is discussed. Several examples that have potential for patient imaging studies in the near future include monitoring adenoviral-based gene therapy, oncolytic herpes virus therapy, adoptive cell-based therapies and Salmonella-based tumor-targeted cancer therapy and imaging. The primary translational applications of noninvasive in vivo reporter gene imaging are likely to be (a) quantitative monitoring of the gene therapy vector and the efficacy of transduction in clinical protocols, by imaging the location, extent and duration of transgene expression; (b) monitoring cell trafficking, targeting

  10. Using gEUD based plan analysis method to evaluate proton vs. photon plans for lung cancer radiation therapy.

    Science.gov (United States)

    Xiao, Zhiyan; Zou, Wei J; Chen, Ting; Yue, Ning J; Jabbour, Salma K; Parikh, Rahul; Zhang, Miao

    2018-03-01

    The goal of this study was to exam the efficacy of current DVH based clinical guidelines draw from photon experience for lung cancer radiation therapy on proton therapy. Comparison proton plans and IMRT plans were generated for 10 lung patients treated in our proton facility. A gEUD based plan evaluation method was developed for plan evaluation. This evaluation method used normal lung gEUD(a) curve in which the model parameter "a" was sampled from the literature reported value. For all patients, the proton plans delivered lower normal lung V 5 Gy with similar V 20 Gy and similar target coverage. Based on current clinical guidelines, proton plans were ranked superior to IMRT plans for all 10 patients. However, the proton and IMRT normal lung gEUD(a) curves crossed for 8 patients within the tested range of "a", which means there was a possibility that proton plan would be worse than IMRT plan for lung sparing. A concept of deficiency index (DI) was introduced to quantify the probability of proton plans doing worse than IMRT plans. By applying threshold on DI, four patients' proton plan was ranked inferior to the IMRT plan. Meanwhile if a threshold to the location of curve crossing was applied, 6 patients' proton plan was ranked inferior to the IMRT plan. The contradictory ranking results between the current clinical guidelines and the gEUD(a) curve analysis demonstrated there is potential pitfalls by applying photon experience directly to the proton world. A comprehensive plan evaluation based on radio-biological models should be carried out to decide if a lung patient would really be benefit from proton therapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  11. Inflammatory bowel disease: adherence to immunomodulators in a biological therapy era.

    Science.gov (United States)

    Campos, Sara; Portela, Francisco; Sousa, Paula; Sofia, Carlos

    2016-11-01

    Combination therapy, with anti-tumor necrosis factor-α agents and immunomodulators, is the most effective option to induce and maintain remission in inflammatory bowel disease (IBD). Infliximab, with its administration features, determines particular conditions of adherence; the same is not possible with thiopurines. Nevertheless, research on adherence to these treatments is scarce. Nonadherence worsens the prognosis of IBD. (a) Assess adherence to immunomodulators and (b) determine therapeutic nonadherence predictors. We included all IBD outpatients consecutively evaluated over a 6-month period in our center. Participants completed a study-specific questionnaire on IBD, IBD therapeutic adherence (Morisky Medication Adherence Scale-8-item), Therapeutics Complexity questionnaire, Beliefs about Medication questionnaire, and Hospital Anxiety and Depression Scale. A total of 112 patients under azathioprine were considered; 49.1% were also under anti-tumor necrosis factor-α. Self-assessed questionnaire showed that 70.5% were adherent to immunosuppression. Similar adherence was found with and without infliximab (68.4%-monotherapy vs. 72.7%-combination therapy; P=0.61). Nonintentional nonadherence was documented in 57.6%; 42.4% reported voluntary nonadherence. Nonadherence was higher in male patients [odds ratio (OR): 3.79; 95% confidence interval (CI): 1.2-11.95; P=0.023], younger patients (OR: 0.93; 95% CI: 0.87-0.98; P=0.01), nonsmokers (OR: 4.90; 95% CI: 1.22-19.73; P=0.025), and those who had depression (OR: 2.22; 95% CI: 1.36-3.62; P=0.001). Most of the IBD patients believed in the necessity of maintaining immunosuppression (86.7%), but 36.6% reported concerns about drugs. Nonadherence to thiopurines plays a significant role in IBD. Nonetheless, it does not increase with association with biological agents. Involuntary nonadherence is higher. Male sex, younger age, nonsmoker, and presence of depression were independent predictors of nonadherence to immunomodulators

  12. The interplay of post-translational modification and gene therapy

    Directory of Open Access Journals (Sweden)

    Osamor VC

    2016-02-01

    Full Text Available Victor Chukwudi Osamor,1–3 Shalom N Chinedu,3,4 Dominic E Azuh,3,5 Emeka Joshua Iweala,3,4 Olubanke Olujoke Ogunlana3,4 1Covenant University Bioinformatics Research (CUBRe Unit, Department of Computer and Information Sciences, College of Science and Technology (CST, Covenant University, Ota, Ogun State, Nigeria; 2Institute of Informatics (Computational biology and Bioinformatics, Faculty of Mathematics, Informatics and Mechanics, University of Warsaw (Uniwersytet Warszawski, Warszawa, Poland; 3Covenant University Public Health and Well-being Research Group (CUPHWERG, Covenant University, 4Biochemistry and Molecular Biology Unit, Department of Biological Sciences, College of Science and Technology, Covenant University, Canaan Land, 5Department of Economics and Development Studies, Covenant University, Ota, Ogun State, Nigeria Abstract: Several proteins interact either to activate or repress the expression of other genes during transcription. Based on the impact of these activities, the proteins can be classified into readers, modifier writers, and modifier erasers depending on whether histone marks are read, added, or removed, respectively, from a specific amino acid. Transcription is controlled by dynamic epigenetic marks with serious health implications in certain complex diseases, whose understanding may be useful in gene therapy. This work highlights traditional and current advances in post-translational modifications with relevance to gene therapy delivery. We report that enhanced understanding of epigenetic machinery provides clues to functional implication of certain genes/gene products and may facilitate transition toward revision of our clinical treatment procedure with effective fortification of gene therapy delivery. Keywords: post-translational modification, gene therapy, epigenetics, histone, methylation

  13. Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eley, John G., E-mail: jeley@som.umaryland.edu [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, Maryland (United States); Friedrich, Thomas [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Homann, Kenneth L.; Howell, Rebecca M. [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); University of Texas Graduate School of Biomedical Sciences, Houston, Texas (United States); Scholz, Michael; Durante, Marco [GSI Helmholtzzentrum für Schwerionenforschung GmbH, Darmstadt (Germany); Newhauser, Wayne D. [Department of Physics and Astronomy, Louisiana State University and Agricultural and Mechanical College, Baton Rouge, Louisiana (United States); Mary Bird Perkins Cancer Center, Baton Rouge, Louisiana (United States)

    2016-05-01

    Purpose: This work proposes a theoretical framework that enables comparative risk predictions for second cancer incidence after particle beam therapy for different ion species for individual patients, accounting for differences in relative biological effectiveness (RBE) for the competing processes of tumor initiation and cell inactivation. Our working hypothesis was that use of carbon-ion therapy instead of proton therapy would show a difference in the predicted risk of second cancer incidence in the breast for a sample of Hodgkin lymphoma (HL) patients. Methods and Materials: We generated biologic treatment plans and calculated relative predicted risks of second cancer in the breast by using two proposed methods: a full model derived from the linear quadratic model and a simpler linear-no-threshold model. Results: For our reference calculation, we found the predicted risk of breast cancer incidence for carbon-ion plans-to-proton plan ratio, , to be 0.75 ± 0.07 but not significantly smaller than 1 (P=.180). Conclusions: Our findings suggest that second cancer risks are, on average, comparable between proton therapy and carbon-ion therapy.

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

    International Nuclear Information System (INIS)

    Raben, David; Helfrich, Barb; Bunn, Paul A.

    2004-01-01

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

  15. Biologic and Conventional Systemic Therapies Show Similar Safety and Efficacy in Elderly and Adult Patients With Moderate to Severe Psoriasis.

    Science.gov (United States)

    Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice

    2015-08-01

    Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly

  16. Acceptance-based behavior therapy to promote HIV medication adherence.

    Science.gov (United States)

    Moitra, Ethan; Herbert, James D; Forman, Evan M

    2011-12-01

    A significant number of adults with HIV in the USA do not maintain adherence to highly active antiretroviral therapy (HAART) at adequate levels. Although traditional cognitive behavioral interventions have shown promise in promoting HAART adherence, acceptance-based behavior therapy (ABBT) may be particularly useful in this population. ABBT has the potential to overcome common avoidance-based barriers associated with poor adherence, including denial of various illness-related factors and avoidance of stigmatization. We describe the rationale for promoting psychological and behavioral acceptance in HIV-positive populations; outline an ABBT to promote HAART adherence targeting primary care patients from urban, minority, low socioeconomic backgrounds; and report preliminary qualitative observations of treatment feasibility and acceptability.

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

    OpenAIRE

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

    2012-01-01

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

  18. Problem-based learning through field investigation: Boosting questioning skill, biological literacy, and academic achievement

    Science.gov (United States)

    Suwono, Hadi; Wibowo, Agung

    2018-01-01

    Biology learning emphasizes problem-based learning as a learning strategy to develop students ability in identifying and solving problems in the surrounding environment. Problem identification skills are closely correlated with questioning skills. By holding this skill, students tend to deliver a procedural question instead of the descriptive one. Problem-based learning through field investigation is an instruction model which directly exposes the students to problems or phenomena that occur in the environment, and then the students design the field investigation activities to solve these problems. The purpose of this research was to describe the improvement of undergraduate biology students on questioning skills, biological literacy, and academic achievement through problem-based learning through field investigation (PBFI) compared with the lecture-based instruction (LBI). This research was a time series quasi-experimental design. The research was conducted on August - December 2015 and involved 26 undergraduate biology students at the State University of Malang on the Freshwater Ecology course. The data were collected during the learning with LBI and PBFI, in which questioning skills, biological literacy, and academic achievement were collected 3 times in each learning model. The data showed that the procedural correlative and causal types of questions are produced by the students to guide them in conducting investigations and problem-solving in PBFI. The biological literacy and academic achievement of the students at PBFI are significantly higher than those at LBI. The results show that PBFI increases the questioning skill, biological literacy, and the academic achievement of undergraduate biology students.

  19. [Achievements and enlightenment of modern acupuncture therapy for stroke based on the neuroanatomy].

    Science.gov (United States)

    Chen, Li-Fang; Fang, Jian-Qiao; Chen, Lu-Ni; Wang, Chao

    2014-04-01

    Up to now, in the treatment of stroke patients by acupuncture therapy, three main representative achievements involving scalp acupuncture intervention, "Xing Nao Kai Qiao" (restoring consciousness and inducing resuscitation) acupuncture technique and nape acupuncture therapy have been got. Regarding their neurobiological mechanisms, the scalp acupuncture therapy is based on the functional localization of the cerebral cortex, "Xing Nao Kai Qiao" acupuncture therapy is closely related to nerve stem stimulation, and the nape acupuncture therapy is based on the nerve innervation of the regional neck-nape area in obtaining therapeutic effects. In fact, effects of these three acupuncture interventions are all closely associated with the modern neuroanatomy. In the treatment of post-stroke spastic paralysis, cognitive disorder and depression with acupuncture therapy, modern neuroanatomical knowledge should be one of the key theoretical basis and new therapeutic techniques should be explored and developed continuously.

  20. Theory-based training strategies for modifying practitioner concerns about exposure therapy.

    Science.gov (United States)

    Farrell, Nicholas R; Deacon, Brett J; Dixon, Laura J; Lickel, James J

    2013-12-01

    Despite the well-established efficacy of exposure therapy in the treatment of pathological anxiety, many therapists believe this treatment carries an unacceptably high risk for harm, is intolerable for patients, and poses a number of ethical quandaries. These beliefs have been shown to account for two related problems: (a) underutilization of exposure therapy, and (b) overly cautious and suboptimal delivery the treatment, which likely attenuates treatment outcomes. At present, there is little guidance for those who train exposure therapists to address these concerns. This article reviews therapist negative beliefs about exposure therapy and discusses their modification based on findings from social and cognitive psychology pertinent to belief change, including dual-processing in reasoning, the need for cognition and affect, and attitude inoculation. A number of strategies are offered for augmenting training in exposure therapy in order to promote positive beliefs about the treatment. These strategies involve: (a) therapists engaging in simulated exposure therapy exercises and presenting arguments in defense of exposure's safety, tolerability, and ethicality, and (b) training therapists using emotion-based appeals (e.g., case examples) to supplement research findings. Directions for future research on practitioner concerns about exposure therapy are discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Alteration of serum thymus and activation-regulated chemokine level during biologic therapy for psoriasis: Possibility as a marker reflecting favorable response to anti-interleukin-17A agents.

    Science.gov (United States)

    Shibuya, Takashi; Honma, Masaru; Iinuma, Shin; Iwasaki, Takeshi; Takahashi, Hidetoshi; Ishida-Yamamoto, Akemi

    2018-06-01

    Biologics show great efficacy in treating psoriasis, a chronic inflammatory skin disease. The high cost and side-effects of biologics, dose-reduction, elongation of administration interval and suspension are possible options. However, there has been no reliable biomarker we can use when we consider these moderations in therapy. This study was conducted to test the possibility of using serum thymus and activation-regulated chemokine (TARC) level as an indicator for step down of biologic therapy. Serum TARC level was measured in 70 psoriatic patients at Asahikawa Medical University, and a correlation of TARC and severity of skin lesions was analyzed. Referring to serum TARC level, psoriatic patients can be divided into two groups. One is a population in which serum TARC level is positively correlated with severity of skin lesions, and the other is a population with low psoriatic severity and high TARC level. Serum TARC level was higher in the group that achieved PASI-clear with biologics than in the group which did not achieve PASI-clear. Among biologics, the group treated with secukinumab, an anti-interleukin (IL)-17A agent, showed significantly higher TARC level compared with the group treated with anti-tumor necrosis factor agents. In certain populations achieving PASI-clear, serum TARC level may be a potent marker reflecting better response to IL-17A inhibitors, and in this case step down of treatment for psoriasis is possible. © 2018 Japanese Dermatological Association.

  2. 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

  3. Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.

    Science.gov (United States)

    Zhang, Rui Xue; Wong, Ho Lun; Xue, Hui Yi; Eoh, June Young; Wu, Xiao Yu

    2016-10-28

    Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Oligonucleotide-based theranostic nanoparticles in cancer therapy

    Science.gov (United States)

    Shahbazi, Reza; Ozpolat, Bulent; Ulubayram, Kezban

    2016-01-01

    Theranostic approaches, combining the functionality of both therapy and imaging, have shown potential in cancer nanomedicine. Oligonucleotides such as small interfering RNA and microRNA, which are powerful therapeutic agents, have been effectively employed in theranostic systems against various cancers. Nanoparticles are used to deliver oligonucleotides into tumors by passive or active targeting while protecting the oligonucleotides from nucleases in the extracellular environment. The use of quantum dots, iron oxide nanoparticles and gold nanoparticles and tagging with contrast agents, like fluorescent dyes, optical or magnetic agents and various radioisotopes, has facilitated early detection of tumors and evaluation of therapeutic efficacy. In this article, we review the advantages of theranostic applications in cancer therapy and imaging, with special attention to oligonucleotide-based therapeutics. PMID:27102380

  5. Mindfulness-based cognitive therapy for seasonal affective disorder : A pilot study

    NARCIS (Netherlands)

    Fleer, Joke; Schroevers, Maya; Panjer, Vera; Geerts, Erwin; Meesters, Ybe

    2014-01-01

    Background: The best available treatment for seasonal affective disorder (SAD) is light therapy. Yet, this treatment does not prevent recurrence of depression in subsequent seasons. The aim of the study is to gain preliminary insight in the efficacy of Mindfulness Based Cognitive Therapy (MBCT) in

  6. H1N1 vaccines in a large observational cohort of patients with inflammatory bowel disease treated with immunomodulators and biological therapy.

    Science.gov (United States)

    Rahier, Jean-François; Papay, Pavol; Salleron, Julia; Sebastian, Shaji; Marzo, Manuela; Peyrin-Biroulet, Laurent; Garcia-Sanchez, Valle; Fries, Walter; van Asseldonk, Dirk P; Farkas, Klaudia; de Boer, Nanne K; Sipponen, Taina; Ellul, Pierre; Louis, Edouard; Peake, Simon T C; Kopylov, Uri; Maul, Jochen; Makhoul, Badira; Fiorino, Gionata; Yazdanpanah, Yazdan; Chaparro, Maria

    2011-04-01

    Safety data are lacking on influenza vaccination in general and on A (H1N1)v vaccination in particular in patients with inflammatory bowel disease (IBD) receiving immmunomodulators and/or biological therapy. The authors conducted a multicentre observational cohort study to evaluate symptoms associated with influenza H1N1 adjuvanted (Pandemrix, Focetria, FluvalP) and non-adjuvanted (Celvapan) vaccines and to assess the risk of flare of IBD after vaccination. Patients with stable IBD treated with immunomodulators and/or biological therapy were recruited from November 2009 until March 2010 in 12 European countries. Harvey-Bradshaw Index and Partial Mayo Score were used to assess disease activity before and 4 weeks after vaccination in Crohn's disease (CD) and ulcerative colitis (UC). Vaccination-related events up to 7 days after vaccination were recorded. Of 575 patients enrolled (407 CD, 159 UC and nine indeterminate colitis; 53.9% female; mean age 40.3 years, SD 13.9), local and systemic symptoms were reported by 34.6% and 15.5% of patients, respectively. The most common local and systemic reactions were pain in 32.8% and fatigue in 6.1% of subjects. Local symptoms were more common with adjuvanted (39.3%) than non-adjuvanted (3.9%) vaccines (p < 0.0001), whereas rates of systemic symptoms were similar with both types (15.0% vs 18.4%, p = 0.44). Among the adjuvanted group, Pandemrix more often induced local reactions than FluvalP and Focetria (51.2% vs 27.6% and 15.4%, p < 0.0001). Solicited adverse events were not associated with any patient characteristics, specific immunomodulatory treatment, or biological therapy. Four weeks after vaccination, absence of flare was observed in 377 patients with CD (96.7%) and 151 with UC (95.6%). Influenza A (H1N1)v vaccines are well tolerated in patients with IBD. Non-adjuvanted vaccines are associated with fewer local reactions. The risk of IBD flare is probably not increased after H1N1 vaccination.

  7. Methadone maintenance therapy as evidence based drug abuse ...

    African Journals Online (AJOL)

    Methadone maintenance therapy as evidence based drug abuse planning in ... drugs are being used as artificial problem-solvers such as frustrations, stress or ... Drug use is a problem to users when it begins to cause some damage to their ...

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

    International Nuclear Information System (INIS)

    Salas Mena, Claudio

    2014-01-01

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

  9. Biological interaction of living cells with COSAN-based synthetic vesicles.

    Science.gov (United States)

    Tarrés, Màrius; Canetta, Elisabetta; Paul, Eleanor; Forbes, Jordan; Azzouni, Karima; Viñas, Clara; Teixidor, Francesc; Harwood, Adrian J

    2015-01-15

    Cobaltabisdicarbollide (COSAN) [3,3'-Co(1,2-C2B9H11)2](-), is a complex boron-based anion that has the unusual property of self-assembly into membranes and vesicles. These membranes have similar dimensions to biological membranes found in cells, and previously COSAN has been shown to pass through synthetic lipid membranes and those of living cells without causing breakdown of membrane barrier properties. Here, we investigate the interaction of this inorganic membrane system with living cells. We show that COSAN has no immediate effect on cell viability, and cells fully recover when COSAN is removed following exposure for hours to days. COSAN elicits a range of cell biological effects, including altered cell morphology, inhibition of cell growth and, in some cases, apoptosis. These observations reveal a new biology at the interface between inorganic, synthetic COSAN membranes and naturally occurring biological membranes.

  10. Integrative radiation systems biology

    International Nuclear Information System (INIS)

    Unger, Kristian

    2014-01-01

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

  11. Art Therapy. Prevention Against the Development of Depression

    DEFF Research Database (Denmark)

    Skov, Vibeke

    2013-01-01

    as a mixed-methods design, with the quantitative part imbedded in the qualitative part. Seven participants were chosen to participate in an art therapy group during a 6-month intervention with a total of 13 meetings. The inclusion criteria were identification of mild to moderate depression based on the test......The aim in this research study was to focus on art therapy as a method to explore the inner life as prevention against the development of depression and to address the possibility for art therapy to be used as an early intervention tool related to depression. A Jungian epistemology was used...... as a frame for the overall understanding of well-being together with a holistic approach, including the biological, psychological, social and spiritual domains in life. Art therapy processes in the clinical part of the study aimed to include all these levels as the activation of these are considered...

  12. Physical Therapy in the Treatment of Central Pain Mechanisms for Female Sexual Pain.

    Science.gov (United States)

    Vandyken, Carolyn; Hilton, Sandra

    2017-01-01

    The complexity of female sexual pain requires an interdisciplinary approach. Physical therapists trained in pelvic health conditions are well positioned to be active members of an interdisciplinary team addressing the assessment and treatment of female sexual pain. Changes within physical therapy practice in the last ten years have resulted in significant utilization of pelvic floor muscle relaxation and manual therapy techniques to address a variety of pelvic pain conditions, including female sexual pain. However, sexual pain is a complex issue giving credence to the necessity of addressing all of the drivers of the pain experience- biological, psychological and social. This review aims to reconcile current pain science with a plan for integrating a biopsychosocial approach into the evaluation and subsequent treatment for female sexual pain for physical therapists. A literature review of the important components of skilled physical therapy interventions is presented including the physical examination, pain biology education, cognitive behavioral influences in treatment design, motivational interviewing as an adjunct to empathetic practice, and the integration of non-threatening movement and mindfulness into treatment. A single case study is used to demonstrate the biopsychosocial framework utilized in this approach. Appropriate measures for assessing psychosocial factors are readily available and inform a reasoned approach for physical therapy design that addresses both peripheral and central pain mechanisms. Decades of research support the integration of a biopsychosocial approach in the treatment of complex pain, including female sexual pain. It is reasonable for physical therapists to utilize evidence based strategies such as CBT, pain biology education, Mindfulness Based Stress Reduction (MBSR), yoga and imagery based exercises to address the biopsychosocial components of female sexual pain. Copyright © 2016 International Society for Sexual Medicine

  13. Development of a Whole Body Atlas for Radiation Therapy Planning and Treatment Optimization

    International Nuclear Information System (INIS)

    Qatarneh, Sharif

    2006-01-01

    The main objective of radiation therapy is to obtain the highest possible probability of tumor cure while minimizing adverse reactions in healthy tissues. A crucial step in the treatment process is to determine the location and extent of the primary tumor and its loco regional lymphatic spread in relation to adjacent radiosensitive anatomical structures and organs at risk. These volumes must also be accurately delineated with respect to external anatomic reference points, preferably on surrounding bony structures. At the same time, it is essential to have the best possible physical and radiobiological knowledge about the radiation responsiveness of the target tissues and organs at risk in order to achieve a more accurate optimization of the treatment outcome. A computerized whole body Atlas has therefore been developed to serve as a dynamic database, with systematically integrated knowledge, comprising all necessary physical and radiobiological information about common target volumes and normal tissues. The Atlas also contains a database of segmented organs and a lymph node topography, which was based on the Visible Human dataset, to form standard reference geometry of organ systems. The reference knowledge base and the standard organ dataset can be utilized for Atlas-based image processing and analysis in radiation therapy planning and for biological optimization of the treatment outcome. Atlas-based segmentation procedures were utilized to transform the reference organ dataset of the Atlas into the geometry of individual patients. The anatomic organs and target volumes of the database can be converted by elastic transformation into those of the individual patient for final treatment planning. Furthermore, a database of reference treatment plans was started by implementing state-of-the-art biologically based radiation therapy planning techniques such as conformal, intensity modulated, and radio biologically optimized treatment planning. The computerized Atlas can

  14. Radiation oncology - Linking technology and biology in the treatment of cancer

    International Nuclear Information System (INIS)

    Coleman, C. Norman

    2002-01-01

    Technical advances in radiation oncology including CT-simulation, 3D-conformal and intensity-modulated radiation therapy (IMRT) delivery techniques, and brachytherapy have allowed greater treatment precision and dose escalation. The ability to intensify treatment requires the identification of the critical targets within the treatment field, recognizing the unique biology of tumor, stroma and normal tissue. Precision is technology based while accuracy is biologically based. Therefore, the intensity of IMRT will undoubtedly mean an increase in both irradiation dose and the use of biological agents, the latter considered in the broadest sense. Radiation oncology has the potential and the opportunity to provide major contributions to the linkage between molecular and functional imaging, molecular profiling and novel therapeutics for the emerging molecular targets for cancer treatment. This process of 'credentialing' of molecular targets will require multi disciplinary imaging teams, clinicians and basic scientists. Future advances will depend on the appropriate integration of biology into the training of residents, continuing post graduate education, participation in innovative clinical research and commitment to the support of basic research as an essential component of the practice of radiation oncology

  15. 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.

  16. Neutron therapy coupling brachytherapy and boron neutron capture therapy (BNCT) techniques

    International Nuclear Information System (INIS)

    Chaves, Iara Ferreira.

    1994-12-01

    In the present dissertation, neutron radiation techniques applied into organs of the human body are investigated as oncologic radiation therapy. The proposal treatment consists on connecting two distinct techniques: Boron Neutron Capture Therapy (BNCT) and irradiation by discrete sources of neutrons, through the brachytherapy conception. Biological and radio-dosimetrical aspects of the two techniques are considered. Nuclear aspects are discussed, presenting the nuclear reactions occurred in tumoral region, and describing the forms of evaluating the dose curves. Methods for estimating radiation transmission are reviewed through the solution of the neutron transport equation, Monte Carlo methodology, and simplified analytical calculation based on diffusion equation and numerical integration. The last is computational developed and presented as a quickly way to neutron transport evaluation in homogeneous medium. The computational evaluation of the doses for distinct hypothetical situations is presented, applying the coupled techniques BNTC and brachytherapy as an possible oncologic treatment. (author). 78 refs., 61 figs., 21 tabs

  17. Outcomes of couples with infidelity in a community-based sample of couple therapy.

    Science.gov (United States)

    Atkins, David C; Marín, Rebeca A; Lo, Tracy T Y; Klann, Notker; Hahlweg, Kurt

    2010-04-01

    Infidelity is an often cited problem for couples seeking therapy, but the research literature to date is very limited on couple therapy outcomes when infidelity is a problem. The current study is a secondary analysis of a community-based sample of couple therapy in Germany and Austria. Outcomes for 145 couples who reported infidelity as a problem in their relationship were compared with 385 couples who sought therapy for other reasons. Analyses based on hierarchical linear modeling revealed that infidelity couples were significantly more distressed and reported more depressive symptoms at the start of therapy but continued improving through the end of therapy and to 6 months posttherapy. At the follow-up assessment, infidelity couples were not statistically distinguishable from non-infidelity couples, replicating previous research. Sexual dissatisfaction did not depend on infidelity status. Although there was substantial missing data, sensitivity analyses suggested that the primary findings were not due to missing data. The current findings based on a large community sample replicated previous work from an efficacy trial and show generally optimistic results for couples in which there has been an affair. 2010 APA, all rights reserved

  18. Enabling individualized therapy through nanotechnology

    Science.gov (United States)

    Sakamoto, Jason H.; van de Ven, Anne L.; Godin, Biana; Blanco, Elvin; Serda, Rita E.; Grattoni, Alessandro; Ziemys, Arturas; Bouamrani, Ali; Hu, Tony; Ranganathan, Shivakumar I.; De Rosa, Enrica; Martinez, Jonathan O.; Smid, Christine A.; Buchanan, Rachel M.; Lee, Sei-Young; Srinivasan, Srimeenakshi; Landry, Matthew; Meyn, Anne; Tasciotti, Ennio; Liu, Xuewu; Decuzzi, Paolo; Ferrari, Mauro

    2010-01-01

    Individualized medicine is the healthcare strategy that rebukes the idiomatic dogma of ‘losing sight of the forest for the trees’. We are entering a new era of healthcare where it is no longer acceptable to develop and market a drug that is effective for only 80% of the patient population. The emergence of “-omic” technologies (e.g. genomics, transcriptomics, proteomics, metabolomics) and advances in systems biology are magnifying the deficiencies of standardized therapy, which often provide little treatment latitude for accommodating patient physiologic idiosyncrasies. A personalized approach to medicine is not a novel concept. Ever since the scientific community began unraveling the mysteries of the genome, the promise of discarding generic treatment regimens in favor of patient-specific therapies became more feasible and realistic. One of the major scientific impediments of this movement towards personalized medicine has been the need for technological enablement. Nanotechnology is projected to play a critical role in patient-specific therapy; however, this transition will depend heavily upon the evolutionary development of a systems biology approach to clinical medicine based upon “-omic” technology analysis and integration. This manuscript provides a forward looking assessment of the promise of nanomedicine as it pertains to individualized medicine and establishes a technology “snapshot” of the current state of nano-based products over a vast array of clinical indications and range of patient specificity. Other issues such as market driven hurdles and regulatory compliance reform are anticipated to “self-correct” in accordance to scientific advancement and healthcare demand. These peripheral, non-scientific concerns are not addressed at length in this manuscript; however they do exist, and their impact to the paradigm shifting healthcare transformation towards individualized medicine will be critical for its success. PMID:20045055

  19. Enabling individualized therapy through nanotechnology.

    Science.gov (United States)

    Sakamoto, Jason H; van de Ven, Anne L; Godin, Biana; Blanco, Elvin; Serda, Rita E; Grattoni, Alessandro; Ziemys, Arturas; Bouamrani, Ali; Hu, Tony; Ranganathan, Shivakumar I; De Rosa, Enrica; Martinez, Jonathan O; Smid, Christine A; Buchanan, Rachel M; Lee, Sei-Young; Srinivasan, Srimeenakshi; Landry, Matthew; Meyn, Anne; Tasciotti, Ennio; Liu, Xuewu; Decuzzi, Paolo; Ferrari, Mauro

    2010-08-01

    Individualized medicine is the healthcare strategy that rebukes the idiomatic dogma of 'losing sight of the forest for the trees'. We are entering a new era of healthcare where it is no longer acceptable to develop and market a drug that is effective for only 80% of the patient population. The emergence of "-omic" technologies (e.g. genomics, transcriptomics, proteomics, metabolomics) and advances in systems biology are magnifying the deficiencies of standardized therapy, which often provide little treatment latitude for accommodating patient physiologic idiosyncrasies. A personalized approach to medicine is not a novel concept. Ever since the scientific community began unraveling the mysteries of the genome, the promise of discarding generic treatment regimens in favor of patient-specific therapies became more feasible and realistic. One of the major scientific impediments of this movement towards personalized medicine has been the need for technological enablement. Nanotechnology is projected to play a critical role in patient-specific therapy; however, this transition will depend heavily upon the evolutionary development of a systems biology approach to clinical medicine based upon "-omic" technology analysis and integration. This manuscript provides a forward looking assessment of the promise of nanomedicine as it pertains to individualized medicine and establishes a technology "snapshot" of the current state of nano-based products over a vast array of clinical indications and range of patient specificity. Other issues such as market driven hurdles and regulatory compliance reform are anticipated to "self-correct" in accordance to scientific advancement and healthcare demand. These peripheral, non-scientific concerns are not addressed at length in this manuscript; however they do exist, and their impact to the paradigm shifting healthcare transformation towards individualized medicine will be critical for its success. Copyright 2010 Elsevier Ltd. All rights

  20. Biological characteristics of human-urine-derived stem cells: potential for cell-based therapy in neurology.

    Science.gov (United States)

    Guan, Jun-Jie; Niu, Xin; Gong, Fei-Xiang; Hu, Bin; Guo, Shang-Chun; Lou, Yuan-Lei; Zhang, Chang-Qing; Deng, Zhi-Feng; Wang, Yang

    2014-07-01

    Stem cells in human urine have gained attention in recent years; however, urine-derived stem cells (USCs) are far from being well elucidated. In this study, we compared the biological characteristics of USCs with adipose-derived stem cells (ASCs) and investigated whether USCs could serve as a potential cell source for neural tissue engineering. USCs were isolated from voided urine with a modified culture medium. Through a series of experiments, we examined the growth rate, surface antigens, and differentiation potential of USCs, and compared them with ASCs. USCs showed robust proliferation ability. After serial propagation, USCs retained normal karyotypes. Cell surface antigen expression of USCs was similar to ASCs. With lineage-specific induction factors, USCs could differentiate toward the osteogenic, chondrogenic, adipogenic, and neurogenic lineages. To assess the ability of USCs to survive, differentiate, and migrate, they were seeded onto hydrogel scaffold and transplanted into rat brain. The results showed that USCs were able to survive in the lesion site, migrate to other areas, and express proteins that were associated with neural phenotypes. The results of our study demonstrate that USCs possess similar biological characteristics with ASCs and have multilineage differentiation potential. Moreover USCs can differentiate to neuron-like cells in rat brain. The present study shows that USCs are a promising cell source for tissue engineering and regenerative medicine.

  1. Do biological-based strategies hold promise to biofouling control in MBRs?

    KAUST Repository

    Malaeb, Lilian

    2013-10-01

    Biofouling in membrane bioreactors (MBRs) remains a primary challenge for their wider application, despite the growing acceptance of MBRs worldwide. Research studies on membrane fouling are extensive in the literature, with more than 200 publications on MBR fouling in the last 3 years; yet, improvements in practice on biofouling control and management have been remarkably slow. Commonly applied cleaning methods are only partially effective and membrane replacement often becomes frequent. The reason for the slow advancement in successful control of biofouling is largely attributed to the complex interactions of involved biological compounds and the lack of representative-for-practice experimental approaches to evaluate potential effective control strategies. Biofouling is driven by microorganisms and their associated extra-cellular polymeric substances (EPS) and microbial products. Microorganisms and their products convene together to form matrices that are commonly treated as a black box in conventional control approaches. Biological-based antifouling strategies seem to be a promising constituent of an effective integrated control approach since they target the essence of biofouling problems. However, biological-based strategies are in their developmental phase and several questions should be addressed to set a roadmap for translating existing and new information into sustainable and effective control techniques. This paper investigates membrane biofouling in MBRs from the microbiological perspective to evaluate the potential of biological-based strategies in offering viable control alternatives. Limitations of available control methods highlight the importance of an integrated anti-fouling approach including biological strategies. Successful development of these strategies requires detailed characterization of microorganisms and EPS through the proper selection of analytical tools and assembly of results. Existing microbiological/EPS studies reveal a number of

  2. Solution-Focused Therapy: Strength-Based Counseling for Children with Social Phobia

    Science.gov (United States)

    George, Cindy M.

    2008-01-01

    Solution-focused therapy is proposed as an effective strength-based model for children with social phobia. Social phobia is described along with the etiology and prevailing treatment approaches. A case illustration demonstrates the application of solution-focused therapy with a child who experienced social phobia. Implications for counseling and…

  3. Long-term changes in the quality of life of patients with rheumatoid arthritis treated with biological therapies.

    Science.gov (United States)

    Ortega-Valín, Luis; Mayorga-Bajo, Isabel; Prieto-Fernández, Carolina; Del Pozo-Ruiz, Javier; Gutiérrez-Gutiérrez, Esperanza; Pérez-Sandoval, Trinidad

    2017-02-27

    To analyze the changes in health-related quality of life (HRQoL) of patients with rheumatoid arthritis (RA) treated with biological therapies. Observational prospective study performed from October 2006 to May 2011. The inclusion criteria were adult patients, diagnosed with RA, treated for at least one year with anti-tumor necrosis factor therapy (infliximab or etanercept), who had not received other biological treatments previously. A total of 41 patients who completed the study undertook the specific and validated questionnaire QoL-RA Scale 3 times: E1 (September 2006-February 2007), E2 (April 2008-January 2009) and E3 (July 2010- May 2011). Data analysis was conducted using Epi-Info version 3.3 2004 for Windows® and Excel 2007; mean comparisons were evaluated by Student's t-test and the relationship between the 3 outcomes for each patient by lineal regression. Overall results show a downward trend which was not statistically significant: 7.09 (standard deviation [SD]=1.15) in E1; 6.90 (SD=1.60) in E2; and 6.52 (SD=1.59) in E3. Items with higher scores were those related to psychosocial aspects (help from family, interaction with family and friends), whereas the physical dimension was valued more poorly (physical ability, arthritis pain, arthritis). Between E2 and E3 there was a significant increase in help from family (P=.0008), whereas level of tension (P=.0119) and mood (P=.0451) decreased significantly. In all, HRQoL reported by patients is good and has remained unchanged after approximately 6 years of study. The stability of HRQoL is probably partly attributable to treatment. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  4. Mesenchymal stem cell-based gene therapy: A promising therapeutic strategy.

    Science.gov (United States)

    Mohammadian, Mozhdeh; Abasi, Elham; Akbarzadeh, Abolfazl

    2016-08-01

    Mesenchymal stem cells (MSCs) are multipotent stromal cells that exist in bone marrow, fat, and so many other tissues, and can differentiate into a variety of cell types including osteoblasts, chondrocytes, and adipocytes, as well as myocytes and neurons. Moreover, they have great capacity for self-renewal while maintaining their multipotency. Their capacity for proliferation and differentiation, in addition to their immunomodulatory activity, makes them very promising candidates for cell-based regenerative medicine. Moreover, MSCs have the ability of mobilization to the site of damage; therefore, they can automatically migrate to the site of injury via their chemokine receptors following intravenous transplantation. In this respect, they can be applied for MSC-based gene therapy. In this new therapeutic method, genes of interest are introduced into MSCs via viral and non-viral-based methods that lead to transgene expression in them. Although stem cell-based gene therapy is a relatively new strategy, it lights a new hope for the treatment of a variety of genetic disorders. In the near future, MSCs can be of use in a vast number of clinical applications, because of their uncomplicated isolation, culture, and genetic manipulation. However, full consideration is still crucial before they are utilized for clinical trials, because the number of studies that signify the advantageous effects of MSC-based gene therapy are still limited.

  5. Lack of Evolution Acceptance Inhibits Students' Negotiation of Biology-Based Socioscientific Issues

    Science.gov (United States)

    Fowler, S. R.; Zeidler, D. L.

    2016-01-01

    The purpose of this study was to explore science content used during college students' negotiation of biology-based socioscientific issues (SSI) and examine how it related to students' conceptual understanding and acceptance of biological evolution. The Socioscientific Issues Questionnaire (SSI-Q) was developed to measure depth of evolutionary…

  6. New treatments for psoriasis: which biologic is best?

    Science.gov (United States)

    Nelson, Andrew A; Pearce, Daniel J; Fleischer, Alan B; Balkrishnan, Rajesh; Feldman, Steven R

    2006-01-01

    Psoriasis is a chronic, debilitating disease affecting not only the skin, but also having a significant impact on a patient's quality of life. The treatment of severe psoriasis is quite challenging due to the chronic, relapsing nature of the disease and the difficulties inherent in treatment planning. Though the biologics are perhaps the most promising of available psoriasis treatments, the decision to institute a given therapy may be fraught with complexity for the clinician. Patients now hear of these promising new treatments for psoriasis via print, television and radio advertising; they frequently come to their physician asking if they are eligible for any of these agents and, if so, 'which biologic is best?'. This paper attempts to determine the ideal biologic agent based upon several parameters: FDA- and EU-approved indications, therapeutic efficacy, impact on quality of life, cost-effectiveness, and safety profile. Certainly the physician is central to medical decision-making, though ultimately patient preference may play the largest role in determining the 'best' biologic agent. There is no single ideal biologic for all patients and a physician's job is to educate patients on the relative advantages and disadvantages of each agent. Through informed discussion, the clinician can help each individual patient decide which biologic agent is ideal for them.

  7. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology

    Directory of Open Access Journals (Sweden)

    Ina Aretz

    2016-04-01

    Full Text Available Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  8. Advantages and Pitfalls of Mass Spectrometry Based Metabolome Profiling in Systems Biology.

    Science.gov (United States)

    Aretz, Ina; Meierhofer, David

    2016-04-27

    Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology.

  9. Biological impact of music and software-based auditory training

    OpenAIRE

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based ...

  10. Occupational Therapy in Medicaid Home and Community-Based Services Waivers.

    Science.gov (United States)

    Friedman, Carli; VanPuymbrouck, Laura

    Medicaid Home and Community-Based Services (HCBS) 1915(c) waivers are the largest provider of long-term services and supports for people with intellectual and developmental disabilities (IDDs). In this study, we explored how HCBS IDD waivers projected providing occupational therapy services in Fiscal Year (FY) 2015. Medicaid HCBS IDD waivers across the nation gathered from the Centers for Medicare and Medicaid Services were qualitatively and quantitatively analyzed to determine how they projected providing occupational therapy services in terms of service expenditures and utilization. In FY 2015, $14.13 million of spending was projected for occupational therapy services of 7,500 participants. However, there was large heterogeneity across states and services in terms of total projected spending, spending per participant, and reimbursement rates. Comparisons across states strengthen the profession's ability to assert the value of its services. These findings can help identify best practices and can advocate for the refinement of state occupational therapy programs. Copyright © 2018 by the American Occupational Therapy Association, Inc.

  11. The new Wuerzburg data base for radiation therapy

    International Nuclear Information System (INIS)

    Richter, J.; Richter, E.; Tausch, J.

    1991-01-01

    Conception, structure and realisation of a new data base for radiation therapy are present. The data base utilizes the commercial data base system ORACLE and the data base language SQL. A program package for statistical analyses including Kaplan-Meier-calculations, logrank test and Gehan/Breslow test was elaborated. The input of the data recorded on form sheets is carried out on a data base of the Tumor Centre in the first instance. From there the data are transfered to the ORACLE data base. Up to now the courses of disease of about 13 000 patients are stored. Therefore, extensive and detailed statistical analyses are practicable. (orig.) [de

  12. Benralizumab: From the Basic Mechanism of Action to the Potential Use in the Biological Therapy of Severe Eosinophilic Asthma

    Directory of Open Access Journals (Sweden)

    Corrado Pelaia

    2018-01-01

    Full Text Available Asthma is a very frequent chronic airway disease that includes many different clinical phenotypes and inflammatory patterns. In particular, eosinophilic bronchial inflammation is often associated with allergic as well as nonallergic asthma. The most important cytokine involved in the induction, maintenance, and amplification of airway eosinophilia in asthma is interleukin-5 (IL-5, released by both T helper 2 (Th2 lymphocytes and group 2 innate lymphoid cells (ILC2. Hence, IL-5 and its receptor are suitable targets for selective biologic drugs which can play a key role in add-on treatment of severe eosinophilic asthma refractory to corticosteroids. Within such a context, the anti-IL-5 monoclonal antibodies mepolizumab and reslizumab have been developed and approved for biological therapy of uncontrolled eosinophilic asthma. In this regard, on the basis of several successful randomized controlled trials, the anti-IL-5 receptor benralizumab has also recently obtained the approval from US Food and Drug Administration (FDA.

  13. Treatment with biologic agents improves the prognosis of patients with rheumatoid arthritis and amyloidosis.

    Science.gov (United States)

    Kuroda, Takeshi; Tanabe, Naohito; Kobayashi, Daisuke; Sato, Hiroe; Wada, Yoko; Murakami, Shuichi; Saeki, Takako; Nakano, Masaaki; Narita, Ichiei

    2012-07-01

    Reactive amyloid A (AA) amyloidosis is a serious and life-threatening systemic complication of rheumatoid arthritis (RA). We evaluated the safety of therapy with anti-tumor necrosis factor and anti-interleukin 6 biologic agents in RA patients with reactive AA amyloidosis, together with prognosis and hemodialysis (HD)-free survival, in comparison with patients with AA amyloidosis without such therapy. One hundred thirty-three patients with an established diagnosis of reactive AA amyloidosis participated in the study. Clinical data were assessed from patient records at the time of amyloid detection and administration of biologics. Survival was calculated from the date when amyloid was first demonstrated histologically or the date when biologic therapy was started until the time of death or to the end of 2010 for surviving patients. Patients who had started HD were selected for inclusion only after the presence of amyloid was demonstrated. Fifty-three patients were treated with biologic agents (biologic group) and 80 were not (nonbiologic group). Survival rate was significantly higher in the biologic group than in the nonbiologic group. Nine patients in the biologics group and 33 in the nonbiologic group started HD. Biologic therapy had a tendency for reduced risk of initiation of HD without any statistical significance. Patients with amyloidosis have a higher mortality rate, but the use of biologic agents can reduce risk of death. The use of biologics may not significantly influence the HD-free survival rate.

  14. Biologic treatment in Sjögren's syndrome.

    Science.gov (United States)

    Sada, Pablo Ruiz; Isenberg, David; Ciurtin, Coziana

    2015-02-01

    SS is a chronic systemic autoimmune disease characterized by decreased exocrine gland function. A variety of other disease manifestations may also be present, including general constitutional symptoms and extraglandular features. A multidisciplinary approach focused on both local and systemic medical therapies is needed as the disease has a wide clinical spectrum. The current treatment for SS is mainly symptomatic. However, there is evidence that systemic drugs are effective in controlling extraglandular manifestations of the disease. Overall evidence for the role of conventional immunosuppressive therapy is limited. A number of attempts to use biologic therapies have led to variable results. Biologic agents targeting B cells, such as rituximab, epratuzumab and belimumab, have shown promising results, but further studies are needed to validate the findings. Early-phase studies with abatacept and alefacept proved that T cell stimulation inhibition is another potentially effective target for SS treatment. Modulation or inhibition of other targets such as IFN, IL-6 and Toll-like receptor are also currently being investigated. We have summarized the available evidence regarding the efficacy of biologic treatments and discuss other potential therapies targeting pathways or molecules recognized as being involved in the pathogenesis of SS. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  15. Undergraduate Biology Lab Courses: Comparing the Impact of Traditionally Based "Cookbook" and Authentic Research-Based Courses on Student Lab Experiences

    Science.gov (United States)

    Brownell, Sara E.; Kloser, Matthew J.; Fukami, Tadishi; Shavelson, Rich

    2012-01-01

    Over the past decade, several reports have recommended a shift in undergraduate biology laboratory courses from traditionally structured, often described as "cookbook," to authentic research-based experiences. This study compares a cookbook-type laboratory course to a research-based undergraduate biology laboratory course at a Research 1…

  16. Evaluation of the published biological bases for regulations concerning non-coherent light

    International Nuclear Information System (INIS)

    Sykes, S.M.; Bockstahler, L.; Felten, R.; Hellman, K.; Jacobson, E.; Krell, K.; Lytle, C.D.; Waxler, M.; Withrow, T.; Zaremba, T.

    1981-01-01

    The development of an information base of light-induced bioeffects data to support regulatory activities is a continuing process. Though standards covering the three spectral regions of light, ultraviolet (UV), visible, and infrared (IR), currently exist, attempts must regularly be made to assess the adequacy of these standards with respect to currently available biological information. In order to establish a starting point for these reassessments, the biological effects of light considered in establishing the standards must first be determined. Using this information, the strengths and weaknesses of each standard can be evaluated, and particularly important areas of future research can be determined. This document analyzes current standards covering non-coherent light with respect to the biological effects considered in their adoption. The current standards covering non-coherent light are based on few biological endpoints. The ACGIH standard for ultraviolet considers only skin erythema and eye keratitis; the visible light standard considers only retinal damage; and the infrared standard considers only lens cataracts. Clearly, other biological effects need to be considered. But any standard represents a state-of-the-art estimate of maximum allowable exposure levels, and while there is considerable qualitative information on many additional biological effects of light, there is little quantitative information. Without this information it is difficult either to incorporate these effects into the regulatory process or to determine if the current standards are adequate to cover them

  17. Biotechnology by Design: An Introductory Level, Project-Based, Synthetic Biology Laboratory Program for Undergraduate Students†

    OpenAIRE

    Beach, Dale L.; Alvarez, Consuelo J.

    2015-01-01

    Synthetic biology offers an ideal opportunity to promote undergraduate laboratory courses with research-style projects, immersing students in an inquiry-based program that enhances the experience of the scientific process. We designed a semester-long, project-based laboratory curriculum using synthetic biology principles to develop a novel sensory device. Students develop subject matter knowledge of molecular genetics and practical skills relevant to molecular biology, recombinant DNA techniq...

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

    Energy Technology Data Exchange (ETDEWEB)

    Lisenko, S A; Kugeiko, M M [Belarusian State University, Minsk (Belarus)

    2015-04-30

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

  19. Simbios: an NIH national center for physics-based simulation of biological structures.

    Science.gov (United States)

    Delp, Scott L; Ku, Joy P; Pande, Vijay S; Sherman, Michael A; Altman, Russ B

    2012-01-01

    Physics-based simulation provides a powerful framework for understanding biological form and function. Simulations can be used by biologists to study macromolecular assemblies and by clinicians to design treatments for diseases. Simulations help biomedical researchers understand the physical constraints on biological systems as they engineer novel drugs, synthetic tissues, medical devices, and surgical interventions. Although individual biomedical investigators make outstanding contributions to physics-based simulation, the field has been fragmented. Applications are typically limited to a single physical scale, and individual investigators usually must create their own software. These conditions created a major barrier to advancing simulation capabilities. In 2004, we established a National Center for Physics-Based Simulation of Biological Structures (Simbios) to help integrate the field and accelerate biomedical research. In 6 years, Simbios has become a vibrant national center, with collaborators in 16 states and eight countries. Simbios focuses on problems at both the molecular scale and the organismal level, with a long-term goal of uniting these in accurate multiscale simulations.

  20. Synthetic biology for microbial production of lipid-based biofuels.

    Science.gov (United States)

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

  1. Synthetic biology for microbial production of lipid-based biofuels

    Energy Technology Data Exchange (ETDEWEB)

    d' Espaux, L; Mendez-Perez, D; Li, R; Keasling, JD

    2015-10-23

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  2. Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases.

    Science.gov (United States)

    Oh, Soo Jin; Choi, Young Ki; Shin, Ok Sarah

    2018-03-01

    Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs. © Copyright: Yonsei University College of Medicine 2018.

  3. What works best for whom? Cognitive Behavior Therapy and Mindfulness-Based Cognitive Therapy for depressive symptoms in patients with diabetes

    NARCIS (Netherlands)

    Tovote, K. Annika; Schroevers, Maya J.; Snippe, Evelien; Emmelkamp, Paul M.G.; Links, Thera P.; Sanderman, Robbert; Fleer, Joke

    2017-01-01

    Objective: Cognitive Behavior Therapy (CBT) and Mindfulness-Based Cognitive Therapy (MBCT) have shown to be effective interventions for treating depressive symptoms in patients with diabetes. However, little is known about which intervention works best for whom (i.e., moderators of efficacy). The

  4. Glucosamine-Based Supramolecular Nanotubes for Human Mesenchymal Cell Therapy.

    Science.gov (United States)

    Talloj, Satish Kumar; Cheng, Bill; Weng, Jen-Po; Lin, Hsin-Chieh

    2018-04-23

    Herein, we demonstrate an example of glucosamine-based supramolecular hydrogels that can be used for human mesenchymal cell therapy. We designed and synthesized a series of amino acid derivatives based on a strategy of capping d-glucosamine moiety at the C-terminus and fluorinated benzyl group at the N-terminus. From a systematic study on chemical structures, we discovered that the glucosamine-based supramolecular hydrogel [pentafluorobenzyl (PFB)-F-Glu] self-assembled with one-dimensional nanotubular structures at physiological pH. The self-assembly of a newly discovered PFB-F-Glu motif is attributed to the synergistic effect of π-π stacking and extensive intermolecular hydrogen bonding network in aqueous medium. Notably, PFB-F-Glu nanotubes are proven to be nontoxic to human mesenchymal stem cells (hMSCs) and have been shown to enhance hMSC proliferation while maintaining their pluripotency. Retaining of pluripotency capabilities provides potentially unlimited source of undifferentiated cells for the treatment of future cell therapies. Furthermore, hMSCs cultured on PFB-F-Glu are able to secrete paracrine factors that downregulate profibrotic gene expression in lipopolysaccharide-treated human skin fibroblasts, which demonstrates that PFB-F-Glu nanotubes have the potential to be used for wound healing applications. Overall, this article addresses the importance of chemical design to generate supramolecular biomaterials for stem cell therapy.

  5. An upconversion nanoparticle - Zinc phthalocyanine based nanophotosensitizer for photodynamic therapy

    NARCIS (Netherlands)

    Xia, L.; Kong, X.; Liu, X.; Tu, L.; Zhang, Y.; Chang, Y.; Liu, K.; Shen, D.; Zhao, H.; Zhang, H.

    2014-01-01

    Recent advances in NIR triggering upconversion-based photodynamic therapy have led to substantial improvements in upconversion-based nanophotosensitizers. How to obtain the high efficiency of singlet oxygen generation under low 980 nm radiation dosage still remains a challenge. A highly efficient

  6. Clinical results of proton beam therapy for skull base chordoma

    International Nuclear Information System (INIS)

    Igaki, Hiroshi; Tokuuye, Koichi; Okumura, Toshiyuki; Sugahara, Shinji; Kagei, Kenji; Hata, Masaharu; Ohara, Kiyoshi; Hashimoto, Takayuki; Tsuboi, Koji; Takano, Shingo; Matsumura, Akira; Akine, Yasuyuki

    2004-01-01

    Purpose: To evaluate clinical results of proton beam therapy for patients with skull base chordoma. Methods and materials: Thirteen patients with skull base chordoma who were treated with proton beams with or without X-rays at the University of Tsukuba between 1989 and 2000 were retrospectively reviewed. A median total tumor dose of 72.0 Gy (range, 63.0-95.0 Gy) was delivered. The patients were followed for a median period of 69.3 months (range, 14.6-123.4 months). Results: The 5-year local control rate was 46.0%. Cause-specific, overall, and disease-free survival rates at 5 years were 72.2%, 66.7%, and 42.2%, respectively. The local control rate was higher, without statistical significance, for those with preoperative tumors <30 mL. Partial or subtotal tumor removal did not yield better local control rates than for patients who underwent biopsy only as the latest surgery. Conclusion: Proton beam therapy is effective for patients with skull base chordoma, especially for those with small tumors. For a patient with a tumor of <30 mL with no prior treatment, biopsy without tumor removal seems to be appropriate before proton beam therapy

  7. New advances in amblyopia therapy I: binocular therapies and pharmacologic augmentation.

    Science.gov (United States)

    Kraus, Courtney L; Culican, Susan M

    2018-05-18

    Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Evolution of magnetic therapy from alternative to traditional medicine.

    Science.gov (United States)

    Vallbona, C; Richards, T

    1999-08-01

    Static or electromagnetic fields have been used for centuries to control pain and other biologic problems, but scientific evidence of their effect had not been gathered until recently. This article explores the value of magnetic therapy in rehabilitation medicine in terms of static magnetic fields and time varying magnetic fields (electromagnetic). A historical review is given and the discussion covers the areas of scientific criteria, modalities of magnetic therapy, mechanisms of the biologic effects of magnetic fields, and perspectives on the future of magnetic therapy.

  9. Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

    Science.gov (United States)

    Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

    2017-01-01

    A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Clinical Study on the Visceral Differentiation-Based Acupuncture Therapy for Insomnia

    Institute of Scientific and Technical Information of China (English)

    LING Li; JIANG Xin-mei; XUE Jin-wei; WANG Miao; KE Rui

    2008-01-01

    objective;To investigate the clinical effects of acupuncture for insomnia on the basis of visceral differentiation.Methods;Seventy cases of insomnia were randomly divided into a treatment group and a control group,The former was treated by acupuncture based on visceral differentiation and the latter by the routine acupuncture therapy.Results;The clinical effcts were significantly better in the treatment group than that of the control group(P<0.05).Conclusion;The visceral difrerentiation-based acupuncture therapy may enhance the therapeutic effects for insomnia patients.

  11. Biologically based neural network for mobile robot navigation

    Science.gov (United States)

    Torres Muniz, Raul E.

    1999-01-01

    The new tendency in mobile robots is to crete non-Cartesian system based on reactions to their environment. This emerging technology is known as Evolutionary Robotics, which is combined with the Biorobotic field. This new approach brings cost-effective solutions, flexibility, robustness, and dynamism into the design of mobile robots. It also provides fast reactions to the sensory inputs, and new interpretation of the environment or surroundings of the mobile robot. The Subsumption Architecture (SA) and the action selection dynamics developed by Brooks and Maes, respectively, have successfully obtained autonomous mobile robots initiating this new trend of the Evolutionary Robotics. Their design keeps the mobile robot control simple. This work present a biologically inspired modification of these schemes. The hippocampal-CA3-based neural network developed by Williams Levy is used to implement the SA, while the action selection dynamics emerge from iterations of the levels of competence implemented with the HCA3. This replacement by the HCA3 results in a closer biological model than the SA, combining the Behavior-based intelligence theory with neuroscience. The design is kept simple, and it is implemented in the Khepera Miniature Mobile Robot. The used control scheme obtains an autonomous mobile robot that can be used to execute a mail delivery system and surveillance task inside a building floor.

  12. [Biologics and mycobacterial diseases].

    Science.gov (United States)

    Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

    2013-03-01

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

  13. Molecular Biology of Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2007-12-01

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

  14. Ilaj bil hijamah (cupping therapy) in the Unani system of medicine: anecdotal practice to evidence based therapy.

    Science.gov (United States)

    Abbas Zaidi, S M; Jameel, S S; Jafri, Kehkashan; Khan, Shariq A; Ahmad, Ehsan

    2016-08-01

    Cupping (Hijamah) therapy is very well documented as a result of several thousand years of clinical experiences in Unani medicine. In this procedure, suction is created by various means either with or without bloodletting. Though this therapy is being widely practiced across the globe for treating many chronic and intractable ailments but many reports reveal its unscientific and improper practices which results in many complications. Therefore to develop standard operative procedures and to propose protocols of cupping therapy in various diseases is the need of hour. A thorough literature review of relevant journals and textbooks was performed to gather the maximum available data on cupping therapy. This paper seeks to introduce the general concepts of cupping therapy in Unani medicine and other traditional systems of medicine, shortcomings and limitations of the currently published studies and suggest ways to improve these technical/methodological flaws. In addition, the authors have also attempted to provide the cupping related materials, hypotheses, observations which will provide the researchers the base for evaluating their usefulness in future clinical trials.

  15. Possible artemisinin-based combination therapy-resistant malaria in Nigeria: a report of three cases

    Directory of Open Access Journals (Sweden)

    Nnennaya Anthony Ajayi

    2013-07-01

    Full Text Available Artemisinin-based combination therapy-resistant malaria is rare in Sub-Saharan Africa. The World Health Organization identifies monitoring and surveillance using day-3 parasitaemia post-treatment as the standard test for identifying suspected artemisinin resistance. We report three cases of early treatment failure due to possible artemisinin-based combination therapy-resistant Plasmodium falciparum malaria. All cases showed adequate clinical and parasitological responses to quinine. This study reveals a need to re-evaluate the quality and efficacy of artemisinin-based combination therapy agents in Nigeria and Sub-Saharan Africa.

  16. Nanotechnology meets 3D in vitro models: tissue engineered tumors and cancer therapies.

    Science.gov (United States)

    da Rocha, E L; Porto, L M; Rambo, C R

    2014-01-01

    Advances in nanotechnology are providing to medicine a new dimension. Multifunctional nanomaterials with diagnostics and treatment modalities integrated in one nanoparticle or in cooperative nanosystems are promoting new insights to cancer treatment and diagnosis. The recent convergence between tissue engineering and cancer is gradually moving towards the development of 3D disease models that more closely resemble in vivo characteristics of tumors. However, the current nanomaterials based therapies are accomplished mainly in 2D cell cultures or in complex in vivo models. The development of new platforms to evaluate nano-based therapies in parallel with possible toxic effects will allow the design of nanomaterials for biomedical applications prior to in vivo studies. Therefore, this review focuses on how 3D in vitro models can be applied to study tumor biology, nanotoxicology and to evaluate nanomaterial based therapies. © 2013.

  17. Plasma cell leukemia: update on biology and therapy.

    Science.gov (United States)

    Mina, Roberto; D'Agostino, Mattia; Cerrato, Chiara; Gay, Francesca; Palumbo, Antonio

    2017-07-01

    Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10 9 /l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM. Novel agents have revolutionized the outcomes of MM patients and have been introduced also for the treatment of PCL. Here, we provide an update on biology and treatment options for PCL.

  18. Experimental models of brain ischemia: a review of techniques, magnetic resonance imaging and investigational cell-based therapies

    Directory of Open Access Journals (Sweden)

    Alessandra eCanazza

    2014-02-01

    Full Text Available Stroke continues to be a significant cause of death and disability worldwide. Although major advances have been made in the past decades in prevention, treatment and rehabilitation, enormous challenges remain in the way of translating new therapeutic approaches from bench to bedside. Thrombolysis, while routinely used for ischemic stroke, is only a viable option within a narrow time window. Recently, progress in stem cell biology has opened up avenues to therapeutic strategies aimed at supporting and replacing neural cells in infarcted areas. Realistic experimental animal models are crucial to understand the mechanisms of neuronal survival following ischemic brain injury and to develop therapeutic interventions. Current studies on experimental stroke therapies evaluate the efficiency of neuroprotective agents and cell-based approaches using primarily rodent models of permanent or transient focal cerebral ischemia. In parallel, advancements in imaging techniques permit better mapping of the spatial-temporal evolution of the lesioned cortex and its functional responses. This review provides a condensed conceptual review of the state of the art of this field, from models and magnetic resonance imaging techniques through to stem cell therapies.

  19. Evidence-Based Management of Anticoagulant Therapy

    Science.gov (United States)

    Schulman, Sam; Witt, Daniel M.; Vandvik, Per Olav; Fish, Jason; Kovacs, Michael J.; Svensson, Peter J.; Veenstra, David L.; Crowther, Mark; Guyatt, Gordon H.

    2012-01-01

    Background: High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. Conclusions: We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied. PMID:22315259

  20. Strategies for Biologic Image-Guided Dose Escalation: A Review

    International Nuclear Information System (INIS)

    Sovik, Aste; Malinen, Eirik; Olsen, Dag Rune

    2009-01-01

    There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice

  1. How to Design and Equip a Mentalization-Based Play Therapy Room.

    Science.gov (United States)

    Rüth, Ulrich; Holch, Astrid

    2018-01-01

    Designing and equipping a play therapy room as a differentiated tool in a psychodynamic approach to child psychotherapy is seldom discussed. This article sketches out the equipment and furnishing of a play therapy room to be used for mentalization-based psychodynamic psychotherapy and gives examples of the use of such a room in practice.

  2. Biological Impact of Music and Software-Based Auditory Training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals--both young and old--encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in…

  3. Play therapy in perspective theory of eco systemic therapy

    Directory of Open Access Journals (Sweden)

    Sofwan Adiputra

    2017-11-01

    Full Text Available Play therapy is a counseling approach for children applying toys, games, and other play media to communicate to the children "language." One of the Play therapy models that combine ecosystems as being formed by an inseparable reciprocal relationship between living things, and their environment is Eco systemic Play Therapy (EPT. Ecosystem Play Therapy as a hybrid model that integrates the concepts of science biology, several models of child psychotherapy, and developmental theories. This model is not eclectic. Rather, it is the integration of several models to create an independent model that is different from the sum of its parts. The focus of EPT is on the process of optimizing the implementation of the child's function as the context of the child's ecosystem or world. EPT is developed from a phenomenological philosophical perspective, in contrast to traditional perspectives.

  4. Magneto-laser-ultrasonic therapy. Scientific materials used in practice. V.4(1)

    International Nuclear Information System (INIS)

    Samosyuk, I.Z.; Chukhraev, N.V.; Myasnikov, V.G.; Samosyuk, N.I.

    2001-01-01

    Contemporary data about the use of magnetotherapy, ultrasound and magnetolaser therapy in resonance energy ranges are presented in this book. Practical methodics of simultaneous and combined use of these physical factors in different branches of clinical medicine (neurology, cardiology, gastroenterology and others) are described. General idea of biological rhythms is given and it is considered as a background of living systems development. Biorhythms are used for determination of 'biological resonance', the optimum correlation between vibrations of the organism and external ones. In such a way the best results of treatment are achieved. Modern principles of the sensitive zone choice, bases of biorhythmic and resonance phenomena are presented. Practical uses of them became more and more important in physiotherapy and acupuncture. Human biological rhythms are taken into consideration during bioresonance treatment. Features of each treatment method are described. Reactions of different organism systems (nervous, hearth and vessel, bone, respiratory systems, internal secretion) on magnetic field influence, obtained treatment effects of magnetotherapy and possible mistakes in treatment are discussed. Special advices on the use of ultrasound therapy and magnetotherapy are given. The most part of magneto-laser-ultrasound therapy uses refers to the new generation of series 'MIT' and 'MIT-11' apparat which combine all three treatment factors

  5. Nanotechnology for Cancer Therapy Based on Chemotherapy

    OpenAIRE

    Chen-Yang Zhao; Rui Cheng; Zhe Yang; Zhong-Min Tian

    2018-01-01

    Chemotherapy has been widely applied in clinics. However, the therapeutic potential of chemotherapy against cancer is seriously dissatisfactory due to the nonspecific drug distribution, multidrug resistance (MDR) and the heterogeneity of cancer. Therefore, combinational therapy based on chemotherapy mediated by nanotechnology, has been the trend in clinical research at present, which can result in a remarkably increased therapeutic efficiency with few side effects to normal tissues. Moreover,...

  6. [Therapy of intermediate uveitis].

    Science.gov (United States)

    Doycheva, D; Deuter, C; Zierhut, M

    2014-12-01

    Intermediate uveitis is a form of intraocular inflammation in which the vitreous body is the major site of inflammation. Intermediate uveitis is primarily treated medicinally and systemic corticosteroids are the mainstay of therapy. When recurrence of uveitis or side effects occur during corticosteroid therapy an immunosuppressive treatment is required. Cyclosporine A is the only immunosuppressive agent that is approved for therapy of uveitis in Germany; however, other immunosuppressive drugs have also been shown to be effective and well-tolerated in patients with intermediate uveitis. In severe therapy-refractory cases when conventional immunosuppressive therapy has failed, biologics can be used. In patients with unilateral uveitis or when the systemic therapy is contraindicated because of side effects, an intravitreal steroid treatment can be carried out. In certain cases a vitrectomy may be used.

  7. Biological standards for the Knowledge-Based BioEconomy: What is at stake.

    Science.gov (United States)

    de Lorenzo, Víctor; Schmidt, Markus

    2018-01-25

    The contribution of life sciences to the Knowledge-Based Bioeconomy (KBBE) asks for the transition of contemporary, gene-based biotechnology from being a trial-and-error endeavour to becoming an authentic branch of engineering. One requisite to this end is the need for standards to measure and represent accurately biological functions, along with languages for data description and exchange. However, the inherent complexity of biological systems and the lack of quantitative tradition in the field have largely curbed this enterprise. Fortunately, the onset of systems and synthetic biology has emphasized the need for standards not only to manage omics data, but also to increase reproducibility and provide the means of engineering living systems in earnest. Some domains of biotechnology can be easily standardized (e.g. physical composition of DNA sequences, tools for genome editing, languages to encode workflows), while others might be standardized with some dedicated research (e.g. biological metrology, operative systems for bio-programming cells) and finally others will require a considerable effort, e.g. defining the rules that allow functional composition of biological activities. Despite difficulties, these are worthy attempts, as the history of technology shows that those who set/adopt standards gain a competitive advantage over those who do not. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Relations between Intuitive Biological Thinking and Biological Misconceptions in Biology Majors and Nonmajors

    Science.gov (United States)

    Coley, John D.; Tanner, Kimberly

    2015-01-01

    Research and theory development in cognitive psychology and science education research remain largely isolated. Biology education researchers have documented persistent scientifically inaccurate ideas, often termed misconceptions, among biology students across biological domains. In parallel, cognitive and developmental psychologists have described intuitive conceptual systems—teleological, essentialist, and anthropocentric thinking—that humans use to reason about biology. We hypothesize that seemingly unrelated biological misconceptions may have common origins in these intuitive ways of knowing, termed cognitive construals. We presented 137 undergraduate biology majors and nonmajors with six biological misconceptions. They indicated their agreement with each statement, and explained their rationale for their response. Results indicate frequent agreement with misconceptions, and frequent use of construal-based reasoning among both biology majors and nonmajors in their written explanations. Moreover, results also show associations between specific construals and the misconceptions hypothesized to arise from those construals. Strikingly, such associations were stronger among biology majors than nonmajors. These results demonstrate important linkages between intuitive ways of thinking and misconceptions in discipline-based reasoning, and raise questions about the origins, persistence, and generality of relations between intuitive reasoning and biological misconceptions. PMID:25713093

  9. 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 ...

  10. Neuroprotective Mechanisms of Glucagon-like Peptide-1-based Therapies in Ischaemic Stroke

    DEFF Research Database (Denmark)

    Marlet, Ida R; Ölmestig, Joakim N E; Vilsbøll, Tina

    2018-01-01

    Review was to systematically evaluate the proposed mechanism of action for GLP-1-based therapies in ischaemic brain damage in animals. We performed a literature search using MEDLINE, EMBASE and The Cochrane Library. GLP-1-based therapies administered before, during or after experimental stroke in diabetic and non......Glucagon-like peptide-1 (GLP-1)-based therapies, GLP-1 receptor agonists (GLP-1RAs) and dipeptidyl peptidase-4 inhibitors (DPP-4Is) are widely used for the treatment of type 2 diabetes. Increasing evidence suggests that they may provide neuroprotection. The aim of this Mini......-diabetic animals were evaluated. We reviewed 27 studies comprised of 20 involving GLP-1RAs and seven involving DPP-4Is. Both GLP-1RAs and DPP-4Is affected the acute inflammatory response secondary to ischaemia by reducing inflammation, endothelial leakage and excitotoxicity. Both treatments also reduced oxidative...

  11. WE-B-304-02: Treatment Planning Evaluation and Optimization Should Be Biologically and Not Dose/volume Based

    International Nuclear Information System (INIS)

    Deasy, J.

    2015-01-01

    The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations

  12. Biological evaluation of silver nanoparticles incorporated into chitosan-based membranes

    NARCIS (Netherlands)

    Shao, J.; Yu, N.; Kolwijck, E.; Wang, B.; Tan, K.W.; Jansen, J.A.; Walboomers, X.F.; Yang, F.

    2017-01-01

    AIM: To evaluate the antibacterial potential and biological performance of silver nanoparticles in chitosan-based membranes. MATERIALS & METHODS: Electrospun chitosan/poly(ethylene oxide) membranes with different amounts of silver nanoparticles were evaluated for antibacterial properties and

  13. Biological Bases for Radiation Adaptive Responses in the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby R. [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Lin, Yong [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Wilder, Julie [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Belinsky, Steven [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States)

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

  14. Impact of region contouring variability on image-based focal therapy evaluation

    Science.gov (United States)

    Gibson, Eli; Donaldson, Ian A.; Shah, Taimur T.; Hu, Yipeng; Ahmed, Hashim U.; Barratt, Dean C.

    2016-03-01

    Motivation: Focal therapy is an emerging low-morbidity treatment option for low-intermediate risk prostate cancer; however, challenges remain in accurately delivering treatment to specified targets and determining treatment success. Registered multi-parametric magnetic resonance imaging (MPMRI) acquired before and after treatment can support focal therapy evaluation and optimization; however, contouring variability, when defining the prostate, the clinical target volume (CTV) and the ablation region in images, reduces the precision of quantitative image-based focal therapy evaluation metrics. To inform the interpretation and clarify the limitations of such metrics, we investigated inter-observer contouring variability and its impact on four metrics. Methods: Pre-therapy and 2-week-post-therapy standard-of-care MPMRI were acquired from 5 focal cryotherapy patients. Two clinicians independently contoured, on each slice, the prostate (pre- and post-treatment) and the dominant index lesion CTV (pre-treatment) in the T2-weighted MRI, and the ablated region (post-treatment) in the dynamic-contrast- enhanced MRI. For each combination of clinician contours, post-treatment images were registered to pre-treatment images using a 3D biomechanical-model-based registration of prostate surfaces, and four metrics were computed: the proportion of the target tissue region that was ablated and the target:ablated region volume ratio for each of two targets (the CTV and an expanded planning target volume). Variance components analysis was used to measure the contribution of each type of contour to the variance in the therapy evaluation metrics. Conclusions: 14-23% of evaluation metric variance was attributable to contouring variability (including 6-12% from ablation region contouring); reducing this variability could improve the precision of focal therapy evaluation metrics.

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

    International Nuclear Information System (INIS)

    Kraft, G.; Grundinger, U.

    1987-07-01

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

  16. Special issue: engineering toxins for 21st-century therapies: introduction.

    Science.gov (United States)

    Acharya, K Ravi

    2011-12-01

    This special issue on 'Engineering toxins for 21st century therapies' provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products. © 2011 The Author Journal compilation © 2011 FEBS.

  17. Computational prediction of multidisciplinary team decision-making for adjuvant breast cancer drug therapies: a machine learning approach.

    Science.gov (United States)

    Lin, Frank P Y; Pokorny, Adrian; Teng, Christina; Dear, Rachel; Epstein, Richard J

    2016-12-01

    Multidisciplinary team (MDT) meetings are used to optimise expert decision-making about treatment options, but such expertise is not digitally transferable between centres. To help standardise medical decision-making, we developed a machine learning model designed to predict MDT decisions about adjuvant breast cancer treatments. We analysed MDT decisions regarding adjuvant systemic therapy for 1065 breast cancer cases over eight years. Machine learning classifiers with and without bootstrap aggregation were correlated with MDT decisions (recommended, not recommended, or discussable) regarding adjuvant cytotoxic, endocrine and biologic/targeted therapies, then tested for predictability using stratified ten-fold cross-validations. The predictions so derived were duly compared with those based on published (ESMO and NCCN) cancer guidelines. Machine learning more accurately predicted adjuvant chemotherapy MDT decisions than did simple application of guidelines. No differences were found between MDT- vs. ESMO/NCCN- based decisions to prescribe either adjuvant endocrine (97%, p = 0.44/0.74) or biologic/targeted therapies (98%, p = 0.82/0.59). In contrast, significant discrepancies were evident between MDT- and guideline-based decisions to prescribe chemotherapy (87%, p machine learning models. A machine learning approach based on clinicopathologic characteristics can predict MDT decisions about adjuvant breast cancer drug therapies. The discrepancy between MDT- and guideline-based decisions regarding adjuvant chemotherapy implies that certain non-clincopathologic criteria, such as patient preference and resource availability, are factored into clinical decision-making by local experts but not captured by guidelines.

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

    Science.gov (United States)

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

    2016-04-01

    Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

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

    International Nuclear Information System (INIS)

    Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael; Malhi, Imran; Niemierko, Andrzej; Rapalino, Otto; Caruso, Paul; Yock, Torunn I.; Tarbell, Nancy J.; Paganetti, Harald; MacDonald, Shannon M.

    2014-01-01

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

  20. Onto2Vec: joint vector-based representation of biological entities and their ontology-based annotations

    KAUST Repository

    Smaili, Fatima Z.; Gao, Xin; Hoehndorf, Robert

    2018-01-01

    We propose the Onto2Vec method, an approach to learn feature vectors for biological entities based on their annotations to biomedical ontologies. Our method can be applied to a wide range of bioinformatics research problems such as similarity-based prediction of interactions between proteins, classification of interaction types using supervised learning, or clustering.

  1. Onto2Vec: joint vector-based representation of biological entities and their ontology-based annotations

    KAUST Repository

    Smaili, Fatima Zohra

    2018-01-31

    We propose the Onto2Vec method, an approach to learn feature vectors for biological entities based on their annotations to biomedical ontologies. Our method can be applied to a wide range of bioinformatics research problems such as similarity-based prediction of interactions between proteins, classification of interaction types using supervised learning, or clustering.

  2. 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.

  3. Gene mutation-based and specific therapies in precision medicine.

    Science.gov (United States)

    Wang, Xiangdong

    2016-04-01

    Precision medicine has been initiated and gains more and more attention from preclinical and clinical scientists. A number of key elements or critical parts in precision medicine have been described and emphasized to establish a systems understanding of precision medicine. The principle of precision medicine is to treat patients on the basis of genetic alterations after gene mutations are identified, although questions and challenges still remain before clinical application. Therapeutic strategies of precision medicine should be considered according to gene mutation, after biological and functional mechanisms of mutated gene expression or epigenetics, or the correspondent protein, are clearly validated. It is time to explore and develop a strategy to target and correct mutated genes by direct elimination, restoration, correction or repair of mutated sequences/genes. Nevertheless, there are still numerous challenges to integrating widespread genomic testing into individual cancer therapies and into decision making for one or another treatment. There are wide-ranging and complex issues to be solved before precision medicine becomes clinical reality. Thus, the precision medicine can be considered as an extension and part of clinical and translational medicine, a new alternative of clinical therapies and strategies, and have an important impact on disease cures and patient prognoses. © 2015 The Author. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  4. Radiobiology of Proton Therapy - Results of an international expert workshop

    DEFF Research Database (Denmark)

    Lühr, Armin; von Neubeck, Cläre; Pawelke, Jörg

    2018-01-01

    The physical properties of proton beams offer the potential to reduce toxicity in tumor-adjacent normal tissues. Toward this end, the number of proton radiotherapy facilities has steeply increased over the last 10-15 years to currently around 70 operational centers worldwide. However, taking full...... in proton therapy combined with systemic treatments, and (4) testing biological effects of protons in clinical trials. Finally, important research avenues for improvement of proton radiotherapy based on radiobiological knowledge are identified. The clinical distribution of radiobiological effectiveness...... of protons alone or in combination with systemic chemo- or immunotherapies as well as patient stratification based on biomarker expressions are key to reach the full potential of proton beam therapy. Dedicated preclinical experiments, innovative clinical trial designs, and large high-quality data...

  5. Incretin-based therapies for type 2 diabetes mellitus in Asian patients: Analysis of clinical trials

    Directory of Open Access Journals (Sweden)

    Melva Louisa

    2010-08-01

    Full Text Available Aim To review the effi cacy and safety data on incretin-based therapies currently available (exenatide, liraglutide, sitagliptin, vildagliptin for the treatment of type 2 diabetes mellitus in Asian population.Methods We conducted Medline search of all relevant randomized clinical trials of incretin-based therapies for type 2 diabetes mellitus in Asian populations. Data pertinent to the efficacy and safety of GLP-1 mimetics and DPP-4 inhibitors were extracted and used.Results We found 14 randomized controlled trials of incretin based-therapy which included 3567 type 2 diabetes mellitus in Asian population (Japanese, Chinese, Korean, Indian. It was shown that incretin-based therapies improved HbA1c at higher extent (up to -1.42% in exenatide 10 mcg bid, -1.85% for liraglutide 0.9 mg qd, -1.4% for sitagliptin 100 mg and -1.4% for vildagliptin 50 mg bid compared to the effects observed in studies with Caucasian population, with comparable safety profile.Conclusion The efficacy of incretin-based therapies in Asian patients improved glycemic parameters in a higher magnitude on some glycemic parameters compared with those in Caucasian population. These results indicate that incretin-based therapies may be more effective in Asian population than in Caucasian. (Med J Indones 2010; 19: 205-12Key words: exenatide, incretin, liraglutide, sitagliptin, type-2 diabetes, vildagliptin

  6. Therapy strategy for intracranial germ-cell tumours and initial results of the GPO therapy study MAKEI 86

    International Nuclear Information System (INIS)

    Goebel, U.; Calaminus, G.; Haasenritter, N.

    1988-01-01

    Pineal tumours are increasingly identified histologically since the introduction of the surgical microscope and microsurgical techniques. A major biological characteristic of germ-cell tumours is the fact that they produce tumour markers. Meaningful therapy planning is determined by the biological behaviour of the individual tumour entity which is strongly influenced by its intracranial localization. Important risk factors need to be identified and weighted according to previous treatment in order to arrive at an adequate therapy with improved curative prospects. Three risk areas can be defined for tumour extension. Therapy planning is also determined by the metastatic spread behaviour of germ-cell tumours. Within the two therapy studies for nontesticular germ-cell tumours MAKEI 83 and 86, a total of 180 germ-cell tumours, 24 of which were localized intercranially, were reported from 46 different clinics. All patients have a survival probability according to Kaplan and Meier of 67 ± 10% at an observation duration of 48 months. (orig./MG) [de

  7. Medical and biological requirements for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Gahbauer, R.; Goodman, J.H.; Kanellitsas, C.; Clendenon, N.; Blue, J.

    1986-01-01

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

  8. Ethical and Safety Issues of Stem Cell-Based Therapy.

    Science.gov (United States)

    Volarevic, Vladislav; Markovic, Bojana Simovic; Gazdic, Marina; Volarevic, Ana; Jovicic, Nemanja; Arsenijevic, Nebojsa; Armstrong, Lyle; Djonov, Valentin; Lako, Majlinda; Stojkovic, Miodrag

    2018-01-01

    Results obtained from completed and on-going clinical studies indicate huge therapeutic potential of stem cell-based therapy in the treatment of degenerative, autoimmune and genetic disorders. However, clinical application of stem cells raises numerous ethical and safety concerns. In this review, we provide an overview of the most important ethical issues in stem cell therapy, as a contribution to the controversial debate about their clinical usage in regenerative and transplantation medicine. We describe ethical challenges regarding human embryonic stem cell (hESC) research, emphasizing that ethical dilemma involving the destruction of a human embryo is a major factor that may have limited the development of hESC-based clinical therapies. With previous derivation of induced pluripotent stem cells (iPSCs) this problem has been overcome, however current perspectives regarding clinical translation of iPSCs still remain. Unlimited differentiation potential of iPSCs which can be used in human reproductive cloning, as a risk for generation of genetically engineered human embryos and human-animal chimeras, is major ethical issue, while undesired differentiation and malignant transformation are major safety issues. Although clinical application of mesenchymal stem cells (MSCs) has shown beneficial effects in the therapy of autoimmune and chronic inflammatory diseases, the ability to promote tumor growth and metastasis and overestimated therapeutic potential of MSCs still provide concerns for the field of regenerative medicine. This review offers stem cell scientists, clinicians and patient's useful information and could be used as a starting point for more in-depth analysis of ethical and safety issues related to clinical application of stem cells.

  9. Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

    Science.gov (United States)

    Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

    2016-02-01

    Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

  10. A Conceptual Model and Clinical Framework for Integrating Mindfulness into Family Therapy with Adolescents.

    Science.gov (United States)

    Brody, Janet L; Scherer, David G; Turner, Charles W; Annett, Robert D; Dalen, Jeanne

    2017-06-07

    Individual and group-based psychotherapeutic interventions increasingly incorporate mindfulness-based principles and practices. These practices include a versatile set of skills such as labeling and attending to present-moment experiences, acting with awareness, and avoiding automatic reactivity. A primary motivation for integrating mindfulness into these therapies is compelling evidence that it enhances emotion regulation. Research also demonstrates that family relationships have a profound influence on emotion regulation capacities, which are central to family functioning and prosocial behavior more broadly. Despite this evidence, no framework exists to describe how mindfulness might integrate into family therapy. This paper describes the benefits of mindfulness-based interventions, highlighting how and why informal mindfulness practices might enhance emotion regulation when integrated with family therapy. We provide a clinical framework for integrating mindfulness into family therapy, particularly as it applies to families with adolescents. A brief case example details sample methods showing how incorporating mindfulness practices into family therapy may enhance treatment outcomes. A range of assessment modalities from biological to behavioral demonstrates the breadth with which the benefits of a family-based mindfulness intervention might be evaluated. © 2017 The Authors. Family Process published by Wiley Periodicals, Inc. on behalf of Family Process Institute.

  11. 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…

  12. 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

  13. Updating biological bases of social behavior.

    Science.gov (United States)

    O'Connor, Thomas G

    2014-09-01

    This month's collation of papers deals with social behaviors that operationalize key constructs in fields covered by the journal, including attachment theory and parenting; emotional regulation; psychopathology of several forms; general and specific cognitive abilities. Notably, many examples are offered of how these social behaviors link with biology. That is an obvious and important direction for clinical research insofar as it helps to erase a perceptual chasm and artificial duality between 'behavior' and 'biology'. But, although it must be the case that social behavior has biological connections of one sort or other, identifying reliable connections with practical application has proved to be a non-trivial challenge. In particular, the challenge seems to be in measuring social behavior meaningfully enough that it could be expected to have a biological pulse, and in measuring biological markers systematically enough that emergent-downstream effects would surface. Associations are not especially uncommon, but it has been a frustrating task in constructing a practically broad model from a bricolage of scattered and disconnected parts and findings in the literature. Several reports in this issue offer contrasts that may help move along this line of study. © 2014 Association for Child and Adolescent Mental Health.

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

    International Nuclear Information System (INIS)

    Watson, J.D.; Siniscalco, M.

    1986-01-01

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

  15. BOWiki: an ontology-based wiki for annotation of data and integration of knowledge in biology

    Directory of Open Access Journals (Sweden)

    Gregorio Sergio E

    2009-05-01

    Full Text Available Abstract Motivation Ontology development and the annotation of biological data using ontologies are time-consuming exercises that currently require input from expert curators. Open, collaborative platforms for biological data annotation enable the wider scientific community to become involved in developing and maintaining such resources. However, this openness raises concerns regarding the quality and correctness of the information added to these knowledge bases. The combination of a collaborative web-based platform with logic-based approaches and Semantic Web technology can be used to address some of these challenges and concerns. Results We have developed the BOWiki, a web-based system that includes a biological core ontology. The core ontology provides background knowledge about biological types and relations. Against this background, an automated reasoner assesses the consistency of new information added to the knowledge base. The system provides a platform for research communities to integrate information and annotate data collaboratively. Availability The BOWiki and supplementary material is available at http://www.bowiki.net/. The source code is available under the GNU GPL from http://onto.eva.mpg.de/trac/BoWiki.

  16. Information fluency for undergraduate biology majors: applications of inquiry-based learning in a developmental biology course.

    Science.gov (United States)

    Gehring, Kathleen M; Eastman, Deborah A

    2008-01-01

    Many initiatives for the improvement of undergraduate science education call for inquiry-based learning that emphasizes investigative projects and reading of the primary literature. These approaches give students an understanding of science as a process and help them integrate content presented in courses. At the same time, general initiatives to promote information fluency are being promoted on many college and university campuses. Information fluency refers to discipline-specific processing of information, and it involves integration of gathered information with specific ideas to form logical conclusions. We have implemented the use of inquiry-based learning to enhance and study discipline-specific information fluency skills in an upper-level undergraduate Developmental Biology course. In this study, an information literacy tutorial and a set of linked assignments using primary literature analysis were integrated with two inquiry-based laboratory research projects. Quantitative analysis of student responses suggests that the abilities of students to identify and apply valid sources of information were enhanced. Qualitative assessment revealed a set of patterns by which students gather and apply information. Self-assessment responses indicated that students recognized the impact of the assignments on their abilities to gather and apply information and that they were more confident about these abilities for future biology courses and beyond.

  17. Mindfulness-based cognitive therapy for depression: trends and developments.

    Science.gov (United States)

    MacKenzie, Meagan B; Kocovski, Nancy L

    2016-01-01

    Mindfulness-based cognitive therapy (MBCT) was developed as a psychological intervention for individuals at risk of depressive relapse. Possible mechanisms of change for this intervention are in line with its theoretical underpinnings, and include increases in mindfulness and/or decreases in negative repetitive thoughts. This review provides an overview of current trends in MBCT research, including efficacy and questions regarding the specific effects of MBCT in light of recent comparisons with structurally equivalent control conditions, mechanisms of change, and moderators of treatment outcome. In addition, future directions are discussed, such as challenges with training an adequate number of therapists and disseminating this therapy.

  18. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2006-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive (OC) therapy. 1...

  19. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George

    2003-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  20. Molecular Biology and Prevention of Endometrial Cancer

    National Research Council Canada - National Science Library

    Maxwell, George L

    2004-01-01

    To increase our understanding of the molecular aberrations associated with endometrial carcinogenesis and the biologic mechanisms underlying the protective effect of oral contraceptive therapy. Methods: 1...

  1. Ketogenic Diets: New Advances for Metabolism-Based Therapies

    Science.gov (United States)

    Kossoff, Eric H.; Hartman, Adam L.

    2014-01-01

    Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

  2. WE-FG-BRB-04: RBEs for Human Lung Cancer Cells Exposed to Protons and Heavier Ions: Implications for Clinical Use of Charged Particles in Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Held, K. [Massachusetts General Hospital (United States)

    2016-06-15

    The physical pattern of energy deposition and the enhanced relative biological effectiveness (RBE) of protons and carbon ions compared to photons offer unique and not fully understood or exploited opportunities to improve the efficacy of radiation therapy. Variations in RBE within a pristine or spread out Bragg peak and between particle types may be exploited to enhance cell killing in target regions without a corresponding increase in damage to normal tissue structures. In addition, the decreased sensitivity of hypoxic tumors to photon-based therapies may be partially overcome through the use of more densely ionizing radiations. These and other differences between particle and photon beams may be used to generate biologically optimized treatments that reduce normal tissue complications. In this symposium, speakers will examine the impact of the RBE of charged particles on measurable biological endpoints, treatment plan optimization, and the prediction or retrospective assessment of treatment outcomes. In particular, an AAPM task group was formed to critically examine the evidence for a spatially-variant RBE in proton therapy. Current knowledge of proton RBE variation with respect to dose, biological endpoint, and physics parameters will be reviewed. Further, the clinical relevance of these variations will be discussed. Recent work focused on improving simulations of radiation physics and biological response in proton and carbon ion therapy will also be presented. Finally, relevant biology research and areas of research needs will be highlighted, including the dependence of RBE on genetic factors including status of DNA repair pathways, the sensitivity of cancer stem-like cells to charged particles, the role of charged particles in hypoxic tumors, and the importance of fractionation effects. In addition to the physical advantages of protons and more massive ions over photons, the future application of biologically optimized treatment plans and their potential to

  3. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  4. Avatar-Based Therapy within Prison Settings: Pilot Evaluation

    Science.gov (United States)

    van Rijn, Biljana; Cooper, Mick; Jackson, Andrew; Wild, Ciara

    2017-01-01

    The paper presents an introduction of a newly developed, avatar-based virtual reality therapy, as an addition to the therapeutic programme, within a therapeutic community prison in the UK. The participants had six group sessions facilitated by a counsellor. The aim of the project was to investigate whether this approach would improve mental health…

  5. Design Issues and Application of Cable-Based Parallel Manipulators for Rehabilitation Therapy

    Directory of Open Access Journals (Sweden)

    E. Ottaviano

    2008-01-01

    Full Text Available In this study, cable-based manipulators are proposed for application in rehabilitation therapies. Cable-based manipulators show good features that are very useful when the system has to interact with humans. In particular, they can be used to aid motion or as monitoring/training systems in rehabilitation therapies. Modelling and simulation of both active and passive cable-based parallel manipulators are presented for an application to help older people, patients or disabled people in the sit-to-stand transfer and as a monitoring/training system. Experimental results are presented by using built prototypes.

  6. Application of Biologically-Based Lumping To Investigate the ...

    Science.gov (United States)

    People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. However, investigators have often considered complex mixtures as one lumped entity. Valuable information can be obtained from these experiments, though this simplification provides little insight into the impact of a mixture's chemical composition on toxicologically-relevant metabolic interactions that may occur among its constituents. We developed an approach that applies chemical lumping methods to complex mixtures, in this case gasoline, based on biologically relevant parameters used in physiologically-based pharmacokinetic (PBPK) modeling. Inhalation exposures were performed with rats to evaluate performance of our PBPK model. There were 109 chemicals identified and quantified in the vapor in the chamber. The time-course kinetic profiles of 10 target chemicals were also determined from blood samples collected during and following the in vivo experiments. A general PBPK model was used to compare the experimental data to the simulated values of blood concentration for the 10 target chemicals with various numbers of lumps, iteratively increasing from 0 to 99. Large reductions in simulation error were gained by incorporating enzymatic chemical interactions, in comparison to simulating the individual chemicals separately. The error was further reduced by lumping the 99 non-target chemicals. Application of this biologic

  7. Preclinical studies on gadolinium neutron capture therapy

    International Nuclear Information System (INIS)

    Akine, Yasuyuki

    1994-01-01

    Gadolinium neutron capture therapy is based on radiations (photons and electrons) produced in the tumor by a nuclear reaction between gadolinium and lower-energy neutrons. Studies with Chinese hamster cells have shown that the radiation effect resulting from gadolinium neutron capture reactions is mostly of low LET and that released electrons are the significant component in the over-all dose. Biological dosimetry revealed that the dose does not seem to increase in proportion to the gadolinium concentration, leading to a conclusion that there is a range of gadolinium concentrations most efficient for gadolinium neutron capture therapy. The in vivo studies with transplantable tumors in mice and rabbits have revealed that close contact between gadolinium and the cell is not necessarily required for cell inactivation and that gadolinium delivery selective to tumors is crucial. The results show that the potential of gadolinium neutron capture therapy as a therapeutic modality appears very promising. (author)

  8. Anti-B cell antibody therapies for inflammatory rheumatic diseases

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Jayne, David R W

    2014-01-01

    Several monoclonal antibodies targeting B cells have been tested as therapeutics for inflammatory rheumatic diseases. We review important observations from randomized clinical trials regarding the efficacy and safety of anti-B cell antibody-based therapies for rheumatoid arthritis, systemic lupus...... and functions in rheumatic disorders. Future studies should also evaluate how to maintain disease control by means of conventional and/or biologic immunosuppressants after remission-induction with anti-B cell antibodies....

  9. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  10. Gene therapy for the inner ear: challenges and promises.

    Science.gov (United States)

    Ryan, Allen F; Dazert, Stefan

    2009-01-01

    Since the recognition of genes as the discrete units of heritability, and of DNA as their molecular substrate, the utilization of genes for therapeutic purposes has been recognized as a potential means of correcting genetic disorders. The tools of molecular biology, which allow the manipulation of DNA sequence, provided the means to put this concept into practice. However, progress in the implementation of these ideas has been slow. Here we review the history of the idea of gene therapy and the complexity of genetic disorders. We also discuss the requirements for sequence-based therapy to be accomplished for different types of inherited diseases, as well as the methods available for gene manipulation. The challenges that have limited the applications of gene therapy are reviewed, as are ethical concerns. Finally, we discuss the promise of gene therapy to address inherited and acquired disorders of the inner ear. Copyright (c) 2009 S. Karger AG, Basel.

  11. Occupational Therapy in Medicaid Home and Community-Based Services Waivers

    Science.gov (United States)

    VanPuymbrouck, Laura

    2018-01-01

    OBJECTIVE. Medicaid Home and Community-Based Services (HCBS) 1915(c) waivers are the largest provider of long-term services and supports for people with intellectual and developmental disabilities (IDDs). In this study, we explored how HCBS IDD waivers projected providing occupational therapy services in Fiscal Year (FY) 2015. METHOD. Medicaid HCBS IDD waivers across the nation gathered from the Centers for Medicare and Medicaid Services were qualitatively and quantitatively analyzed to determine how they projected providing occupational therapy services in terms of service expenditures and utilization. RESULTS. In FY 2015, $14.13 million of spending was projected for occupational therapy services of 7,500 participants. However, there was large heterogeneity across states and services in terms of total projected spending, spending per participant, and reimbursement rates. CONCLUSION. Comparisons across states strengthen the profession’s ability to assert the value of its services. These findings can help identify best practices and can advocate for the refinement of state occupational therapy programs. PMID:29426389

  12. Targeted Alpha Therapy: From Alpha to Omega

    International Nuclear Information System (INIS)

    Allen, Barry J; Clarke, Raymond; Huang Chenyu

    2013-01-01

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

  13. Synthesis and biological evaluation of porphyrin-polyamine conjugates as potential agents in photodynamic therapy

    International Nuclear Information System (INIS)

    Lamarche, Francois

    2004-01-01

    The synthesis of photosensitizers that specifically recognize tumoral cells constitutes a challenging step in the field of photodynamic therapy. To this end, we designed a new class of porphyrins linked to natural polyamines (spermidine, spermine). As a first step, we synthesized para and ortho-carboxy-propyl-oxy-phenyl-tritolyl-porphyrins bearing spermidine or spermine. Then, we designed two precursors, N4-aminobutyl-spermidine-Boc2 and N4-aminobutyl-spermine-Boc3. These derivatives have been fixed on carboxy-porphyrins, protoporphyrin IX and chlorin e6. These new compounds have been characterized by MALDI spectrometry, UV-Visible and 1 H NMR spectroscopy. They have been found to produce singlet oxygen. Biological activity study of these photosensitizers has been realized on K562 cell line, irradiated with fluorescent bulbs. In vitro tests of these porphyrins have shown their photo-cytotoxic activity and protoporphyrins-polyamines have been able to trigger early apoptotic events. Finally, preliminary results obtained with chlorin e6-polyamines, irradiated with red light, seem to show that these structures are good candidates for an application in PDT. (author) [fr

  14. ‘Third wave’ cognitive therapy versus mentalization-based therapy for major depressive disorder. A protocol for a randomised clinical trial

    Directory of Open Access Journals (Sweden)

    Jakobsen Janus Christian

    2012-12-01

    Full Text Available Abstract Background Most interventions for depression have shown small or no effects. ‘Third wave‘ cognitive therapy and mentalization-based therapy have both gained some ground as treatments of psychological problems. No randomised trial has compared the effects of these two interventions for patients with major depression. Methods/ design We plan a randomised, parallel group, assessor-blinded superiority clinical trial. During two years we will include 84 consecutive adult participants diagnosed with major depressive disorder. The participants will be randomised to either ‘third wave‘ cognitive therapy versus mentalization-based therapy. The primary outcome will be the Hamilton Rating Scale for Depression at cessation of treatment at 18 weeks. Secondary outcomes will be the proportion of patients with remission, Symptom Checklist 90 Revised, Beck’s Depression Inventory, and The World Health Organisation-Five Well-being Index 1999. Discussion Interventions for depression have until now shown relatively small effects. Our trial results will provide knowledge about the effects of two modern psychotherapeutic interventions. Trial registration ClinicalTrials: NCT01070134

  15. A rapid Q-PCR titration protocol for adenovirus and helper-dependent adenovirus vectors that produces biologically relevant results

    Science.gov (United States)

    Gallaher, Sean D.; Berk, Arnold J.

    2013-01-01

    Adenoviruses are employed in the study of cellular processes and as expression vectors used in gene therapy. The success and reproducibility of these studies is dependent in part on having accurate and meaningful titers of replication competent and helper-dependent adenovirus stocks, which is problematic due to the use of varied and divergent titration protocols. Physical titration methods, which quantify the total number of viral particles, are used by many, but are poor at estimating activity. Biological titration methods, such as plaque assays, are more biologically relevant, but are time consuming and not applicable to helper-dependent gene therapy vectors. To address this, a protocol was developed called “infectious genome titration” in which viral DNA is isolated from the nuclei of cells ~3 h post-infection, and then quantified by Q-PCR. This approach ensures that only biologically active virions are counted as part of the titer determination. This approach is rapid, robust, sensitive, reproducible, and applicable to all forms of adenovirus. Unlike other Q-PCR-based methods, titers determined by this protocol are well correlated with biological activity. PMID:23624118

  16. Design of synthetic biological logic circuits based on evolutionary algorithm.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

    2013-08-01

    The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

  17. PHARMACOECONOMIC ISSUES OF ADALIMUMAB THERAPY IN JUVENILE IDIOPATHIC ARTHRITIS

    Directory of Open Access Journals (Sweden)

    K. Simpson

    2012-01-01

    Full Text Available Background. Juvenile idiopathic arthritis (JIA is the most common type of arthritis in children and is associated with reduced quality of life and increased health care costs. Objective. To evaluate the cost effectiveness of the tumour necrosis factor inhibitor adalimumab (ADA vs. non-biologic therapy for the treatment of JIA in Russian children and adolescents. Materials and Methods. A Markov model was developed on the basis of the DE038 clinical trial, which compared ADA plus methotrexate (MTX vs. placebo plus MTX for the treatment of JIA in children aged 4–17 years. Cost-effectiveness analyses were performed from the standpoint of the Russian health care system and society as a whole. Base case analyses followed 11-year-old patients with JIA for a period of 7 years (until the age of 18 years or over an expected lifetime. Additional analyses followed patients aged 7 years at treatment initiation for a period of 11 years or over a simulated lifetime. The cost of treating severe JIA was assumed to be the same as reported in a published investigation. The cost of ADA therapy was based on the expected cost assuming inclusion in the List of Vital and Essential Medicinal Products. This took into account the Value Added Tax and a 10% trade mark-up. Treatment outcomes were measured in quality-adjusted life years (QALYs. Results and Discussion. Over a 7-year time horizon, the incremental cost-utility ratio (ICUR for ADA vs. conventional nonbiologic therapy in the treatment of JIA in 11-year-old patients was 1,571,500 roubles/QALY when using a health care system perspective and 1,515,000 roubles/QALY when using a societal perspective. Over a simulated patient lifetime, the corresponding ICURs were 286,300 roubles/QALY and 275,300 roubles/QALY, respectively. Over an 11-year time horizon, the ICUR for ADA vs. conventional non-biologic therapy in the treatment of JIA in patients aged 7 years at the start of therapy was 852,400 roubles/QALY when

  18. 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...

  19. 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...

  20. 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.

  1. 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. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  2. The molecular biology of WHO grade I astrocytomas.

    Science.gov (United States)

    Marko, Nicholas F; Weil, Robert J

    2012-12-01

    World Health Organization (WHO) grade I astrocytomas include pilocytic astrocytoma (PA) and subependymal giant cell astrocytoma (SEGA). As technologies in pharmacologic neo-adjuvant therapy continue to progress and as molecular characteristics are progressively recognized as potential markers of both clinically significant tumor subtypes and response to therapy, interest in the biology of these tumors has surged. An updated review of the current knowledge of the molecular biology of these tumors is needed. We conducted a Medline search to identify published literature discussing the molecular biology of grade I astrocytomas. We then summarized this literature and discuss it in a logical framework through which the complex biology of these tumors can be clearly understood. A comprehensive review of the molecular biology of WHO grade I astrocytomas is presented. The past several years have seen rapid progress in the level of understanding of PA in particular, but the molecular literature regarding both PA and SEGA remains nebulous, ambiguous, and occasionally contradictory. In this review we provide a comprehensive discussion of the current understanding of the chromosomal, genomic, and epigenomic features of both PA and SEGA and provide a logical framework in which these data can be more readily understood.

  3. The potential of standards-based agriculture biology as an alternative to traditional biology in California

    Science.gov (United States)

    Sellu, George Sahr

    schools. Thoron & Meyer (2011) suggested that research into the contribution of integrated science courses toward higher test scores yielded mixed results. This finding may have been due in part to the fact that integrated science courses only incorporate select topics into agriculture education courses. In California, however, agriculture educators have developed standards-based courses such as Agriculture Biology (AgBio) that cover the same content standards as core traditional courses such as traditional biology. Students in both AgBio and traditional biology take the same standardized biology test. This is the first time there has been an opportunity for a fair comparison and a uniform metric for an agriscience course such as AgBio to be directly compared to traditional biology. This study will examine whether there are differences between AgBio and traditional biology with regard to standardized test scores in biology. Furthermore, the study examines differences in perception between teachers and students regarding teaching and learning activities associated with higher achievement in science. The findings of the study could provide a basis for presenting AgBio as a potential alternative to traditional biology. The findings of this study suggest that there are no differences between AgBio and traditional biology students with regard to standardized biology test scores. Additionally, the findings indicate that co-curricular activities in AgBio could contribute higher student achievement in biology. However, further research is required to identify specific activities in AgBio that contribute to higher achievement in science.

  4. Biological Select Agents and Toxins: Risk-Based Assessment Management and Oversight.

    Energy Technology Data Exchange (ETDEWEB)

    Burnett, LouAnn Crawford; Brodsky, Benjamin H.

    2016-12-01

    Sandia National Laboratories' International Biological and Chemical Threat Reduction (SNL/IBCTR) conducted, on behalf of the Federal Select Agent Program (FSAP), a review of risk assessment in modern select agent laboratories. This review and analysis consisted of literature review, interviews of FSAP staff, entities regulated by FSAP, and deliberations of an expert panel. Additionally, SNL/IBCTR reviewed oversight mechanisms used by industries, US agencies, and other countries for high-consequence risks (e.g, nuclear, chemical, or biological materials, aviation, off-shore drilling, etc.) to determine if alternate oversight mechanisms existed that might be applicable to FSAP oversight of biological select agents and toxins. This report contains five findings, based on these reviews and analyses, with recommendations and suggested actions for FSAP to consider.

  5. Assessment of refinery effluents and receiving waters using biologically-based effect methods

    International Nuclear Information System (INIS)

    2012-01-01

    Within the EU it is apparent that the regulatory focus on the use of biologically-based effects methods in the assessment of refinery effluents and receiving waters has increased in the past decade. This has been reflected in a recent refinery survey which revealed an increased use of such methods for assessing the quality of refinery effluents and their receiving waters. This report provides an overview of recent techniques used for this purpose. Several case studies provided by CONCAWE member companies describe the application of biological methods to effluent discharge assessment and surface water monitoring. The case studies show that when biological methods are applied to refinery effluents and receiving waters they raise different questions compared with those obtained using physical and chemical methods. Although direct measurement of the toxicity of effluent and receiving to aquatic organisms is the most cited technique, more recent efforts include tests that also address the persistence of effluent toxicity once discharged into the receiving water. Similarly, ecological monitoring of receiving waters can identify effects of effluent inputs arising from species interactions and other secondary effects that would not always be apparent from the results of biological tests conducted on single aquatic organisms. In light of recent and proposed regulatory developments the objectives of this report are therefore to: Discuss the application of biologically-based effects methods (including ecological monitoring) to refinery discharges and receiving waters; Assess the implications of such methods for future regulation of refinery discharges; and Provide guidance on good practice that can be used by refineries and the downstream oil industry to carry out and interpret data obtained using biologically-based effects methods. While the emphasis is on the toxic effects of effluents, other properties will also be covered because of their interdependency in determining

  6. Assessment of refinery effluents and receiving waters using biologically-based effect methods

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2012-01-15

    Within the EU it is apparent that the regulatory focus on the use of biologically-based effects methods in the assessment of refinery effluents and receiving waters has increased in the past decade. This has been reflected in a recent refinery survey which revealed an increased use of such methods for assessing the quality of refinery effluents and their receiving waters. This report provides an overview of recent techniques used for this purpose. Several case studies provided by CONCAWE member companies describe the application of biological methods to effluent discharge assessment and surface water monitoring. The case studies show that when biological methods are applied to refinery effluents and receiving waters they raise different questions compared with those obtained using physical and chemical methods. Although direct measurement of the toxicity of effluent and receiving to aquatic organisms is the most cited technique, more recent efforts include tests that also address the persistence of effluent toxicity once discharged into the receiving water. Similarly, ecological monitoring of receiving waters can identify effects of effluent inputs arising from species interactions and other secondary effects that would not always be apparent from the results of biological tests conducted on single aquatic organisms. In light of recent and proposed regulatory developments the objectives of this report are therefore to: Discuss the application of biologically-based effects methods (including ecological monitoring) to refinery discharges and receiving waters; Assess the implications of such methods for future regulation of refinery discharges; and Provide guidance on good practice that can be used by refineries and the downstream oil industry to carry out and interpret data obtained using biologically-based effects methods. While the emphasis is on the toxic effects of effluents, other properties will also be covered because of their interdependency in determining

  7. Multidisciplinary approach of early breast cancer: The biology applied to radiation oncology

    International Nuclear Information System (INIS)

    Bourgier, Céline; Ozsahin, Mahmut; Azria, David

    2010-01-01

    Early breast cancer treatment is based on a multimodality approach with the application of clinical and histological prognostic factors to determine locoregional and systemic treatments. The entire scientific community is strongly involved in the management of this disease: radiologists for screening and early diagnosis, gynecologists, surgical oncologists and radiation oncologists for locoregional treatment, pathologists and biologists for personalized characterization, genetic counselors for BRCA mutation history and medical oncologists for systemic therapies. Recently, new biological tools have established various prognostic subsets of breast cancer and developed predictive markers for miscellaneous treatments. The aim of this article is to highlight the contribution of biological tools in the locoregional management of early breast cancer

  8. Considerations on hypoxic conditions. On the past setback of classic radiation biology

    International Nuclear Information System (INIS)

    Nakatsugawa, Shigekazu; Klimova, S.V.; Tamasu, Shogo; Nakamura, Hideaki; Murayama, Chieko

    2002-01-01

    Considerations on hypoxic cancer cell environment are made on classic radiation biology concept and on a new proposal of the anti-cancer strategy. Classic radiation biology knowledge of hypoxic cancer cells has produced many of clinical trials, which, however, have failed after all. This is because the knowledge is that the cells are recognized to be in a rather static hypoxic condition. Based on authors' investigations, made is the proposal that improvement of dynamic, acute hypoxic conditions yielded via blood circulation between the heterogeneous malignant cancer cells and the dynamic homeostatic systems of normal cells including immunity is important as one of cancer therapy approaches. (N.I.)

  9. Use of biologics in severe food allergies.

    Science.gov (United States)

    Fiocchi, Alessandro; Pecora, Valentina; Valluzzi, Rocco L; Fierro, Vincenzo; Mennini, Maurizio

    2017-06-01

    Severe cases of food allergy account for the majority of the burden in terms of risks, quality of life, and resource expenditure. The traditional approach to these forms has been strict avoidance. More recently, Oral ImmunoTherapy (OIT) has gained a role in their management. However, in severe food allergies OIT is often infeasible. Case reports, observational, and prospective studies have recently proposed different approaches to severe food allergy. The majority of them include the use of biologics. Omalizumab has been the most studied drug for severe food allergies, and its role as adjuvant treatment to OIT is well established. Interest has been raised on other biologics, as dupilumab, reslizumab, and mepolizumab. Toll-like receptor agonists, and gene therapy using adeno-associated virus coding for Omalizumab are promising alternatives. The recent studies are deeply influencing the clinical practice. We review the modifications of the clinical approach to severe food allergies so far available. We indicate the possible evolutions of treatment with biologics in severe food allergies.

  10. On the cost-effectiveness of Carbon ion radiation therapy for skull base chordoma

    International Nuclear Information System (INIS)

    Jaekel, Oliver; Land, Beate; Combs, Stephanie Elisabeth; Schulz-Ertner, Daniela; Debus, Juergen

    2007-01-01

    Aim: The cost-effectiveness of Carbon ion radiotherapy (RT) for patients with skull base chordoma is analyzed. Materials and Methods: Primary treatment costs and costs for recurrent tumors are estimated. The costs for treatment of recurrent tumors were estimated using a sample of 10 patients presenting with recurrent chordoma at the base of skull at DKFZ. Using various scenarios for the local control rate and reimbursements of Carbon ion therapy the cost-effectiveness of ion therapy for these tumors is analyzed. Results: If local control rate for skull base chordoma achieved with carbon ion therapy exceeds 70.3%, the overall treatment costs for carbon RT are lower than for conventional RTI. The cost-effectiveness ratio for carbon RT is 2539 Euro per 1% increase in survival, or 7692 Euro per additional life year. Conclusion: Current results support the thesis that Carbon ion RT, although more expensive, is at least as cost-effective as advanced photon therapies for these patients. Ion RT, however, offers substantial benefits for the patients such as improved control rates and less severe side effects

  11. Persistent phosphors for painting, medical and biological applications

    International Nuclear Information System (INIS)

    Nazarov, M.

    2013-01-01

    Multiphase micro and nanoparticle persistent phosphors are synthesized and applied for different fields including painting, medical and biological investigations. A lot of examples show a broad range of applications of persistent luminescence from bulk materials to high tech products, especially in medicine. The development of high efficiency nanosized phosphor makes it possible to propose persistent materials as very good candidates for photodynamic therapy of cancer. An artificial block from slag, concrete, and sand covered with SrAl 2 O 4 :Eu 2+ , Dy 3+ based phosphor is prepared, and a new direction in biology for algae cultivation and artificial reef is discussed. For the first time, underwater luminescence is experimentally studied under real sea conditions. Bright blue-green long-lasting afterglow is registered at a depth of 5 m. The fishes are attracted by the light of the artificial reef. (author)

  12. 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)

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

    Science.gov (United States)

    Arivarasan, K; Bhardwaj, Vaishali; Sud, Sukrit; Sachdeva, Sanjeev; Puri, Amarender Singh

    2016-10-01

    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.

  14. Biodegradable nanoparticles for gene therapy technology

    International Nuclear Information System (INIS)

    Hosseinkhani, Hossein; He, Wen-Jie; Chiang, Chiao-Hsi; Hong, Po-Da; Yu, Dah-Shyong; Domb, Abraham J.; Ou, Keng-Liang

    2013-01-01

    Rapid propagations in materials technology together with biology have initiated great hopes in the possibility of treating many diseases by gene therapy technology. Viral and non-viral gene carriers are currently applied for gene delivery. Non-viral technology is safe and effective for the delivery of genetic materials to cells and tissues. Non-viral systems are based on plasmid expression containing a gene encoding a therapeutic protein and synthetic biodegradable nanoparticles as a safe carrier of gene. Biodegradable nanoparticles have shown great interest in drug and gene delivery systems as they are easy to be synthesized and have no side effect in cells and tissues. This review provides a critical view of applications of biodegradable nanoparticles on gene therapy technology to enhance the localization of in vitro and in vivo and improve the function of administered genes

  15. Facilitation of research-based evidence within occupational therapy in stroke rehabilitation

    DEFF Research Database (Denmark)

    Kristensen, Hanne Kaae; Borg, T.; Hounsgaard, Lise

    2011-01-01

    Purpose: This study investigated the facilitation of evidence-based practice with the use of everyday life occupations and client-centred practice within occupational therapy in three settings of stroke rehabilitation. Method: The study was based on a phenomenological hermeneutical research...

  16. The role of incretin-based therapies in prediabetes: a review.

    Science.gov (United States)

    Ahmadieh, Hala; Azar, Sami T

    2014-12-01

    Prediabetes, a high-risk state for future development of diabetes, is prevalent globally. Abnormalities in the incretin axis are important in the progression of B-cell failure in type 2 diabetes. Incretin based therapy was found to improve B cell mass and glycaemic control in addition to having multiple beneficial effects on the systolic and diastolic blood pressure, weight loss in addition to their other beneficial effects on the liver and cardiovascular system. In prediabetes, several well-designed preventive trials have shown that lifestyle and pharmacologic interventions such as metformin, thiazolidinediones (TZD), acarbose and, nateglinide and orlistat, are effective in reducing diabetes development. In recent small studies, incretin based therapy (DPP IV inhibitors and GLP-1 agonists) have also been extended to patients with prediabetes since it was shown to better preserve B-cell function and mass in animal studies and in clinical trials and it was also shown to help maintain good long term metabolic control. Because of the limited studies and clinical experience, their side effects and costs currently guidelines do not recommend incretin-based therapies as an option for treatment in patients with prediabetes. With future clinical trials and studies they may be recommended for patients with impaired fasting glucose or impaired glucose tolerance. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  17. Incretin-based therapies in prediabetes: Current evidence and future perspectives

    Science.gov (United States)

    Papaetis, Georgios S

    2014-01-01

    The prevalence of type 2 diabetes (T2D) is evolving globally at an alarming rate. Prediabetes is an intermediate state of glucose metabolism that exists between normal glucose tolerance (NGT) and the clinical entity of T2D. Relentless β-cell decline and failure is responsible for the progression from NGT to prediabetes and eventually T2D. The huge burden resulting from the complications of T2D created the need of therapeutic strategies in an effort to prevent or delay its development. The beneficial effects of incretin-based therapies, dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, on β-cell function in patients with T2D, together with their strictly glucose-depended mechanism of action, suggested their possible use in individuals with prediabetes when greater β-cell mass and function are preserved and the possibility of β-cell salvage is higher. The present paper summarizes the main molecular intracellular mechanisms through which GLP-1 exerts its activity on β-cells. It also explores the current evidence of incretin based therapies when administered in a prediabetic state, both in animal models and in humans. Finally it discusses the safety of incretin-based therapies as well as their possible role in order to delay or prevent T2D. PMID:25512784

  18. Advances in biologic augmentation for rotator cuff repair

    Science.gov (United States)

    Patel, Sahishnu; Gualtieri, Anthony P.; Lu, Helen H.; Levine, William N.

    2016-01-01

    Rotator cuff tear is a very common shoulder injury that often necessitates surgical intervention for repair. Despite advances in surgical techniques for rotator cuff repair, there is a high incidence of failure after surgery because of poor healing capacity attributed to many factors. The complexity of tendon-to-bone integration inherently presents a challenge for repair because of a large biomechanical mismatch between the tendon and bone and insufficient regeneration of native tissue, leading to the formation of fibrovascular scar tissue. Therefore, various biological augmentation approaches have been investigated to improve rotator cuff repair healing. This review highlights recent advances in three fundamental approaches for biological augmentation for functional and integrative tendon–bone repair. First, the exploration, application, and delivery of growth factors to improve regeneration of native tissue is discussed. Second, applications of stem cell and other cell-based therapies to replenish damaged tissue for better healing is covered. Finally, this review will highlight the development and applications of compatible biomaterials to both better recapitulate the tendon–bone interface and improve delivery of biological factors for enhanced integrative repair. PMID:27750374

  19. Clinical Implications for the Timely Diagnosis of Mycobacterium marinum in the Age of Biologic Therapy: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Chris J. Lata

    2017-01-01

    Full Text Available Mycobacterium marinum infections typically present as cutaneous nodular lesions with a sporotrichoid lymphatic spread on extensor surfaces of extremities. The natural history of this infection can be altered if the host is immunosuppressed, leading to disseminated presentations. A detailed exposure history and high degree of suspicion for this indolent pathogen are often required for the correct diagnosis of this disease. We present a case of a 67-year-old male misdiagnosed with seronegative rheumatoid arthritis presenting with rheumatic nodules. Initiation of chronic immunosuppressant therapy including biologic monoclonal antibodies resulted in the exacerbation of initially localized disease to broadly disseminated lymphatic, joint, and myotendinous granulomatous disease and led to delay in the correct diagnosis. Cessation of immunosuppressants, with a prolonged course of antimicrobial therapy and multiple surgical debridements were required for cure.

  20. Construction of a Linux based chemical and biological information system.

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.