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Sample records for biologically based therapies

  1. 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

  2. Biological Therapies for Cancer

    Science.gov (United States)

    ... Page What is biological therapy? What is the immune system and what role does it have in biological therapy for cancer? ... trials (research studies involving people). What is the immune system and what role does it have in biological therapy for cancer? ...

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

    Science.gov (United States)

    Sanina, Cristina; Hare, Joshua M

    2015-07-17

    Cell-based treatment represents a new generation in the evolution of biological therapeutics. A prototypic cell-based therapy, the mesenchymal stem cell, has successfully entered phase III pivotal trials for heart failure, signifying adequate enabling safety and efficacy data from phase I and II trials. Successful phase III trials can lead to approval of a new biological therapy for regenerative medicine. © 2015 American Heart Association, Inc.

  4. Biological therapy of psoriasis

    Directory of Open Access Journals (Sweden)

    Sivamani Raja

    2010-01-01

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

  5. 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

  6. 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...... development. This information, in turn, has led to new opportunities for the treatment of cancer. Normal cells, however, are also dependent on these pathways to maintain their function and, consequently, their survival. Interfering with this function in normal cells may result in the risk of serious adverse...

  7. The biological effectiveness of targeted radionuclide therapy based on a whole-body pharmacokinetic model

    Science.gov (United States)

    Grudzinski, Joseph J; Tomé, Wolfgang; Weichert, Jamey P; Jeraj, Robert

    2013-01-01

    Biologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumour response relationships. By taking into account the dose rate and tissue-specific parameters such as repair and radiosensitivity, it is possible to compare the relative biological effects of different targeted radionuclide therapy (TRT) agents. The aim of this work was to develop an analytical tumour BED calculation for TRT that could predict a relative biological effect based on normal body and tumour pharmacokinetics. This work represents a step in the direction of establishing relative pharmacokinetic criteria of when the BED formalism is more applicable than absorbed dose for TRT. A previously established pharmacokinetic (PK) model for TRT was used and adapted into the BED formalism. An analytical equation for the protraction factor, which incorporates dose rate and repair rate, was derived. Dose rates within the normal body and tumour were related to the slopes of their time–activity curves which were determined by the ratios of their respective PK parameters. The relationships between the tumour influx-to-efflux ratio (k34:k43), central compartment efflux-to-influx ratio (k12:k21), central elimination (kel), and tumour repair rate (μ), and tumour BED were investigated. As the k34:k43 ratio increases and the k12:k21 ratio decreases, the difference between tumour BED and D increases. In contrast, as the k34:k43 ratios decrease and the k12:k21 ratios increase, the tumour BED approaches D. At large k34:k43 ratios, the difference between tumour BED and D increases to a maximum as kel increases. At small k34:k43 ratios, the tumour BED approaches D at very small kel. At small μ and small k34:k43 ratios, the tumour BED approaches D. For large k34:k43 ratios, large μ values cause tumour BED to approach D. This work represents a step in the direction of establishing relative PK criteria of when the BED formalism is more applicable than absorbed dose for

  8. 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.

  9. Future biologic therapies in asthma.

    Science.gov (United States)

    Quirce, Santiago; Bobolea, Irina; Domínguez-Ortega, Javier; Barranco, Pilar

    2014-08-01

    Despite the administration of appropriate treatment, a high number of patients with asthma remain uncontrolled. This suggests the need for alternative treatments that are effective, safe and selective for the established asthma phenotypes, especially in patients with uncontrolled severe asthma. The most promising options among the new asthma treatments in development are biological therapies, particularly those monoclonal antibodies directed at selective targets. It should be noted that the different drugs, and especially the new biologics, act on very specific pathogenic pathways. Therefore, determination of the individual profile of predominant pathophysiological alterations of each patient will be increasingly important for prescribing the most appropriate treatment in each case. The treatment of severe allergic asthma with anti-IgE monoclonal antibody (omalizumab) has been shown to be effective in a large number of patients, and new anti-IgE antibodies with improved pharmacodynamic properties are being investigated. Among developing therapies, biologics designed to block certain pro-inflammatory cytokines, such as IL-5 (mepolizumab) and IL-13 (lebrikizumab), have a greater chance of being used in the clinic. Perhaps blocking more than one cytokine pathway (such as IL-4 and IL-13 with dulipumab) might confer increased efficacy of treatment, along with acceptable safety. Stratification of asthma based on the predominant pathogenic mechanisms of each patient (phenoendotypes) is slowly, but probably irreversibly, emerging as a tailored medical approach to asthma, and is becoming a key factor in the development of drugs for this complex respiratory syndrome. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  10. Biologic therapy and surgery for crohn disease.

    Science.gov (United States)

    Paulson, E Carter

    2013-06-01

    In 1998, infliximab, an antitumor necrosis factor alpha (anti-TNF-α) antibody, was approved for use in the treatment of Crohn disease (CD). Since then, other biologic therapies, including adalimumab and certolizumab pegol (newer anti-TNF-α antibodies), and natalizumab, an antibody against alpha-4 integrin, have also been approved. Here, we review the published studies that examine the relationship between pre- and postoperative biologic therapy and postoperative complications in patients with CD. This body of literature is composed of numerous small, retrospective, heterogeneous studies that demonstrate conflicting and varied results. Overall, the receipt of biologic therapy in the pre- or postoperative period does not appear to significantly increase the risk of postoperative complications. It is, however, difficult to draw any firm conclusions based on the existing level of data. In the future, larger prospective studies are needed to better elucidate the true risks, if any, that the use of biologic therapy poses to patients with CD requiring operation.

  11. NOTE: Implementation of biologically conformal radiation therapy (BCRT) in an algorithmic segmentation-based inverse planning approach

    Science.gov (United States)

    Vanderstraeten, Barbara; DeGersem, Werner; Duthoy, Wim; DeNeve, Wilfried; Thierens, Hubert

    2006-08-01

    The development of new biological imaging technologies offers the opportunity to further individualize radiotherapy. Biologically conformal radiation therapy (BCRT) implies the use of the spatial distribution of one or more radiobiological parameters to guide the IMRT dose prescription. Our aim was to implement BCRT in an algorithmic segmentation-based planning approach. A biology-based segmentation tool was developed to generate initial beam segments that reflect the biological signal intensity pattern. The weights and shapes of the initial segments are optimized by means of an objective function that minimizes the root mean square deviation between the actual and intended dose values within the PTV. As proof of principle, [18F]FDG-PET-guided BCRT plans for two different levels of dose escalation were created for an oropharyngeal cancer patient. Both plans proved to be dosimetrically feasible without violating the planning constraints for the expanded spinal cord and the contralateral parotid gland as organs at risk. The obtained biological conformity was better for the first (2.5 Gy per fraction) than for the second (3 Gy per fraction) dose escalation level.

  12. Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies.

    Science.gov (United States)

    Schmalz, Gottfried; Smith, Anthony J

    2014-04-01

    The traditional concept of replacing diseased tooth/pulp tissues by inert materials (restoration) is being challenged by recent advances in pulp biology leading to regenerative strategies aiming at the generation of new vital tissue. New tissue formation in the pulp chamber can be observed after adequate infection control and the formation of a blood clot. However, differentiation of true odontoblasts is still more speculative, and the approach is largely limited to immature teeth with open apices. A more systematic approach may be provided by the adoption of the tissue engineering concepts of using matrices, suitable (stem) cells, and signaling molecules to direct tissue events. With these tools, pulplike constructs have already been generated in experimental animals. However, a number of challenges still remain for clinical translation of pulp regeneration (eg, the cell source [resident vs nonresident stem cells, the latter associated with cell-free approaches], mechanisms of odontoblast differentiation, the pulp environment, the role of infection and inflammation, dentin pretreatment to release fossilized signaling molecules from dentin, and the provision of suitable matrices). Transition as a process, defined by moving from one form of "normal" to another, is based not only on the progress of science but also on achieving change to established treatment concepts in daily practice. However, it is clear that the significant recent achievements in pulp biology are providing an exciting platform from which clinical translation of dental pulp regeneration can advance. Copyright © 2014. Published by Elsevier Inc.

  13. 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

  14. Biologic therapy of rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    Damjanov Nemanja

    2009-01-01

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

  15. A View of the Therapy for Bell's Palsy Based on Molecular Biological Analyses of Facial Muscles.

    Science.gov (United States)

    Moriyama, Hiroshi; Mitsukawa, Nobuyuki; Itoh, Masahiro; Otsuka, Naruhito

    2017-12-01

    Details regarding the molecular biological features of Bell's palsy have not been widely reported in textbooks. We genetically analyzed facial muscles and clarified these points. We performed genetic analysis of facial muscle specimens from Japanese patients with severe (House-Brackmann facial nerve grading system V) and moderate (House-Brackmann facial nerve grading system III) dysfunction due to Bell's palsy. Microarray analysis of gene expression was performed using specimens from the healthy and affected sides, and gene expression was compared. Changes in gene expression were defined as an affected side/healthy side ratio of >1.5 or Bell's palsy changes with the degree of facial nerve palsy. Especially, muscle, neuron, and energy category genes tended to fluctuate with the degree of facial nerve palsy. It is expected that this study will aid in the development of new treatments and diagnostic/prognostic markers based on the severity of facial nerve palsy.

  16. Switching profiles in a population-based cohort of rheumatoid arthritis receiving biologic therapy: results from the KOBIO registry.

    Science.gov (United States)

    Park, Dong-Jin; Choi, Sung Jae; Shin, Kichul; Kim, Hyoun-Ah; Park, Yong-Beom; Kang, Seong Wook; Kwok, Seung-Ki; Kim, Seong-Kyu; Nam, Eon Jeong; Sung, Yoon-Kyoung; Lee, Jaejoon; Lee, Chang Hoon; Jeon, Chan Hong; Lee, Shin-Seok

    2017-05-01

    Despite improved quality of care for rheumatoid arthritis (RA) patients, many still experience treatment failure with a biologic agent and eventually switch to another biologic agent. We investigated patterns of biologic treatment and reasons for switching biologics in patients with RA. Patients with RA who had started on a biologic agent or had switched to another biologic agent were identified from the prospective observational Korean nationwide Biologics (KOBIO) registry. The KOBIO registry contained 1184 patients with RA at the time of initiation or switching of biologic agents. Patients were categorized according to the chronological order of the introduction of biologic agents, and reasons for switching biologics were also evaluated. Of the 1184 patients with RA, 801 started with their first biologic agent, 228 were first-time switchers, and 89 were second-time or more switchers. Second-time or more switchers had lower rheumatoid factor and anti-CCP positivity, and higher disease activity scores at the time of enrollment than the other groups. Among these patients, tocilizumab was the most commonly prescribed biologic agent, followed by adalimumab and etanercept. The most common reason for switching biologics was inefficacy, followed by adverse events, including infusion reactions, infections, and skin eruptions. Furthermore, the proportion of inefficacy, as a reason for switching, was significantly higher with respect to switching between biologics with different mechanisms of action than between biologics with similar mechanisms. In this registry, we showed diverse prescribing patterns and differing baseline profiles based on the chronological order of biologic agents.

  17. 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.

  18. 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.

  19. Adverse Reactions to Biologic Therapy.

    Science.gov (United States)

    Patel, Sheenal V; Khan, David A

    2017-05-01

    Biologic therapies are emerging as a significant therapeutic option for many with debilitating inflammatory and autoimmune conditions. As expansion in the number of FDA-approved agents continue to be seen, more unanticipated adverse reactions are likely to occur. Currently, the diagnostic tools, including skin testing and in vitro testing, to evaluate for immediate hypersensitivity reactions are insufficient. In this review, management strategies for common acute infusion reactions, injection site reactions, and immediate reactions suggestive of IgE-mediated mechanisms are discussed. Desensitization can be considered for reactions suggestive of IgE-mediated mechanisms, but allergists/immunologists should be involved in managing these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Corneal neovascularization and biological therapy.

    Science.gov (United States)

    Voiculescu, O B; Voinea, L M; Alexandrescu, C

    2015-01-01

    Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their ability to reduce blood and lymphatic vessel ingrowth into the cornea, and to reduce inflammation. Numerous studies have shown that biologics with specificity for VEGF A such as bevacizumab and ranibizumab (a recombinant antibody and an antibody fragment, respectively) or anti-tumor necrosis factor-α microantibody, are effective in the treatment of corneal neovascularization.

  1. 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.

  2. Biologic therapy in inflammatory bowel disease

    DEFF Research Database (Denmark)

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

    2013-01-01

    is not preferred. Further treatment strategy depends on the response to induction therapy. Treatment efficacy is assessed by symptoms, clinical markers, paraclinical parameters and possibly by endoscopy. Effect of maintenance therapy should be evaluated at least every 26-52 weeks. During treatment with biologic...

  3. 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

  4. 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.

  5. 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.

  6. Optimization of biologic therapy in Crohn's disease.

    Science.gov (United States)

    Razvi, Mohammed; Lazarev, Mark

    2018-03-01

    Crohn's disease (CD) is a manifestation of inflammatory bowel disease (IBD), which can result in significant morbidity. Biologic therapy with anti-TNF medication has been effective in treating inflammation and reducing complications in CD. It is important for clinicians to have better knowledge of the various biologic therapies including mechanisms of action and optimization strategies. Areas covered: The review describes optimization of biologic therapy in CD including different mechanisms of loss of response, therapeutic drug monitoring in CD, clinical implications and management strategies which utilize drug monitoring, and areas of future development and research in optimization of biologic therapy. Expert opinion: Achieving adequate levels of the drug (antibody unbound) is one of the most important determinants of attaining clinical remission and mucosal healing. Drug level is also critical in determining if a patient requires combination therapy with an immunomodulator. Certain populations, including those with active perianal disease, may require higher serum levels to achieve healing or closure. Treat to target level is an algorithm that is not universally accepted and more data is need. Additionally, there are numerous assays that don't always correlate, especially regarding measuring anti-drug antibodies.

  7. 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. 

  8. Step Therapy And Biologics: No Easy Answers

    OpenAIRE

    HAGLAND, MARK

    2006-01-01

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

  9. Comparison of Biologic Disease-Modifying Antirheumatic Drug Therapy Persistence Between Biologics Among Rheumatoid Arthritis Patients Switching from Another Biologic.

    Science.gov (United States)

    Johnston, Stephen S; McMorrow, Donna; Farr, Amanda M; Juneau, Paul; Ogale, Sarika

    2015-06-01

    To compare biologic disease-modifying antirheumatic drug therapy persistence between biologics among patients with rheumatoid arthritis (RA) who previously used ≥1 other biologic. Using a large United States administrative claims dataset, we identified adult patients with RA initiating abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, or tocilizumab between January 1, 2010 and January 1, 2012 (initiation date = index). Patients were required to have used ≥1 other biologic before index. Outcomes were biologic persistence, defined in two alternative ways: (1) time from initiation until switching to a different biologic (time to switch) and (2) time from initiation until switching or the first occurrence of a 90-day gap in treatment with the initiated biologic (time to switch/discontinuation). Rituximab was excluded from analyses due to retreatment based on clinical evaluation, which complicates the measurement of persistence. Multivariable survival analyses compared persistence outcomes between tocilizumab and the other biologics, adjusting for patient characteristics. The sample comprised 9,782 biologic initiations; mean age 54 years and 82% female. Compared with tocilizumab, the hazards of switching biologic therapy were significantly higher for abatacept [hazard ratio (HR) = 1.19, P = 0.041], adalimumab (HR = 1.39, P biologic therapy were significantly higher for adalimumab (HR = 1.16, P = 0.014) and certolizumab (HR = 1.15, P biologic persistence to focus specifically on patients with RA who are not naïve to biologic treatment. Among patients with RA who previously used ≥1 other biologic, tocilizumab-treated patients had similar or significantly better biologic persistence compared with other biologics.

  10. Breast Cancer Biology: Clinical Implications for Breast Radiation Therapy.

    Science.gov (United States)

    Horton, Janet K; Jagsi, Reshma; Woodward, Wendy A; Ho, Alice

    2018-01-01

    Historically, prognosis and treatment decision making for breast cancer patients have been dictated by the anatomic extent of tumor spread. However, in recent years, "breast cancer" has proven to be a collection of unique phenotypes with distinct prognoses, patterns of failure, and treatment responses. Recent advances in biologically based assays and targeted therapies designed to exploit these unique phenotypes have profoundly altered systemic therapy practice patterns and treatment outcomes. Data associating locoregional outcomes with tumor biology are emerging. However, the likelihood of obtaining level I evidence for fundamental radiation therapy questions within each of the specific subtypes in the immediate future is low. As such, this review aims to summarize the existing data and provide practical context for the incorporation of breast tumor biology into clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-10-21

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

  13. 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.

  14. 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.

  15. Triple Therapy Versus Biologic Therapy for Active Rheumatoid Arthritis: A Cost-Effectiveness Analysis.

    Science.gov (United States)

    Bansback, Nick; Phibbs, Ciaran S; Sun, Huiying; O'Dell, James R; Brophy, Mary; Keystone, Edward C; Leatherman, Sarah; Mikuls, Ted R; Anis, Aslam H

    2017-07-04

    The RACAT (Rheumatoid Arthritis Comparison of Active Therapies) trial found triple therapy to be noninferior to etanercept-methotrexate in patients with active rheumatoid arthritis (RA). To determine the cost-effectiveness of etanercept-methotrexate versus triple therapy as a first-line strategy. A within-trial analysis based on the 353 participants in the RACAT trial and a lifetime analysis that extrapolated costs and outcomes by using a decision analytic cohort model. The RACAT trial and sources from the literature. Patients with active RA despite at least 12 weeks of methotrexate therapy. 24 weeks and lifetime. Societal and Medicare. Etanercept-methotrexate first versus triple therapy first. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). The within-trial analysis found that etanercept-methotrexate as first-line therapy provided marginally more QALYs but accumulated substantially higher drug costs. Differences in other costs between strategies were negligible. The ICERs for first-line etanercept-methotrexate and triple therapy were $2.7 million per QALY and $0.98 million per QALY over 24 and 48 weeks, respectively. The lifetime analysis suggested that first-line etanercept-methotrexate would result in 0.15 additional lifetime QALY, but this gain would cost an incremental $77 290, leading to an ICER of $521 520 per QALY per patient. Considering a long-term perspective, an initial strategy of etanercept-methotrexate and biologics with similar cost and efficacy is unlikely to be cost-effective compared with using triple therapy first, even under optimistic assumptions. Data on the long-term benefit of triple therapy are uncertain. Initiating biologic therapy without trying triple therapy first increases costs while providing minimal incremental benefit. The Cooperative Studies Program, Department of Veterans Affairs Office of Research and Development, Canadian Institutes for Health Research, and an

  16. Simulation of biological therapies for degenerated intervertebral discs.

    Science.gov (United States)

    Zhu, Qiaoqiao; Gao, Xin; Temple, H Thomas; Brown, Mark D; Gu, Weiyong

    2016-04-01

    The efficacy of biological therapies on intervertebral disc repair was quantitatively studied using a three-dimensional finite element model based on a cell-activity coupled multiphasic mixture theory. In this model, cell metabolism and matrix synthesis and degradation were considered. Three types of biological therapies-increasing the cell density (Case I), increasing the glycosaminoglycan (GAG) synthesis rate (Case II), and decreasing the GAG degradation rate (Case III)-to the nucleus pulposus (NP) of each of two degenerated discs [one mildly degenerated (e.g., 80% viable cells in the NP) and one severely degenerated (e.g., 30% viable cells in the NP)] were simulated. Degenerated discs without treatment were also simulated as a control. The cell number needed, nutrition level demanded, time required for the repair, and the long-term outcomes of these therapies were analyzed. For Case I, the repair process was predicted to be dependent on the cell density implanted and the nutrition level at disc boundaries. With sufficient nutrition supply, this method was predicted to be effective for treating both mildly and severely degenerated discs. For Case II, the therapy was predicted to be effective for repairing the mildly degenerated disc, but not for the severely degenerated disc. Similar results were predicted for Case III. No change in cell density for Cases II and III were predicted under normal nutrition level. This study provides a quantitative guide for choosing proper strategies of biological therapies for different degenerated discs. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. 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.

  18. 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).

  19. The impact of biologic therapy in chronic plaque psoriasis from a societal perspective: an analysis based on Italian actual clinical practice.

    Science.gov (United States)

    Polistena, B; Calzavara-Pinton, P; Altomare, G; Berardesca, E; Girolomoni, G; Martini, P; Peserico, A; Puglisi Guerra, A; Spandonaro, F; Vena Gino, A; Chimenti, S; Ayala, F

    2015-12-01

    Psoriasis is one of the most common forms of chronic dermatitis, affecting 2-3% of the worldwide population. It has a serious effect on the way patients perceive themselves and others, thereby prejudicing their quality of life and giving rise to a significant deterioration in their psycho-physical well-being; it also poses greater difficulties for them in leading a normal social life, including their ability to conduct a normal working life. All the above-mentioned issues imply a cost for the society. This study proposes to evaluate the impact on societal costs for the treatment of chronic plaque psoriasis with biologics (etanercept, infliximab and adalimumab) in the Italian clinical practice. A prospective observational study has been conducted in 12 specialized centres of the Psocare network, located throughout Italy. Direct and indirect costs (as well as the health-related quality of life of patients with plaque psoriasis undergoing biologic treatments) have been estimated, while the societal impact has been determined using a cost-utility approach. Non-medical and indirect costs account for as much as 44.97% of the total cost prior to treatment and to 6.59% after treatment, with an overall 71.38% decrease. Adopting a societal perspective in the actual clinical practice of the Italian participating centres, the ICER of biologic therapies for treating plaque psoriasis amounted to €18634.40 per QALY gained--a value far from the €28656.30 obtained by adopting a third-party payer perspective. Our study confirms that chronic psoriasis subjects patients to a considerable burden, together with their families and caregivers, stressing how important it is to take the societal perspective into consideration during the appraisal process. Besides, using data derived from Italian actual practice, treatment with biologics shows a noteworthy benefit in social terms. © 2015 European Academy of Dermatology and Venereology.

  20. Principles and practice of the biologic therapy of cancer

    National Research Council Canada - National Science Library

    Rosenberg, Steven A

    2000-01-01

    ... are not covered by the above-mentioned copyright. Printed in the USA Library of Congress Cataloging-in-Publication Data Principles and practice of the biologic therapy of cancer / edited by Steven A. Rosenberg- 3rd ed. p.; cm. Includes bibliographical references and index. ISBN 0-7817-2272-1 1. Biological response modifiers- Therapeutic use. ...

  1. Biologic Therapy in Inflammatory Eye Conditions (Ophtalmology): Safety Profile.

    Science.gov (United States)

    Neri, Piergiorgio; Arapi, Ilir; Nicolai, Michele; Pirani, Vittorio; Saitta, Andrea; Luchetti, Michele M; Giovannini, Alfonso; Mariotti, Cesare

    2016-01-01

    Non-infectious uveitis can be a potentially sight threatening disease. Very recently, therapeutic strategies have turned towards a new methodology, which includes biologic agents. The introduction of biologic drugs has started a Copernican revolution in ophthalmology: biologic therapies represent a revolutionary option for those patients who present non-responder, sight threatening uveitis. The availability of these therapies has improved the uveitis outcome. The present review shows the most relevant medical literature on biologic agents in ophthalmology, such as tumor necrosis factor blockers, anti-interleukins and other related biologics. Several papers reported the efficacy of biologic agents in a large number of refractory uveitides, which suggest a promising role of biologic drugs for selected cases. On the other hand, the medical literature does not have consistent numbers yet, which hopefully will validate the promising preliminary results. Biologic agents are not only promising drugs for the treatment of nonresponder uveitis, but also they show an apparently favourable safety profile, although several topics remain unsolved: it is still not clear when commencing the treatment, which agent to choose, and the length of biologic therapy. Moreover, the high costs and the still not clear safety profile have very often limited their use only for severe, non-responder uveitis in highly specialized uveitis centres.

  2. 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.

  3. Potential of biological images for radiation therapy of cancer

    International Nuclear Information System (INIS)

    Ling, C.

    2001-01-01

    Full text: Recent technical advances in 3D conformal and intensity modulated radiotherapy (3DCRT and IMRT) based, on patient-specific CT and MRI images, have the potential of delivering exquisitely conformal dose distributions to the target volume while avoiding critical structures. Emerging clinical results in terms of reducing treatment-related morbidity and increasing local control appear promising. Recent developments in imaging have suggested that biological images may further positively impact cancer diagnosis, characterization and therapy. While in the past radiological images are largely anatomical, the new types of images can provide metabolic, biochemical, physiological, functional and molecular (genotypic and phenotypic) information. For radiation therapy, images that give information about factors (e.g. tumor hypoxia, T pot ) that influence radiosensitivity and treatment outcome can be regarded as radiobiological images. The ability of IMRT to 'paint' (in 2D) or 'sculpt' (in 3D) the dose, and produce exquisitely conformal dose distributions begs the '64 million dollar question' as to how to paint or sculpt, and whether biological imaging may provide the pertinent information. Can this new approach provide 'radiobiological phenotypes' non-invasively, and incrementally improve upon the predictive assays of radiobiological characteristics such as proliferative activity (T pot - the potential doubling time), radiosensitivity (SF 2 - the surviving fraction at a dose of 2 Gy), energy status (relative to sublethal damage repair), pH (a possible surrogate of hypoxia), tumor hypoxia, etc. as prognosticator(s) of radiation treatment outcome. Important for IMRT, the spatial (geometrical) distribution of the radiobiological phenotypes provide the basis for dose distribution design to conform to both the physical (geometrical) and the biological attributes. Copyright (2001) Australasian College of Physical Scientists and Engineers in Medicine

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

    Science.gov (United States)

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

    2013-07-01

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

  5. Portuguese Recommendations for the use of biological therapies in patients with rheumatoid arthritis- 2016 update

    Directory of Open Access Journals (Sweden)

    Catia Duarte

    2017-04-01

    Full Text Available Objective: To update the recommendations for the treatment of Rheumatoid Arthritis (RA with biological therapies, endorsed by the Portuguese Society of Rheumatology (SPR. Methods: These treatment recommendations were formulated by Portuguese rheumatologists based on literature evidence and consensus opinion. At a national meeting the 10 recommendations were discussed and updated. The document resulting from this meeting circulated to all Portuguese rheumatologists, who anonymously voted online on the level of agreement with the recommendations. Results: These recommendations cover general aspects as shared decision, prospective registry in Reuma.pt, assessment of activity and RA impact and treatment objective. Consensus was also achieved regarding specific aspects as initiation of biologic therapy, assessment of response, switching and definition of persistent remission. Conclusion: These recommendations may be used for guidance of treatment with biological therapies in patients with RA. As more evidence becomes available and more therapies are licensed, these recommendations will be updated.

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

    Science.gov (United States)

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

    2016-07-01

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

  7. 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)

  8. 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

  9. Cell-Based Therapy

    Directory of Open Access Journals (Sweden)

    Masaaki Kitada

    2012-01-01

    Full Text Available Cell transplantation is a strategy with great potential for the treatment of Parkinson's disease, and many types of stem cells, including neural stem cells and embryonic stem cells, are considered candidates for transplantation therapy. Mesenchymal stem cells are a great therapeutic cell source because they are easy accessible and can be expanded from patients or donor mesenchymal tissues without posing serious ethical and technical problems. They have trophic effects for protecting damaged tissues as well as differentiation ability to generate a broad spectrum of cells, including dopamine neurons, which contribute to the replenishment of lost cells in Parkinson's disease. This paper focuses mainly on the potential of mesenchymal stem cells as a therapeutic cell source and discusses their potential clinical application in Parkinson's disease.

  10. 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).

  11. 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.

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

    Directory of Open Access Journals (Sweden)

    Larsen L

    2016-10-01

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

  13. Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies.

    Science.gov (United States)

    Ahluwalia, Bani; Moraes, Luiza; Magnusson, Maria K; Öhman, Lena

    2018-03-09

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial pathophysiology. Full comprehension of IBD pathology is still out of reach and, therefore, treatment is far from ideal. Nevertheless, components involved in IBD pathogenesis including environmental, genetic, microbial, and immunological factors are continuously being investigated and the improved knowledge contributes to the development of new therapies. In this article we review the aspects of the immunopathogenesis of IBD, with focus on mucosal immunity, and discuss mechanisms of action for current and emerging biological therapies.

  14. The Biological Bases of Conformity

    Directory of Open Access Journals (Sweden)

    Thomas Joshau Henry Morgan

    2012-06-01

    Full Text Available Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favour adaptive learning strategies that facilitate effective use of social information in decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behaviour in nonhuman animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history and ontogeny of conformity and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behaviour conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subject’s behaviour is the result of both social and asocial influences, the resultant behaviour may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for

  15. The Biological Bases of Conformity

    Science.gov (United States)

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  16. The biological bases of conformity.

    Science.gov (United States)

    Morgan, T J H; Laland, K N

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects' behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning.

  17. Genetically-Based Biologic Technologies. Biology and Human Welfare.

    Science.gov (United States)

    Mayer, William V.; McInerney, Joseph D.

    The purpose of this six-part booklet is to review the current status of genetically-based biologic technologies and to suggest how information about these technologies can be inserted into existing educational programs. Topic areas included in the six parts are: (1) genetically-based technologies in the curriculum; (2) genetic technologies…

  18. 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.

  19. Risk-benefit analysis of adalimumab versus traditional non-biologic therapies for patients with Crohn's disease.

    Science.gov (United States)

    Loftus, Edward V; Johnson, Scott J; Wang, Si-Tien; Wu, Eric; Mulani, Parvez M; Chao, Jingdong

    2011-01-01

    Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease (CD). A systematic analysis of risks and benefits of adalimumab versus traditional non-biologic therapies for patients refractory to non-biologic therapy is lacking. A base-case analysis compared expected benefits of adalimumab therapy with a 12-week stopping rule for non-responders versus non-biologic therapies using data from clinical trials (CHARM, CLASSIC I). Adverse events (AEs) recorded in clinical trials (CHARM, CLASSIC I, CLASSIC II, GAIN, open-label extensions) were compiled. Sensitivity analyses incorporated all observed benefits of adalimumab and placebo (CHARM, CLASSIC I, GAIN) and observed AEs from a systematic literature review of non-biologic therapies (MEDLINE search of randomized trials 1990-2007). Distributional information from maintenance clinical trial observations and benefit model predictions were used in a probabilistic simulation. Incremental net benefits were estimated based on utility estimates from the literature. Average time in remission (i.e., CDAI traditional non-biologic therapies. Adalimumab was associated with fewer expected hospitalizations, better fistula closure rates, and lower AE rates. These findings were robust in sensitivity analyses. In the probabilistic simulation, with serious AEs as a composite of risks, adalimumab provided greater benefits with fewer AEs versus non-biologic therapies (P therapies. Adalimumab demonstrated greater benefits and lower rates of AEs versus traditional non-biologic therapies for patients with moderately to severely active CD who were refractory to non-biologic therapies. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  20. AIEgen-Based Fluorescent Nanomaterials: Fabrication and Biological Applications

    Directory of Open Access Journals (Sweden)

    Hui Gao

    2018-02-01

    Full Text Available In recent years, luminogens with the feature of aggregation-induced emission (AIEgen have emerged as advanced luminescent materials for fluorescent nanomaterial preparation. AIEgen-based nanomaterials show enhanced fluorescence efficiency and superior photostability, which thusly offer unique advantages in biological applications. In this review, we will summarize the fabrication methods of AIEgen-based nanomaterials and their applications in in vitro/in vivo imaging, cell tracing, photodynamic therapy and drug delivery, focusing on the recent progress.

  1. 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.

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    Elena Aleksandrovna Aseeva

    2013-01-01

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

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

    Science.gov (United States)

    Machado, Pedro; Cerqueira, Marcos; Ávila-Ribeiro, Pedro; Aguiar, Renata; Bernardo, Alexandra; Sepriano, Alexandre; Águeda, Ana; Cordeiro, Ana; Raposo, Ana; Rodrigues, Ana M; Barcelos, Anabela; Malcata, Armando; Lopes, Carina; Vaz, Cláudia C; Nour, Dolores; Godinho, Fátima; Alvarenga, Fernando; Pimentel-Santos, Fernando; Canhão, Helena; Santos, Helena; Cunha, Inês; Neves, Joana Sousa; Fonseca, João Eurico; Gomes, João Lagoas; Tavares-Costa, José; Costa, Lúcia; Cunha-Miranda, Luís; Maurício, Luís; Cruz, Margarida; Afonso, Maria Carmo; Santos, Maria José; Bernardes, Miguel; Valente, Paula; Figueira, Ricardo; Pimenta, Sofia; Ramiro, Sofia; Pedrosa, Teresa; Costa, Tiago Afonso; Vieira-Sousa, Elsa

    2017-01-01

    To update the recommendations for the treatment of axial spondyloarthritis (axSpA) with biological therapies, endorsed by the Portuguese Society of Rheumatology. 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. 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 considered, either a gradual increase in the

  6. Medulloblastoma: toward biologically based management.

    Science.gov (United States)

    Samkari, Ayman; White, Jason C; Packer, Roger J

    2015-03-01

    Medulloblastoma is the most common malignant brain tumor in children and, as such, has been the focus of tremendous efforts to genomically characterize it. What was once thought to be a single disease has been divided into multiple, molecularly unique subgroups through gene expression profiling. Each subgroup is not only unique in its origin and pathogenesis but also in the prognosis and potential therapeutic options. Targeted therapy of malignancies has long been the goal of clinical oncology. The progress made in the classification of medulloblastoma should be used as a model for future studies. With the evolution of epigenetic and genomic sequencing, especially when used in tandem with high-throughput pharmacologic screening protocols, the potential for subgroup-specific targeting is closer than ever. This review focuses on the development of the molecular classification system and its potential use in developing prognostic models as well as for the advancement of targeted therapeutic interventions. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Persistence with biologic therapies in the Medicare coverage gap.

    Science.gov (United States)

    Tamariz, Leonardo; Uribe, Claudia L; Luo, Jiacong; Hanna, John W; Ball, Daniel E; Krohn, Kelly; Meadows, Eric S

    2011-11-01

    To describe persistence with teriparatide and other biologic therapies in Medicare Part D plans with and without a coverage gap. Retrospective (2006) cohort study of Medicare Part D prescription drug plan beneficiaries from a large benefits company. Two plans with a coverage gap (defined as "basic") were combined and compared with a single plan with coverage for generic and branded medications (defined as "complete"). Patients taking alendronate (nonbiologic comparator), teriparatide, etanercept, adalimumab, interferon β-1a, or glatiramer acetate were selected for the study. For patients with complete coverage, equivalent financial thresholds were used to define the "gap."The definition of discontinuation was failure to fill the index prescription after reaching the gap. For alendronate, 27% of 133,260 patients had enrolled in the complete plan. Patients taking biologic therapies had more commonly enrolled in complete plans: teriparatide (66% of 6221), etanercept (58% of 1469), adalimumab (52% of 824), interferon β-1a (60% of 438), and glatiramer acetate (53% of 393). For patients taking either alendronate or teriparatide, discontinuation rates were higher in the basic, versus complete, plan (adjusted odds ratios, 2.02 and 3.56, respectively). Discontinuation did not significantly vary by plan type for etanercept, adalimumab, interferon β-1a, or glatiramer acetate. For patients who reached the coverage gap, discontinuation was more likely for patients taking osteoporosis (OP) medication. Not having a coverage gap was associated with improved persistence with OP treatment.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. Biological bases of human musicality.

    Science.gov (United States)

    Perrone-Capano, Carla; Volpicelli, Floriana; di Porzio, Umberto

    2017-04-01

    Music is a universal language, present in all human societies. It pervades the lives of most human beings and can recall memories and feelings of the past, can exert positive effects on our mood, can be strongly evocative and ignite intense emotions, and can establish or strengthen social bonds. In this review, we summarize the research and recent progress on the origins and neural substrates of human musicality as well as the changes in brain plasticity elicited by listening or performing music. Indeed, music improves performance in a number of cognitive tasks and may have beneficial effects on diseased brains. The emerging picture begins to unravel how and why particular brain circuits are affected by music. Numerous studies show that music affects emotions and mood, as it is strongly associated with the brain's reward system. We can therefore assume that an in-depth study of the relationship between music and the brain may help to shed light on how the mind works and how the emotions arise and may improve the methods of music-based rehabilitation for people with neurological disorders. However, many facets of the mind-music connection still remain to be explored and enlightened.

  13. 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)

  14. Biological Treatment of Solvent-Based Paint

    Science.gov (United States)

    2011-01-01

    COVERED (From - To) Mar 2005- Mar 2010 4. TITLE AND SUBTITLE Biological Treatment of Solvent-Based Paint 5a. CONTRACT NUMBER WP 200520 5b...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Torres, Tom; Hoffard, Theresa 5d. PROJECT NUMBER WP 200520 Lagerquist, Jenny 5e. TASK...nonhazardous and can be landfarmed, composted , or captured in a filter press and landfilled. Most industrial biological treatment systems will also require

  15. Microneedle-based automated therapy for diabetes mellitus.

    Science.gov (United States)

    Khanna, Puneet; Strom, Joel A; Malone, John I; Bhansali, Shekhar

    2008-11-01

    This article discusses the use of microneedles in automated diabetes therapy systems. Advanced bioengineered systems have the potential to close the loop between diagnostic and therapeutic elements of diabetes treatment, thus constituting a "smart" system. Prevalent insulin therapies, and most glucose sensing techniques, involve the transfer of physical entities through the skin. Micromachined needles (microneedles) can achieve this in a noninvasive or minimally invasive manner while contributing various other technological merits. The dynamics of autonomous diabetes therapy systems include highly complex interdependencies between the various physical and biological entities involved, thus warranting multidisciplinary research initiatives. The iterative development of a noninvasive, bioengineered interface such as microneedles necessitates a better understanding of the human skin, its molecular architecture as a polymer film, and its role as a functional biological unit. This review addresses application-specific requirements of a microneedle-based interface system specifically for autonomous diabetes therapy. Key design issues and related parametric interdependencies specific to this application are discussed.

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

    International Nuclear Information System (INIS)

    Perez, Rolando; Moreno, Ernesto; Garrido, Greta; Crombet, Tania

    2011-01-01

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

  17. Instance-Based Generative Biological Shape Modeling.

    Science.gov (United States)

    Peng, Tao; Wang, Wei; Rohde, Gustavo K; Murphy, Robert F

    2009-01-01

    Biological shape modeling is an essential task that is required for systems biology efforts to simulate complex cell behaviors. Statistical learning methods have been used to build generative shape models based on reconstructive shape parameters extracted from microscope image collections. However, such parametric modeling approaches are usually limited to simple shapes and easily-modeled parameter distributions. Moreover, to maximize the reconstruction accuracy, significant effort is required to design models for specific datasets or patterns. We have therefore developed an instance-based approach to model biological shapes within a shape space built upon diffeomorphic measurement. We also designed a recursive interpolation algorithm to probabilistically synthesize new shape instances using the shape space model and the original instances. The method is quite generalizable and therefore can be applied to most nuclear, cell and protein object shapes, in both 2D and 3D.

  18. 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

  19. 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

  20. 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).

  1. 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.

  2. Drug-Encoded Biomarkers for Monitoring Biological Therapies.

    Directory of Open Access Journals (Sweden)

    Desislava Tsoneva

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

  3. Cell based therapy in Parkinsonism

    NARCIS (Netherlands)

    de Munter, J.P.J.M.; Lee, C.; Wolters, E.C.

    2013-01-01

    Parkinson's disease (PD) is a synucleinopathy-induced chronic progressive neurodegenerative disorder, worldwide affecting about 5 million humans. As of yet, actual therapies are symptomatic, and neuroprotective strategies are an unmet need. Due to their capability to transdifferentiate, to immune

  4. 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

  5. Advances in biologic therapy for ulcerative colitis and Crohn's disease

    NARCIS (Netherlands)

    D'Haens, Geert; Daperno, Marco

    2006-01-01

    The medical management of inflammatory bowel disease (IBD) has changed considerably since the advent of biologic treatments. In this review we offer a critical evaluation of controlled studies with biologic agents for the management of both Crohn's disease (CD) and ulcerative colitis (UC). Biologics

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

    Science.gov (United States)

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

    2015-06-01

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

  7. Boron analysis and boron imaging in biological materials for Boron Neutron Capture Therapy (BNCT).

    Science.gov (United States)

    Wittig, Andrea; Michel, Jean; Moss, Raymond L; Stecher-Rasmussen, Finn; Arlinghaus, Heinrich F; Bendel, Peter; Mauri, Pier Luigi; Altieri, Saverio; Hilger, Ralf; Salvadori, Piero A; Menichetti, Luca; Zamenhof, Robert; Sauerwein, Wolfgang A G

    2008-10-01

    Boron Neutron Capture Therapy (BNCT) is based on the ability of the stable isotope 10B to capture neutrons, which leads to a nuclear reaction producing an alpha- and a 7Li-particle, both having a high biological effectiveness and a very short range in tissue, being limited to approximately one cell diameter. This opens the possibility for a highly selective cancer therapy. BNCT strongly depends on the selective uptake of 10B in tumor cells and on its distribution inside the cells. The chemical properties of boron and the need to discriminate different isotopes make the investigation of the concentration and distribution of 10B a challenging task. The most advanced techniques to measure and image boron are described, both invasive and non-invasive. The most promising approach for further investigation will be the complementary use of the different techniques to obtain the information that is mandatory for the future of this innovative treatment modality.

  8. The impact of prior biologic therapy on adalimumab response in patients with rheumatoid arthritis.

    Science.gov (United States)

    Feuchtenberger, Martin; Kleinert, Stefan; Scharbatke, Eva-Christina; Gnann, Holger; Behrens, Frank; Wittig, Bianca M; Greger, Gerd; Tony, Hans-Peter

    2015-01-01

    The aim of this study is to use data from a non-interventional study of adalimumab in patients with rheumatoid arthritis (RA) during routine clinical practice to evaluate the impact of prior treatment with biologics on the effectiveness of current therapy. Efficacy parameters were evaluated for all patients with values at baseline and month 12. Subgroup analyses were performed on patients with 0, 1, or ≥2 prior biologic agents. Key outcome measures included Disease Activity Score- 28 joints (DAS28) and Funktionsfragebogen Hannover (FFbH) functional ability score. A total of 4700 RA adalimumab-treated patients were included in this analysis. Baseline disease activity increased with an increasing number of prior biologic agents and therapeutic response diminished. After 12 months of adalimumab therapy, DAS28 and FFbH scores showed improvements in all groups, but the group with 0 prior biologic agents had the best outcomes, while the group with ≥2 prior biologic agents had the worst. Clinical response (EULAR and DAS28-dcrit) and remission rates showed a similar pattern. Nevertheless, 44% to 67% of patients treated with ≥2 prior biologic agents achieved a clinical response. Multiple regression analyses identified prior biologic therapy as a significant negative predictor for response to therapy. Treatment with adalimumab leads to decreases in disease activity and improvements in function. Improvements are most pronounced in patients with 0 or 1 prior biologic agent, but a substantial proportion of patients treated with ≥2 prior biologic agents experience significant benefit from adalimumab therapy.

  9. Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohn's disease in the United States.

    Science.gov (United States)

    Patel, Haridarshan; Lissoos, Trevor; Rubin, David T

    2017-01-01

    This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only). Kaplan-Meier analyses were used. A total of 1,699 UC and 4,569 CD patients were included. Among UC patients, 51.1% and 90.9% experienced ≥1 indicator of suboptimal biologic therapy within 6 months and 36 months of biologic therapy initiation, respectively. Among CD patients, 54.3% and 91.4% experienced ≥1 indicator of suboptimal biologic therapy within 6 and 36 months of biologic therapy initiation, respectively. For both UC and CD patients, the most frequent indicators of suboptimal biologic therapy were discontinuation, dose escalation and augmentation. In conclusion, this study found that the occurrence of suboptimal biologic therapy is common among patients with UC and CD, with approximately 90% of patients experiencing at least one indicator of suboptimal biologic therapy within 36 months of biologic treatment initiation.

  10. The Association Between Biological Subtype and Isolated Regional Nodal Failure After Breast-Conserving Therapy

    International Nuclear Information System (INIS)

    Wo, Jennifer Y.; Taghian, Alphonse G.; Nguyen, Paul L.; Raad, Rita Abi; Sreedhara, Meera B.A.; Bellon, Jennifer R.; Wong, Julia S.; Gadd, Michele A.; Smith, Barbara L.; Harris, Jay R.

    2010-01-01

    Purpose: To evaluate the risk of isolated regional nodal failure (RNF) among women with invasive breast cancer treated with breast-conserving surgery (BCS) and radiation therapy (RT) and to determine factors, including biological subtype, associated with RNF. Methods and Materials: We retrospectively studied 1,000 consecutive women with invasive breast cancer who received breast-conserving surgery and RT from 1997 through 2002. Ninety percent of patients received adjuvant systemic therapy; none received trastuzumab. Sentinel lymph node biopsy was done in 617 patients (62%). Of patients with one to three positive nodes, 34% received regional nodal irradiation (RNI). Biological subtype classification into luminal A, luminal B, HER-2, and basal subtypes was based on estrogen receptor status-, progesterone receptor status-, and HER-2-status of the primary tumor. Results: Median follow-up was 77 months. Isolated RNF occurred in 6 patients (0.6%). On univariate analysis, biological subtype (p = 0.0002), lymph node involvement (p = 0.008), lymphovascular invasion (p = 0.02), and Grade 3 histology (p = 0.01) were associated with significantly higher RNF rates. Compared with luminal A, the HER-2 (p = 0.01) and basal (p = 0.08) subtypes were associated with higher RNF rates. The 5-year RNF rate among patients with one to three positive nodes treated with tangents alone was 2.4%; we could not identify a subset of these patients with a substantial risk of RNF. Conclusions: Isolated RNF is a rare occurrence after breast-conserving therapy. Patients with the HER-2 (not treated with trastuzumab) and basal subtypes appear to be at higher risk of developing RNF although this risk is not high enough to justify the addition of RNI. Low rates of RNF in patients with one to three positive nodes suggest that tangential RT without RNI is reasonable in most patients.

  11. 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.

  12. Superheroes in autoimmune warfare: Biologic therapies in current ...

    African Journals Online (AJOL)

    Biologic drugs targeting immune cells or cytokines underlying systemic inflammation have dramatically improved outcomes in patients with rheumatological and autoimmune diseases. Nine biologic drugs are currently available in South Africa (SA) – all showing good efficacy and safety profiles. Their high cost and potential ...

  13. Liposome based radiosensitizer cancer therapy

    DEFF Research Database (Denmark)

    Pourhassan, Houman

    Liposome-encapsulated chemotherapeutics have been used in the treatment of a variety of cancers and are feasible for use as mono-therapeutics as well as for combination therapy in conjunction with other modalities. Despite widespread use of liposomal drugs in cancer patient care, insufficient drug...... biomolecules. By modulating the liposomal membrane, liposomes can become sensitive towards enzymatically-driven destabilization and/or functionalization, thereby allowing control of the release of encapsulated therapeutics within the diseased tissue upon intrinsic stimulation from tumor-associated enzymes...... in tumor-bearing mice.The safety and efficacy of sPLA2-sensitive liposomal L-OHP was assessed in sPLA2-deficient FaDu hypopharyngeal squamous cell carcinoma and sPLA2-expressing Colo205 colorectal adenocarcinoma. Also, the feasibility of multimodal cancer therapy employing L-OHP encapsulated in MMP...

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

    DEFF Research Database (Denmark)

    Hesse, D; Krakauer, M; Lund, H

    2010-01-01

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

  15. Ethnic variations in the provision of biologic therapy for Crohn's disease: a Freedom of Information study.

    Science.gov (United States)

    Farrukh, Affifa; Mayberry, John F

    2015-06-01

    In this study, we investigate whether the provision of biologic therapy for Crohn's disease is equitable across South Asian and English groups in NHS Trusts, which serve areas with significant ethnic variation. Data were requested from 10 NHS Trusts using a Freedom of Information (FOI) approach. Details of numbers of patients by ethnicity treated with infliximab or adalumimab for Crohn's disease between 2010 and 2012 were requested. Using population-based estimates of disease prevalence and Census data on population structure, observed and expected numbers who should have received treatment were calculated. In three Trusts, the number of South Asian patients who received such treatment was significantly less than British/White patients. These were: Pennine Acute Hospitals NHS Trust covering Oldham and North Manchester, Barking, Havering & Redbridge University Hospitals NHS Trust and University Hospitals of Leicester NHS Trust. The study is limited by several factors: 1. The only data available on prevalence in both English and South Asian communities comes from Leicester and was published in 1993. More recent data suggests that the prevalence of Crohn's disease now approaches 150/10(5) compared to the 76/10(5) for English patients which was recorded in Leicester. However, the two subsequent studies on prevalence which were published in 2000 from the North of England and 2010 from Scotland do not provide a breakdown by ethnicity. 2. The data were collected by administrative staff using a variety of approaches to their Trust's data bases and so the techniques used in each Trust are not comparable. In addition, studies from elsewhere suggest that the quality of FOI data is affected by the motivation of staff who collect the data. 3. With the exception of Leicester, there was no quality check on the accuracy of the data. In Leicester, 139 patients were on a register of biologic therapy and this compared with 343 patients reported by the FOI request. However, the

  16. Economic evaluation of biologic therapies for the treatment of moderate to severe psoriasis in the United States.

    Science.gov (United States)

    Anis, Aslam H; Bansback, Nick; Sizto, Sonia; Gupta, Shiraz R; Willian, Mary K; Feldman, Steve R

    2011-04-01

    New biologic therapies are available for moderate to severe psoriasis. To determine the most cost-effective sequence of biologic treatments. Through modeling of the clinical pathway of biologic agents, adalimumab, alefacept, efalizumab, etanercept, and infliximab, the costs and benefits (quality-adjusted life-years [QALYs]) were determined. A decision rule determined the optimal treatment sequence comparing costs and QALYs. While infliximab was found to provide the most incremental QALY and etanercept was found to be the least costly, on balance, the incremental cost-effectiveness ratio of adalimumab was the most favorable (ICER = $544/QALY). Consequently, the optimal sequence would begin with adalimumab and be followed by etanercept, infliximab, efalizumab, and alefacept, respectively. The limitations of this study are that evidence was based on indirect comparisons of biologic effectiveness, and toxicities were not included in the model. In consideration of cost-effectiveness in prescribing biologics for moderate to severe psoriasis, the optimal sequence would begin with adalimumab.

  17. Longitudinal observational study of hidradenitis suppurativa: impact of surgical intervention with adjunctive biologic therapy.

    Science.gov (United States)

    Shanmugam, Victoria K; Mulani, Shaunak; McNish, Sean; Harris, Sarah; Buescher, Teresa; Amdur, Richard

    2018-01-01

    Hidradenitis supppurativa (HS) is a chronic inflammatory disease of the apocrine sweat glands affecting 1-4% of the population. While surgical excision is a mainstay of therapy, lesions often recur. Biologic therapies, including tumor necrosis factor-α and IL-12/23 inhibitors, are effective for mild to moderate HS. However, longitudinal studies investigating biologic therapy in conjunction with surgery are limited. The purpose of this analysis was to investigate impact of surgery and biologic therapy on HS disease activity. Data from 68 HS patients were analyzed. Outcome measures included hidradenitis suppurativa Sartorius Score (HSS), active nodule (AN) count, Hurley stage, and probability of achieving 75% reduction in active nodule count (AN75). Mean age was 40 ± 14 years; 66% were female and 72% were African American. Mean disease duration was 10 years, and Hurley stage III disease was seen in 63% of patients. Patients who received biologics had a larger drop in HSS and AN count than those who never received biologics (P = 0.002). Biologic treatment was associated with average reduction in 22 (15-29) HSS points (P biologics was greater in patients who also underwent surgery (P = 0.013). Timing of biologics relative to surgery did not impact efficacy. Patients who received HS surgery with biologic therapy were most likely to achieve the AN75 (P = 0.017). In this diverse cohort of patients with severe HS, biologic therapy was associated with a more rapid decline in disease activity, with the greatest effect in patients who also underwent HS surgery. © 2017 The International Society of Dermatology.

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

    DEFF Research Database (Denmark)

    Hesse, D; Krakauer, M; Lund, H

    2010-01-01

    as reliable indicators of treatment response, despite substantial, biologically measurable effects. We studied the biologic response to treatment in a cohort of NAb-negative patients to test whether difference in responsiveness could segregate patients with and without breakthrough disease during therapy....

  19. Magnetic nanoparticle-based cancer therapy

    International Nuclear Information System (INIS)

    Yu Jing; Yousaf Muhammad Zubair; Hou Yang-Long; Huang Dong-Yan; Gao Song

    2013-01-01

    Nanoparticles (NPs) with easily modified surfaces have been playing an important role in biomedicine. As cancer is one of the major causes of death, tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy. Recently, magnetic nanoparticles (MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy. Compared with traditional cancer therapy, magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way. In this review, we will discuss the recent progress in cancer therapies based on MNPs, mainly including magnetic hyperthermia, magnetic specific targeting, magnetically controlled drug delivery, magnetofection, and magnetic switches for controlling cell fate. Some recently developed strategies such as magnetic resonance imaging (MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed. (topical review - magnetism, magnetic materials, and interdisciplinary research)

  20. Magnetic nanoparticle-based cancer therapy

    Science.gov (United States)

    Yu, Jing; Huang, Dong-Yan; Muhammad Zubair, Yousaf; Hou, Yang-Long; Gao, Song

    2013-02-01

    Nanoparticles (NPs) with easily modified surfaces have been playing an important role in biomedicine. As cancer is one of the major causes of death, tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy. Recently, magnetic nanoparticles (MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy. Compared with traditional cancer therapy, magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way. In this review, we will discuss the recent progress in cancer therapies based on MNPs, mainly including magnetic hyperthermia, magnetic specific targeting, magnetically controlled drug delivery, magnetofection, and magnetic switches for controlling cell fate. Some recently developed strategies such as magnetic resonance imaging (MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.

  1. Novel insights into mesothelioma biology and implications for therapy.

    Science.gov (United States)

    Yap, Timothy A; Aerts, Joachim G; Popat, Sanjay; Fennell, Dean A

    2017-07-25

    Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth in our understanding of mesothelioma pathobiology, which is set to revolutionize therapeutic strategies. From a genomic standpoint, mesothelioma is characterized by a preponderance of tumour suppressor alterations, for which novel therapies are currently in development. Other promising antitumour agents include inhibitors against angiogenesis, mesothelin and immune checkpoints, which are at various phases of clinical trial testing.

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

    Science.gov (United States)

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

    2015-01-01

    The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia/SBR) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis (RA) and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

  3. 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.)

  4. Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis

    NARCIS (Netherlands)

    van Schouwenburg, Pauline A.; Rispens, Theo; Wolbink, Gerrit Jan

    2013-01-01

    Currently, five anti-TNF biologic agents are approved for the treatment of rheumatoid arthritis (RA): adalimumab, infliximab, etanercept, golimumab and certolizumab pegol. Formation of anti-drug antibodies (ADA) has been associated with all five agents. In the case of adalimumab and infliximab,

  5. Trends in biologic therapies for rheumatoid arthritis: results from a survey of payers and providers.

    Science.gov (United States)

    Greenapple, Rhonda

    2012-03-01

    Advances in therapies for rheumatoid arthritis (RA), particularly biologics, have transformed the treatment paradigm for RA. However, the associated costs of these therapies result in a significant economic burden on the healthcare system. As a chronic disease requiring lifelong treatment, most health plans now position RA drugs as a high-priority therapeutic category. To identify provider and payer practices and perceptions regarding coverage of RA biologics in the current marketplace, as well as emerging trends in reimbursement practices. In November 2011, Reimbursement Intelligence, a healthcare research company, collected and analyzed quantitative and qualitative data via parallel-structure online surveys of 100 rheumatologists and 50 health plan payers (medical and pharmacy directors) who represent more than 80 million covered lives. The surveys included approximately 150 questions, and the surveys were designed to force a response for each question. Payers reported using tier placement, prior authorization, and contracting in determining coverage strategies for RA biologics. Among providers, experience with older RA agents remains the key driver for the choice of a biologic agent. A majority of payers and providers (68% and 54%, respectively) reported that they did not anticipate a change in the way their plans would manage biologics over the next 2 to 4 years. Payers' responses indicated uncertainty about how therapeutic positioning of newer, small-molecule drugs at price parity to biologics would affect the current reimbursement landscape. Survey responses show that approval of an indication for early treatment of RA is not likely to change the prescribing and reimbursement landscape for RA biologics. This survey further shows that payers and providers are generally aligned in terms of perceptions of current and future treatments for RA. Advances in RA therapies allow patients increasing options for effective disease management. However, the high cost of

  6. Biologic therapy response and drug survival for females compared to males with rheumatoid arthritis: a cohort study.

    Science.gov (United States)

    Lee, Jeffrey; Mason, Randal; Martin, Liam; Barnabe, Cheryl

    2014-10-01

    Prior research has identified differences between sexes in rheumatoid arthritis (RA) disease characteristics and treatment response, but not how these differences affect therapeutic decision making to switch therapy. Our objective was to assess for sex differences in RA disease activity during the course of biologic therapy and how these differences impact drug survival and therapeutic switching. Data from the Alberta Biologics Pharmacosurveillance Program, a population-based observational cohort of patients receiving biologic therapy for RA, were used for a sex-stratified analysis of disease activity. Linear mixed-model analysis was applied to compare continuous effectiveness outcomes (DAS28, HAQ scores, visual analogue scales of patient-reported outcomes). Chi-squared tests and log-rank tests were used to determine differences in the frequency of switching and drug survival between females and males. At biologic initiation, females (n = 419) and males (n = 148) had similar disease activity (DAS28 in females 5.83, males 5.72), but females reported worse function (HAQ 1.64 vs 1.51, p = 0.037) and more fatigue (6.7 vs 5.9/10, p = 0.013), but the same global score as males (6.9 vs 6.8/10). During biologic therapy, females reported more fatigue (β = -0.454, 95 % CI -0.852, -0.056, p = 0.0252), worse function (β = -0.183, 95 % CI -0.291, -0.074, p = 0.0010) and higher DAS28 scores (β = -0.401, 95 % CI -0.617, -0.184, p = 0.0003). A new composite disease activity index, the HUPI, eliminated the observed differences in disease activity scores between females and males. Median survival for biologic-naïve patients was similar between sexes (3.7 years males, 3.3 years females, log-rank test p = 0.25). The frequency of switching and survival on subsequent biologics were the same between females and males. Guided by traditional outcome measurement tools, worse disease activity and patient-reported outcomes through the course of therapy did not translate into differences

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

    Directory of Open Access Journals (Sweden)

    Joel Sng

    2012-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  9. 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.

  10. 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

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

    Science.gov (United States)

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

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

  12. Nanotechnology for Cancer Therapy Based on Chemotherapy.

    Science.gov (United States)

    Zhao, Chen-Yang; Cheng, Rui; Yang, Zhe; Tian, Zhong-Min

    2018-04-04

    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.

  13. 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.

  14. Mentalization-based therapy (MBT): an overview.

    Science.gov (United States)

    Daubney, Michael; Bateman, Anthony

    2015-04-01

    This paper provides an overview of mentalization-based therapy (MBT). Multiple strands of research evidence converge to suggest that affect dysregulation, impulsivity and unstable interpersonal relationships are core features of borderline personality disorder (BPD). The MBT approach to BPD attempts to provide a theoretically consistent way of conceptualising the inter-relationship of these features. MBT makes mentalizing a core focus of therapy and was initially developed for the treatment of BPD in routine clinical services, delivered in group and individual modalities. This article provides a brief overview of mentalizing and its relevance to BPD, provides an overview of MBT and notes a number of current trends in MBT. MBT provides clinicians with an empirically supported approach to BPD and its treatment. Whilst mentalizing is viewed as an integrative framework for therapy, more knowledge is needed as to which of the therapies are of most benefit for individual patients. © The Royal Australian and New Zealand College of Psychiatrists 2015.

  15. Brillouin Spectroscopy Data Base for Biological Threats

    National Research Council Canada - National Science Library

    Rubel, Glenn

    2003-01-01

    .... Brillouin scattering from DNA, ovalbumen, the Bacillus spores globigii and thuringiensis were measured to determine the feasibility of biological material discrimination using Brillouin scattering...

  16. 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.

  17. 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

  18. Cell-Based Therapies for Diabetic Complications

    Directory of Open Access Journals (Sweden)

    Stella Bernardi

    2012-01-01

    Full Text Available In recent years, accumulating experimental evidence supports the notion that diabetic patients may greatly benefit from cell-based therapies, which include the use of adult stem and/or progenitor cells. In particular, mesenchymal stem cells and the circulating pool of endothelial progenitor cells have so far been the most studied populations of cells proposed for the treatment of vascular complications affecting diabetic patients. We review the evidence supporting their use in this setting, the therapeutic benefits that these cells have shown so far as well as the challenges that cell-based therapies in diabetic complications put out.

  19. 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

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

    Directory of Open Access Journals (Sweden)

    Sinuhe eHahn

    2015-02-01

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

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

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

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

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

    Science.gov (United States)

    Hahn, Sinuhe

    2015-01-01

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

  3. Network-Based Models in Molecular Biology

    Science.gov (United States)

    Beyer, Andreas

    Biological systems are characterized by a large number of diverse interactions. Interaction maps have been used to abstract those interactions at all biological scales ranging from food webs at the ecosystem level down to protein interaction networks at the molecular scale.

  4. Myocardial function and effects of biologic therapy in patients with severe psoriasis

    DEFF Research Database (Denmark)

    Ahlehoff, O.; Hansen, P. R.; Gislason, G. H.

    2016-01-01

    function in patients with severe psoriasis who initiated biologic therapy. Methods Between November 1 2013 and May 31 2014 the study subjects underwent physical, laboratory and comprehensive echocardiographic examination at baseline and after 3 months of treatment. Pearson correlation coefficients...... and Student's t-test were applied to assess changes in diastolic function (defined as the E/e' ratio) and global longitudinal strain (GLS). Results Eighteen patients with severe psoriasis treated with biologic therapy with a mean follow-up of 85.6 ± 18.2 days were included. The patients had a baseline.......74). Likewise, no changes were seen in total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, estimated glomerular filtration rate and glycosylated haemoglobin. Conclusion In patients with severe psoriasis treatment with biologic therapy was associated with improved PASI...

  5. 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....

  6. 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

  7. 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...

  8. Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation.

    Science.gov (United States)

    Lam, Avery J; Hoeppli, Romy E; Levings, Megan K

    2017-10-01

    Cellular therapy with CD4FOXP3 T regulatory (Treg) cells is a promising strategy to induce tolerance after solid-organ transplantation or prevent graft-versus-host disease after transfer of hematopoietic stem cells. Treg cells currently used in clinical trials are either polyclonal, donor- or antigen-specific. Aside from variations in isolation and expansion protocols, however, most therapeutic Treg cell-based products are much alike. Ongoing basic science work has provided considerable new insight into multiple facets of Treg cell biology, including their stability, homing, and functional specialization; integrating these basic science discoveries with clinical efforts will support the development of next-generation therapeutic Treg cells with enhanced efficacy. In this review, we summarize recent advances in knowledge of how Treg cells home to lymphoid and peripheral tissues, and control antibody production and tissue repair. We also discuss newly appreciated pathways that modulate context-specific Treg cell function and stability. Strategies to improve and tailor Treg cells for cell therapy to induce transplantation tolerance are highlighted.

  9. 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

  10. 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.

  11. Position Paper of the European Society of Cardiology Working Group Cellular Biology of the Heart : Cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure

    NARCIS (Netherlands)

    Madonna, Rosalinda; Van Laake, Linda W.; Davidson, Sean M.; Engel, Felix B.; Hausenloy, Derek J.; Lecour, Sandrine; Leor, Jonathan; Perrino, Cinzia; Schulz, Rainer; Ytrehus, Kirsti; Landmesser, Ulf; Mummery, Christine L.; Janssens, Stefan; Willerson, James; Eschenhagen, Thomas; Ferdinandy, Pter; Sluijter, Joost P G

    2016-01-01

    Despite improvements in modern cardiovascular therapy, the morbidity and mortality of ischaemic heart disease (IHD) and heart failure (HF) remain significant in Europe and worldwide. Patients with IHD may benefit from therapies that would accelerate natural processes of postnatal collateral vessel

  12. [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'.

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

    Directory of Open Access Journals (Sweden)

    Nicolae VASILE

    2015-09-01

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

  14. 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.

  15. Gadolinium neutron capture therapy for brain tumors. Biological aspects

    International Nuclear Information System (INIS)

    Takagaki, Masao; Oda, Yoshifumi; Matsumoto, Masato; Kikuchi, Haruhiko; Kobayashi, Tooru; Kanda, Keiji; Ujeno, Yowri.

    1994-01-01

    This study investigated the tumoricidal effect of gadolinium neutron capture therapy (Gd-NCT) in in vitro and in vivo systems using Gd-DTPA. In in vitro study, a certain amount of Gd-DTPA, yielding 5000 ppm Gd-n, was added to human glioma cells, T98G, upon which thermal neutrons were exposed. After irradiation, the cells were incubated and the colonies were counted 10 days later. In in vivo study, Fisher-344 rats with experimentally induced gliosarcoma cells (9L) were exposed to thermal neutrons at a fluence rate of 3E+9/s for 1 h immediately after iv injection of Gd-DTPA. Two weeks after irradiation, brain samples were histologically examined. Tumor clearance of Gd-DTPA was also determined. In vitro analysis showed that a 1% survival level was obtained at 3.75E+12 (n/cm 2 ) for the Gd (+) medium and 2.50E+13 (n/cm 2 ) for the Gd (-) medium. In in vivo analysis, the concentration of Gd in 9L-rat brain tumor after iv injection of 0.2 mg/kg Gd-DTPA was found to be less than 100 ppm, but Gd-NCT on 9L-rat brain tumor administered with a ten-fold dose showed a substantial killing effect on tumor without serious injury to the normal brain structure. The killing effect of Gd-NCT was confirmed in in vitro and in vivo systems. (N.K.)

  16. Metabolic oxidative stress in cancer biology and therapy

    International Nuclear Information System (INIS)

    Spitz, Douglas R.

    2014-01-01

    Cancer cells (relative to normal cells) exhibit increased glycolysis and pentose cycle activity. These metabolic alterations were thought to arise from damage to the respiratory mechanism and cancer cells were thought to compensate for this defect by increasing glycolysis (Science 132:309). In addition to its role in ATP production, glucose metabolism results in the formation of pyruvate and NADPH which both play an integral role in peroxide detoxification (Ann. NY Acad. Sci. 899:349). Recently, cancer cells have been shown to have enhanced susceptibility to glucose deprivation-induced oxidative stress, relative to normal cells, that is mediated by reactive oxygen species (ROS; Biochem.J. 418:29-37). These results support the hypothesis that cancer cells may have a defect in mitochondrial respiration leading to increased steady-state levels of ROS (i.e., O 2 and H 2 O 2 ) and glucose metabolism may be increased to provide reducing equivalents to compensate for this defect. The application of these findings to developing new combined modality cancer therapy protocols will be discussed. (author)

  17. Extracellular Vesicles in Hematological Malignancies: From Biology to Therapy

    Science.gov (United States)

    Caivano, Antonella; La Rocca, Francesco; Laurenzana, Ilaria; Trino, Stefania; De Luca, Luciana; Lamorte, Daniela; Del Vecchio, Luigi; Musto, Pellegrino

    2017-01-01

    Extracellular vesicles (EVs) are a heterogeneous group of particles, between 15 nanometers and 10 microns in diameter, released by almost all cell types in physiological and pathological conditions, including tumors. EVs have recently emerged as particularly interesting informative vehicles, so that they could be considered a true “cell biopsy”. Indeed, EV cargo, including proteins, lipids, and nucleic acids, generally reflects the nature and status of the origin cells. In some cases, EVs are enriched of peculiar molecular cargo, thus suggesting at least a degree of specific cellular packaging. EVs are identified as important and critical players in intercellular communications in short and long distance interplays. Here, we examine the physiological role of EVs and their activity in cross-talk between bone marrow microenvironment and neoplastic cells in hematological malignancies (HMs). In these diseases, HM EVs can modify tumor and bone marrow microenvironment, making the latter “stronger” in supporting malignancy, inducing drug resistance, and suppressing the immune system. Moreover, EVs are abundant in biologic fluids and protect their molecular cargo against degradation. For these and other “natural” characteristics, EVs could be potential biomarkers in a context of HM liquid biopsy and therapeutic tools. These aspects will be also analyzed in this review. PMID:28574430

  18. 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

  19. Somatostatin Receptor Based Imaging and Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Caiyun Xu

    2015-01-01

    Full Text Available Somatostatin (SST receptors (SSTRs belong to the typical 7-transmembrane domain family of G-protein-coupled receptors. Five distinct subtypes (termed SSTR1-5 have been identified, with SSTR2 showing the highest affinity for natural SST and synthetic SST analogs. Most neuroendocrine tumors (NETs have high expression levels of SSTRs, which opens the possibility for tumor imaging and therapy with radiolabeled SST analogs. A number of tracers have been developed for the diagnosis, staging, and treatment of NETs with impressive results, which facilitates the applications of human SSTR subtype 2 (hSSTr2 reporter gene based imaging and therapy in SSTR negative or weakly positive tumors to provide a novel approach for the management of tumors. The hSSTr2 gene can act as not only a reporter gene for in vivo imaging, but also a therapeutic gene for local radionuclide therapy. Even a second therapeutic gene can be transfected into the same tumor cells together with hSSTr2 reporter gene to obtain a synergistic therapeutic effect. However, additional preclinical and especially translational and clinical researches are needed to confirm the value of hSSTr2 reporter gene based imaging and therapy in tumors.

  20. Somatostatin Receptor Based Imaging and Radionuclide Therapy

    Science.gov (United States)

    Zhang, Hong

    2015-01-01

    Somatostatin (SST) receptors (SSTRs) belong to the typical 7-transmembrane domain family of G-protein-coupled receptors. Five distinct subtypes (termed SSTR1-5) have been identified, with SSTR2 showing the highest affinity for natural SST and synthetic SST analogs. Most neuroendocrine tumors (NETs) have high expression levels of SSTRs, which opens the possibility for tumor imaging and therapy with radiolabeled SST analogs. A number of tracers have been developed for the diagnosis, staging, and treatment of NETs with impressive results, which facilitates the applications of human SSTR subtype 2 (hSSTr2) reporter gene based imaging and therapy in SSTR negative or weakly positive tumors to provide a novel approach for the management of tumors. The hSSTr2 gene can act as not only a reporter gene for in vivo imaging, but also a therapeutic gene for local radionuclide therapy. Even a second therapeutic gene can be transfected into the same tumor cells together with hSSTr2 reporter gene to obtain a synergistic therapeutic effect. However, additional preclinical and especially translational and clinical researches are needed to confirm the value of hSSTr2 reporter gene based imaging and therapy in tumors. PMID:25879040

  1. 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)

  2. Analysis of 4-year Dutch reimbursement application data of biological therapies for psoriatic arthritis.

    NARCIS (Netherlands)

    Driessen, R.J.B.; Jong, E.M.G.J. de; Salemink, G.W.; Burer, J.H.G.; Kerkhof, P.C.M. van de; Hoogen, F.H.J. van den

    2010-01-01

    OBJECTIVES: To get the approval for reimbursement of biological therapies for PsA, patients need to fulfil specific criteria in many countries. The aim of this study was to evaluate the 4-year Dutch reimbursement application data, including the diagnostic, disease activity and response criteria that

  3. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  4. Patterns of biologic therapy use in the management of psoriasis: cohort study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    Science.gov (United States)

    Iskandar, I Y K; Ashcroft, D M; Warren, R B; Evans, I; McElhone, K; Owen, C M; Burden, A D; Smith, C H; Reynolds, N J; Griffiths, C E M

    2017-05-01

    Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naïve and non-naïve patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). The study cohort included adults with chronic plaque psoriasis who were followed up for ≥ 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79·2% were biologic-naïve. Over 12 months, 77·4% of patients continued the biologic, 2·6% restarted therapy after a break of ≥ 90 days, 2·5% discontinued, and 17·5% switched biologic therapy. Most patients (85·7%) received the RCD of the biologic, although 8·1% were exposed to a higher CD. In total, 749 (25·1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61·2%). Of those using combination therapy, 454 (60·6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies. © 2016 British Association of Dermatologists.

  5. 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

  6. An oral administration of a recombinant anti-TNF fusion protein is biologically active in the gut promoting regulatory T cells: Results of a phase I clinical trial using a novel oral anti-TNF alpha-based therapy.

    Science.gov (United States)

    Almon, Einat; Khoury, Tawfik; Drori, Ariel; Gingis-Velitski, Svetlana; Alon, Sari; Chertkoff, Raul; Mushkat, Mordechai; Shaaltiel, Yoseph; Ilan, Yaron

    2017-07-01

    An orally administered BY-2 plant cell-expressed recombinant anti-TNF fusion protein (PRX-106) consists of the soluble form of the human TNF receptor (TNFR) fused to the Fc component of a human IgG1 domain. Aim This study aim at determining the safety and the immune modulatory effect of an oral administration of PRX-106 in humans. Three different doses (2, 8 or 16mg/day) of PRX-106 were orally administered for five consecutive days in 14 healthy volunteered participants. Subjects were followed for safety parameters and for an effect on T lymphocytes subsets and cytokine levels. An oral administration of PRX-106 was safe and well tolerated. The PK study showed that PRX106 is not absorbed. No effect on white blood cells and lymphocytes counts were noted. A dose dependent effect was noted on systemic lymphocytes. The oral administration of all three dosages was associated with an increase in CD4+CD25+ and CD8+CD25+ subset of suppressor lymphocytes. A marked increase in CD4+CD25+FoxP3 regulatory T cells was noted in the 8mg treated group. In addition, NKT regulatory cells, CD3+CD69+ and CD4+CD62 lymphocyte subsets increased with treatment. No changes in serum TNF alpha were observed. An oral administration of the non-absorbable recombinant anti-TNF fusion protein, PRX-106, is safe, not associated with immune suppression, while inducing a favorable anti-inflammatory immune modulation. The PRX-106 may provide a safe orally administered effective anti-TNF alpha-based immune therapy for inflammatory bowel diseases and non-alcoholic steatohepatitis, as well as other autoimmune, TNF-mediated diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Nuclear Physics meets Medicine and Biology: Boron Neutron Capture Therapy

    CERN Document Server

    F. Ballarini, F; S. Bortolussi, S; P. Bruschi, P; A.M. Clerici, A M; A. De Bari, A; P. Dionigi, P; C. Ferrari, C; M.A. Gadan, M A; N. Protti, N; S. Stella, S; C. Zonta, C; A. Zonta, A; S. Altieri, S

    2010-01-01

    BNCT is a tumour treatment based on thermal-neutron irradiation of tissues enriched with 10B, which according to the 10B(n, )7Li reaction produces particles with high Linear Energy Transfer and short range. Since this treatment can deliver a therapeutic tumour dose sparing normal tissues, BNCT represents an alternative for diffuse tumours and metastases, which show poor response to surgery and photontherapy. In 2001 and 2003, in Pavia BNCT was applied to an isolated liver, which was infused with boron, explanted, irradiated and re-implanted. A new project was then initiated for lung tumours, developing a protocol for Boron concentration measurements and performing organ-dose Monte Carlo calculations; in parallel, radiobiology studies are ongoing to characterize the BNCT effects down to cellular level. After a brief introduction, herein we will present the main activities ongoing in Pavia including the radiobiological ones, which are under investigation not only experimentally but also theoretically, basing on...

  8. Influence of Biologic Subtype of Inflammatory Breast Cancer on Response to Neoadjuvant Therapy and Cancer Outcomes.

    Science.gov (United States)

    Hieken, Tina J; Murphy, Brittany L; Boughey, Judy C; Degnim, Amy C; Glazebrook, Katrina N; Hoskin, Tanya L

    2017-10-07

    Few data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes. We studied 57 clinical stage T4dM0 IBC patients operated on at our institution from October 2008 to July 2015. Comparisons across biologic subtypes were performed by Wilcoxon rank-sum or chi-square tests; Kaplan-Meier and log-rank tests were used to analyze survival outcomes. All patients received neoadjuvant systemic therapy; 54 (95%) completed postmastectomy radiation. Ninety-one percent (52/57) had clinically node-positive disease at presentation. Pathologic complete response (pCR) rates in the breast and axilla differed significantly by approximated biologic subtype, defined as estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER-2) negative; and HER-2 positive and ER negative/HER-2 negative (all P biologic subtype. Five-year DFS was 46% for patients with ER-positive/HER-2-negative tumors, 82% for HER-2-positive tumors, and 33% for ER-negative/HER-2-negative tumors (P biologic subtypes. Multimodal treatment and modern systemic therapies have markedly improved DFS and BCSS. These data provide further evidence to suggest that IBC is not a distinct biologic entity transcending standard breast tumor marker subclassification. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Regulatory issues in cell-based therapy for clinical purposes.

    Science.gov (United States)

    Casaroli-Marano, Ricardo P; Tabera, Jaime; Vilarrodona, Anna; Trias, Esteve

    2014-01-01

    Rapid development in the fields of cellular and molecular biology, biotechnology, and bioengineering medicine has brought new, highly innovative treatments and medicinal products, some of which contain viable cells and tissues associated with scaffolds and devices. These new cell-based therapy approaches in regenerative medicine have great potential for use in the treatment of a number of diseases that at present cannot be managed effectively. Given the unique challenges associated with the development of human cell-based medicinal products, great care is required in the development of procedures, practices, and regulation. In cell therapy, appropriate methodologies in the areas of production, reproducibility, maintenance, and delivery are essential for accurate definition and reliable assurance of the suitability and quality of the final products. Recently, the official European Community agencies (EMA) and the relevant authority in the USA (FDA) have made significant efforts to establish regulatory guidance for use in the application of the cell-based therapies for human patients. The guidelines surrounding cell-based therapy take into account the current legislation, but focus less on the heterogeneity and requirements of individual human cell-based products, including specific combination products and applications. When considering guidelines and regulation, a risk assessment approach is an effective method of identifying priority areas for the development of human cell-based medicinal products. Additionally, effective design and thorough validation of the manufacturing process in line with existing Good Manufacturing Practices (GMPs) and quality control regimes and a program that ensures the traceability and biovigilance of the final products are also all essential elements to consider. © 2014 S. Karger AG, Basel.

  10. 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.

  11. Biological Based Risk Assessment for Space Exploration

    Science.gov (United States)

    Cucinotta, Francis A.

    2011-01-01

    Exposures from galactic cosmic rays (GCR) - made up of high-energy protons and high-energy and charge (HZE) nuclei, and solar particle events (SPEs) - comprised largely of low- to medium-energy protons are the primary health concern for astronauts for long-term space missions. Experimental studies have shown that HZE nuclei produce both qualitative and quantitative differences in biological effects compared to terrestrial radiation, making risk assessments for cancer and degenerative risks, such as central nervous system effects and heart disease, highly uncertain. The goal for space radiation protection at NASA is to be able to reduce the uncertainties in risk assessments for Mars exploration to be small enough to ensure acceptable levels of risks are not exceeded and to adequately assess the efficacy of mitigation measures such as shielding or biological countermeasures. We review the recent BEIR VII and UNSCEAR-2006 models of cancer risks and their uncertainties. These models are shown to have an inherent 2-fold uncertainty as defined by ratio of the 95% percent confidence level to the mean projection, even before radiation quality is considered. In order to overcome the uncertainties in these models, new approaches to risk assessment are warranted. We consider new computational biology approaches to modeling cancer risks. A basic program of research that includes stochastic descriptions of the physics and chemistry of radiation tracks and biochemistry of metabolic pathways, to emerging biological understanding of cellular and tissue modifications leading to cancer is described.

  12. Function-Based Algorithms for Biological Sequences

    Science.gov (United States)

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  13. [Conceptual bases of biological safety. Part 1].

    Science.gov (United States)

    Onishchenko, G G; Smolenskiĭ, V Iu; Ezhlova, E B; Demina, Iu V; Toporkov, V P; Toprokov, A V; Liapin, M N; Kutyrev, V V

    2013-01-01

    Up to date there is a narrow and broad interpretation of the term biological safety (BS) the world over. In the narrow sense it is defined as availability of international regulations applied to diagnostic, manufacturing, or experimental works with pathogenic biological agents (PBA) in accordance with specified levels of biological hazard and BS. In a broader context it has no national, conceptual, terminological or defying basis. Therewith, establishment of this framework has become the core issue of the study. Investigations have revealed that BS should conceptually cover the whole sphere of sanitary-and-epidemiological welfare as well as related fields such as veterinary-sanitary, phytosanitary provision, ecological safety, environmental conditions (occupational, socio-economic and geopolitical infrastructures, ecological system), and be exercised to prevent and control emergency situations (ES) of biological character. It is demonstrated that this type of ES differs from ES in the sphere of public health care of international concern which is formalized in IHR (2005), in the way that it is characterized by high socio-economic and geopolitical significance of the negative influence on human vital activities, comparable with national and international security hazard. Elaborated is the conceptual, terminological and defying toolkit of the BS broad interpretation (27 terms).

  14. 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,...

  15. 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)

  16. The risk of post-operative complications in psoriasis and psoriatic arthritis patients on biologic therapy undergoing surgical procedures.

    Science.gov (United States)

    Bakkour, W; Purssell, H; Chinoy, H; Griffiths, C E M; Warren, R B

    2016-01-01

    There is limited evidence as to whether biologic therapy should be stopped or continued in patients with psoriasis and/or psoriatic arthritis (PsA) who are undergoing surgical procedures. Current guidelines of care recommend a planned break from biologic therapy in those undergoing major surgical procedures. To audit current practice of managing biologic therapy peri-operatively in a tertiary referral psoriasis clinic against guidelines of care and to investigate the effects of continuing/stopping biologic therapy in psoriasis and PsA patients. A retrospective audit of psoriasis and PsA patients who had a surgical procedure whilst on biologic therapy. A proforma was used to collect information on the biologics used, whether they were stopped peri-operatively and whether patients developed post-operative complications and/or disease flare. A total of 42 patients who had 77 procedures were identified. Procedures ranged from skin surgery to orthopaedic and cardiothoracic surgery. Biologic therapy was continued in the majority of procedures (76%). There was no significant difference in post-operative risk of infection and delayed wound healing between those patients who continued and those who stopped biologic therapy, including those undergoing major surgery. Interrupting biologic therapy peri-operatively was associated with a significant (P = 0.003) risk of flare of psoriasis or PsA. Continuing biologic therapy in psoriasis and PsA patients peri-operatively did not increase the risk of post-operative complications. Interrupting biologic therapy peri-operatively significantly increased the risk of disease flare. This study is limited by cohort size and requires replication, ideally in a prospective randomized controlled manner. © 2015 European Academy of Dermatology and Venereology.

  17. Psychotherapy for borderline personality disorder: mentalization based therapy and cognitive analytic therapy compared.

    Science.gov (United States)

    Bateman, Anthony W; Ryle, Anthony; Fonagy, Peter; Kerr, Ian B

    2007-02-01

    Mentalization Based Therapy (MBT) and Cognitive Analytic Therapy (CAT) are among a small number of psychotherapy approaches offering specific methods for the treatment of Borderline Personality Disorder (BPD). They share a number of features, notably both seek to integrate ideas and methods from psychoanalysis and cognitive psychology, pay attention to early attachment experiences and see harsh and inconsistent care, in combination with biological vulnerability, as playing an important part in the genesis of BPD offer treatment based on a developmental understanding of BPD, taking account of recent developments in observational research seek to provide therapy appropriate for use in the public service. These similarities, however, conceal a number of differences in underlying assumptions and emphases and are linked with contrasting therapeutic techniques. In this paper we present a discussion of key features of our models of normal and pathological development and a consideration of the conceptual underpinnings and of how far they are compatible with what is reliably known in the general field of psychology and how far it offers a model accessible to patients and clinician. Where our views diverge significantly, the reader will have some of the evidence on which to make a personal choice.

  18. Strains, Mechanism, and Perspective: Salmonella-Based Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Cheng-Zhi Wang

    2016-01-01

    Full Text Available Recently, investigation of bacterial-based tumor therapy has regained focus due to progress in molecular, cellular, and microbial biology. Many bacteria such as Salmonella, Listeria, Escherichia, and Clostridium have proved to have tumor targeting and in some cases even tumor-destroying phenotypes. Furthermore, bacterial clinical treatments for cancer have been improved by combination with other therapeutic methods such as chemotherapeutic drugs and radioactive agents. Synthetic biology techniques have also driven the development of new bacterial-based cancer therapies. However, basic questions about the mechanisms of bacterial-mediated tumor targeting and destruction are still being elucidated. In this review, we focus on three tumor-therapeutic Salmonella models, the most intensively studied bacterial genus in this field. One of these Salmonella models is our Salmonella enterica serovar Typhimurium LT2 derived strain CRC2631, engineered to minimize toxicity but maximize tumor-targeting and destruction effects. The other two are VNP20009 and A1-R. We compare the means by which these therapeutic candidate strain models were selected for study, their tumor targeting and tumor destruction phenotypes in vitro and in vivo, and what is currently known about the mechanisms by which they target and destroy tumors.

  19. Use of Biologic Therapy by Pregnant Women With Inflammatory Bowel Disease Does Not Affect Infant Response to Vaccines.

    Science.gov (United States)

    Beaulieu, Dawn B; Ananthakrishnan, Ashwin N; Martin, Christopher; Cohen, Russell D; Kane, Sunanda V; Mahadevan, Uma

    2018-01-01

    biologic therapies. Vaccination of infants against HiB and tetanus toxin, based on antibody titers measured when infants were at least 7 months old, does not appear to be affected by in utero exposure to biologic therapy. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. Quality of life of patients with rheumatoid arthritis under biological therapy

    Directory of Open Access Journals (Sweden)

    Amanda Figueiredo Barbosa Azevedo

    2015-04-01

    Full Text Available Summary Objective: assessing health-related quality of life (HRQL in patients with rheumatoid arthritis (RA, before and after treatment with biological therapy. Methods: a longitudinal study, conducted from November 2010 to September 2011, with implementation of the instruments HAQ II (health assessment questionnaire and SF-36 (medical outcomes short-from health survey. Barlett test, Anova, Friedman and paired t-test were performed for multiple extracts. Results: 30 patients were evaluated, mean age of 47.6 (SD: 12.25 years and prevalence of females (90%. The mean score of HAQ II before treatment was 1.97, with significant reduction of up to 1.23 after six months of biological therapy (p<0.01. Most of the SF-36 domains showed significant improvement after six months of treatment (p<0.01, highlighting the social aspects, pain, physical functioning, emotional issues, vitality and physical aspects. Conclusion: the use of biologic therapy in patients with RA refractory to standard therapies proved to be an important pharmacological strategy for improving HRQL.

  2. Differential Drug Survival of Second-Line Biologic Therapies in Patients with Psoriasis: Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    Science.gov (United States)

    Iskandar, Ireny Y K; Warren, Richard B; Lunt, Mark; Mason, Kayleigh J; Evans, Ian; McElhone, Kathleen; Smith, Catherine H; Reynolds, Nick J; Ashcroft, Darren M; Griffiths, Christopher E M

    2018-04-01

    Little is known about the drug survival of second-line biologic therapies for psoriasis in routine clinical practice. We assessed drug survival of second-line biologic therapies and estimated the risk of recurrent discontinuation due to adverse events or ineffectiveness in patients with psoriasis who had failed a first biologic therapy and switched to a second in a large, multicenter pharmacovigilance registry (n = 1,239; adalimumab, n = 538; etanercept, n = 104; ustekinumab, n = 597). The overall drug survival rate in the first year after switching was 77% (95% confidence interval = 74-79%), falling to 58% (55-61%) in the third year. Female sex, multiple comorbidities, concomitant therapy with cyclosporine, and a high Psoriasis Area and Severity Index at switching to the second-line biologic therapy were predictors of overall discontinuation (multivariable Cox proportional hazard model). Compared to adalimumab, patients receiving etanercept were more likely to discontinue therapy (hazard ratio = 1.87, 95% confidence interval = 1.24-2.83), whereas patients receiving ustekinumab were more likely to persist (hazard ratio = 0.46; 95% confidence interval = 0.33-0.64). Discontinuation of the first biologic therapy because of adverse events was associated with an increased rate of second drug discontinuation because of adverse events (hazard ratio = 2.55; 95% confidence interval = 1.50-4.32). In conclusion, drug survival rates differed among biologic therapies and decreased over time; second-line discontinuation because of adverse events was more common among those who discontinued first-line treatment for this reason. The results of this study should support clinical decision making when choosing second-line biologic therapy for patients with psoriasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. 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

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

    Science.gov (United States)

    Tarr, G; Hodkinson, B; Reuter, H

    2014-11-01

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

  5. 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)

  6. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    Process calculus is the common denominator for a class of compact, idealised, domain-specific formalisms normally associated with the study of reactive concurrent systems within Computer Science. With the rise of the interactioncentred science of Systems Biology a number of bio-inspired process......), is context insensitive, while the other, a poly-variant analysis (2CFA), is context-sensitive. These analyses compute safe approximations to the set of spatial configurations that are reachable according to a given model. This is useful in the qualitative study of cellular self-organisation and, e.......g., the effects of receptor defects or drug delivery mechanisms. The property of sequential realisability. which is closely related to the function of biochemical pathways, is addressed by a variant of traditional Data Flow Analysis (DFA). This so-called ‘Pathway Analysis’ computes safe approximations to the set...

  7. [Cyclosporine A based therapy for myelodysplastic syndrome].

    Science.gov (United States)

    Li, Zhen-Ling; Gong, Ming; Xu, Shao-Hua; Huang, Fan-Zhou; Chen, Yan-Rong; Ma, Yi-Gai

    2005-10-01

    To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and

  8. Evaluating the influence of organ motion during photon vs. proton therapy for locally advanced prostate cancer using biological models

    DEFF Research Database (Denmark)

    Busch, Kia; G Andersen, Andreas; Casares-Magaz, Oscar

    2017-01-01

    beam angles for pelvic irradiation, we aimed to evaluate the influence of organ motion for PT using biological models, and to compare this with contemporary photon-based RT. MATERIAL AND METHODS: Eight locally advanced prostate cancer patients with a planning CT (pCT) and 8-9 repeated CT scans (r......BACKGROUND: Proton therapy (PT) may have a normal tissue sparing potential when co-irradiating pelvic lymph nodes in patients with locally advanced prostate cancer, but may also be more sensitive towards organ motion in the pelvis. Building upon a previous study identifying motion-robust proton...

  9. Clinical and biological predictors of response to electroconvulsive therapy (ECT): a review.

    Science.gov (United States)

    Pinna, Martina; Manchia, Mirko; Oppo, Rossana; Scano, Filomena; Pillai, Gianluca; Loche, Anna Paola; Salis, Piergiorgio; Minnai, Gian Paolo

    2018-03-16

    Electroconvulsive therapy (ECT), developed in the 30's by Bini and Cerletti, remains a key element of the therapeutic armamentarium in psychiatry, particularly for severe and life-threatening psychiatric symptoms. However, despite its well-established clinical efficacy, the prescription of ECT has declined constantly over the years due to concerns over its safety (cognitive side effects) and an increasingly negative public perception. As for other treatments in the field of psychiatry, ECT is well suited to a personalized approach that would increment its efficacy, as well as reducing the impact of side effects. This should be based on the priori identification of sub-populations of patients sharing common clinical and biological features that predict a good response to ECT. In this review we have selectively reviewed the evidence on clinical and biological predictors of ECT response. Clinical features such as an older age, presence of psychotic and melancholic depression, a high severity of suicide behavior, and speed of response, appear to be shared by ECT good responders with depressive symptoms. In mania, a greater severity of the index episode, and a reduction of whole brain cortical blood flow are associated with ECT good response. Biological determinants of ECT response in depressive patients are the presence of pre-treatment hyperconnectivity between key areas of brain circuitry of depression, as well as of reduced glutamine/glutamate levels, particularly in the anterior cingulated cortex (ACC). Furthermore, pre ECT high plasma homovanillic acid (HVA) levels, as well as of tumor necrosis factor (TNF)-α, and low pre-ECT levels of S-100B protein, appear to predict ECT response. Finally, polymorphisms within the genes encoding for the brain-derived neurotrophic factor (BDNF), the dopamine 2 receptor gene (DRD2), the dopamine receptor 3 gene (DRD3), the cathechol-o-methyltransferase (COMT), the serotonin-transporter (5-HTT), the 5-hydroxytryptamine 2A receptor

  10. 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.

  11. Risks of herpes zoster in patients with rheumatoid arthritis according to biologic disease-modifying therapy.

    Science.gov (United States)

    Yun, Huifeng; Xie, Fenglong; Delzell, Elizabeth; Chen, Lang; Levitan, Emily B; Lewis, James D; Saag, Kenneth G; Beukelman, Timothy; Winthrop, Kevin; Baddley, John W; Curtis, Jeffrey R

    2015-05-01

    To evaluate whether the risks of herpes zoster (HZ) differed by biologic agents with different mechanisms of action (MOAs) in older rheumatoid arthritis (RA) patients. Using Medicare data from 2006-2011, among RA patients with prior biologic agent use and no history of cancer or other autoimmune diseases, this retrospective cohort study identified new treatment episodes of abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, and tocilizumab. Followup started on initiation of the new biologic agent and ended at any of the following: first incidence of HZ, a 30-day gap in current exposure, death, a diagnosis of other autoimmune disease or cancer, loss of insurance coverage, or December 31, 2011. We calculated the proportion of RA patients vaccinated for HZ in each calendar year prior to biologic agent initiation and HZ incidence rate for each biologic agent. We compared HZ risks among therapies using Cox regression adjusted for potential confounders. Of 29,129 new biologic treatment episodes, 28.7% used abatacept, 15.9% adalimumab, 14.8% rituximab, 12.4% infliximab, 12.2% etanercept, 6.1% tocilizumab, 5.8% certolizumab, and 4.4% golimumab. The proportion of RA patients vaccinated for HZ prior to biologic agent initiation ranged from 0.4% in 2007 to 4.1% in 2011. We identified 423 HZ diagnoses with the highest HZ incidence rate for certolizumab (2.45 per 100 person-years) and the lowest for golimumab (1.61 per 100 person-years). Neither the crude incidence rate nor the adjusted hazard ratio differed significantly among biologic agents. Glucocorticoid use had a significant association with HZ. Among older patients with RA, the HZ risk was similar across biologic agents, including those with different MOAs. © 2015, American College of Rheumatology.

  12. 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.

  13. Biological activity of N(4)-boronated derivatives of 2'-deoxycytidine, potential agents for boron-neutron capture therapy.

    Science.gov (United States)

    Nizioł, Joanna; Uram, Łukasz; Szuster, Magdalena; Sekuła, Justyna; Ruman, Tomasz

    2015-10-01

    Boron-neutron capture therapy (BNCT) is a binary anticancer therapy that requires boron compound for nuclear reaction during which high energy alpha particles and lithium nuclei are formed. Unnatural, boron-containing nucleoside with hydrophobic pinacol moiety was investigated as a potential BNCT boron delivery agent. Biological properties of this compound are presented for the first time and prove that boron nucleoside has low cytotoxicity and that observed apoptotic effects suggest alteration of important functions of cancer cells. Mass spectrometry analysis of DNA from cancer cells proved that boron nucleoside is inserted into nucleic acids as a functional nucleotide derivative. NMR studies present very high degree of similarity of natural dG-dC base pair with dG-boron nucleoside system. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-04-15

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

  15. Use of Biologic Therapy in Racial Minorities With Rheumatoid Arthritis From 2 US Health Care Systems.

    Science.gov (United States)

    Kerr, Gail S; Swearingen, Christopher; Mikuls, Ted R; Yazici, Yusuf

    2017-01-01

    In the United States, there is racial/ethnic disparity in the care of rheumatoid arthritis (RA), yet there are limited data regarding the impact of varied health care systems on treatment outcomes. The aim fo this study was to compare the frequencies of use of disease-modifying antirheumatic drugs and biologic agents in racial minorities with RA in a single-payer and variable-access health systems. Rheumatoid arthritis disease status was examined in the Ethnic Minority Rheumatoid Arthritis Consortium (EMRAC) and Veterans Affairs Rheumatoid Arthritis Registry (VARA); frequencies of prednisone and disease-modifying antirheumatic drugs and biologic agent use at enrollment were documented. Comparisons in frequencies of RA therapies between RA cohorts and white and nonwhite racial subsets were evaluated. The combined cohorts provided 2899 subjects for analysis (EMRAC = 943, VARA = 1956). Routine Assessment of Patient Index Data 3 and Disease Activity Score in 28 Joints scores were equivalent (cohort, racial subsets), as was biologic agent use (26% vs. 28%) between whites and nonwhites. Disease-modifying antirheumatic drug use was greater in EMRAC nonwhites compared with their white counterparts, but similar to all VARA patients (33% vs. 22% [P biologic agent use was significantly greater in EMRAC versus VARA patients (37% vs. 22%, P biologic agent use among racial subsets (22% vs. 21%). In EMRAC patients, biologic agent use was greater in whites than in nonwhites (EMRAC white 45% vs. EMRAC nonwhite 33%, P biologic agent use. When compared with more variable-access systems, a VA system of care that includes a single-payer insurance may afford equality in use of biologic agents among different racial subsets.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Tang, Tianyi; Eldabaje, Robert; Yang, Lixi

    2016-07-01

    Compared to early-stage melanoma when surgical excision is possible, metastatic disease continues to offer a much grimmer prognosis as traditional chemotherapy treatment regimens offer relatively little survival benefit. This has led to changes in treatment approaches over the preceding two decades as contemporary methods for the treatment of advanced or metastatic melanoma now involve a number of biological modalities, which include immunotherapeutic approaches, targeted therapies and epigenetic modification therapies. Clinically available immunotherapeutic agents include interleukin 2 (IL-2), as well as drugs targeting the important immune checkpoint molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). The targeted therapeutic agents modulate specific pro-oncogenic mutations such as v-Raf murine sarcoma viral oncogene homolog B (BRAF), receptor tyrosine kinases, MEK inhibitors and potential future therapeutic targets, such as the CDK4/CDK6, PTEN and GNAQ/GNA11 genes. Additionally, an increasing understanding of the role of epigenetic alterations in the development and progression of melanoma now offers a new potential drug target. Several of these agents have shown promising results; however, in many investigations, combinations of different therapeutic approaches, each with different mechanisms of action, have yielded improved outcomes as treatment regimens continue to be further optimized by active research and patient disease sub-group analyses. This review summarizes the novel biological agents and new treatments, directly contributing to the significant improvement of biological therapies and markedly advancing knowledge of clinical application of newly approved and developed therapies in treatment of patients with metastatic melanoma. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. Ontology- and graph-based similarity assessment in biological networks.

    Science.gov (United States)

    Wang, Haiying; Zheng, Huiru; Azuaje, Francisco

    2010-10-15

    A standard systems-based approach to biomarker and drug target discovery consists of placing putative biomarkers in the context of a network of biological interactions, followed by different 'guilt-by-association' analyses. The latter is typically done based on network structural features. Here, an alternative analysis approach in which the networks are analyzed on a 'semantic similarity' space is reported. Such information is extracted from ontology-based functional annotations. We present SimTrek, a Cytoscape plugin for ontology-based similarity assessment in biological networks. http://rosalind.infj.ulst.ac.uk/SimTrek.html francisco.azuaje@crp-sante.lu Supplementary data are available at Bioinformatics online.

  20. Nanotechnology-Based Strategies for siRNA Brain Delivery for Disease Therapy.

    Science.gov (United States)

    Zheng, Meng; Tao, Wei; Zou, Yan; Farokhzad, Omid C; Shi, Bingyang

    2018-02-05

    Small interfering RNA (siRNA)-based gene silencing technology has demonstrated significant potential for treating brain-associated diseases. However, effective and safe systemic delivery of siRNA into the brain remains challenging because of biological barriers such as enzymatic degradation, short circulation lifetime, the blood-brain barrier (BBB), insufficient tissue penetration, cell endocytosis, and cytosolic transport. Nanotechnology offers intriguing potential for addressing these challenges in siRNA brain delivery in conjunction with chemical and biological modification strategies. In this review, we outline the challenges of systemic delivery of siRNA-based therapy for brain diseases, highlight recent advances in the development and engineering of siRNA nanomedicines for various brain diseases, and discuss our perspectives on this exciting research field for siRNA-based therapy towards more effective brain disease therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Antiretroviral Therapy Dose Adjustments Based On Calculated ...

    African Journals Online (AJOL)

    Background: Whereas therapy for HIV is dependent on level of creatinine clearance, most laboratories locally only report an absolute creatinine value. There is likelihood that the patients already on antiretroviral therapy (ART) may have required dosage adjustment at the time of initiation of therapy or sometime during ...

  2. 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

  3. A literature-based similarity metric for biological processes

    Directory of Open Access Journals (Sweden)

    Chagoyen Monica

    2006-07-01

    Full Text Available Abstract Background Recent analyses in systems biology pursue the discovery of functional modules within the cell. Recognition of such modules requires the integrative analysis of genome-wide experimental data together with available functional schemes. In this line, methods to bridge the gap between the abstract definitions of cellular processes in current schemes and the interlinked nature of biological networks are required. Results This work explores the use of the scientific literature to establish potential relationships among cellular processes. To this end we haveused a document based similarity method to compute pair-wise similarities of the biological processes described in the Gene Ontology (GO. The method has been applied to the biological processes annotated for the Saccharomyces cerevisiae genome. We compared our results with similarities obtained with two ontology-based metrics, as well as with gene product annotation relationships. We show that the literature-based metric conserves most direct ontological relationships, while reveals biologically sounded similarities that are not obtained using ontology-based metrics and/or genome annotation. Conclusion The scientific literature is a valuable source of information from which to compute similarities among biological processes. The associations discovered by literature analysis are a valuable complement to those encoded in existing functional schemes, and those that arise by genome annotation. These similarities can be used to conveniently map the interlinked structure of cellular processes in a particular organism.

  4. Nanoparticle-based therapy for respiratory diseases

    Directory of Open Access Journals (Sweden)

    ADRIANA L. DA SILVA

    2013-03-01

    Full Text Available Nanotechnology is an emerging science with the potential to create new materials and strategies involving manipulation of matter at the nanometer scale (<100 nm. With size-dependent properties, nanoparticles have introduced a new paradigm in pharmacotherapy – the possibility of cell-targeted drug delivery with minimal systemic side effects and toxicity. The present review provides a summary of published findings, especially regarding to nanoparticle formulations for lung diseases. The available data have shown some benefits with nanoparticle-based therapy in the development of the disease and lung remodeling in respiratory diseases. However, there is a wide gap between the concepts of nanomedicine and the published experimental data and clinical reality. In addition, studies are still required to determine the potential of nanotherapy and the systemic toxicity of nanomaterials for future human use.

  5. 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

  6. Second-line biologic therapy optimization in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.

    Science.gov (United States)

    Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Cassarà, Emanuele; Kaloudi, Olga; Giulio Favalli, Ennio; Becciolini, Andrea; Benucci, Maurizio; Gobbi, Francesca Li; Guiducci, Serena; Foti, Rosario; Mosca, Marta; Goletti, Delia

    2017-10-01

    The Italian board for the TAilored BIOlogic therapy (ITABIO) reviewed the most consistent literature to indicate the best strategy for the second-line biologic choice in patients with rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA). Systematic review of the literature to identify English-language articles on efficacy of second-line biologic choice in RA, PsA, and ankylosing spondylitis (AS). Data were extracted from available randomized, controlled trials, national biologic registries, national healthcare databases, post-marketing surveys, and open-label observational studies. Some previously stated variables, including the patients׳ preference, the indication for anti-tumor necrosis factor (TNF) monotherapy in potential childbearing women, and the intravenous route with dose titration in obese subjects resulted valid for all the three rheumatic conditions. In RA, golimumab as second-line biologic has the highest level of evidence in anti-TNF failure. The switching strategy is preferable for responder patients who experience an adverse event, whereas serious or class-specific side effects should be managed by the choice of a differently targeted drug. Secondary inadequate response to etanercept (ETN) should be treated with a biologic agent other than anti-TNF. After two or more anti-TNF failures, the swapping to a different mode of action is recommended. Among non-anti-TNF targeted biologics, to date rituximab (RTX) and tocilizumab (TCZ) have the strongest evidence of efficacy in the treatment of anti-TNF failures. In PsA and AS patients failing the first anti-TNF, the switch strategy to a second is advisable, taking in account the evidence of adalimumab efficacy in patients with uveitis. The severity of psoriasis, of articular involvement, and the predominance of enthesitis and/or dactylitis may drive the choice toward ustekinumab or secukinumab in PsA, and the latter in AS. Taking in account the paucity of controlled trials

  7. Biologic therapy for inflammatory arthritis and latent tuberculosis: real world experience from a high prevalence area in the United Kingdom.

    Science.gov (United States)

    Nisar, Muhammad K; Rafiq, Aneesa; Östör, Andrew J K

    2015-12-01

    Biologic therapies have resulted in a sea change in the management of inflammatory arthritis; however, a higher risk of opportunistic infection, particularly tuberculosis (TB), is well recognised. This has led to the development of TB screening guidelines. The aim of this study was to investigate the prevalence of latent TB in patients prescribed biologic therapy in an endemic area (prevalence of TB 50/100,000) and to assess the risk of subsequent reactivation. Retrospective case note review of all patients with inflammatory arthritis ever prescribed biologic therapy between 1998 and 2014 at our centre. Two hundred ninety-nine patients (109 men, 190 women) who had ever been prescribed biologic therapy over a 16-year period were included. Mean age upon commencing the biologic therapy was 51 years. Two hundred eighteen (73 %) patients were Caucasian with remaining from ethnic minorities. Two hundred thirty-nine (80 %) prescriptions were for TNF inhibitors. Median duration of biologic therapy was 4.2 years for those who remained on treatment prior to stopping or switching therapies. During 1998-2007, 112 patients underwent clinical assessment, chest X-ray and check for BCG scar. One patient of Asian origin developed extrapulmonary TB within 6 weeks of adalimumab initiation. Following a year of anti-TB treatment, he restarted the biologic therapy with no ill effects. One hundred eighty-seven participants (who started on biologic therapy between 2008 and 2014) underwent additional interferon gamma release assays (IGRA) testing as part of a new TB screening protocol (T-spot test). Eighteen (10 %) had positive test with normal chest X-rays. Six patients were white, nine of Asian origin and three others. Three Caucasian patients had a borderline result. All had 3 months of isoniazid and rifampicin with simultaneous prescription of biologic agent (13 had TNF antagonist, 5 rituximab and 3 tocilizumab). No cases of active TB infection were observed. Overall prevalence of

  8. 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

  9. 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

  10. Computer-based speech therapy for childhood speech sound disorders.

    Science.gov (United States)

    Furlong, Lisa; Erickson, Shane; Morris, Meg E

    2017-07-01

    With the current worldwide workforce shortage of Speech-Language Pathologists, new and innovative ways of delivering therapy to children with speech sound disorders are needed. Computer-based speech therapy may be an effective and viable means of addressing service access issues for children with speech sound disorders. To evaluate the efficacy of computer-based speech therapy programs for children with speech sound disorders. Studies reporting the efficacy of computer-based speech therapy programs were identified via a systematic, computerised database search. Key study characteristics, results, main findings and details of computer-based speech therapy programs were extracted. The methodological quality was evaluated using a structured critical appraisal tool. 14 studies were identified and a total of 11 computer-based speech therapy programs were evaluated. The results showed that computer-based speech therapy is associated with positive clinical changes for some children with speech sound disorders. There is a need for collaborative research between computer engineers and clinicians, particularly during the design and development of computer-based speech therapy programs. Evaluation using rigorous experimental designs is required to understand the benefits of computer-based speech therapy. The reader will be able to 1) discuss how computerbased speech therapy has the potential to improve service access for children with speech sound disorders, 2) explain the ways in which computer-based speech therapy programs may enhance traditional tabletop therapy and 3) compare the features of computer-based speech therapy programs designed for different client populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. 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

  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. [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.

  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. Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy.

    Science.gov (United States)

    Fernandez-Moure, Joseph; Moore, Caitlyn A; Kim, Keemberly; Karim, Azim; Smith, Kevin; Barbosa, Zonia; Van Eps, Jeffrey; Rameshwar, Pranela; Weiner, Bradley

    2018-01-01

    Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.

  16. Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

    Science.gov (United States)

    Yiu, Zenas Z N; Smith, Catherine H; Ashcroft, Darren M; Lunt, Mark; Walton, Shernaz; Murphy, Ruth; Reynolds, Nick J; Ormerod, Anthony D; Griffiths, Christopher E M; Warren, Richard B

    2018-03-01

    Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. [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.

  18. 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

  19. 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.

  20. High rate of serious infection in juvenile idiopathic arthritis patients under biologic therapy in a real-life setting.

    Science.gov (United States)

    Brunelli, Juliana Barbosa; Schmidt, Ana Renata; Sallum, Adriana Maluf Elias; Goldenstein-Schainberg, Claudia; Bonfá, Eloisa; Silva, Clovis A; Aikawa, Nádia Emi

    2018-03-01

    To assess the rate of serious and/or opportunistic infections in juvenile idiopathic arthritis (JIA) patients from a single tertiary center under biologic therapy and to identify possible risk factors associated to these complications. A total of 107 JIA patients followed at the biologic therapy center of our tertiary university hospital using a standardized electronic database protocol including demographic data, clinical and laboratorial findings and treatment at baseline and at the moment of infection. Opportunistic infections included tuberculosis, herpes zoster and systemic mycosis. A total of 398 patient-yrs(py) were included. The median time of biologic exposure was 3.0 years (0.15-11.5). We observed 35 serious/opportunistic infectious events in 27 (25%) patients: 31(88.6%) were serious infections and four (11.4%) opportunistic infections. Serious/opportunistic infections rates were 10.6/100py for ETN, 10.9/100py for ADA, 2.6/100py for ABA and 14.8/100py for TCZ. Comparison of 27 patients with and 80 without infection showed a higher frequency of systemic-onset JIA, lower age at biologic therapy initiation and a history of previous serious infection (p biologic therapy in a real-life setting. Systemic-onset JIA, lower age at biologic therapy start and history of previous serious infections were important risk factors for these complications. Also, higher rates of severe infections comparing to the former studies was possibly due to elevated MTX doses in our patients.

  1. Art Therapy, Research and Evidence-Based Practice

    OpenAIRE

    Gilroy, Andrea

    2007-01-01

    Art Therapy around the world is under increasing pressure to become more "evidence-based". As a result, practitioners now need to get to grips with what constitutes "evidence", how to apply research in appropriate ways and also how to contribute to the body of evidence through their own research and other related activities.\\ud \\ud Written specifically for art therapy practitioners and students, Art Therapy, Research & Evidence Based Practice traces the background to EBP, critically reviews t...

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

    International Nuclear Information System (INIS)

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

    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 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 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.

  3. 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…

  4. 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…

  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. Development of Biologically Based Therapies for Basal-Like Tumors

    Science.gov (United States)

    2007-04-01

    34boost/nested" PCR strategy was used where first a PCR reaction is performed to generate a larger DNA fragment, which is then used as a template for...the nested reaction with a second set of PCR primers. Double stranded sequencing was performed on the nested product using the nested PCR primers as...breast cell lines. Environmental Health Perspectives Toxicogenomics 112(16): 1607-1613. Troester MA, Herschokowitz JI, Oh DS, He X, Hoadley KA, Barbier

  7. 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.

  8. 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 ...

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Gruen, Rebecca Antonia

    2014-06-03

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

  11. 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

  12. 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.

  13. 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.

  14. Synthesis, characterization and biological evaluation of tryptamine based benzamide derivatives.

    Science.gov (United States)

    Aftab, Kiran; Aslam, Kinza; Kousar, Shazia; Nadeem, Muhammad Jawad Ul Hasan

    2016-03-01

    Benzamides and tryptamine are biologically significant compounds, therefore, various benzamide analogous of tryptamine have been efficiently synthesized using tryptamine and different benzoyl chlorides, in order to find new biologically active compounds. The resulting products were then characterized by melting point determination, calculation of Rf values and LC-MS techniques. At last, structure activity relationship (SAR) of the synthesized compounds was evaluated against two microbial strains; Bacillus subtilis and Aspergillus niger. All the five prepared products have shown high yield, sharp characterization and significant resistance against the growth of tested microorganism, providing a new range of tryptamine based benzamide derivatives having significant antimicrobial activities.

  15. 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.

  16. 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...

  17. 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...

  18. Biological markers of prognosis, response to therapy and outcome in ovarian carcinoma.

    Science.gov (United States)

    Szajnik, Marta; Czystowska-Kuźmicz, Małgorzata; Elishaev, Esther; Whiteside, Theresa L

    2016-08-01

    Ovarian cancer (OvCa) is among the most common types of cancer and is the leading cause of death from gynecological malignancies in western countries. Cancer biomarkers have a potential for improving the management of OvCa patients at every point from screening and detection, diagnosis, prognosis, follow up, response to therapy and outcome. The literature search has indicated a number of candidate biomarkers have recently emerged that could facilitate the molecular definition of OvCa, providing information about prognosis and predicting response to therapy. These potentially promising biomarkers include immune cells and their products, tumor-derived exosomes, nucleic acids and epigenetic biomarkers. Expert commentary: Although most of the biomarkers available today require prospective validation, the development of noninvasive liquid biopsy-based monitoring promises to improve their utility for evaluations of prognosis, response to therapy and outcome in OvCa.

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

    Science.gov (United States)

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

    2005-01-01

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

  20. Stem Cell-Based Therapies in Chagasic Cardiomyopathy.

    Science.gov (United States)

    de Carvalho, Antonio Carlos Campos; Carvalho, Adriana Bastos

    2015-01-01

    Chagas disease is caused by Trypanosoma cruzi and can lead to a dilated cardiomyopathy decades after the prime infection by the parasite. As with other dilated cardiomyopathies, conventional pharmacologic therapies are not always effective and as heart failure progresses patients need heart transplantation. Therefore alternative therapies are highly desirable and cell-based therapies have been investigated in preclinical and clinical studies. In this paper we review the main findings of such studies and discuss future directions for stem cell-based therapies in chronic chagasic cardiomyopathy.

  1. 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.

  2. 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

  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. 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

  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. 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

  7. 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.

  8. 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

  9. Nano-systems for medical applications: biological detection, drug delivery, diagnosis and therapy; Applications medicales des nanoparticules: detection biologique, delivrance de medicaments, diagnostic, therapie

    Energy Technology Data Exchange (ETDEWEB)

    Riviere, Ch. [Nano-H SAS, 69 - Lyon (France); Roux, S.; Tillement, O. [Lyon-1 Univ. Claude Bernard, Lab. de Physico-Chimie des Materiaux Luminescents, UMR 5620 CNRS, 69 - Villeurbanne (France); Billotey, C. [Lyon-1 Univ. Claude Bernard, Lab. CREATIS-Animage, UMR 5515 CNRS, U630 INSERM, INSA de Lyon, 69 - Villeurbanne (France); Perriat, P. [Groupe d' Etudes de Metallurgie Physique et de Physique des Materiaux, UMR 5510 CNRS-INSA de Lyon, 69 - Villeurbanne (France)

    2006-05-15

    A review. For a couple of decades, greater and greater connections have been made between nano-technology, biology and medicine. After a rapid description of the particles most often used for biological and medical purposes, the review will detail their potential applications in both domains. In the field of biological detection, a large number of new detection systems is offered by noble metals and semi-conductors, which exhibit very specific nanometer-scale induced properties. In the field of diagnosis and therapeutic applications, particles become more and more sophisticated with an increased possibility of specific targeting, drug delivery triggering and combination of both diagnosis and therapy. (authors)

  10. 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...

  11. 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)

  12. 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.

  13. 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...

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

    Science.gov (United States)

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

    2010-01-01

    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

  15. 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

  16. Competency-based reforms of the undergraduate biology curriculum: integrating the physical and biological sciences.

    Science.gov (United States)

    Thompson, Katerina V; Chmielewski, Jean; Gaines, Michael S; Hrycyna, Christine A; LaCourse, William R

    2013-06-01

    The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students' conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination.

  17. What is infidelity? Perceptions based on biological sex and personality

    OpenAIRE

    Thornton, Victoria; Nagurney, Alexander

    2011-01-01

    Victoria Thornton, Alexander NagurneyTexas State University – San Marcos, San Marcos, Texas, USAAbstract: The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist ...

  18. Cell-based therapies for chronic kidney disease

    NARCIS (Netherlands)

    van Koppen, A.N.|info:eu-repo/dai/nl/314088350

    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

  19. Evidence Based Therapeutic Outcome of Multimodal Therapy on ...

    African Journals Online (AJOL)

    info

    Abstract. Previous efforts at remediating sexual decision of adolescents in Nigeria have been based on unimodal therapies. Therefore, this study investigated the effectiveness of. Multimodal Therapy (MMT) on sexual decisions of adolescents studying in Remedial. Centres in Rivers state, Nigeria. Pre-test post control group ...

  20. 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

  1. 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).

  2. Properties and uses of embryonic stem cells: prospects for application to human biology and gene therapy.

    Science.gov (United States)

    Rathjen, P D; Lake, J; Whyatt, L M; Bettess, M D; Rathjen, J

    1998-01-01

    Embryonic stem cells are pluripotent cells derived from the early mouse embryo that can be propagated stably in the undifferentiated state in vitro. They retain the ability to differentiate into all cell types found in an embryonic and adult mouse in vivo, and can be induced to differentiate into many cell types in vitro. Exploitation of ES cell technology for the creation of mice bearing predetermined genetic alterations has received widespread attention because of the sophistication that it brings to the study of gene function in mammals. Analysis of cell differentiation in vitro has also been of value, leading to the identification of novel bioactive factors and the elucidation of cell specification mechanisms. In this paper, we summarise the features of pluripotent cell lines and their applications, foreshadowing the impact that these systems may have on human biology. While the isolation of definitive human pluripotent cell lines has not yet been achieved, potential applications for these cells in the study of human biology, particularly cell specification, can be envisaged. Of particular interest is the possibility that human embryonic stem cells with properties similar to mouse embryonic stem cells might provide a generic system for gene therapy.

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

    Science.gov (United States)

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

    2017-07-01

    Atopic dermatitis (AD) is a complex, chronic inflammatory skin disorder affecting more than 10% of U.K. children and is a major cause of occupation-related disability. A subset of patients, particularly those with severe AD, are persistently colonized with Staphylococcus aureus and exacerbation of disease is commonly associated with this bacterium by virtue of increased inflammation and allergic sensitization, aggravated by skin barrier defects. Understanding the complex biology of S. aureus is an important factor when developing new drugs to combat infection. Staphylococcus aureus generates exoproteins that enable invasion and dissemination within the host skin but can also damage the skin and activate the host immune system. Antibiotics are often used by dermatologists to aid clearance of S. aureus; however, these are becoming less effective and chronic usage is discouraged with the emergence of multiple antibiotic-resistant strains. New ways to target S. aureus using monoclonal antibodies and vaccines are now being developed. This review will attempt to evaluate the key biology of S. aureus, current treatment of S. aureus infections in AD and recent advances in developing new anti-S. aureus therapies that have potential in severe AD. © 2016 British Association of Dermatologists.

  4. Retinal toxicities of cancer therapy drugs: biologics, small molecule inhibitors, and chemotherapies.

    Science.gov (United States)

    Liu, Catherine Y; Francis, Jasmine H; Brodie, Scott E; Marr, Brian; Pulido, Jose S; Marmor, Michael F; Abramson, David H

    2014-07-01

    To review reported retinal side effects from current cancer therapy drugs. Retinal toxicities from ophthalmologic or oncologic case reports, case series, and clinical trials were identified by a systematic literature search using Lexicomp and PubMed. Four biologics, 8 small molecule inhibitors, and 17 traditional chemotherapy agents had reported retinal side effects. For biologics, interferon alpha 2b was associated with retinopathy, denileukin diftitiox with pigmentary retinopathy, ipilimumab with a Vogt-Koyanagi-Harada-like syndrome, and trastuzumab with retinal ischemia. For small molecule inhibitors, v-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitors were associated with uveitis, mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitors with pigment epithelium detachments, and tyrosine kinase inhibitors with macular edema. Steroid antagonists were associated with crystalline retinopathy and macular edema. Nitrosoureas, platinum analogs, and cytosine arabinoside were associated with retinal vascular occlusions. Antimicrotubular agents were associated with cystoid macular edema but without fluorescein leakage. Retinoic acid derivatives were associated with impaired night vision, and mitotane was associated with a pigmentary retinopathy and papilledema. Certain agents used in the treatment of systemic cancer are associated with ocular complications. Awareness of these complications will allow early detections and maybe reversal of some of the ocular problems.

  5. Repository corticotropin injection in patients with rheumatoid arthritis resistant to biologic therapies.

    Science.gov (United States)

    Fischer, Peter A; Rapoport, Ronald J

    2018-01-01

    Although synthetic and biologic disease-modifying antirheumatic drugs are available, many patients with rheumatoid arthritis have a difficult-to-control disease and need other treatment options. Repository corticotropin injection (RCI) may alleviate symptoms and exacerbations in patients with refractory disease. Nine patients with refractory rheumatoid arthritis were included in this study. Patients were maintained on their baseline therapies with a minimum of 7.5 mg prednisone daily. RCI was given daily at 40 U for 7 days. Patients who had an adequate disease response were given 40 U twice weekly through Week 12. For patients who had inadequate disease response, the dose was increased to 80 U daily for 7 days, followed by 80 U twice weekly through Week 12. The primary endpoint was >1.2 point reduction in the Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at Week 12. Secondary endpoints were improvements in Health Assessment Questionnaire-Disease Index and Functional Assessment of Chronic Illness Therapy scores. Six of the nine patients met the primary endpoint. The average change in DAS28-CRP from baseline to Week 12 was numerically greater with 40 U than with 80 U RCI. Functional Assessment of Chronic Illness Therapy and Health Assessment Questionnaire-Disease Index improved as early as Week 1, and the improvements remained throughout treatment. There was no association between cortisol levels and low-dose RCI response. No serious adverse events occurred. RCI produced a clinically meaningful reduction in markers of disease activity, improved health-related quality of life, and a favorable safety profile. The response rate to RCI was substantial and shows promise in this difficult-to-treat population.

  6. 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.

  7. 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.

  8. 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.

  9. What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis?

    OpenAIRE

    Swart, Joost F; de Roock, Sytze; Wulffraat, Nico M

    2013-01-01

    This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication, very common side effects, expected time of response and average cost in the first year). The emphasis of this review is on the immunological side effects that have been encount...

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

    OpenAIRE

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

    2017-01-01

    Background 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. Methods An interpretative phenomenological analysis (IPA) was undertaken to...

  11. 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 technical variations significantly. DBS-based miRNA profiles will potentially further the translational character of miRNA biomarker studies. © 2017 American Association for Clinical Chemistry.

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

    Science.gov (United States)

    Oldroyd, John; Schachna, Lionel; Buchbinder, Rachelle; Staples, Margaret; Murphy, Bridie; Bond, Molly; Briggs, Andrew; Lassere, Marissa; March, Lyn

    2009-01-01

    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. PMID:20107564

  13. 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

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

    Science.gov (United States)

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

    2011-06-03

    Ionizing radiation causes many types of DNA damage, including base damage and single- and double-strand breaks. Photons, including X-rays and γ-rays, are the most widely used type of ionizing radiation in radiobiology experiments, and in radiation cancer therapy. Charged particles, including protons and carbon ions, are seeing increased use as an alternative therapeutic modality. Although the facilities needed to produce high energy charged particle beams are more costly than photon facilities, particle therapy has shown improved cancer survival rates, reflecting more highly focused dose distributions and more severe DNA damage to tumor cells. Despite early successes of charged particle radiotherapy, there is room for further improvement, and much remains to be learned about normal and cancer cell responses to charged particle radiation. 2011 Elsevier B.V. All rights reserved.

  15. Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes.

    Science.gov (United States)

    Creusot, Remi J; Battaglia, Manuela; Roncarolo, Maria-Grazia; Fathman, C Garrison

    2016-04-01

    The evolution of Type 1 diabetes (T1D) therapy has been marked by consecutive shifts, from insulin replacement to immunosuppressive drugs and targeted biologics (following the understanding that T1D is an autoimmune disease), and to more disease-specific or patient-oriented approaches such as antigen-specific and cell-based therapies, with a goal to provide efficacy, safety, and long-term protection. At the same time, another important paradigm shift from treatment of new onset T1D patients to prevention in high-risk individuals has taken place, based on the hypothesis that therapeutic approaches deemed sufficiently safe may show better efficacy if applied early enough to maintain endogenous β cell function, a concept supported by many preclinical studies. This new strategy has been made possible by capitalizing on a variety of biomarkers that can more reliably estimate the risk and rate of progression of the disease. More advanced ("omic"-based) biomarkers that also shed light on the underlying contributors of disease for each individual will be helpful to guide the choice of the most appropriate therapies, or combinations thereof. In this review, we present current efforts to stratify patients according to biomarkers and current alternatives to conventional drug-based therapies for T1D, with a special emphasis on cell-based therapies, their status in the clinic and potential for treatment and/or prevention. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  16. [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

  17. Understanding the molecular biology of intervertebral disc degeneration and potential gene therapy strategies for regeneration: a review.

    Science.gov (United States)

    Sampara, Prasanthi; Banala, Rajkiran Reddy; Vemuri, Satish Kumar; Av, Gurava Reddy; Gpv, Subbaiah

    2018-03-22

    Intervertebral disc degeneration (IVDD) is a multi-factorial process characterized by phenotypic and genotypic changes, which leads to low back pain and disability. Prolonged imbalance between anabolism and catabolism in discs alters their composition resulting in progressive loss of proteoglycans and hydration leading to IVDD. The current managements for IVDD are only able to relieve the symptoms but do not address the underlying pathology of degeneration. Researchers have tried to find out differences between the aging and degeneration of the disc. Intense attempts are in progress for identifying the various factors responsible for disc degeneration, as well as strategies for regeneration. Recently biological approaches have gained thrust in the field of IVDD. The present review illustrates the current understanding of intervertebral disc degeneration and aims to put forth recent advancements in regeneration strategies involving different biological therapies such as growth factor, cell, and gene therapy. The potentials and consequences of these therapies are also extensively discussed along with citing the most suitable method, that is, the gene therapy in detail. Initially, gene therapy was mediated by viral vectors but recent progress has enabled researchers to opt for non-virus-mediated gene therapy methods, which ensure that there are no risks of mutagenicity and infection in target cells. With constant efforts, non-virus-mediated gene therapy may prove to be an extremely powerful tool in treatment of IVDD in future.

  18. 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

  19. 15th Annual Scientific Meeting of the Society for Biological Therapy. 26-29 October 2000, Seattle, Washington, USA.

    Science.gov (United States)

    Dillman, R O

    2001-01-01

    The 15th Annual Scientific Meeting of the Society for Biological Therapy (SBT) was held at the Four Seasons Olympic Hotel in Seattle, USA. The meeting was organised on behalf of the society by John A Thompson from the University of Washington (Seattle, USA), Michael B Widmer of Immunex Corp. (Seattle, USA) and Bernard A Fox from the Earle A Chiles Research Institute (Portland, Oregon, USA). The purpose of the organisation, which was founded in 1984 and currently has 300 members, is to bring together those diverse individuals actively investigating biologicals and biological response modifiers in the diagnosis and treatment of cancer, including clinicians and basic scientists from industry, government and academia.

  20. 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...

  1. Hibernation Based Therapy to Improve Survival of Severe Blood Loss

    Science.gov (United States)

    2016-06-01

    AWARD NUMBER: W81XWH-10-2-0121 TITLE: Hibernation -Based Therapy to Improve Survival of Severe Blood Loss PRINCIPAL INVESTIGATOR: Greg Beilman... Hibernation -Based Therapy to Improve Survival of Severe Blood 5a. CONTRACT NUMBER Loss 5b. GRANT NUMBER W81XWH-10-2-0121 5c. PROGRAM ELEMENT NUMBER...patients who are risk for bleeding to death. Our overall strategy in this series of studies is to use physiologic adaptive responses in hibernating

  2. Distinguishing among incretin-based therapies. Introduction.

    Science.gov (United States)

    Campbell, R Keith; Cobble, Michael E; Reid, Timothy S; Shomali, Mansur E

    2010-09-01

    The "treat to target" approach is to quickly achieve the target glycosylated hemoglobin (AIC) goal of <7% in most people, and then intensify or change therapy as needed to maintain glycemic control. Results of an online survey demonstrate uncertainty regarding the clinical differences between glucagon-like peptide (GLP-1) agonists and dipeptidyl peptidase (DPP)-4 inhibitors. The increasingly important roles of the GLP-1 agonists and DPP-4 inhibitors stem from their overall good efficacy and safety profiles compared with other treatment options.

  3. 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.

  4. 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.

  5. Long-term effects of cognitive therapy on biological rhythms and depressive symptoms: A randomized clinical trial.

    Science.gov (United States)

    Mondin, Thaíse Campos; Cardoso, Taiane de Azevedo; Jansen, Karen; Silva, Giovanna Del Grande da; Souza, Luciano Dias de Mattos; Silva, Ricardo Azevedo da

    2015-11-15

    To evaluate the effect of cognitive therapy on biological rhythm and depressive and anxious symptoms in a twelve-month follow-up period. In addition, correlations between the reduction of depression and anxiety symptoms and the regulation of biological rhythm were observed. This was a randomized clinical trial with young adults from 18 to 29 years of age who were diagnosed with depression. Two models of psychotherapy were used: Cognitive Behavioral Therapy (CBT) and Narrative Cognitive Therapy (NCT). Biological rhythm was assessed with the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). Severity of depressive and anxious symptoms was assessed by the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS), respectively. The sample included 97 patients who were divided within the protocols of psychotherapy. There was a significant reduction in depressive and anxious symptoms (pbiological rhythm (pbiological rhythm (r=0.638; pbiological rhythm (r=0.438; pbiological rhythm at a twelve-month follow-up evaluation. This study highlights the association between biological rhythm and symptoms of depression and anxiety. We did not assess genetic, hormonal or neurochemical factors and we did not include patients under pharmaceutical treatment or those with severe symptomatology. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. [Levofloxacin-based triple therapy versus bismuth-based quadruple therapy in the treatment of Helicobacter pylori as the rescue therapy: a meta analysis].

    Science.gov (United States)

    Zhang, M; Chen, C Y; Wang, X T; Lyu, B

    2017-05-01

    Objective: To evaluate the efficacy of levofloxacin-based triple therapy and bismuth-based quadruple therapy in the treatment of Helicobacter pylori (Hp) infection as rescue regimens. Methods: Related randomized controlled trials assessing the efficacy and safety of levofloxacin-based triple therapy eradicating Hp as salvage treatment were retrieved from Pubmed, Cochrane Library, SPRINGER, VIP database, WanFang database and CKNI database. The literature quality was evaluated by the improved Jadad criterion. RevMan5.3 sofeware was applied to data analysis. The mergment model was chosen on the basis of the outcome of the heterogeneity tests and original data was pooled for meta-analysis. Publication bias assessed with funnel plots. Results: Ultimately seventeen literatures were included for meta-analysis, the analysis showed that the eradication rate of levofloxacin-based triple therapy was higher comparing to the bismuth-based quadruple therapy but the difference was not statistically significant(77.0% vs 68.7%, OR =1.52, 95% CI 0.96-2.42, P =0.34). In European countries, levofloxacin-based triple therapy was more effective than quadruple therapy(80.6% vs 68.5%, OR =2.18, 95% CI 1.25-3.81, P bismuth-based quadruple therapy, levofloxacin-based triple therapy has higher eradication rate, compliance rate and lesser side effects, so we recommend it as a second-line rescue therapy after front-line Hp eradication failure. The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.

  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. [Crohns disease and ulcerative colitis - current view on genetic determination, immunopathogenesis and biologic therapy].

    Science.gov (United States)

    Buc, M

    2017-01-01

    Crohns disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the intestine, also called inflammatory bowel diseases (IBD), which are not caused by pathogenic microorganisms but result from non-specific inflammatory processes in the bowel. IBD are polygenic diseases, as evidenced by the genome-wide association studies (GWAS), which have discovered more than 200 genes or genetic regions to be associated with IBD. Some of them are specific for CD or UC; however, there are 110 overlapping genes. In the pathogenesis of CD, activation of adaptive immunity mediated by TH1, TH17, or TH1/TH17 cells is induced because of disturbances in the mechanisms of innate immunity and autophagocytosis. By comparison, the major events that trigger autoimmune processes in UC are an increased translocation of commensal bacteria into the submucosa because of loose inter-epithelial connections with subsequent activation of ILC2, TH9, TH2, and NKT cells. Knowledge of the pathogenesis of a disease enables an effective therapy, which is especially true for biological therapy. It is noteworthy that monoclonal antibodies directed against the major protagonists underlying both CD and UC have failed. It points to the complexity of immunopathologic processes that run in both diseases. One can suppose that a blockade of one inflammatory pathway is circumvented by an alternative pathway. TNF is the principal pro-inflammatory cytokine that plays a major role in CD and UC as well. It was therefore decided to treat IBD patients with anti-TNF monoclonal antibodies, infliximab or adalimumab. Approximately one half of the CD patients and one third of the UC patients respond to this treatment.

  9. 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...

  10. 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.

  11. The European hadron therapy community touches base

    CERN Multimedia

    Audrey Ballantine, Manuela Cirilli, Evangelia Dimovasili, Manjit Dosanjh, Seamus Hegarty

    2010-01-01

    The European hadron therapy community gathered in Stockholm from 3 to 5 September for the annual ENLIGHT workshops. Three of the four EC-funded projects born under the umbrella of ENLIGHT (see box) were discussed in the prestigious Nobel Forum at the Karolinska Institutet.   Souvenir photo from the ENLIGHT workshops On its second birthday, the PARTNER Initial Training Network was especially under the spotlight, as the European Commission conducted a formal project review bringing together the institutes, companies and young researchers involved. The 21 PARTNER researchers experienced the thrill of presenting their work in this privileged setting. During the coffee breaks, they joked about this being their only chance in life to speak in the Nobel Forum – but who knows what these brilliant young minds will achieve! They certainly impressed the European Commission’s Project Officer Gianluca Coluccio and Expert Reviewer Kaisa Hellevuo, who stated that PARTNER is a showcase proj...

  12. 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.

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

    DEFF Research Database (Denmark)

    Olsen, Kjeld J.; Hansen, Johnny W.

    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....

  14. 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…

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-01

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

  17. Richter syndrome in chronic lymphocytic leukemia: updates on biology, clinical features and therapy.

    Science.gov (United States)

    Jamroziak, Krzysztof; Tadmor, Tamar; Robak, Tadeusz; Polliack, Aaron

    2015-07-01

    Richter syndrome (RS) or Richter transformation is the development of secondary aggressive lymphoma in the setting of underlying chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Most frequently CLL transforms into diffuse large B-cell lymphoma (DLBCL) (90%) and rarely (10%) into Hodgkin lymphoma, termed Hodgkin variant of Richter syndrome (HvRS). RS is generally characterized by an aggressive clinical course and poor prognosis. In recent years, major advances have been made in understanding genetic events which relate to the progression of CLL or transformation into RS. Better understanding of the molecular pathways has revealed that RS is not a single homogeneous entity. The majority of cases are clonally related to the original CLL clone, while a minority develop from an unrelated clone. This review summarizes new data relating to the molecular biology and the genetic/epigenetic changes occurring during Richter transformation, and also considers the clinical features and therapy for both DLBCL-RS and Hodgkin variant-RS.

  18. 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

  19. Biology

    Indian Academy of Sciences (India)

    I am particularly happy that the Academy is bringing out this document by Professor M S. Valiathan on Ayurvedic Biology. It is an effort to place before the scientific community, especially that of India, the unique scientific opportunities that arise out of viewing Ayurveda from the perspective of contemporary science, its tools ...

  20. Accelerator-based neutron capture therapy

    International Nuclear Information System (INIS)

    JONES, D.T.L.; Sabbert, J.K.

    1998-01-01

    The possibilities of neutron capture therapy (NCT) were mooted as long ago as 1936. This treatment modality depends on the uptake in tumours of a nucleus with a high thermal neutron capture cross section and subsequent exposure to a thermal neutron beam. The capture reaction which has received most attention is 10 B(n,a) 7 Li in which the high-LET products have ranges of the order of cell dimensions. The boron must therefore be taken up in the tumour cells themselves. The 157 Gd(n,Y) 158 Gd reaction has also been examined as it has a cross section 67 times greater than 10 B neutron capture. The low-LET products have longer ranges and therefore do not need to be taken up precisely in the tumour cells. The chemistry of Gd compounds are also well known as they are used as contrast agents in MRI. fe The first patients with advanced brain tumours were treated in the USA in the 1950's and in Japan in the 1960's using reactor beams and boron compounds, Some encouraging results were obtained. Reactor beams have energies in the MeV range end need to be moderated for NCT. However, thermal beams do riot have sufficient penetration for the treatment of deep-seated tumours and the generation of intense epithermal (keV) beams is now receiving considerable attention. Reactors themselves are not ideal for medical treatments: they cannot generally be located in hospitals because of safety factors and public resistance; they are often located at remote locations which are inconvenient and conventional fractionation may not be feasible; fixed horizontal beams have to be used resulting in limited treatment planning options. The use of low-energy accelerators to produce epithermal neutron beams is under serious consideration. These can be relatively small devices providing multi directional beams and which could be located in hospitals. They therefore offer an attractive alternative to reactor beams. The reactions considered most favourable are 7 Li(p,n) 7 Be and 9 Be(p,n) 9 B with

  1. Attachment-Based Family Therapy: A Review of the Empirical Support.

    Science.gov (United States)

    Diamond, Guy; Russon, Jody; Levy, Suzanne

    2016-09-01

    Attachment-based family therapy (ABFT) is an empirically supported treatment designed to capitalize on the innate, biological desire for meaningful and secure relationships. The therapy is grounded in attachment theory and provides an interpersonal, process-oriented, trauma-focused approach to treating adolescent depression, suicidality, and trauma. Although a process-oriented therapy, ABFT offers a clear structure and road map to help therapists quickly address attachment ruptures that lie at the core of family conflict. Several clinical trials and process studies have demonstrated empirical support for the model and its proposed mechanism of change. This article provides an overview of the clinical model and the existing empirical support for ABFT. © 2016 Family Process Institute.

  2. 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

  3. Antibody-Based Therapies in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yu-Tzu Tai

    2011-01-01

    Full Text Available The unmet need for improved multiple myeloma (MM therapy has stimulated clinical development of monoclonal antibodies (mAbs targeting either MM cells or cells of the bone marrow (BM microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA approval of therapeutic Abs for cancer and other diseases.

  4. 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) GPU dose 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.

  5. Tofacitinib Therapy for Rheumatoid Arthritis: A Direct Comparison Study between Biologic-naïve and Experienced Patients.

    Science.gov (United States)

    Mori, Shunsuke; Yoshitama, Tamami; Ueki, Yukitaka

    2018-03-01

    Objective This study was designed to directly compare the outcomes of tofacitinib therapy for methotrexate-refractory rheumatoid arthritis (RA) between biologic-naïve patients and patients who had experienced an inadequate response to biological agents. Methods We prospectively enrolled and followed 113 patients who had a high or moderate clinical disease activity index (CDAI) (36 biologic-naïve patients and 77 biologic-experienced patients). Patients received 5 mg of tofacitinib twice daily. Effectiveness and adverse events were examined at month 6 of treatment. Results At month 6, 65 patients (57.5%) reached CDAI50, which is defined as achieving ≥50% improvement. The number of previous biological agents was twice as high in CDAI50 non-responders as in responders (2.2 versus 1.1, pbiological agents [odds ratio (OR) 4.48, p=0.002] and the concurrent use of prednisolone (OR 2.40, p=0.047) were associated with a failure to achieve a CDAI 50 response. Biologic-naïve patients were more likely to achieve CDAI50 than biologic-experienced patients (80.6% versus 46.8%, p=0.001). Mean CDAI values were higher in biologic-experienced patients (11.4 versus 4.8, p=0.001), and remission rates were higher in biologic-naïve patients (41.7% versus 11.7%, p=0.001). Biologic-naïve patients more rapidly achieved remission. Rates of discontinuation resulting from adverse events were similar in both groups. Conclusion Although tofacitinib can provide an effective treatment option for intractable RA patients, its impact on outcomes is lower in patients with previous biologic failure.

  6. Art-Based Learning Strategies in Art Therapy Graduate Education

    Science.gov (United States)

    Deaver, Sarah P.

    2012-01-01

    This mixed methods research study examined the use of art-based teaching methods in master's level art therapy graduate education in North America. A survey of program directors yielded information regarding in which courses and how frequently art-based methods (individual in-class art making, dyad or group art making, student art projects as…

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.

    2010-07-01

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

  9. Robot-based hand motor therapy after stroke.

    Science.gov (United States)

    Takahashi, Craig D; Der-Yeghiaian, Lucy; Le, Vu; Motiwala, Rehan R; Cramer, Steven C

    2008-02-01

    Robots can improve motor status after stroke with certain advantages, but there has been less emphasis to date on robotic developments for the hand. The goal of this study was to determine whether a hand-wrist robot would improve motor function, and to evaluate the specificity of therapy effects on brain reorganization. Subjects with chronic stroke producing moderate right arm/hand weakness received 3 weeks therapy that emphasized intense active movement repetition as well as attention, speed, force, precision and timing, and included virtual reality games. Subjects initiated hand movements. If necessary, the robot completed movements, a feature available at all visits for seven of the subjects and at the latter half of visits for six of the subjects. Significant behavioural gains were found at end of treatment, for example, in Action Research Arm Test (34 +/- 20 to 38 +/- 19, Parm motor Fugl-Meyer score (45 +/- 10 to 52 +/- 10, P robotic assistance in all sessions as compared to those receiving robotic assistance in half of sessions. The grasp task practiced during robotic therapy, when performed during functional MRI, showed increased sensorimotor cortex activation across the period of therapy, while a non-practiced task, supination/pronation, did not. A robot-based therapy showed improvements in hand motor function after chronic stroke. Reorganization of motor maps during the current therapy was task-specific, a finding useful when considering generalization of rehabilitation therapy.

  10. 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.

  11. Biological therapy utilization, switching, and cost among patients with psoriasis: retrospective analysis of administrative databases in Southern Italy

    Directory of Open Access Journals (Sweden)

    Guerriero F

    2017-12-01

    Full Text Available Francesca Guerriero, Valentina Orlando, Valeria Marina Monetti, Veronica Russo, Enrica Menditto Center of Pharmacoeconomics (CIRFF, University of Naples Federico II, Naples, Italy Purpose: The aim was to describe the current use of biological therapies among patients affected by psoriasis and to analyze a drug utilization profile in naïve patients in terms of switching and treatment costs in a Local Health Unit (LHU of Southern Italy. Methods: We conducted an observational retrospective cohort analysis using the health-related administrative databases of a LHU in Southern Italy covering a population of about one million inhabitants. All subjects with a main or secondary diagnosis of psoriasis who received at least one prescription of biological therapies between January 1, 2010 and December 31, 2014 were analyzed. Switching rate was evaluated in naïve patients within the first year of treatment. Drug cost was calculated for all drugs prescribed and comprised both costs for psoriasis drugs and costs for other treatments. Results: About 20% of patients identified with a diagnosis of psoriasis were under treatment with biological drugs. Among 385 subjects treated with biological therapy, 51.2% were in treatment with etanercept and 33% with adalimumab. Among naïve patients, switching rate to a different biological drug, within the first year of treatment, was 7.3%. The per patient yearly drug cost was €10,536: 96.8% for psoriasis-related drugs and 3.2% for other pharmaceutical treatments. The annual average cost per patient switching from the initial treatment was €13,021, while for those who did not switch from the initial treatment, the annual average cost was €10,342, with a significant difference of about €2,680 per patient per year (p=0.002. Conclusion: Our data may be useful in exploring the dynamics that characterize the use of biological therapy within a specific context and to optimize the use of resources for a better

  12. Evidence-based therapies for upper extremity dysfunction.

    Science.gov (United States)

    Liepert, Joachim

    2010-12-01

    The diversity of interventions aimed at improving upper extremity dysfunction is increasing. This article reviews the effectiveness of different therapeutic approaches that have been published in 2009 and 2010. Evidence is based on randomized controlled trials, systematic reviews, and meta-analyses. Application of constraint-induced movement therapy in acute stroke patients was not more effective than a control intervention, and a more intense therapy may even be harmful. Botulinum toxin injections do not only reduce spasticity but, in children, also improve motor functions if combined with occupational therapy. Strength training improves arm function but not necessarily activities of daily living. Bilateral arm training is as effective as other interventions. Extrinsic feedback and sensory training may further improve motor functions. Mirror therapy was particularly effective for patients with initial hand plegia. For some interventions (e.g. constraint-induced movement therapy, botulinum toxin), efficacy is evident, for others (e.g. mental practice, virtual reality), well designed studies with sufficient numbers of patients are needed. The ultimate goal still is to develop evidence-based therapies for all different degrees of motor impairment.

  13. 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.

  14. REIMBURSEMENT OF CELL-BASED REGENERATIVE THERAPY IN THE UK AND FRANCE.

    Science.gov (United States)

    Mahalatchimy, Aurélie

    2016-01-01

    Cell-based regenerative therapies are presented as being able to cure the diseases of the twenty-first century, especially those coming from the degeneration of the aging human body. But their specific nature based on biological materials raises particular challenging issues on how regulation should frame biomedical innovation for society's benefit regarding public health. The European Union (EU) supports the development of cell-based regenerative therapies that are medicinal products with a specific regulation providing their wide access to the European market for European patients. However, once these medicinal products have obtained a European marketing authorisation, they are still far away from being fully accessible to European patients in all EU Member States. Whereas there is much written on the EU regulatory system for new biotechnologies, there is no systematic legal study comparing the insurance provisions in two EU countries. Focussing on the situation in the UK and France that are based on two different healthcare systems, this paper is based on a comparative methodological approach. It raises the question of regulatory reimbursement mechanisms that determine access to innovative treatments and their consequences for social protection systems in the general context of public health. After having compared the French and English regulations of cell-based regenerative therapy regarding pricing and reimbursement, this papers analyses how England and France are addressing two main challenges of cell-based regenerative therapy, to take into account their long-term benefit through their potential curative nature and their high upfront cost, towards their adoption within the English and French healthcare systems. It concludes that England and France have different general legal frameworks that are not specific to the reimbursement of cell-based regenerative therapy, although their two current and respective trends would bring more convergence between the two

  15. MO-F-BRCD-01: Stereotactic Body Radiation Therapy: Updates on Clinical, Biological, and Physics/QA:SBRT (Part 1): Biological and Clinical Updates.

    Science.gov (United States)

    Read, P

    2012-06-01

    Stereotactic Body Radiation Therapy (SBRT) is an important form of cancer therapy with increasingly broad application across a spectrum of tumor types in primary and metastatic settings. In this presentation the radiation biology, clinical experience from various trials, and cautionary updates on normal tissue tolerances will be presented. The effective radiobiology of SBRT and hypofractionated courses of therapy has become more evident with the increasing reports of retrospective clinical outcomes and prospective clinical trial results. Current open multi-institutional national cooperative trials will be reviewed. Accumulating clinical experiences are yielding new insights into practical aspects of tumor and normal tissue responses to high dose per fraction treatment. Indeed, SBRT has produced profound tumoricidal and ablative effects, however there is potential for grave toxicity and this demands that clinicians be knowledgeable regarding normal tissue tolerances for various hypofractionated courses. As a final note, the technology associated with SBRT has evolved remarkably in the last decade, and procedures that originally required hours to plan, with cumbersome quality assurance methods, arduous set-up times, and long protracted deliveries can now be performed in ever shorter time periods. Given these technology improvements and recognizing the great palliative potential of hypofractionated radiation therapy to relieve cancer symptoms quickly and efficiently, a new strategy to deliver SBRT in a single session called STAT RAD is presented for discussion. © 2012 American Association of Physicists in Medicine.

  16. The cytokinesis-block micronucleus assay as a biological dosimeter for targeted alpha therapy

    Energy Technology Data Exchange (ETDEWEB)

    Song, Emma Y [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia); Rizvi, Syed M A [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia); Qu, Chang F [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia); Yuen, Johnson [Division of cancer Services, St George Hospital, Gray St, Kogarah (Australia); Li, Yong [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia); Morgenstern, Alfred [European Commission, Joint Research Centre, Institute for Transuranium Elements, 76125 Karlsruhe (Germany); Apostolidis, Christos [European Commission, Joint Research Centre, Institute for Transuranium Elements, 76125 Karlsruhe (Germany); Allen, Barry J [Centre for Experimental Radiation Oncology, Cancer Care Centre, St George Hospital, Gray St, 2217 Kogarah (Australia)

    2008-01-21

    Ionizing radiation causes structural chromosomal aberrations, a proportion of which give rise to chromosome fragments without spindle attachment organelles. When a cell divides, some of these fragments are excluded from the main daughter nuclei and form small nuclei within the cytoplasm. The cytokinesis-block micronucleus assay allows these micronuclei (MN) to be counted, providing an in situ biological dosimeter. In this study, we evaluated the micronucleus frequency in peripheral blood lymphocytes after in vitro incubation with the alpha conjugates {sup 213}BiI{sub 3} and {sup 213}Bi-9.2.27 (AIC). Lymphocytes were inoculated in vitro AIC for 3 h. Further, we report the first MN measurements in melanoma patients after targeted alpha therapy (TAT) with {sup 213}Bi-9.2.27. Patients were injected with 260-360 MBq of AIC, and blood samples taken at 3 h, 2 weeks and 4 weeks post-treatment. Absorbed dose (MIRD) and effective total body dose (PED) were calculated. The MN frequency in lymphocytes was similar for equal in vitro incubation activities of {sup 213}BiI{sub 3} and {sup 213}Bi-9.2.27 (P = 0.5), indicating that there is no selective targeting of lymphocytes by the alpha conjugates. After inoculation with 10-1200 kBq mL - 1 of AIC, there was a substantial activity-related increase in MN. The number of MN in the blood of treated patients peaked at 3 h post-TAT, slowly returning to baseline levels by 4 weeks. The mean photon equivalent dose (PED) is 0.43 Gy (SD 0.15) and the mean MIRD calculated absorbed dose is 0.11 Gy (SD 0.03), giving an RBE = 4 {+-} 0.4 for this study.

  17. Biology of classical Hodgkin lymphoma: implications for prognosis and novel therapies.

    Science.gov (United States)

    Mottok, Anja; Steidl, Christian

    2018-03-02

    Hodgkin lymphoma is considered a prime example of treatment success with cure rates exceeding 80% using modern combined modality therapies. However, especially in adolescents and young adults, treatment-related toxicity and long-term morbidity still represent persistent challenges. Moreover, outcomes in patients with relapsed or refractory disease remain unfavorable in the era of high-dose chemotherapy and stem cell transplantation. Hence, there is a high demand for novel and innovative alternative treatment approaches. In recent years many new therapeutic agents have emerged from preclinical and clinical studies that target molecular hallmarks of Hodgkin lymphoma, including the aberrant phenotype of the tumor cells, deregulated oncogenic pathways and immune escape. The antibody drug conjugate BV and immune checkpoint inhibitors have already shown great success in patients with relapsed/refractory disease, leading to FDA approval and new trials testing these agents in various clinical settings. Fundamentally important for the success of these and other novel agents continues to be the expanding knowledge and understanding of Hodgkin lymphoma biology and disease progression, as well as the development of robust tools for biomarker-driven risk stratification and therapeutic decision making. We anticipate that the availability and clinical implementation of novel molecular assays will be instrumental in an era of rapid shifts in the treatment landscape of this disease. Here, we review the current knowledge of Hodgkin lymphoma pathobiology, highlighting the related development of novel treatment strategies and prognostic models that hold the promise to continually challenge and change the current standard of care in classical Hodgkin lymphoma. Copyright © 2018 American Society of Hematology.

  18. What is infidelity? Perceptions based on biological sex and personality

    Science.gov (United States)

    Thornton, Victoria; Nagurney, Alexander

    2011-01-01

    The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist that assessed their perceptions of specific items that could potentially be construed as infidelity. It was hypothesized that females would construe more items as infidelity than would males. It was also predicted that unmitigated communion and communion would be positively correlated with these perceptions and that unmitigated agency would be negatively correlated with these perceptions. No correlation was predicted between agency and infidelity. All hypotheses were supported. Implications and suggestions for future research are discussed. PMID:22114535

  19. What is infidelity? Perceptions based on biological sex and personality

    Directory of Open Access Journals (Sweden)

    Thornton V

    2011-05-01

    Full Text Available Victoria Thornton, Alexander NagurneyTexas State University – San Marcos, San Marcos, Texas, USAAbstract: The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist that assessed their perceptions of specific items that could potentially be construed as infidelity. It was hypothesized that females would construe more items as infidelity than would males. It was also predicted that unmitigated communion and communion would be positively correlated with these perceptions and that unmitigated agency would be negatively correlated with these perceptions. No correlation was predicted between agency and infidelity. All hypotheses were supported. Implications and suggestions for future research are discussed.Keywords: infidelity, communion, agency, questionnaire, relationship

  20. What is infidelity? Perceptions based on biological sex and personality.

    Science.gov (United States)

    Thornton, Victoria; Nagurney, Alexander

    2011-01-01

    The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist that assessed their perceptions of specific items that could potentially be construed as infidelity. It was hypothesized that females would construe more items as infidelity than would males. It was also predicted that unmitigated communion and communion would be positively correlated with these perceptions and that unmitigated agency would be negatively correlated with these perceptions. No correlation was predicted between agency and infidelity. All hypotheses were supported. Implications and suggestions for future research are discussed.

  1. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. We first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Incretin-based therapy and type 2 diabetes

    DEFF Research Database (Denmark)

    Hare, Kristine J; Knop, Filip Krag

    2010-01-01

    secretion, and inappropriately regulated glucagon secretion which in combination eventually result in hyperglycemia and in the longer term microvascular and macrovascular diabetic complications. Traditional treatment modalities--even multidrug approaches--for type 2 diabetes are often unsatisfactory....... Two new drug classes based on the actions of the incretin hormones have been approved for therapy of type 2 diabetes: injectable long-acting stable analogs of GLP-1, incretin mimetics, and orally available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for the rapid degradation...... of incretin mimetics and incretin enhancers, review clinical experience gathered so far, and discuss future expectations for incretin-based therapy....

  3. [Biological and non-biological elimination therapy of acute liver failure. Experimental study on large laboratory animal].

    Science.gov (United States)

    Ryska, M; Lásziková, E; Pantoflícek, T; Kieslichová, E; Ryska, O; Prazák, J; Koblihová, E; Skibová, J

    2008-01-01

    Development of biological and non-biological artificial liver devices in the previous 20 years enabled effective treatment of acute liver failure (ALF) of patients waiting for liver transplantation or for spontaneous liver parenchyma regeneration. Aim of the study was the evaluation of the effectiveness of biological (BAL - bioartificial liver) and non-biological (FPSA - Fractionated plasma separation and adsorption) methods in the treatment of experimental ALF on large laboratory animal. Surgical model of ALF with liver devascularization in pigs (weight 25-40 kg) was provided following monitoring of ALF markers (AST, ALT, bilirubin, ammoniac, glycaemia, INR) including intracranial pressure (ICP). Control group included animals without treatment of ALF. Results of both experimental groups were compared and statistically worked-out with that of controls by T-test and Mann-Whitney non-parametric test by EXCEL and QUATRO. BAL group: 10 pigs (weight 30 +/- 5 kg) with ALF were treated by BAL with isolated hepatocytes. When plasma bilirubin was compared, significant differences (p < 0.05) in 6 and 9 hours interval were found favouring BAL group (18.1 vs. 13.1, 22.9 vs. 13.2 mmol/l). The value of ICP in both groups was no significant. Prometheus group: 14 pigs weight 35 kg (35 +/- 5 kg) with the identical ALF were treated by Prometheus (FPSA). Level of serum bilirubin in experimental group when compared to control group was significantly lower (p < 0.01) at 6 hour interval 12.81 +/- 6.54 vs. 29.84 +/- 9.99 at 9 hour 11.94 +/- 4.14 vs. 29.95 +/- 12.36 and at 12 hour 13.88 +/- 6.31 vs. 26.10 +/- 12.23 mmol/l. No significant difference in serum ammonia level was found. ICP was significantly different from 9 hour to 12 hour interval in favour of FPSA group (p < 0.01): 9 hour 19.1 +/- 4.09 vs. 24.1 +/- 2.85, 10 hour 21.9 +/- 3.63 vs. 25.1 +/- 2.19, 11 hour 22.5 +/- 3.98 vs. 26.3 +/- 3.50 and 12 hour 24.0 +/- 4.66 vs. 29.8 +/- 5.88 mm Hg. Significant improvement of bilirubin

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

    DEFF Research Database (Denmark)

    Larsen, Lone; Jensen, Michael Dam; Larsen, Michael Due

    2016-01-01

    assessment, pregnancy and breastfeeding (women), height (children), weight, dosage (current biological agent), adverse events, surgery, endoscopic procedures, and radiology. DESCRIPTIVE DATA: Eleven clinical indicators have been selected to monitor the quality of biological treatment. For each indicator...

  5. Understanding Manual-Based Behavior Therapy: Some Theoretical Foundations of Parent-Child Interaction Therapy.

    Science.gov (United States)

    Greco, Laurie A.; Sorrell, John T.; McNeil, Cheryl B.

    2001-01-01

    Provides a model of understanding and evaluating manualized treatments by beginning with a review of the theory and data-driven principles upon which one treatment, Parent-Child Interaction Therapy (PCIT), is based. As a point of illustration, several principles of PCIT, such as reinforcement, punishment, and stimulus control, are highlighted, and…

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

    Directory of Open Access Journals (Sweden)

    Keng-Liang Ou

    2016-06-01

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

  7. Evidence-based therapy relationships: research conclusions and clinical practices.

    Science.gov (United States)

    Norcross, John C; Wampold, Bruce E

    2011-03-01

    In this closing article of the special issue, we present the conclusions and recommendations of the interdivisional task force on evidence-based therapy relationships. The work was based on a series of meta-analyses conducted on the effectiveness of various relationship elements and methods of treatment adaptation. A panel of experts concluded that several relationship elements were demonstrably effective (alliance in individual psychotherapy, alliance in youth psychotherapy, alliance in family therapy, cohesion in group therapy, empathy, collecting client feedback) while others were probably effective (goal consensus, collaboration, positive regard). Three other relationship elements (congruence/genuineness, repairing alliance ruptures, and managing countertransference) were deemed promising but had insufficient evidence to conclude that they were effective. Multiple recommendations for practice, training, research, and policy are advanced. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  8. Development of Smart Phthalocyanine-based Photosensitizers for Photodynamic Therapy

    Science.gov (United States)

    Chow, Yun Sang

    Phthalocyanines are versatile functional dyes that have shown great potential in cancer theranostics, especially in photodynamic therapy (PDT). This research work aims to develop "smart" phthalocyanine-based photosensitizers for targeted PDT. This thesis describes the synthesis, spectroscopic characterization, photophysical properties, and in vitro photodynamic activities of several series of carefully designed phthalocyanine-based photosensitizers. Chapter 1 presents an overview of PDT, including its historical development, photophysical mechanisms, and biological mechanisms. Various classes of photosensitizers are introduced with emphasis putting on phthalocyanines, which exhibit ideal characteristics of photosensitizers for PDT. In recent years, several approaches have been used to develop photosensitizers with higher tumor selectivity and minimal skin photosensitivity after PDT. Activatable photosensitizers can provide a "turn on" mechanism to offer an additional control of the specificity of treatment. Photosensitizers can also work cooperatively with the tumor-targeting groups or anticancer drugs so as to achieve targeted or dual therapy, which can enhance the efficacy of PDT. The novel approaches mentioned above have been widely used and combined to form multi-functional photosensitizing agents. These novel concepts and development of PDT are discussed and illustrated with relevant examples at the end of this chapter. To minimize the prolonged skin photosensitivity, photosensitizers that can only be activated by tumor-associated stimuli have been developed. Due to the abnormal metabolism in tumor tissues, their surface usually exhibits a lower pH compared to that of the normal tissues. Also, the pH difference between the intracellular and the physiological environment provides a pH-activation mechanism. Chapter 2 presents the synthesis and spectroscopic characterization of a pH-responsive zinc(II) phthalocyanine tetramer, in which the phthalocyanine units

  9. Patient Preference for Dosing Frequency Based on Prior Biologic Experience.

    Science.gov (United States)

    Zhang, Mingliang; Carter, Chureen; Olson, William H; Johnson, Michael P; Brennem, Susan K; Lee, Seina; Farahi, Kamyar

    2017-03-01

    There is limited research exploring patient preferences regarding dosing frequency of biologic treatment of psoriasis. Patients with moderate-to-severe plaque psoriasis identified in a healthcare claims database completed a survey regarding experience with psoriasis treatments and preferred dosing frequency. Survey questions regarding preferences were posed in two ways: (1) by likelihood of choosing once per week or 2 weeks, or 12 weeks; and (2) by choosing one option among once every 1-2 or 3-4 weeks or 1-2 or 2-3 months. Data were analyzed by prior biologic history (biologic-experienced vs biologic-naïve, and with one or two specific biologics). Overall, 426 patients completed the survey: 163 biologic-naïve patients and 263 biologic-experienced patients (159 had some experience with etanercept, 105 with adalimumab, and 49 with ustekinumab). Among patients who indicated experience with one or two biologics, data were available for 219 (30 with three biologics and 14 did not specify which biologic experience). The majority of biologic-naïve (68.8%) and overall biologic-experienced (69.4%) patients indicated that they were very likely to choose the least frequent dosing option of once every 12 weeks (Table 1). In contrast, fewer biologic-naïve (9.1% and 16.7%) and biologic-experienced (22.5% and 25.3%) patients indicated that they were very likely to choose the 1-week and 2-week dosing interval options, respectively. In each cohort grouped by experience with specific biologics, among those with no experience with ustekinumab, the most chosen option was 1-2 weeks. The most frequently chosen option was every 2-3 months, among patients with any experience with ustekinumab, regardless of their experience with other biologics. The least frequent dosing interval was preferred among biologic naïve patients and patients who had any experience with ustekinumab. Dosing interval may influence the shared decision-making process for psoriasis treatment with biologics. J

  10. Systematically biological prioritizing remediation sites based on datasets of biological investigations and heavy metals in soil

    Science.gov (United States)

    Lin, Wei-Chih; Lin, Yu-Pin; Anthony, Johnathen

    2015-04-01

    Heavy metal pollution has adverse effects on not only the focal invertebrate species of this study, such as reduction in pupa weight and increased larval mortality, but also on the higher trophic level organisms which feed on them, either directly or indirectly, through the process of biomagnification. Despite this, few studies regarding remediation prioritization take species distribution or biological conservation priorities into consideration. This study develops a novel approach for delineating sites which are both contaminated by any of 5 readily bioaccumulated heavy metal soil contaminants and are of high ecological importance for the highly mobile, low trophic level focal species. The conservation priority of each site was based on the projected distributions of 6 moth species simulated via the presence-only maximum entropy species distribution model followed by the subsequent application of a systematic conservation tool. In order to increase the number of available samples, we also integrated crowd-sourced data with professionally-collected data via a novel optimization procedure based on a simulated annealing algorithm. This integration procedure was important since while crowd-sourced data can drastically increase the number of data samples available to ecologists, still the quality or reliability of crowd-sourced data can be called into question, adding yet another source of uncertainty in projecting species distributions. The optimization method screens crowd-sourced data in terms of the environmental variables which correspond to professionally-collected data. The sample distribution data was derived from two different sources, including the EnjoyMoths project in Taiwan (crowd-sourced data) and the Global Biodiversity Information Facility (GBIF) ?eld data (professional data). The distributions of heavy metal concentrations were generated via 1000 iterations of a geostatistical co-simulation approach. The uncertainties in distributions of the heavy

  11. Biological Detection System Technologies Technology and Industrial Base Study. A Primer on Biological Detection Technologies

    National Research Council Canada - National Science Library

    2001-01-01

    .... and Canadian military personnel. In light of these concerns both defense departments have increased efforts to develop and field biological agent detection systems to help protect their military forces and fixed assets...

  12. Global Regulatory Differences for Gene- and Cell-Based Therapies

    DEFF Research Database (Denmark)

    Coppens, Delphi G M; De Bruin, Marie L; Leufkens, Hubert G M

    2017-01-01

    Gene- and cell-based therapies (GCTs) offer potential new treatment options for unmet medical needs. However, the use of conventional regulatory requirements for medicinal products to approve GCTs may impede patient access and therapeutic innovation. Furthermore, requirements differ between juris...

  13. Facilitating problem based learning in an online biology laboratory course

    Science.gov (United States)

    Wesolowski, Meredith C.

    Online instruction offers many benefits to underserved populations in higher education, particularly increased access. However, incorporation of preferred pedagogical methods, particularly those involving student collaboration, can be more difficult to facilitate in online courses due to geographic separation. In the area of laboratory science education, there is a strong argument for use of constructivist, collaborative pedagogy to promote many facets of student learning. This EPP describes the process used to develop two problem based learning (PBL) laboratory activities based on recommendations found in the literature, their incorporation into an online biology laboratory science course (BIO101) and their impact on student achievement and critical thinking skills. Data analysis revealed a high level of achievement within the study semester. In addition, use of synchronous group discussions as part of the PBL framework resulted in a broad range of discussions reflective of successful problem solving interactions described in the literature. Together, these suggest a observed benefit from incorporation of PBL in this online course. In addition, specific areas for modification were identified as potential future improvements.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

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

  15. 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.

  16. 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.

  17. 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…

  18. 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.

  19. Mesenchymal Stem Cell-Based Therapy for Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs; Jeffrey Karp ...clinical trials for CRPC. The team is composed of Drs. Jeffrey Karp Co-Director of Regenerative Therapeutics at the Brigham & Women’s Hospital...encapsulating a PSA-activated thapsigargin-based prodrug (G115, Fig. 5) were generated by the Karp lab with the properties outlined in Table 7. These

  20. CAMERA-BASED SOFTWARE IN REHABILITATION/THERAPY INTERVENTION

    DEFF Research Database (Denmark)

    Brooks, Anthony Lewis

    2014-01-01

    Use of an affordable, easily adaptable, ‘non-specific camera-based software’ that is rarely used in the field of rehabilitation is reported in a study with 91 participants over the duration of six workshop sessions. ‘Non-specific camera-based software’ refers to software that is not dependent......, and accessible software EyeCon is a potent and significant tool in the field of rehabilitation/therapy and warrants wider exploration....

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

    International Nuclear Information System (INIS)

    Somlyai, G.; Jancso, G.; Jakli, Gy.; Berkenyi, T.; Laskay, G.; Gyoengyi, Z.

    2000-01-01

    It is known that the deuterium/hydrogen mass ratio is the largest of stable isotopes of the same element, causing differences in the physical and chemical behaviour between the two hydrogen isotopes. The possible role of naturally occurring deuterium - whose concentration is over 16 mmol/l in surface water, 12-14 mmol/l in living organisms - in biological systems was first investigated in the early 90s. The results revealed that deuterium depleted water (DDW): i) inhibits cell proliferation of different cell lines in vitro (MDA and MCF-7: human breast, PC-3: human prostate, M14: human melanoma, HT-29: human colon, L 929 : mouse fibroblast, A4: murine haemopoietic); ii) as drinking water causes partial or complete tumour regression in xenotransplanted mice (MDA, MCF-7, PC-3); iii) can induce complete or partial tumour regression in dogs and cats with different tumours; iv) induced apoptosis in vitro and vivo; v) has a significant influence on the e-mye, Ha-ras and p53 genes by reducing their expression; vi) shows efficacy in Phase II double blind clinical trial with human prostate cancer. It is generally accepted that the earliest event in the response of mammalian cells to mitogens is the elevation of pH i , which may be the proliferative trigger. It is also known that the binding site for protons to be transported by plasma membrane H 4 -ATPasc of yeast does not accept deuterons with the same case as H 4 or perhaps not at all. It is therefore reasonable to assume that when the cell eliminates the H 4 to govern the pH i by activating the Na + /H 4 antiport system the D/H ratio increases in the intracellular space. We suggest that the cell cycle regulating system is somehow able to recognize the change in the D/H ratio and when this ratio reaches a certain threshold this will trigger the molecular mechanism which causes the cell to enter the S phase. The decrease of D concentration caused by DDW can interfere with the signal transduction pathways thus leading to

  2. 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.

  3. Organization of a radioisotope based molecular biology laboratory

    International Nuclear Information System (INIS)

    2006-12-01

    Polymerase chain reaction (PCR) has revolutionized the application of molecular techniques to medicine. Together with other molecular biology techniques it is being increasingly applied to human health for identifying prognostic markers and drug resistant profiles, developing diagnostic tests and genotyping systems and for treatment follow-up of certain diseases in developed countries. Developing Member States have expressed their need to also benefit from the dissemination of molecular advances. The use of radioisotopes, as a step in the detection process or for increased sensitivity and specificity is well established, making it ideally suitable for technology transfer. Many molecular based projects using isotopes for detecting and studying micro organisms, hereditary and neoplastic diseases are received for approval every year. In keeping with the IAEA's programme, several training activities and seminars have been organized to enhance the capabilities of developing Member States to employ in vitro nuclear medicine technologies for managing their important health problems and for undertaking related basic and clinical research. The background material for this publication was collected at training activities and from feedback received from participants at research and coordination meetings. In addition, a consultants' meeting was held in June 2004 to compile the first draft of this report. Previous IAEA TECDOCS, namely IAEA-TECDOC-748 and IAEA-TECDOC-1001, focused on molecular techniques and their application to medicine while the present publication provides information on organization of the laboratory, quality assurance and radio-safety. The technology has specific requirements of the way the laboratory is organized (e.g. for avoiding contamination and false positives in PCR) and of quality assurance in order to provide accurate information to decision makers. In addition while users of the technology accept the scientific rationale of using radio

  4. A systematic review of the evidence base for Schema Therapy.

    Science.gov (United States)

    Masley, Samantha A; Gillanders, David T; Simpson, Susan G; Taylor, Morag A

    2012-01-01

    Schema Therapy is becoming an increasingly popular psychological model for working with individuals who have a variety of mental health and personality difficulties. The aim of this review is to look at the current evidence base for Schema Therapy and highlight directions for further research. A systematic search of the literature was conducted up until January 2011. All studies that had clinically tested the efficacy of Schema Therapy as described by Jeffrey Young (1994 and 2003) were considered. These studies underwent detailed quality assessments based on Scottish Intercollegiate Guidelines Network (SIGN-50) culminating in 12 studies being included in the review. The culminative message (both from the popularity of this model and the medium-to-large effect sizes) is of a theory that has already demonstrated clinically effective outcomes in a small number of studies and that would benefit from ongoing research and development with complex client groups. It is imperative that psychological practice be guided by high-quality research that demonstrates efficacious, evidence-based interventions. It is therefore recommended that researchers and clinicians working with Schema Therapy seek to build on these positive outcomes and further demonstrate the clinical effectiveness of this model through ongoing research.

  5. Modern methods for vancomycin determination in biological fluids by methods based on high-performance liquid chromatography--A review.

    Science.gov (United States)

    Javorska, Lenka; Krcmova, Lenka Kujovska; Solichova, Dagmar; Solich, Petr; Kaska, Milan

    2016-01-01

    Vancomycin is a glycopeptide antibiotic used in the therapy of severe bacterial infection. The monitoring of vancomycin levels is recommended because of its narrow therapeutic index and toxicity. This measurement is especially appropriate in patients with unstable renal functions, who receive high doses of vancomycin or present serious bacterial infections accompanied by important sequestration of liquids when it could be difficult to achieve the optimal therapeutic dose. Most of the methods for vancomycin determination in routine practice are immunoassays. However, chromatography-based techniques in combination with UV or mass spectrometry detection provide results with greater accuracy and precision also in complicated biological matrices. This review provides a detailed overview of modern approaches for the chromatographic separation of vancomycin in various biological samples and useful sample preparation procedures for vancomycin determination in various biological fluids. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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.

  7. 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

  8. 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.

  9. A Color-Opponency Based Biological Model for Color Constancy

    Directory of Open Access Journals (Sweden)

    Yongjie Li

    2011-05-01

    Full Text Available Color constancy is the ability of the human visual system to adaptively correct color-biased scenes under different illuminants. Most of the existing color constancy models are nonphysiologically plausible. Among the limited biological models, the great majority is Retinex and its variations, and only two or three models directly simulate the feature of color-opponency, but only of the very earliest stages of visual pathway, i.e., the single-opponent mechanisms involved at the levels of retinal ganglion cells and lateral geniculate nucleus (LGN neurons. Considering the extensive physiological evidences supporting that both the single-opponent cells in retina and LGN and the double-opponent neurons in primary visual cortex (V1 are the building blocks for color constancy, in this study we construct a color-opponency based color constancy model by simulating the opponent fashions of both the single-opponent and double-opponent cells in a forward manner. As for the spatial structure of the receptive fields (RF, both the classical RF (CRF center and the nonclassical RF (nCRF surround are taken into account for all the cells. The proposed model was tested on several typical image databases commonly used for performance evaluation of color constancy methods, and exciting results were achieved.

  10. 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.

  11. Applying science in practice: the optimization of biological therapy in rheumatoid arthritis

    NARCIS (Netherlands)

    Ramiro, Sofia; Machado, Pedro; Singh, Jasvinder A.; Landewé, Robert B.; da Silva, José António P.

    2010-01-01

    Most authorities recommend starting biological agents upon failure of at least one disease-modifying agent in patients with rheumatoid arthritis. However, owing to the absence of head-to-head studies, there is little guidance about which biological to select. Still, the practicing clinician has to

  12. [Ten-day Sequential Therapy versus Bismuth Based Quadruple Therapy as Second Line Treatment for Helicobacter pylori Infection].

    Science.gov (United States)

    Kim, Sung Bum; Lee, Si Hyung; Kim, Kyeong Ok; Jang, Byung Ik; Kim, Tae Nyeun

    2015-11-01

    Ten-day sequential therapy has been evaluated as the first line therapy for Helicobacter pylori eradication but studies on sequential therapy as a second line therapy is lacking. The aim of this study was to compare the efficacy of 10-day sequential therapy and quadruple therapy as second line treatment for H. pylori eradication after failure of standard triple therapy. Patients who did not respond to standard triple therapy for H. pylori eradication were assigned to either 10-day sequential or bismuth based quadruple therapy as second line treatment from January 2009 to December 2014 at Yeungnam University Medical Center. Post treatment H. pylori status was determined by rapid urease test, giemsa staining, or (13)C-urea breath test. Eradication rate and side effects of both therapies were compared. A total of 158 H. pylori infected patients were included and 70 patients were treated by bismuth based quadruple therapy and 88 patients by 10-day sequential therapy. Age and sex were not significantly different between the two groups. Eradication rate was 84.3% (59/70) in quadruple group and 56.8% (50/88) in sequential group. Side effects occurred significantly higher in quadruple group than sequential group (27.1% vs. 11.4%, p=0.011). For second line H. pylori eradication after failure of standard triple therapy, bismuth based quadruple therapy showed significantly higher H. pylori eradication rate than 10-day sequential therapy. Further prospective studies are needed to evaluate the efficacy of 10-day sequential therapy as a second line H. pylori eradication treatment.

  13. Sustainable production of biologically active molecules of marine based origin.

    Science.gov (United States)

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. 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.

  15. Stem Cell-Based Therapies for Liver Diseases: State of the Art and New Perspectives

    Directory of Open Access Journals (Sweden)

    Anna Chiara Piscaglia

    2010-01-01

    Full Text Available Millions of patients worldwide suffer from end-stage liver pathologies, whose only curative therapy is liver transplantation (OLT. Given the donor organ shortage, alternatives to OLT have been evaluated, including cell therapies. Hepatocyte transplantation has been attempted to cure metabolic liver disorders and end-stage liver diseases. The evaluation of its efficacy is complicated by the shortage of human hepatocytes and their difficult expansion and cryopreservation. Recent advances in cell biology have led to the concept of “regenerative medicine”, based on the therapeutic potential of stem cells (SCs. Different types of SCs are theoretically eligible for liver cell replacement. These include embryonic and fetal SCs, induced pluripotent cells, annex SCs, endogenous liver SCs, and extrahepatic adult SCs. Aim of this paper is to critically analyze the possible sources of SCs suitable for liver repopulation and the results of the clinical trials that have been published until now.

  16. 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. .

  17. 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.

  18. Biomaterial-Based Implantable Devices for Cancer Therapy.

    Science.gov (United States)

    Chew, Sue Anne; Danti, Serena

    2017-01-01

    This review article focuses on the current local therapies mediated by implanted macroscaled biomaterials available or proposed for fighting cancer and also highlights the upcoming research in this field. Several authoritative review articles have collected and discussed the state-of-the-art as well as the advancements in using biomaterial-based micro- and nano-particle systems for drug delivery in cancer therapy. On the other hand, implantable biomaterial devices are emerging as highly versatile therapeutic platforms, which deserve an increased attention by the healthcare scientific community, as they are able to offer innovative, more effective and creative strategies against tumors. This review summarizes the current approaches which exploit biomaterial-based devices as implantable tools for locally administrating drugs and describes their specific medical applications, which mainly target resected brain tumors or brain metastases for the inaccessibility of conventional chemotherapies. Moreover, a special focus in this review is given to innovative approaches, such as combined delivery therapies, as well as to alternative approaches, such as scaffolds for gene therapy, cancer immunotherapy and metastatic cell capture, the later as promising future trends in implantable biomaterials for cancer applications. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. 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.

  20. Clinical applicability of biologically effective dose calculation for spinal cord in fractionated spine stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jinho; Ahn, So Hyun; Lee, Seok Ho; Sung, Ki Hoon; Kil, Se Hee

    2015-01-01

    The aim of the study was to investigate whether biologically effective dose (BED) based on linear-quadratic model can be used to estimate spinal cord tolerance dose in spine stereotactic body radiation therapy (SBRT) delivered in 4 or more fractions. Sixty-three metastatic spinal lesions in 47 patients were retrospectively evaluated. The most frequently prescribed dose was 36 Gy in 4 fractions. In planning, we tried to limit the maximum dose to the spinal cord or cauda equina less than 50% of prescription or 45 Gy 2/2 . BED was calculated using maximum point dose of spinal cord. Maximum spinal cord dose per fraction ranged from 2.6 to 6.0 Gy (median 4.3 Gy). Except 4 patients with 52.7, 56.4, 62.4, and 67.9 Gy 2/2 , equivalent total dose in 2-Gy fraction of the patients was not more than 50 Gy 2/2 (12.1–67.9, median 32.0). The ratio of maximum spinal cord dose to prescription dose increased up to 82.2% of prescription dose as epidural spinal cord compression grade increased. No patient developed grade 2 or higher radiation-induced spinal cord toxicity during follow-up period of 0.5 to 53.9 months. In fractionated spine SBRT, BED can be used to estimate spinal cord tolerance dose, provided that the dose per fraction to the spinal cord is moderate, e.g. < 6.0 Gy. It appears that a maximum dose of up to 45–50 Gy 2/2 to the spinal cord is tolerable in 4 or more fractionation regimen

  1. Biological therapy in the management of recent-onset Crohn's disease

    NARCIS (Netherlands)

    Lowenberg, Mark; Peppelenbosch, Maikel; Hommes, Daniel

    2006-01-01

    Crohn's disease is a chronic inflammatory bowel disease that may involve any part of the gastrointestinal tract. Conventional therapy consists of corticosteroids, azathioprine or methotrexate, but the clinical management of Crohn's disease is significantly hampered by adverse effects. With the

  2. Biological therapy in the management of recent-onset Crohn's disease: why, when and how?

    NARCIS (Netherlands)

    Löwenberg, Mark; Peppelenbosch, Maikel; Hommes, Daniel

    2006-01-01

    Crohn's disease is a chronic inflammatory bowel disease that may involve any part of the gastrointestinal tract. Conventional therapy consists of corticosteroids, azathioprine or methotrexate, but the clinical management of Crohn's disease is significantly hampered by adverse effects. With the

  3. 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…

  4. 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…

  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

    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...... with a higher DAS28 due to subjective parameters and with the more frequent use of biological treatments. This raises the question of whether the more frequent use of biologics in these patients is justified by inflammation, or is instead due to persistent pain and other centrally mediated symptoms....

  6. 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.

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

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Tomac Junior, U.

    1990-01-01

    The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of glyemas and gluoblastomas grade III and IV than other therapies. During the treatment the levels of Na 2 10 B 12 H 11 SH must be known in several compartiments of the organism and with this purpose the method of colorimetric determination of boron using curcumine was established. This method is simple, reprodutible and adequate sensitivity for this control. (author) [pt

  8. A colorimetric determination of boron in biological sample for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Camilo, M.A.P.; Tomac Junior, U.

    1989-01-01

    The boron neutron capture therapy (BNCT) has shown better prognosis in the treatment of gliomas and glioblastomas grade III and IV than other therapies. During the treatment of levels of Na 2 10 B 12 H 11 S H must be known in several compartments of the organism and with this purpose the method of colorimetric determination of boron using curcumin was established. This method is simples, reproducible and has adequate sensitivity for this control. (author). 7 refs, 3 figs, 1 tab

  9. Potential for Stem Cell-Based Periodontal Therapy

    Science.gov (United States)

    Bassir, Seyed Hossein; Wisitrasameewong, Wichaya; Raanan, Justin; Ghaffarigarakani, Sasan; Chung, Jamie; Freire, Marcelo; Andrada, Luciano C.; Intini, Giuseppe

    2015-01-01

    Periodontal diseases are highly prevalent and are linked to several systemic diseases. The goal of periodontal treatment is to halt the progression of the disease and regenerate the damaged tissue. However, achieving complete and functional periodontal regeneration is challenging because the periodontium is a complex apparatus composed of different tissues, including bone, cementum, and periodontal ligament. Stem cell-based regenerative therapy may represent an effective therapeutic tool for periodontal regeneration due to their plasticity and ability to differentiate into different cell lineages. This review presents and critically analyzes the available information on stem cell-based therapy for the regeneration of periodontal tissues and suggests new avenues for the development of more effective therapeutic protocols. PMID:26058394

  10. The cell based therapy and the policy implications in India.

    Science.gov (United States)

    Mukhopadhyay, Bratati; Basak, Saroj K; Ganguly, Nirmal K

    2011-01-01

    The recent scientific development using stem or other differentiated cells has generated great hopes for treatment of various diseases. Major thrust has been given to formulate country specific laws and regulations considering international guidelines to conduct research and clinical applications of "Cell Based Therapy" (CBT) all over the world. Attempts have made in this review to discuss the current policies that are practiced by various countries in the areas related to CBT with special emphasis on CBT related research and development in India. The two major funding agencies of Government of India e.g. Department of Biotechnology (DBT) and Indian Council of Medical Research (ICMR), have jointly formulated the "Guidelines for Stem Cell Research and Therapy" in 2007 which requires update and revision. Based on the review of the current world scenario of CBT research and development, suggestions have been made for the development of a new CBT policy that will help in progress of research and patient treatment in India.

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

    Directory of Open Access Journals (Sweden)

    Amir Rumman

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Adrian Matthew Shields

    2012-02-01

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

  14. Blastic plasmacytoid dendritic cell neoplasm: update on molecular biology, diagnosis, and therapy.

    Science.gov (United States)

    Riaz, Wasif; Zhang, Ling; Horna, Pedro; Sokol, Lubomir

    2014-10-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with an aggressive clinical course. Most patients with BPDCN have skin lesions and simultaneous involvement of the peripheral blood, bone marrow, and lymph nodes. A search of PubMed and Medline was conducted for English-written articles relating to BPDCN, CD4(+)CD56(+) hematodermic neoplasm, and blastic natural killer cell lymphoma. Data regarding diagnosis, prognosis, and treatment were analyzed. BPDCN is derived from precursor plasmacytoid dendritic cells. The diagnosis of BPDCN is based on the characteristic cytology and immunophenotype of malignant cells coexpressing CD4, CD56, CD123, blood dendritic cell antigens 2 and 4, and CD2AP markers. Multiple chromosomal abnormalities and gene mutations previously reported in patients with myeloid and selected lymphoid neoplasms were identified in approximately 60% of patients with BPDCN. Prospectively controlled studies to guide treatment decisions are lacking. The overall response rate with aggressive acute lymphoblastic leukemia-type induction regimens was as high as 90%, but the durability of response was short. Median survival rates ranged between 12 and 16 months. Patients with relapsed disease may respond to L-asparaginase-containing regimens. Allogeneic hematopoietic stem cell transplantation, particularly when performed during the first remission, may produce durable remissions in selected adults. BPDCN is a rare aggressive disease that typically affects elderly patients. The most commonly affected nonhematopoietic organ is the skin. Although BPDCN is initially sensitive to conventional chemotherapy regimens, this response is relatively short and long-term prognosis is poor. In the near future, novel targeted therapies may improve outcomes for patients with BPDCN.

  15. Optimizing biologic therapies for inflammatory bowel disease (ulcerative colitis and Crohn's disease)

    NARCIS (Netherlands)

    Ferrante, Marc; D'Haens, Geert; Rutgeerts, Paul; Vermeire, Séverine; van Assche, Gert

    2009-01-01

    The introduction of biologic agents and particularly of anti-tumor necrosis factor antibodies dramatically changed the therapeutic algorithm in patients with inflammatory bowel diseases. Although the efficacy of these agents has been demonstrated clearly, optimal treatment strategies are debated.

  16. 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)

  17. 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.

  18. Evidence-based use of pulsed electromagnetic field therapy in clinical plastic surgery.

    Science.gov (United States)

    Strauch, Berish; Herman, Charles; Dabb, Richard; Ignarro, Louis J; Pilla, Arthur A

    2009-01-01

    The initial development of pulsed electromagnetic field (PEMF) therapy and its evolution over the last century for use in clinical surgery has been slow, primarily because of lack of scientifically-derived, evidence-based knowledge of the mechanism of action. Our objective was to review the major scientific breakthroughs and current understanding of the mechanism of action of PEMF therapy, providing clinicians with a sound basis for optimal use. A literature review was conducted, including mechanism of action and biologic and clinical studies of PEMF. Using case illustrations, a holistic exposition on the clinical use of PEMF in plastic surgery was performed. PEMF therapy has been used successfully in the management of postsurgical pain and edema, the treatment of chronic wounds, and in facilitating vasodilatation and angiogenesis. Using scientific support, the authors present the currently accepted mechanism of action of PEMF therapy. This review shows that plastic surgeons have at hand a powerful tool with no known side effects for the adjunctive, noninvasive, nonpharmacologic management of postoperative pain and edema. Given the recent rapid advances in development of portable and economical PEMF devices, what has been of most significance to the plastic surgeon is the laboratory and clinical confirmation of decreased pain and swelling following injury or surgery.

  19. 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.

  20. Mindfulness-based cognitive therapy for generalized anxiety disorder.

    Science.gov (United States)

    Evans, Susan; Ferrando, Stephen; Findler, Marianne; Stowell, Charles; Smart, Colette; Haglin, Dean

    2008-05-01

    While cognitive behavior therapy has been found to be effective in the treatment of generalized anxiety disorder (GAD), a significant percentage of patients struggle with residual symptoms. There is some conceptual basis for suggesting that cultivation of mindfulness may be helpful for people with GAD. Mindfulness-based cognitive therapy (MBCT) is a group treatment derived from mindfulness-based stress reduction (MBSR) developed by Jon Kabat-Zinn and colleagues. MBSR uses training in mindfulness meditation as the core of the program. MBCT incorporates cognitive strategies and has been found effective in reducing relapse in patients with major depression (Teasdale, J. D., Segal, Z. V., Williams, J. M. G., Ridgeway, V., Soulsby, J., & Lau, M. (2000). Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. Journal of Consulting and Clinical Psychology, 6, 615-623). Eligible subjects recruited to a major academic medical center participated in the group MBCT course and completed measures of anxiety, worry, depressive symptoms, mood states and mindful awareness in everyday life at baseline and end of treatment. Eleven subjects (six female and five male) with a mean age of 49 (range=36-72) met criteria and completed the study. There were significant reductions in anxiety and depressive symptoms from baseline to end of treatment. MBCT may be an acceptable and potentially effective treatment for reducing anxiety and mood symptoms and increasing awareness of everyday experiences in patients with GAD. Future directions include development of a randomized clinical trial of MBCT for GAD.

  1. 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.

  2. IL-12 based gene therapy in veterinary medicine.

    Science.gov (United States)

    Pavlin, Darja; Cemazar, Maja; Sersa, Gregor; Tozon, Natasa

    2012-11-21

    The use of large animals as an experimental model for novel treatment techniques has many advantages over the use of laboratory animals, so veterinary medicine is becoming an increasingly important translational bridge between preclinical studies and human medicine. The results of preclinical studies show that gene therapy with therapeutic gene encoding interleukin-12 (IL-12) displays pronounced antitumor effects in various tumor models. A number of different studies employing this therapeutic plasmid, delivered by either viral or non-viral methods, have also been undertaken in veterinary oncology. In cats, adenoviral delivery into soft tissue sarcomas has been employed. In horses, naked plasmid DNA has been delivered by direct intratumoral injection into nodules of metastatic melanoma. In dogs, various types of tumors have been treated with either local or systemic IL-12 electrogene therapy. The results of these studies show that IL-12 based gene therapy elicits a good antitumor effect on spontaneously occurring tumors in large animals, while being safe and well tolerated by the animals. Hopefully, such results will lead to further investigation of this therapy in veterinary medicine and successful translation into human clinical trials.

  3. 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

  4. Ketogenic diets: new advances for metabolism-based therapies.

    Science.gov (United States)

    Kossoff, Eric H; Hartman, Adam L

    2012-04-01

    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 diet, modified Atkins diet, and low glycemic index treatment. 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; this group of patients previously was 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 neurological conditions other than epilepsy, including Alzheimer's disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, in terms of both an anticonvulsant and possibly a neuroprotective effect. Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy.

  5. Biologic therapy adherence, discontinuation, switching, and restarting among patients with psoriasis in the US Medicare population

    Science.gov (United States)

    Doshi, Jalpa A.; Takeshita, Junko; Pinto, Lionel; Li, Penxiang; Yu, Xinyan; Rao, Preethi; Viswanathan, Hema N.; Gelfand, Joel M.

    2016-01-01

    Background Studies indicate adherence to biologics among patients with psoriasis is low, yet little is known about their use in the Medicare population. Objective We sought to investigate real-world utilization patterns in a national sample of Medicare beneficiaries with psoriasis initiating infliximab, etanercept, adalimumab, or ustekinumab. Methods We conducted a retrospective claims analysis using 2009 through 2012 100% Medicare Chronic Condition Data Warehouse Part A, B, and D files, with 12-month follow-up after index prescription. Descriptive and multivariate analyses were used to examine rates of and factors associated with biologic adherence, discontinuation, switching, and restarting. Results We examined 2707 patients initiating adalimumab (40.0%), etanercept (37.9%), infliximab (11.7%), and ustekinumab (10.3%); during 12-month follow-up, 38% were adherent and 46% discontinued treatment, with 8% switching to another biologic and 9% later restarting biologic treatment. Being female and being ineligible for low-income subsidies were associated with increased odds of decreased adherence. Outcomes varied by index biologic. Limitations Patient-reported reasons for nonadherence or gaps in treatment are unavailable in claims data. Conclusion Medicare patients initiating biologics for psoriasis had low adherence and high discontinuation rates. Further investigation into reasons for inconsistent utilization, including exploration of patient and provider decision-making and barriers to more consistent treatment, is needed. PMID:26946986

  6. Current perspectives and challenges in understanding the role of nitrite as an integral player in nitric oxide biology and therapy.

    Science.gov (United States)

    Vitturi, Dario A; Patel, Rakesh P

    2011-08-15

    Beyond an inert oxidation product of nitric oxide (NO) metabolism, current thinking posits a key role for nitrite as a mediator of NO signaling, especially during hypoxia. This concept has been discussed in the context of nitrite serving a role as an endogenous modulator of NO homeostasis, but also from a novel clinical perspective whereby nitrite therapy may replenish NO signaling and prevent ischemic tissue injury. Indeed, the relatively rapid translation of studies delineating mechanisms of action to ongoing and planned clinical trials has been critical in fuelling interest in nitrite biology, and several excellent reviews have been written on this topic. In this article we limit our discussions to current concepts and what we feel are questions that remain unanswered within the paradigm of nitrite being a mediator of NO biology. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. High Incidence of Tuberculosis Infection in Rheumatic Diseases and Impact for Chemoprophylactic Prevention of Tuberculosis Activation during Biologics Therapy

    Science.gov (United States)

    Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying

    2013-01-01

    We conducted a long-term follow-up study in patients with rheumatic diseases who were candidates for biologics treatment to evaluate the effects of biologic agents on the risk of tuberculosis infection and the effect of prophylactic treatment on tuberculosis activation. One hundred one patients with rheumatic diseases who were candidates for biologics treatment were recruited, and 57 healthy subjects were recruited as controls. Tuberculin skin test (TST) and the T-SPOT.TB test were performed for all subjects at baseline. Follow-up testing by the T-SPOT.TB assay was performed every 6 months in patients with rheumatic diseases and at 2 years of recruitment in the healthy controls. In patients with rheumatic diseases and healthy controls, the TST-positive (induration, ≥10 mm) rates were 37.6% (38/101) and 34.0% (18/53), respectively (P > 0.05), while the T-SPOT.TB-positive rates were 46.5% (47/101) and 21.1 (12/57), respectively (P = 0.0019). Fifty-two patients were followed up at month 6 with a T-SPOT.TB-positive rate of 40.4%, and 49 were followed up for ≥12 months with a T-SPOT.TB-positive rate of 36.7%, with no significant difference in the positive rate at different time points including baseline (P > 0.05). Long-term follow-up revealed that conversion to T-SPOT.TB positivity occurred only in the biologics treatment group, with a positive conversion rate of 11.2% (4/38). Most importantly, no latent tuberculosis developed into active tuberculosis during follow-up with T-SPOT.TB screening and preemptive treatment with isoniazid. Biologics treatment appears to increase the risk of tuberculosis infection. However, tuberculosis activation could be prevented by preemptive isoniazid treatment in patients with latent tuberculosis infection while receiving biologics therapy. PMID:23554465

  8. Bridging cancer biology and the patients' needs with nanotechnology-based approaches.

    Science.gov (United States)

    Fonseca, Nuno A; Gregório, Ana C; Valério-Fernandes, Angela; Simões, Sérgio; Moreira, João N

    2014-06-01

    Cancer remains as stressful condition and a leading cause of death in the western world. Actual cornerstone treatments of cancer disease rest as an elusive alternative, offering limited efficacy with extensive secondary effects as a result of severe cytotoxic effects in healthy tissues. The advent of nanotechnology brought the promise to revolutionize many fields including oncology, proposing advanced systems for cancer treatment. Drug delivery systems rest among the most successful examples of nanotechnology. Throughout time they have been able to evolve as a function of an increased understanding from cancer biology and the tumor microenvironment. Marketing of Doxil® unleashed a remarkable impulse in the development of drug delivery systems. Since then, several nanocarriers have been introduced, with aspirations to overrule previous technologies, demonstrating increased therapeutic efficacy besides decreased toxicity. Spatial and temporal targeting to cancer cells has been explored, as well as the use of drug combinations co-encapsulated in the same particle as a mean to take advantage of synergistic interactions in vivo. Importantly, targeted delivery of siRNA for gene silencing therapy has made its way to the clinic for a "first in man" trial using lipid-polymeric-based particles. Focusing in state-of-the-art technology, this review will provide an insightful vision on nanotechnology-based strategies for cancer treatment, approaching them from a tumor biology-driven perspective, since their early EPR-based dawn to the ones that have truly the potential to address unmet medical needs in the field of oncology, upon targeting key cell subpopulations from the tumor microenvironment. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Home-based exercise during preoperative therapy for pancreatic cancer.

    Science.gov (United States)

    Ngo-Huang, An; Parker, Nathan H; Wang, Xuemei; Petzel, Maria Q B; Fogelman, David; Schadler, Keri L; Bruera, Eduardo; Fleming, Jason B; Lee, Jeffrey E; Katz, Matthew H G

    2017-12-01

    Exercise concurrent with neoadjuvant chemotherapy and/or chemoradiation for pancreatic adenocarcinoma (PDAC) may mitigate the decline in function that may occur as a result of the disease or its treatment in the preoperative period. The primary objective of this single-arm prospective trial was to determine adherence to a home-based exercise program administered during preoperative therapy. Twenty patients from a quaternary cancer center with potentially resectable PDAC were enrolled. Patients were prescribed a minimum of 120 min of moderate-intensity exercise weekly: at least 60 min of aerobic exercise and 60 min of resistance exercise. Self-reported exercise was recorded in daily logs. Functional and survey measures were collected upon enrollment, following preoperative therapy, and 1 month after surgery. Fifteen out of 20 patients participated in the program. They reported a mean (standard deviation (SD)) of 98.6 (69.8) min of aerobic exercise weekly and 57.4 (36.0) min of strengthening exercise weekly over a median of 17 weeks (range, 5-35 weeks) of preoperative therapy, for a mean (SD) of 156.0 (64.5) min of total exercise weekly. Eighty percent reported a mean of least 120 min of total exercise weekly during preoperative therapy. Patients with low baseline physical activity based on the International Physical Activity Questionnaire significantly increased their preoperative physical activity (p = .01). There were no adverse events associated with the exercise program. Patients with PDAC will participate in a home-based exercise program of aerobic and strengthening exercise and will increase physical activity, concurrent with preoperative chemotherapy and/or chemoradiation.

  10. 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.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D 95% ) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower

  12. Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis.

    Science.gov (United States)

    Jabbar-Lopez, Zarif K; Yiu, Zenas Z N; Ward, Victoria; Exton, Lesley S; Mohd Mustapa, M Firouz; Samarasekera, Eleanor; Burden, A David; Murphy, Ruth; Owen, Caroline M; Parslew, Richard; Venning, Vanessa; Warren, Richard B; Smith, Catherine H

    2017-08-01

    Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538). Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Stem cell-based therapies for osteoarthritis: challenges and opportunities.

    Science.gov (United States)

    Diekman, Brian O; Guilak, Farshid

    2013-01-01

    Regenerative medicine offers the exciting potential of developing alternatives to total joint replacement for treating osteoarthritis. In this article, we highlight recent work that addresses key challenges of stem cell-based therapies for osteoarthritis and provide examples of innovative ways in which stem cells can aid in the treatment of osteoarthritis. Significant progress has been made in understanding the challenges to successful stem cell therapy, such as the effects of age or disease on stem cell properties, altered stem cell function due to an inflammatory joint environment and phenotypic instability in vivo. Novel scaffold designs have been shown to enhance the mechanical properties of tissue-engineered cartilage and have also improved the integration of newly formed tissue within the joint. Emerging strategies such as injecting stem cells directly into the joint, manipulating endogenous stem cells to enhance regenerative capacity and utilizing stem cells for drug discovery have expanded the potential uses of stem cells in treating osteoarthritis. Several recent studies have greatly advanced the development and preclinical evaluation of potential stem cell-based treatments for osteoarthritis through novel approaches focused on cell therapy, tissue engineering and drug discovery.

  14. Activins and Follistatin in Chronic Hepatitis C and Its Treatment with Pegylated-Interferon-α Based Therapy

    Directory of Open Access Journals (Sweden)

    Bassem Refaat

    2015-01-01

    Full Text Available Pegylated-interferon-α based therapy for the treatment of chronic hepatitis C (CHC is considered suboptimal as not all patients respond to the treatment and it is associated with several side effects that could lead to dose reduction and/or termination of therapy. The currently used markers to monitor the response to treatment are based on viral kinetics and their performance in the prediction of treatment outcome is moderate and does not combine accuracy and their values have several limitations. Hence, the development of new sensitive and specific predictor markers could provide a useful tool for the clinicians and healthcare providers, especially in the new era of interferon-free therapy, for the classification of patients according to their response to the standard therapy and only subscribing the novel directly acting antiviral drugs to those who are anticipated not to respond to the conventional therapy and/or have absolute contraindications for its use. The importance of activins and follistatin in the regulation of immune system, liver biology, and pathology has recently emerged. This review appraises the up-to-date knowledge regarding the role of activins and follistatin in liver biology and immune system and their role in the pathophysiology of CHC.

  15. Design, synthesis and biological evaluation of Arylpiperazine-based ...

    Indian Academy of Sciences (India)

    Understanding of apoptosis or programmed cell death has provided the basis for novel therapeutics that has resulted in rationally designed anticancer strategies. Recently, inducers of apoptosis have been used in cancer therapy. In this work, we describe the role of chiral phthalimides functionalized with piperazines ...

  16. Community-based model for speech therapy in Thailand: implementation.

    Science.gov (United States)

    Prathanee, Benjamas; Lorwatanapongsa, Preeya; Makarabhirom, Kalyanee; Suphawatjariyakul, Ratchanee; Thinnaithorn, Rattana; Thanwiratananich, Panida

    2010-10-01

    To establish a Community-Based Model for Speech Therapy in Thailand and to implement it. The development of a Community-Based Model for Speech Therapy was based on the principles of primary healthcare, community-based rehabilitation and institutional sharing. Workshops for speech and language pathologists (SLPs), including "Training for Trainers" and six "Smart Smile & Speech" workshops were held. We held 1) a workshop for training SLPs in how to manage speech and language problems in cleft lip and palate (CLP); 2) a workshop for training healthcare providers who are not speech and language pathologists (para-speech and language pathologists: para-SLPs) how to identify speech, language and hearing problems in CLP and undertake early intervention; and, 3) four speech camps for continuing education via life demonstration and practice. Standard guidelines were produced for SLPs to remedy speech and language disorders in children with CLP in Thailand and para-SLP manuals for speech and language intervention for CLP were developed. Para-SLPs will be better equipped to identify and then provide early intervention for individuals with CLP, as well as to refer children with CLP and complicated speech and language disorders to speech clinics for the further management. Percentage of agreement among SLP, audiologists and para-SLPs ranged 50-93.33 while the Kappa coefficients ranged -0.07 to 0.86. The Community-Based Model for Speech Therapy for Children with CLP was an appropriate approach for coming up with solutions for the lack of speech services for children with CLP in Thailand.

  17. 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

  18. GPU-based High-Performance Computing for Radiation Therapy

    Science.gov (United States)

    Jia, Xun; Ziegenhein, Peter; Jiang, Steve B.

    2014-01-01

    Recent developments in radiotherapy therapy demand high computation powers to solve challenging problems in a timely fashion in a clinical environment. Graphics processing unit (GPU), as an emerging high-performance computing platform, has been introduced to radiotherapy. It is particularly attractive due to its high computational power, small size, and low cost for facility deployment and maintenance. Over the past a few years, GPU-based high-performance computing in radiotherapy has experienced rapid developments. A tremendous amount of studies have been conducted, in which large acceleration factors compared with the conventional CPU platform have been observed. In this article, we will first give a brief introduction to the GPU hardware structure and programming model. We will then review the current applications of GPU in major imaging-related and therapy-related problems encountered in radiotherapy. A comparison of GPU with other platforms will also be presented. PMID:24486639

  19. GPU-based high-performance computing for radiation therapy

    International Nuclear Information System (INIS)

    Jia, Xun; Jiang, Steve B; Ziegenhein, Peter

    2014-01-01

    Recent developments in radiotherapy therapy demand high computation powers to solve challenging problems in a timely fashion in a clinical environment. The graphics processing unit (GPU), as an emerging high-performance computing platform, has been introduced to radiotherapy. It is particularly attractive due to its high computational power, small size, and low cost for facility deployment and maintenance. Over the past few years, GPU-based high-performance computing in radiotherapy has experienced rapid developments. A tremendous amount of study has been conducted, in which large acceleration factors compared with the conventional CPU platform have been observed. In this paper, we will first give a brief introduction to the GPU hardware structure and programming model. We will then review the current applications of GPU in major imaging-related and therapy-related problems encountered in radiotherapy. A comparison of GPU with other platforms will also be presented. (topical review)

  20. GPU-based high-performance computing for radiation therapy

    Science.gov (United States)

    Jia, Xun; Ziegenhein, Peter; Jiang, Steve B.

    2014-02-01

    Recent developments in radiotherapy therapy demand high computation powers to solve challenging problems in a timely fashion in a clinical environment. The graphics processing unit (GPU), as an emerging high-performance computing platform, has been introduced to radiotherapy. It is particularly attractive due to its high computational power, small size, and low cost for facility deployment and maintenance. Over the past few years, GPU-based high-performance computing in radiotherapy has experienced rapid developments. A tremendous amount of study has been conducted, in which large acceleration factors compared with the conventional CPU platform have been observed. In this paper, we will first give a brief introduction to the GPU hardware structure and programming model. We will then review the current applications of GPU in major imaging-related and therapy-related problems encountered in radiotherapy. A comparison of GPU with other platforms will also be presented.

  1. GPU-based high-performance computing for radiation therapy.

    Science.gov (United States)

    Jia, Xun; Ziegenhein, Peter; Jiang, Steve B

    2014-02-21

    Recent developments in radiotherapy therapy demand high computation powers to solve challenging problems in a timely fashion in a clinical environment. The graphics processing unit (GPU), as an emerging high-performance computing platform, has been introduced to radiotherapy. It is particularly attractive due to its high computational power, small size, and low cost for facility deployment and maintenance. Over the past few years, GPU-based high-performance computing in radiotherapy has experienced rapid developments. A tremendous amount of study has been conducted, in which large acceleration factors compared with the conventional CPU platform have been observed. In this paper, we will first give a brief introduction to the GPU hardware structure and programming model. We will then review the current applications of GPU in major imaging-related and therapy-related problems encountered in radiotherapy. A comparison of GPU with other platforms will also be presented.

  2. Stem cells: a revolution in therapeutics-recent advances in stem cell biology and their therapeutic applications in regenerative medicine and cancer therapies.

    Science.gov (United States)

    Mimeault, M; Hauke, R; Batra, S K

    2007-09-01

    Basic and clinical research accomplished during the last few years on embryonic, fetal, amniotic, umbilical cord blood, and adult stem cells has constituted a revolution in regenerative medicine and cancer therapies by providing the possibility of generating multiple therapeutically useful cell types. These new cells could be used for treating numerous genetic and degenerative disorders. Among them, age-related functional defects, hematopoietic and immune system disorders, heart failures, chronic liver injuries, diabetes, Parkinson's and Alzheimer's diseases, arthritis, and muscular, skin, lung, eye, and digestive disorders as well as aggressive and recurrent cancers could be successfully treated by stem cell-based therapies. This review focuses on the recent advancements in adult stem cell biology in normal and pathological conditions. We describe how these results have improved our understanding on critical and unique functions of these rare sub-populations of multipotent and undifferentiated cells with an unlimited self-renewal capacity and high plasticity. Finally, we discuss some major advances to translate the experimental models on ex vivo and in vivo expanded and/or differentiated stem cells into clinical applications for the development of novel cellular therapies aimed at repairing genetically altered or damaged tissues/organs in humans. A particular emphasis is made on the therapeutic potential of different tissue-resident adult stem cell types and their in vivo modulation for treating and curing specific pathological disorders.

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

    Directory of Open Access Journals (Sweden)

    Bolge SC

    2015-01-01

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

  4. Evidence-based therapy for sleep disorders in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    LIU Ling

    2013-08-01

    Full Text Available Objective To evaluate the effectiveness of the treatments for sleep disorders in neurodegenerative diseases so as to provide the best therapeutic regimens for the evidence-based treatment. Methods Search PubMed, MEDLINE, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure (CNKI databases with "sleep disorder or sleep disturbance", "neurodegenerative diseases", "Parkinson's disease or PD", "Alzheimer's disease or AD", "multiple system atrophy or MSA" as retrieval words. The quality of the articles were evaluated with Jadad Scale. Results A total of 35 articles, including 2 systematic reviews, 5 randomized controlled trials, 13 clinical controlled trials, 13 case series and 2 epidemiological investigation studies were included for evaluation, 13 of which were high grade and 22 were low grade articles. Clinical evidences showed that: 1 advice on sleep hygiene, careful use of dopaminergic drugs and hypnotic sedative agents should be considered for PD. Bright light therapy (BLT may improve circadian rhythm sleep disorders and clonazepam may be effective for rapid eye movement sleep behavior disorder (RBD. However, to date, very few controlled studies are available to make a recommendation for the management of sleep disorders in PD; 2 treatments for sleep disorders in AD include drug therapy (e.g. melatonin, acetylcholinesterase inhibitors, antipsychotic drugs, antidepressants and non-drug therapy (e.g. BLT, behavior therapy, but very limited evidence shows the effectiveness of these treatments; 3 the first line treatment for sleep-related breathing disorder in MSA is nasal continuous positive airway pressure (nCPAP, and clonazepam is effective for RBD in MSA; 4 there is rare evidence related to the treatment of sleep disorders in dementia with Lewy body (DLB and amyotrophic lateral sclerosis (ALS. Conclusion Evidence-based medicine can provide the best clinical evidence on sleep disorders' treatment in neurodegenerative

  5. 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.

  6. Systems Biology based studies on anti-inflammatory compounds

    NARCIS (Netherlands)

    Verhoeckx, Kitty Catharina Maria

    2005-01-01

    The introduction of the ‘omics’ techniques (transcriptomics, proteomics, and metabolomics) and systems biology, has caused fundamental changes in the drug discovery process and many other fields in the life science area. In this thesis we explored the possibilities to apply these holistic

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  8. Recent achievements in the development of radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors

    International Nuclear Information System (INIS)

    Larson, S.M.; Macapinlac, H.A.; Scott, A.M.; Divgi, C.R.

    1993-01-01

    Human tumors express antigenic sites that can serve as targets for radiolabeled monoclonal antibodies for diagnosis, therapy and biologic characterization of human tumors in vivo. Over the last decade, nearly 200 clinical trials have been performed which demonstrate that tumors can be detected with excellent sensitivity and specificity. Tumors which are otherwise occult, particularly for colorectal (anti-CEA and anti-TAG-72 antibodies) and ovarian cancer (anti-TAG-72 and anti-HMFG), are detected in a significant fraction of problem patients. Therapy using radiolabeled antibodies has been effective in lymphomas, leukemias and neuroblastomas, and is beginning to show promise in other solid tumors. Biologic characterization of tumors is likely to become more and more important in the future as monoclonal antibodies against oncogene products, such as her-2-neu, are developed. Development of new antibody forms through genetic engineering techniques, and the continual evolution toward higher resolution imaging instruments, such as PET and SPECT, will lead to further clinical improvements in cancer detection. (orig.)

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

    Science.gov (United States)

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

    2009-01-01

    Microdosimetric quantities such as lineal energy, y, are better indexes for expressing the RBE of HZE particles in comparison to LET. However, the use of microdosimetric quantities in computational dosimetry is severely limited because of the difficulty in calculating their probability densities in macroscopic matter. We therefore improved the particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric probability densities in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the probability densities around the trajectory of HZE particles with a precision equivalent to that of a microscopic track-structure simulation. A new method for estimating biological dose, the product of physical dose and RBE, from charged-particle therapy was established using the improved PHITS coupled with a microdosimetric kinetic model. The accuracy of the biological dose estimated by this method was tested by comparing the calculated physical doses and RBE values with the corresponding data measured in a slab phantom irradiated with several kinds of HZE particles. The simulation technique established in this study will help to optimize the treatment planning of charged-particle therapy, thereby maximizing the therapeutic effect on tumors while minimizing unintended harmful effects on surrounding normal tissues.

  10. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Introduction).

    Science.gov (United States)

    Fernández-Ruiz, M; Meije, Y; Manuel, O; Akan, H; Carratalà, J; Aguado, J M; Delaloye, J

    2018-02-07

    The field of new biological agents is increasing exponentially over the past years, thus making prevention and management of associated infectious complications a challenge for nonspecialized clinicians. The present consensus document is an initiative of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) aimed at analysing, from an infectious diseases perspective, the safety of targeted and biological therapies. Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. The document is structured in sections according to the targeted site of action of each drug class: proinflammatory cytokines; interleukins, immunoglobulins and other soluble immune mediators; cell surface receptors and associated signaling pathways; intracellular signaling pathways; lymphoma and leukaemia cells surface antigens; and other targeted therapies. A common outline is followed for each agent: summary of mechanism of action, approved indications and common off-label uses; expected impact on the host's susceptibility to infection; available clinical evidence (i.e. pivotal clinical trials, postmarketing studies, case series and case reports); and suggested prevention and risk minimization strategies. The methodologic and practical difficulties of assessing the specific risk posed by a given agent are also discussed. This ESGICH consensus document constitutes not only a comprehensive overview of the molecular rationale and clinical experience on the risk of infection associated with approved targeted therapies but also an attempt to propose a series of recommendations with the purpose of guiding physicians from different disciplines into this emerging framework. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  11. [Acute bronchiolitis: evaluation of evidence-based therapy].

    Science.gov (United States)

    Martinón-Torres, F; Rodríguez Núñez, A; Martinón Sánchez, J M

    2001-10-01

    Bronchiolitis is the leading cause of lower respiratory tract infection in infants and produces significant morbidity. Limited progress has been made in the treatment of this disease and, in many cases, the therapy employed is controversial and mainly based on general recommendations and not on evidence-based strategies. This report uses evidence-based methodology to provide a critical review of the data available on the treatment of acute bronchiolitis (understood as the first episode of respiratory syncytial virus bronchiolitis in a previously healthy infant). After this analysis, we conclude that the only justifiable therapeutic interventions in these patients are supportive treatment, nebulized epinephrine and mechanical ventilation. Other therapies such us physiotherapy, nebulization, heliox, anticholinergics or exogenous surfactant, among others, require further randomized controlled trials to determine their utility. No evidence supports the routine use of corticosteroids, beta-adrenergic drugs, antibiotics, immunoglobulins, interferon, vitamin A or ribavirin in these patients. Finally, we consider that a national consensus review for the implementation of evidence-based clinical practical guidelines on the management of acute bronchiolitis would be of great interest.

  12. Biologic therapies in rheumatoid arthritis and the risk of opportunistic infections: a meta-analysis.

    Science.gov (United States)

    Kourbeti, Irene S; Ziakas, Panayiotis D; Mylonakis, Eleftherios

    2014-06-01

    Biologic agents are increasingly used to treat patients with rheumatoid arthritis (RA). We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpesvirus-related infections), tuberculosis and other mycobacterial infections. We searched PubMed and EMBASE through June 24, 2013, and complemented the search with the reference lists of eligible articles. The analysis included randomized trials on RA that compared any approved biologic agent with controls and reported the risk of OIs. A total of 70 trials that included 32 504 patients (21 916 patients receiving biologic agents and 10 588 receiving placebo) were deemed eligible. Biologic agents increased the risk of OIs (pooled Peto odds ratio [OR], 1.79; 95% confidence interval [CI], 1.17-2.74; I(2) = 3%), resulting in 1.7 excess infections per 1000 patients treated (number needed to harm, 582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2) = 0), and viral (OR, 1.91; 95% CI, 1.02-3.58; I(2) = 0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (1.31; 95% CI, .46-3.72), invasive fungal infections (2.85; .68-11.91), P. jirovecii pneumonia (1.77; .42-7.47), varicella-zoster virus (1.51; .71-3.22), as well as overall mortality attributed to OIs (1.91; .29-12.64). Among patients with RA, biologic agents are associated with a small but significant risk of specific OIs. This increase is associated with mycobacterial diseases and does not seem to affect overall mortality. Because OIs are a relatively rare complication of biologic agents, large registries are needed to identify the exact effect in different OIs and to compare the different biologic agents. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron-Based Radionuclide Therapy

    DEFF Research Database (Denmark)

    Thisgaard, Helge; Olsen, Birgitte Brinkmann; Dam, Johan Hygum

    2014-01-01

    The somatostatin receptor, which is overexpressed by many neuroendocrine tumors, is a well-known target for molecular imaging and peptide receptor radionuclide therapy. Recently, (57)Co-labeled DOTATOC, an octreotide analog, was shown to have the highest affinity yet found for somatostatin receptor...... subtype 2. The aim of this study was to evaluate the biologic effects of novel cobalt-labeled octreotide analogs targeting the somatostatin receptor to identify promising candidates for molecular imaging and Auger electron-based radionuclide therapy. METHODS: Cobalt-labeled DOTATATE, DOTATOC, and DOTANOC...... were prepared with (57)Co or (58m)Co for SPECT or Auger electron-based therapy, respectively. The cellular uptake and intracellular distribution of the radioligands were characterized with the pancreatic tumor cell line AR42J in vitro, including assessment of the therapeutic effects of (58m...

  14. Degradable Polyethylenimine-Based Gene Carriers for Cancer Therapy.

    Science.gov (United States)

    Jiang, Hu-Lin; Islam, Mohammad Ariful; Xing, Lei; Firdous, Jannatul; Cao, Wuji; He, Yu-Jing; Zhu, Yong; Cho, Ki-Hyun; Li, Hui-Shan; Cho, Chong-Su

    2017-04-01

    Gene therapy using recombinant DNA or gene silencing using siRNA have become a prominent area of research in cancer therapy. However, their use in clinical applications is limited due to overall safety concerns and suboptimal efficacy. Although non-viral vectors such as polycationic polymers do not offer the same level of transfection efficiency as their viral counterparts, they still demonstrate immense potential as alternatives to viral vectors, given their versatility, low immunogenicity, ease of large-scale production, and ability to accelerate gene transfer with well-designed delivery platforms. Among these polymers, polyethylenimine (PEI) is considered a state-of-the-art gene carrier, owing to its ability to improve gene transfer capacity and intracellular delivery. Nonetheless, PEI suffers from the critical shortcoming of non-degradability that can lead to severe cytotoxic effects, despite the fact that the level of this toxicity decreases with molecular weight (MW). As a result, a considerable amount of effort has been devoted to designing low-MW PEI derivatives with degradable linkages. This review will categorize the recent advances in these degradable PEI derivatives based on their degradable chemistries, including ester, disulfide, imine, carbamate, amide, and ketal linkages, and summarize their application in gene therapies against various major cancer malignancies.

  15. An evidence-based review of natalizumab therapy in the management of Crohn’s disease

    Directory of Open Access Journals (Sweden)

    Raja GR Edula

    2009-11-01

    Full Text Available Raja GR Edula, Michael F PiccoMayo Clinic, Jacksonville, Florida, USAAbstract: Treatment options for Crohn’s disease have evolved beyond the early goals of induction and remission and are now more focused on preventing complications by altering the natural history of the disease. The advent of biologic therapies has revolutionized the management of Crohn’s disease. Specifically, antibodies to tumor necrosis factor alpha induce rapid mucosal healing. This translates into improved patient outcomes. However, many patients will fail these and other therapies. Natalizumab is a new biologic agent that has been approved for the treatment of moderately to severely active Crohn’s disease in patients who have failed or are intolerant to immunosuppressants and/or tumor necrosis factor inhibitors. It is a selective adhesion molecule inhibitor to alpha-4 integrin resulting in inhibition of the migration of inflammatory cells across the endothelium. This unique mechanism of action has been shown to be effective in the treatment of Crohn’s disease, making it an important option for otherwise refractory patients. Its use has been limited to these refractory patients because of concerns about the development of complications, especially progressive multifocal leukoencephalopathy. In this review, evidence-based data on the indications, efficacy and safety of natalizumab will be presented and its role in the management of patients with Crohn’s disease will be defined.Keywords: Crohn’s disease, natalizumab, alpha-4 integrin

  16. Zirconia based ceramics, some clinical and biological aspects: Review

    Directory of Open Access Journals (Sweden)

    Ossama Saleh Abd El-Ghany

    2016-12-01

    Full Text Available Improved material strength, enhanced esthethic and high biocompatibility give Zirconia ceramic a great possibility to be used for a wide range of promising clinical applications. This review presents the different types of zirconia materials available for dental application, the effect of machining procedures on these materials, the esthetic of zirconia ceramics and bonding of the veneering ceramics in addition to the biologic properties of these new materials.

  17. Gene-based therapy for alpha-1 antitrypsin deficiency.

    Science.gov (United States)

    Mueller, Christian; Flotte, Terence R

    2013-03-01

    Alpha-1 antitrypsin Deficiency (AATD) has been an attractive target for the development of gene therapy because it is a common single gene disorder, for which there would appear to be significant benefit to be gained for lung disease patients by augmentation of plasma levels of wild-type (M) alpha-1 antitrypsin (AAT). While a significant proportion of patients also have liver disease, which is unlikely to be benefitted by augmentation, the potential to treat or prevent lung disease by replacement of plasma levels to at least 11 microMolar (571 mcg/ml) is the basis upon which several protein replacement therapies have been licensed for human use. Further enhancing the likelihood of success of gene therapy is the fact that the AAT coding sequence is relatively short and the protein appears to function primarily in the plasma and extracellular space. This means that AAT production from any cell or tissue capable of secreting it could be useful therapeutically for augmentation. Based on these considerations, attempts have been made to develop AAT therapies using nonviral gene transfer, gammaretrovirus, recombinant adenovirus (rAd), and recombinant adeno-associated virus (rAAV) vectors. These have resulted in three phase I clinical trials (one of cationic liposome, one of rAAV2, and one of rAAV1) and one phase II clinical trial (with rAAV1). The results of the latter trial, while promising, demonstrated levels were only 3 to 5% of the target range. This indicates the need to further increase the dose of the vector and/or to increase the levels to within the therapeutic range.

  18. What are the immunological consequences of long-term use of biological therapies for juvenile idiopathic arthritis?

    Science.gov (United States)

    Swart, Joost F; de Roock, Sytze; Wulffraat, Nico M

    2013-01-01

    This review summarizes the immunological consequences of biological therapies used in juvenile idiopathic arthritis (JIA). For every frequently used biological agent the characteristics are clearly specified (molecular target, isotype, registered indication for JIA, route of administration, half-life, contraindication, very common side effects, expected time of response and average cost in the first year). The emphasis of this review is on the immunological side effects that have been encountered for every separate agent in JIA populations. For each agent these adverse events have been calculated as incidence per 100 patient-years for the following categories: serious infections, tuberculosis, malignancies, response to vaccination, new-onset autoimmune diseases and development of anti-drug antibodies. There are large differences in side effects between various agents and there is a clear need for an international and standardized collection of post-marketing surveillance data of biologicals in the vulnerable group of JIA patients. Such an international pharmacovigilance database, called Pharmachild, has now been started.

  19. [Music therapy and neuropsychology: a proposal to music therapy based on the cognitive processing of music].

    Science.gov (United States)

    Satoh, Masayuki; Takeda, Katsuhiko; Kuzuhara, Shigeki

    2007-11-01

    In the last decade, a considerable number of studies have been made on the cognitive processing of music. A patient with pure amusia due to the infarction of anterior portion of bilateral temporal lobes revealed the disturbance of the discrimination of chords. Using positron emission tomography, these regions were activated when musically naive normal subjects listened to the harmony compared to the rhythm of identical music. So, we concluded that anterior temporal portion might participate in the recognition of chords. Several articles reported that the musician's brain was different from nonmusicians' functionally and anatomically. This difference was considered to be caused by the musical training for a long time. Recent studies clarified that the reorganization might occur by musical training for a few months. Melodic intonation therapy (MIT) is a method aimed to improve speech output of aphasic patients, using short melodic phrase with a word. The literatures of mental processing of music suggested that right hemisphere might participate in the expression of music, namely singing and playing instrumentals. So, it was supposed that MIT utilized the compensational function of right hemisphere for damaged left hemisphere. We also reported that mental singing improved the gait disturbance of patients with Parkinson's disease. Music therapy is changing from a social science model based on the individual experiences to a neuroscience-guided model based on brain function and cognitive processing of the perception and expression of music.

  20. Head-to-head comparison of aggressive conventional therapy and three biological treatments and comparison of two de-escalation strategies in patients who respond to treatment

    DEFF Research Database (Denmark)

    Glinatsi, Daniel; Heiberg, Marte S; Rudin, Anna

    2017-01-01

    -to-head comparison between csDMARD plus glucocorticoid therapy and three different biological DMARD (bDMARD) therapies with different modes of action and (2) two de-escalation strategies in patients who respond to first-line therapy. METHODS/DESIGN: In a pragmatic, 80-160-week, multicenter, randomized, open......-label, assessor-blinded, phase 4 study, 800 patients with early RA (symptom duration less than 24 months) are randomized 1:1:1:1 to one of four different treatment arms: (1) aggressive csDMARD therapy with methotrexate + sulphasalazine + hydroxychloroquine + i.a. glucocorticoids (arm 1A) or methotrexate...

  1. Costs of Providing Infusion Therapy for Rheumatoid Arthritis in a Hospital-based Infusion Center Setting.

    Science.gov (United States)

    Schmier, Jordana; Ogden, Kristine; Nickman, Nancy; Halpern, Michael T; Cifaldi, Mary; Ganguli, Arijit; Bao, Yanjun; Garg, Vishvas

    2017-08-01

    Many hospital-based infusion centers treat patients with rheumatoid arthritis (RA) with intravenous biologic agents, yet may have a limited understanding of the overall costs of infusion in this setting. The purposes of this study were to conduct a microcosting analysis from a hospital perspective and to develop a model using an activity-based costing approach for estimating costs associated with the provision of hospital-based infusion services (preparation, administration, and follow-up) in the United States for maintenance treatment of moderate to severe RA. A spreadsheet-based model was developed. Inputs included hourly wages, time spent providing care, supply/overhead costs, laboratory testing, infusion center size, and practice pattern information. Base-case values were derived from data from surveys, published studies, standard cost sources, and expert opinion. Costs are presented in year-2017 US dollars. The base case modeled a hospital infusion center serving patients with RA treated with abatacept, tocilizumab, infliximab, or rituximab. Estimated overall costs of infusions per patient per year were $36,663 (rituximab), $36,821 (tocilizumab), $44,973 (infliximab), and $46,532 (abatacept). Of all therapies, the biologic agents represented the greatest share of overall costs, ranging from 87% to $91% of overall costs per year. Excluding infusion drug costs, labor accounted for 53% to 57% of infusion costs. Biologic agents represented the highest single cost associated with RA infusion care; however, personnel, supplies, and overhead costs also contributed substantially to overall costs (8%-16%). This model may provide a helpful and adaptable framework for use by hospitals in informing decision making about services offered and their associated financial implications. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-01

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

  3. Updates in the biology and therapy for infant acute lymphoblastic leukemia.

    Science.gov (United States)

    Guest, Erin M; Stam, Ronald W

    2017-02-01

    The prognosis for infants less than 12 months of age who are diagnosed with acute lymphoblastic leukemia (ALL) remains poor despite overall advances in the treatment of childhood ALL. In this review, we highlight the recent advances in the understanding of the pathogenesis of infant ALL and discuss opportunities for translating these findings into clinical trials. Infant ALL can be divided into two major disease types, defined by the presence or absence of KMT2A (MLL) rearrangement (KMT2A-R). Recent molecular profiling studies have found that infant ALL with KMT2A-R is an epigenomic disease that lacks other somatic driver mutations. Strategies to intensify therapy have not improved survival for infants with KMT2A-R ALL. In contrast, infant ALL without KMT2A-R is more similar to ALL of older children and survival has improved modestly with intensification of chemotherapy. Discovery of clonal molecular markers that predict chemoresistance will allow further risk classification and development of novel treatment strategies. Modern clinical trials are integrating molecularly targeted therapies into the treatment of infant ALL. Advances in molecular profiling and integration of targeted therapy have the potential to reduce toxicity and improve survival for infants with ALL.

  4. Advances in evidence-based cancer adoptive cell therapy.

    Science.gov (United States)

    Ge, Chunlei; Li, Ruilei; Song, Xin; Qin, Shukui

    2017-04-01

    Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field. This review also provided future research directions to make sure ACT widely available in clinic.

  5. Developing evidence-based physical therapy clinical practice guidelines.

    Science.gov (United States)

    Kaplan, Sandra L; Coulter, Colleen; Fetters, Linda

    2013-01-01

    Recommended strategies for developing evidence-based clinical practice guidelines (CPGs) are provided. The intent is that future CPGs developed with the support of the Section on Pediatrics of the American Physical Therapy Association would consistently follow similar developmental processes to yield consistent quality and presentation. Steps in the process of developing CPGs are outlined and resources are provided to assist CPG developers in carrying out their task. These recommended processes may also be useful to CPG developers representing organizations with similar structures, objectives, and resources.

  6. Mindfulness-based cognitive therapy for multiple chemical sensitivity

    DEFF Research Database (Denmark)

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

    2012-01-01

    ABSTRACT: BACKGROUND: Multiple chemical sensitivity (MCS) is a condition characterized by recurrent, self-reported symptoms from multiple organ systems, attributable to exposure to a wide range of chemically unrelated substances at low levels. The pathophysiology is unknown, and there are currently...... 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.......5 hour sessions, and 45 minutes of mindfulness home practice 6 days each week. Participants will be asked to complete questionnaires at baseline, post-treatment, and at 6 and 12 months' follow-up. Based on sample size estimation, 82 participants will be randomized to either the MBCT intervention...

  7. 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.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    after ESWT. Interleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, vascular endothelial growth factor and interferon-γ were quantified using a cytometric bead array while gelatinase activity (MMP-2 and -9) was examined using zymography. There were no statistical differences between...... significantly elevated for four hours post-ESWT (p MMP-2 and -9 also increased after ESWT (p MMP forms. In addition, the biological response to ESWT treatment could be differentiated between possible responders and non...... the biological tissue response to ESWT in healthy and pathological tendons. IL-1β, IL-2, IL-6 and IL-8 were the cytokines predominantly detected in the tendon dialysate. IL-1β and IL-2 did not change significantly with ESWT. IL-6 and IL-8 concentrations were elevated immediately after ESWT and remained...

  9. Biomaterials-Based Electronics: Polymers and Interfaces for Biology and Medicine

    Science.gov (United States)

    Muskovich, Meredith; Bettinger, Christopher J.

    2012-01-01

    Advanced polymeric biomaterials continue to serve as a cornerstone of new medical technologies and therapies. The vast majority of these materials, both natural and synthetic, interact with biological matter without direct electronic communication. However, biological systems have evolved to synthesize and employ naturally-derived materials for the generation and modulation of electrical potentials, voltage gradients, and ion flows. Bioelectric phenomena can be interpreted as 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 the use of natural and synthetic biological materials as integral components in technologies such as thin film electronics, in vitro cell culture models, and implantable medical devices. Future perspectives and emerging challenges will also be highlighted. PMID:23184740

  10. Chemical Properties of Caffeic and Ferulic Acids in Biological System: Implications in Cancer Therapy. A Review.

    Science.gov (United States)

    Damasceno, Sarah S; Dantas, Bruna B; Ribeiro-Filho, Jaime; Antônio M Araújo, Demetrius; Galberto M da Costa, José

    2017-01-01

    The antioxidant properties of caffeic and ferulic acids in biological systems have been extensively demonstrated. As antioxidants, these compounds prevent the production of reactive oxygen species (ROS), which cause cell lesions that are associated with the development of several diseases, including cancer. Recent findings suggest that the chemoprotective action of these phenolic acids occurs through the following mechanisms: regulation of gene expression, chelation and / or reduction of transition metals, formation of covalent adducts and direct toxicity. The biological efficacy of these promising chemoprotective agents is strongly related with their chemical structure. Therefore, in this study, we discuss the structural characteristics of ferulic and caffeic acids that are responsible for their biological activities, as well as the mechanisms of action involved with the anti-cancer activity. Several reports indicated that the antioxidant effect of these phenylpropanoids results from reactions with free radicals with formation of stable products in the cells. The chelating effect of these compounds was also reported as an important protective mechanism against oxidative. Finally, the lipophilicity of these agents facilitates their entry into the cells, and thus, contributes to the anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. How war veterans with post-traumatic stress disorder experience nature-based therapy in a forest therapy garden

    DEFF Research Database (Denmark)

    Poulsen, Dorthe Varning

    treatments. The objective of this Ph.D. project was to explore the impact of nature-based therapy (NBT) from the perspective of veterans suffering from PTSD. The thesis consists of two studies: A systematic literature review and a qualitative single-case study. The review aims to describe state...... in relation to the veterans’ mental and physical wellbeing. It was concluded that more qualitative and quantitative studies are needed to contribute with knowledge that will enable us to establish nature-assisted therapy for veterans with PTSD on the basis of the evidence. The single-case study took place......-of-the-art research within the area of NBT, the evidence for treatment offered to veterans with PTSD, nature-assisted therapy (therapy that uses nature with the purpose of recovery), and the nature setting in which the therapy was conducted. The results pointed towards a positive benefit of nature-assisted therapy...

  12. 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.

  13. 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

  14. 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.

  15. Event-based text mining for biology and functional genomics.

    Science.gov (United States)

    Ananiadou, Sophia; Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B

    2015-05-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of 'events', i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. © The Author 2014. Published by Oxford University Press.

  16. Event-based text mining for biology and functional genomics

    Science.gov (United States)

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  17. Safety of Biologic and Nonbiologic Disease-modifying Antirheumatic Drug Therapy in Veterans with Rheumatoid Arthritis and Hepatitis C Virus Infection.

    Science.gov (United States)

    Burton, Mary Jane; Curtis, Jeffrey R; Yang, Shuo; Chen, Lang; Singh, Jasvinder A; Mikuls, Ted R; Winthrop, Kevin L; Baddley, John W

    2017-05-01

    To examine the effect of disease-modifying antirheumatic drug (DMARD) therapy on hepatotoxicity among patients with rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection. We identified biologic and nonbiologic treatment episodes of patients with RA using the 1997-2011 national data from the US Veterans Health Administration. Eligible episodes had HCV infection (defined by detectable HCV RNA) and subsequently initiated a new biologic or nonbiologic DMARD. Cohort entry required a baseline alanine aminotransferase (ALT) biologic/DMARD therapy. The primary outcome of interest was hepatotoxicity, defined as ALT elevation ≥ 100 IU/l or increase in HCV RNA of 1 log or more, and was examined within the first year of biologic/DMARD use. Results were reported as the cumulative incidence of treatment episodes achieving predefined hepatotoxicity at 3, 6, and 12 months after biologic/DMARD initiation. RA patients with HCV (n = 748) were identified and contributed 1097 biologic/DMARD treatment episodes. Overall, ALT elevations were uncommon, with 37 (3.4%) hepatotoxicity events occurring within 12 months. Treatment episodes with biologic DMARD demonstrated more frequency of hepatotoxicity than did nonbiologic DMARD (4.8% vs 2.3%, p = 0.03). Among treatment episodes involving hepatotoxicity events, the majority occurred within 6 months of DMARD initiation (29/37, 78%). In US veterans with HCV and RA receiving biologic and nonbiologic DMARD, the frequency of hepatotoxicity (ALT ≥ 100 IU/l) was low, with a higher frequency observed in treatment episodes with current biologic use.

  18. Lung lavage therapy to lessen the biological effects of inhaled 144Ce in dogs

    International Nuclear Information System (INIS)

    Muggenburg, B.A.; Boecker, B.B.; Hahn, F.F.; McClellan, R.O.

    1990-01-01

    To evaluate the therapeutic effects of removal of an internally deposited radionuclide on long-term biological effects, lung lavage was used to treat dogs that had inhaled 144Ce in a relatively insoluble form, in fused aluminosilicate particles. Either 10 lung lavages were performed between Days 2 and 56 after exposure or 20 lung lavages were performed between Days 2 and 84 after exposure. Approximately one-half of the 144Ce was removed by the lavages, resulting in a corresponding reduction in the total absorbed beta dose to lung. The mean survival time of the treated dogs was 1270 days compared to 370 days for untreated dogs whose initial pulmonary burdens of 144Ce were similar. Treated dogs died late from cancers of the lung or liver, whereas the untreated dogs died at much earlier times from radiation pneumonitis. Dogs treated with lung lavage but not exposed to 144Ce had a mean survival of 4770 days. We concluded that removal of 144Ce from the lung by lavage resulted in increased survival time and in a change in the biological effects from inhaled 144Ce from early-occurring inflammatory disease to late-occurring effects, principally cancer. In addition, the biological effects occurring in the treated dogs could be better predicted from the total absorbed beta dose in the lung and the dose rate after treatment rather than from the original dose rate to the lung. Therefore, we concluded that prompt treatment to remove radioactive materials could be of significant benefit to persons accidentally exposed to high levels of airborne, relatively insoluble, radioactive particles

  19. Metabolic cancer biology: structural-based analysis of cancer as a metabolic disease, new sights and opportunities for disease treatment.

    Science.gov (United States)

    Masoudi-Nejad, Ali; Asgari, Yazdan

    2015-02-01

    The cancer cell metabolism or the Warburg effect discovery goes back to 1924 when, for the first time Otto Warburg observed, in contrast to the normal cells, cancer cells have different metabolism. With the initiation of high throughput technologies and computational systems biology, cancer cell metabolism renaissances and many attempts were performed to revise the Warburg effect. The development of experimental and analytical tools which generate high-throughput biological data including lots of information could lead to application of computational models in biological discovery and clinical medicine especially for cancer. Due to the recent availability of tissue-specific reconstructed models, new opportunities in studying metabolic alteration in various kinds of cancers open up. Structural approaches at genome-scale levels seem to be suitable for developing diagnostic and prognostic molecular signatures, as well as in identifying new drug targets. In this review, we have considered these recent advances in structural-based analysis of cancer as a metabolic disease view. Two different structural approaches have been described here: topological and constraint-based methods. The ultimate goal of this type of systems analysis is not only the discovery of novel drug targets but also the development of new systems-based therapy strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Stem Cell-Based Therapies for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Lei Hao

    2014-01-01

    Full Text Available In recent years, stem cell-based approaches have attracted more attention from scientists and clinicians due to their possible therapeutical effect on stroke. Animal studies have demonstrated that the beneficial effects of stem cells including embryonic stem cells (ESCs, inducible pluripotent stem cells (iPSCs, neural stem cells (NSCs, and mesenchymal stem cell (MSCs might be due to cell replacement, neuroprotection, endogenous neurogenesis, angiogenesis, and modulation on inflammation and immune response. Although several clinical studies have shown the high efficiency and safety of stem cell in stroke management, mainly MSCs, some issues regarding to cell homing, survival, tracking, safety, and optimal cell transplantation protocol, such as cell dose and time window, should be addressed. Undoubtably, stem cell-based gene therapy represents a novel potential therapeutic strategy for stroke in future.

  1. Mindfulness-based cognitive therapy to treat multiple chemical sensitivities

    DEFF Research Database (Denmark)

    Skovbjerg, S; Hauge, Christian Riis; Rasmussen, Alice

    2012-01-01

    Multiple chemical sensitivities (MCS) is a medically unexplained and socially disabling disorder characterized by negative health effects attributed to exposure to common airborne chemicals. Currently, there is no evidence-based treatment. The objectives of the study were to assess the feasibility...... of an 8-week mindfulness-based cognitive therapy program (MBCT) for adults with MCS and to evaluate possible effects on psychological distress and illness perception. The study design was a randomized clinical trial. The MBCT programme comprised 8 weekly sessions of 2½ hours. Forty-two adults were...... screened for eligibility and 37 were included. Mean age of the participants was 51.6 years, 35 (94.6%) were female and 21 (56.8%) were unemployed. Measures of psychological distress and illness perceptions were assessed at baseline, 4 weeks, 8 weeks and at 3 months follow-up. No significant differences...

  2. Proton therapy for tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Munzenrider, J.E.; Liebsch, N.J. [Dept. of Radiation Oncology, Harvard Univ. Medical School, Boston, MA (United States)

    1999-06-01

    Charged particle beams are ideal for treating skull base and cervical spine tumors: dose can be focused in the target, while achieving significant sparing of the brain, brain stem, cervical cord, and optic nerves and chiasm. For skull base tumors, 10-year local control rates with combined proton-photon therapy are highest for chondrosarcomas, intermediate for male chordomas, and lowest for female chordomas (94%, 65%, and 42%, respectively). For cervical spine tumors, 10-year local control rates are not significantly different for chordomas and chondrosarcomas (54% and 48%, respectively), nor is there any difference in local control between males and females. Observed treatment-related morbidity has been judged acceptable, in view of the major morbidity and mortality which accompany uncontrolled tumor growth. (orig.)

  3. CAMERA-BASED SOFTWARE IN REHABILITATION/THERAPY INTERVENTION

    Directory of Open Access Journals (Sweden)

    Anthony Lewis Brooks

    2014-06-01

    Full Text Available Use of an affordable, easily adaptable, ‘non-specific camera-based software’ that is rarely used in the field of rehabilitation is reported in a study with 91 participants over the duration of six workshop sessions. ‘Non-specific camera-based software’ refers to software that is not dependent on specific hardware. Adaptable means that human tracking and created artefact interaction in the camera field of view is relatively easily changed as one desires via a user-friendly GUI. The significance of having both available for contemporary intervention is argued. Conclusions are that the mature, robust, and accessible software EyeCon is a potent and significant user-friendly tool in the field of rehabilitation/therapy and warrants wider exploration.

  4. Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology.

    Science.gov (United States)

    Dubois-Camacho, Karen; Ottum, Payton A; Franco-Muñoz, Daniel; De la Fuente, Marjorie; Torres-Riquelme, Alejandro; Díaz-Jiménez, David; Olivares-Morales, Mauricio; Astudillo, Gonzalo; Quera, Rodrigo; Hermoso, Marcela A

    2017-09-28

    Inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, are chronic pathologies associated with a deregulated immune response in the intestinal mucosa, and they are triggered by environmental factors in genetically susceptible individuals. Exogenous glucocorticoids (GCs) are widely used as anti-inflammatory therapy in IBDs. In the past, patients with moderate or severe states of inflammation received GCs as a first line therapy with an important effectiveness in terms of reduction of the disease activity and the induction of remission. However, this treatment often results in detrimental side effects. This downside drove the development of second generation GCs and more precise (non-systemic) drug-delivery methods. Recent clinical trials show that most of these new treatments have similar effectiveness to first generation GCs with fewer adverse effects. The remaining challenge in successful treatment of IBDs concerns the refractoriness and dependency that some patients encounter during GCs treatment. A deeper understanding of the molecular mechanisms underlying GC response is key to personalizing drug choice for IBDs patients to optimize their response to treatment. In this review, we examine the clinical characteristics of treatment with GCs, followed by an in depth analysis of the proposed molecular mechanisms involved in its resistance and dependence associated with IBDs. This thorough analysis of current clinical and biomedical literature may help guide physicians in determining a course of treatment for IBDs patients and identifies important areas needing further study.

  5. A shift in paradigm towards human biology-based systems for cholestatic-liver diseases.

    Science.gov (United States)

    Noor, Fozia

    2015-12-01

    Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  6. Photoacoustic-Based Multimodal Nanoprobes: from Constructing to Biological Applications.

    Science.gov (United States)

    Gao, Duyang; Yuan, Zhen

    2017-01-01

    Multimodal nanoprobes have attracted intensive attentions since they can integrate various imaging modalities to obtain complementary merits of single modality. Meanwhile, recent interest in laser-induced photoacoustic imaging is rapidly growing due to its unique advantages in visualizing tissue structure and function with high spatial resolution and satisfactory imaging depth. In this review, we summarize multimodal nanoprobes involving photoacoustic imaging. In particular, we focus on the method to construct multimodal nanoprobes. We have divided the synthetic methods into two types. First, we call it "one for all" concept, which involves intrinsic properties of the element in a single particle. Second, "all in one" concept, which means integrating different functional blocks in one particle. Then, we simply introduce the applications of the multifunctional nanoprobes for in vivo imaging and imaging-guided tumor therapy. At last, we discuss the advantages and disadvantages of the present methods to construct the multimodal nanoprobes and share our viewpoints in this area.

  7. EZH2: biology, disease, and structure-based drug discovery

    Science.gov (United States)

    Tan, Jin-zhi; Yan, Yan; Wang, Xiao-xi; Jiang, Yi; Xu, H Eric

    2014-01-01

    EZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is a highly conserved histone methyltransferase that methylates lysine 27 of histone 3. Overexpression of EZH2 has been found in a wide range of cancers, including those of the prostate and breast. In this review, we address the current understanding of the oncogenic role of EZH2, including its PRC2-dependent transcriptional repression and PRC2-independent gene activation. We also discuss the connections between EZH2 and other silencing enzymes, such as DNA methyltransferase and histone deacetylase. We comprehensively address the architecture of the PRC2 complex and the crucial roles of each subunit. Finally, we summarize new progress in developing EZH2 inhibitors, which could be a new epigenetic therapy for cancers. PMID:24362326

  8. Tumor Acidity/NIR Controlled Interaction of Transformable Nanoparticle with Biological Systems for Cancer Therapy.

    Science.gov (United States)

    Li, Dongdong; Ma, Yinchu; Du, Jinzhi; Tao, Wei; Du, Xiaojiao; Yang, Xianzhu; Wang, Jun

    2017-05-10

    Precisely controlling the interaction of nanoparticles with biological systems (nanobio interactions) from the injection site to biological targets shows great potential for biomedical applications. Inspired by the ability of nanoparticles to alter their physicochemical properties according to different stimuli, we explored the tumor acidity and near-infrared (NIR) light activated transformable nanoparticle DA TAT-NP IR&DOX . This nanoparticle consists of a tumor acidity-activated TAT [the TAT lysine residues' amines was modified with 2,3-dimethylmaleic anhydride (DA)], a flexible chain polyphosphoester core coencapsulated a NIR dye IR-780, and DOX (doxorubicin). The physicochemical properties of the nanoparticle can be controlled in a stepwise fashion using tumor acidity and NIR light, resulting in adjustable nanobio interactions. The resulting transformable nanoparticle DA TAT-NP IR&DOX efficiently avoids the interaction with mononuclear phagocyte system (MPS) ("stealth" state) due to the masking of the TAT peptide during blood circulation. Once it has accumulated in the tumor tissues, DA TAT-NP IR&DOX is reactivated by tumor acidity and transformed into the "recognize" state in order to promote interaction with tumor cells and enhance cellular internalization. Then, this nanoparticle is transformed into "attack" state under NIR irradiation, achieving the supersensitive DOX release from the flexible chain polyphosphoester core in order to increase the DOX-DNA interaction. This concept provides new avenues for the creation of transformable drug delivery systems that have the ability to control nanobio interactions.

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

    CERN Document Server

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sandro Carrara

    2010-01-01

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

  11. 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.

  12. Outcome predictors of internet-based brief sex therapy for sexual dysfunctions in heterosexual men

    NARCIS (Netherlands)

    Blanken, I.; Leusink, P.; van Diest, S.; Gijs, L.; van Lankveld, J.J.D.M.

    2014-01-01

    The authors investigated whether baseline and therapy process characteristics of 82 heterosexual men participating in an Internet-based sex therapy study predict posttreatment sexual functioning. Problem severity, baseline sexual desire and baseline sexual satisfaction, but also partner problems and

  13. 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.

  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. Biologically-based signal processing system applied to noise removal for signal extraction

    Science.gov (United States)

    Fu, Chi Yung; Petrich, Loren I.

    2004-07-13

    The method and system described herein use a biologically-based signal processing system for noise removal for signal extraction. A wavelet transform may be used in conjunction with a neural network to imitate a biological system. The neural network may be trained using ideal data derived from physical principles or noiseless signals to determine to remove noise from the signal.

  16. 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.

  17. 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…

  18. Comparison of hybridization-based and sequencing-based gene expression technologies on biological replicates.

    Science.gov (United States)

    Liu, Fang; Jenssen, Tor-Kristian; Trimarchi, Jeff; Punzo, Claudio; Cepko, Connie L; Ohno-Machado, Lucila; Hovig, Eivind; Kuo, Winston Patrick

    2007-06-07

    High-throughput systems for gene expression profiling have been developed and have matured rapidly through the past decade. Broadly, these can be divided into two categories: hybridization-based and sequencing-based approaches. With data from different technologies being accumulated, concerns and challenges are raised about the level of agreement across technologies. As part of an ongoing large-scale cross-platform data comparison framework, we report here a comparison based on identical samples between one-dye DNA microarray platforms and MPSS (Massively Parallel Signature Sequencing). The DNA microarray platforms generally provided highly correlated data, while moderate correlations between microarrays and MPSS were obtained. Disagreements between the two types of technologies can be attributed to limitations inherent to both technologies. The variation found between pooled biological replicates underlines the importance of exercising caution in identification of differential expression, especially for the purposes of biomarker discovery. Based on different principles, hybridization-based and sequencing-based technologies should be considered complementary to each other, rather than competitive alternatives for measuring gene expression, and currently, both are important tools for transcriptome profiling.

  19. Comparison of hybridization-based and sequencing-based gene expression technologies on biological replicates

    Directory of Open Access Journals (Sweden)

    Cepko Connie L

    2007-06-01

    Full Text Available Abstract Background High-throughput systems for gene expression profiling have been developed and have matured rapidly through the past decade. Broadly, these can be divided into two categories: hybridization-based and sequencing-based approaches. With data from different technologies being accumulated, concerns and challenges are raised about the level of agreement across technologies. As part of an ongoing large-scale cross-platform data comparison framework, we report here a comparison based on identical samples between one-dye DNA microarray platforms and MPSS (Massively Parallel Signature Sequencing. Results The DNA microarray platforms generally provided highly correlated data, while moderate correlations between microarrays and MPSS were obtained. Disagreements between the two types of technologies can be attributed to limitations inherent to both technologies. The variation found between pooled biological replicates underlines the importance of exercising caution in identification of differential expression, especially for the purposes of biomarker discovery. Conclusion Based on different principles, hybridization-based and sequencing-based technologies should be considered complementary to each other, rather than competitive alternatives for measuring gene expression, and currently, both are important tools for transcriptome profiling.

  20. Importancia de la biología molecular para la Fisioterapia moderna Importance of molecular biology for the modern Physical Therapy

    Directory of Open Access Journals (Sweden)

    Carolina Ramírez Ramírez

    2011-12-01

    Full Text Available Para que el cuerpo de conocimiento de una profesión crezca y se fortalezca debe estar al día con los avances científicos y tecnológicos que surgen continuamente para incluirlos en el repertorio de recursos que usa para la investigación de problemas específicos de su saber. Recientemente el desciframiento del código genético y la secuenciación del genoma humano creó la base para el surgimiento de metodologías y técnicas en el área de la biología molecular, las cuales permitieron profundizar en el conocimiento de la estructura y función de los tejidos humanos y también mejoraron el entendimiento de los mecanismos por los cuales actúan formas de intervención usadas cotidianamente por profesionales en salud. La Fisioterapia utiliza modalidades físicas que interactúan con los tejidos corporales, por ello la biología molecular permite un mejor entendimiento de los efectos que las dichas modalidades generan en el tejido sobre el cual son aplicadas. Por tanto el objetivo de este artículo es reflexionar sobre la necesidad de que el Fisioterapeuta se apropie del conocimiento en ésta área de las ciencias básicas, usarlo como herramienta para la solución de preguntas relevantes de su quehacer clínico y así contribuir de manera efectiva con la generación de nuevo conocimiento que promueva la práctica basada en la evidencia y fomente el crecimiento de la profesión. Salud UIS 2011; 43 (3: 317-320A profession can be improved through the development and application of scientific and technological advances around the issues relating to their expertise. Recently, the deciphering of the genetic code and human genome sequencing creates the basis for the development of methodologies and techniques of molecular biology. These resources have allowed a deeper understanding of the human tissue structure and function, and intervention mechanisms used by health professionals. Physiotherapy uses physical modalities affecting the tissues of the

  1. Dynamic model of thermal reaction of biological tissues to laser-induced fluorescence and photodynamic therapy.

    Science.gov (United States)

    Seteikin, Alexey Yu; Krasnikov, Ilya V; Drakaki, Eleni; Makropoulou, Mersini

    2013-07-01

    The aim of this work was to evaluate the temperature fields and the dynamics of heat conduction into the skin tissue under several laser irradiation conditions with both a pulsed ultraviolet (UV) laser (λ=337  nm) and a continuous-wave (cw) visible laser beam (λ=632.8  nm) using Monte Carlo modeling. Finite-element methodology was used for heat transfer simulation. The analysis of the results showed that heat is not localized on the surface, but is collected inside the tissue in lower skin layers. The simulation was made with the pulsed UV laser beam (used as excitation source in laser-induced fluorescence) and the cw visible laser (used in photodynamic therapy treatments), in order to study the possible thermal effects.

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

    International Nuclear Information System (INIS)

    Silva, Gerald S.; Camillo, Maria A.P.; Higa, Olga Z.; Pugliesi, Reynaldo; Fermamdes, Edson G.R.; Queiroz, Alvaro A.A. de

    2005-01-01

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

  3. Small Gold Nanorods: Recent Advances in Synthesis, Biological Imaging, and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Lu An

    2017-11-01

    Full Text Available Over the past few decades, the synthetic development of ultra-small nanoparticles has become an important strategy in nano-medicine, where smaller-sized nanoparticles are known to be more easily excreted from the body, greatly reducing the risk caused by introducing nano-theranostic agents. Gold nanorods are one of the most important nano-theranostic agents because of their special optical and electronic properties. However, the large size (diameter > 6 nm of most obtained gold nanorods limits their clinical application. In recent years, more and more researchers have begun to investigate the synthesis and application of small gold nanorods (diameter < 6 nm, which exhibit similar optical and electronic properties as larger gold nanorods. In this review, we summarize the recent advances of synthesis of the small gold nanorods and their application for near-infrared light-mediated bio-imaging and cancer therapy.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Easily accessible predictors of disease course in inflammatory bowel disease (IBD) are scarce, and it remains largely unknown whether a family history of IBD predicts the course of Crohn's disease (CD) and ulcerative colitis (UC). We aimed to compare the course of disease in familial...... and sporadic cases of IBD. However, patients with familial CD had significantly higher risk of major surgery than sporadic CD cases after 2 years of disease duration (hazard ratio, 1.62; 95% confidence interval, 1.26-2.07). Also, sensitivity analysis suggested a slightly reduced time from diagnosis to first......-related hospitalization, biological treatment, and surgery in familial versus sporadic cases of IBD. RESULTS: A total of 27,886 IBD cases, including 1006 IBD-relative pairs, were followed-up for up to 16 years, totaling 164,979 person-years. We observed no difference in risk of hospital admissions between familial...

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

    Science.gov (United States)

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

    2015-08-01

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

  6. 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)

  7. 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...

  8. Onychomycosis in patients of nail psoriasis on biologic therapy: a randomized, prospective open label study comparing Etanercept, Infliximab and Adalimumab.

    Science.gov (United States)

    Al-Mutairi, Nawaf; Nour, Tarek; Al-Rqobah, Duha

    2013-05-01

    The association between patients of psoriasis on anti TNF therapy and onychomycosis has not been explored. The aim of this study was to determine the rate of onychomycosis in patients of psoriasis with nail involvement on anti TNF therapy. All patients of psoriasis with nail involvement seen between February 2007 - July 2012 were examined. All the patients with negative nail scrapings for fungus were enrolled. Patients found fit for biologics after investigations were randomly divided into 3 groups (Group A: Infliximab, Group B: Etanercept and Group C: Adalimumab). The patients were followed up every 4 weeks for 24 weeks. Repeat nail scrapings were done at week 24. The results were compared with controls. In total, 315 (178 males and 137 females) patients were enrolled. The mean age was 37.5 ± 11.4 years. The results for scraping for fungus at the end of 24 weeks were as follows: 33% (33/100) in patients on Infliximab followed by 15.45% (17/110), 13.33% (14/105) in patients on treatment with Etanercept and Adalimumab respectively as compared to 13.89% (25/180) among controls. Onychomycosis in association with nail psoriasis was more common in males. This study revealed statistically significant association between fungal infections of the nail in patients of psoriasis on treatment with Infliximab.

  9. Microsponges based novel drug delivery system for augmented arthritis therapy.

    Science.gov (United States)

    Osmani, Riyaz Ali M; Aloorkar, Nagesh H; Ingale, Dipti J; Kulkarni, Parthasarathi K; Hani, Umme; Bhosale, Rohit R; Jayachandra Dev, Dandasi

    2015-10-01

    The motive behind present work was to formulate and evaluate gel containing microsponges of diclofenac diethylamine to provide prolonged release for proficient arthritis therapy. Quasi-emulsion solvent diffusion method was implied using Eudragit RS-100 and microsponges with varied drug-polymer ratios were prepared. For the sake of optimization, diverse factors affecting microparticles physical properties were too investigated. Microsponges were characterized by SEM, DSC, FT-IR, XRPD and particle size analysis, and evaluated for morphology, drug loading, in vitro drug release and ex vivo diffusion as well. There were no chemical interactions between drug and polymers used as revealed by compatibility studies outcomes. The drug polymer ratio reflected notable effect on drug content, encapsulation efficiency and particle size. SEM results revealed spherical microsponges with porous surface, and had 7.21 μm mean particle size. The microsponges were then incorporated in gel; which exhibited viscous modulus along with pseudoplastic behavior. In vitro drug release results depicted that microsponges with 1:2 drug-polymer ratio were more efficient to give extended drug release of 75.88% at the end of 8 h; while conventional formulation get exhausted incredibly earlier by releasing 81.11% drug at the end of 4 h only. Thus the formulated microsponge-based gel of diclofenac diethylamine would be a promising alternative to conventional therapy for safer and efficient treatment of arthritis and musculoskeletal disorders.

  10. Mindfulness-based therapy: a comprehensive meta-analysis.

    Science.gov (United States)

    Khoury, Bassam; Lecomte, Tania; Fortin, Guillaume; Masse, Marjolaine; Therien, Phillip; Bouchard, Vanessa; Chapleau, Marie-Andrée; Paquin, Karine; Hofmann, Stefan G

    2013-08-01

    Mindfulness-based therapy (MBT) has become a popular form of intervention. However, the existing reviews report inconsistent findings. To clarify these inconsistencies in the literature, we conducted a comprehensive effect-size analysis to evaluate the efficacy of MBT. A systematic review of studies published in journals or in dissertations in PubMED or PsycINFO from the first available date until May 10, 2013. A total of 209 studies (n=12,145) were included. Effect-size estimates suggested that MBT is moderately effective in pre-post comparisons (n=72; Hedge's g=.55), in comparisons with waitlist controls (n=67; Hedge's g=.53), and when compared with other active treatments (n=68; Hedge's g=.33), including other psychological treatments (n=35; Hedge's g=.22). MBT did not differ from traditional CBT or behavioral therapies (n=9; Hedge's g=-.07) or pharmacological treatments (n=3; Hedge's g=.13). MBT is an effective treatment for a variety of psychological problems, and is especially effective for reducing anxiety, depression, and stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy

    Science.gov (United States)

    2017-01-01

    Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies. PMID:28122047

  12. Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy.

    Directory of Open Access Journals (Sweden)

    Daniel Rodríguez-Martínez

    Full Text Available Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE, a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80% and yield (>70%. Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies.

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

    Directory of Open Access Journals (Sweden)

    Massimo S. Fiandaca

    2012-06-01

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

  14. Design, synthesis and biological evaluation of Arylpiperazine-based ...

    Indian Academy of Sciences (India)

    years, several piperazine-based molecules have been reported to possess strong apoptotic activity on cancer- ous cells.21 28 Piperazine based small amides such as. AK301 (I), have been stated to induce mitotic arrest and to increase ligand-dependent apoptosis in HT29 human colon cancer cells (ED50: 115nM).21 Also,.

  15. 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.

  16. Cell-based therapies of liver diseases: age-related challenges

    Directory of Open Access Journals (Sweden)

    Yarygin KN

    2015-12-01

    Full Text Available Konstantin N Yarygin, Alexei Y Lupatov, Irina V Kholodenko Laboratory of Cell Biology, Institute of Biomedical Chemistry, Moscow, Russia Abstract: The scope of this review is to revise recent advances of the cell-based therapies of liver diseases with an emphasis on cell donor’s and patient’s age. Regenerative medicine with cell-based technologies as its integral part is focused on the structural and functional restoration of tissues impaired by sickness or aging. Unlike drug-based medicine directed primarily at alleviation of symptoms, regenerative medicine offers a more holistic approach to disease and senescence management aimed to achieve restoration of homeostasis. Hepatocyte transplantation and organ engineering are very probable forthcoming options of liver disease treatment in people of different ages and vigorous research and technological innovations in this area are in progress. Accordingly, availability of sufficient amounts of functional human hepatocytes is crucial. Direct isolation of autologous hepatocytes from liver biopsy is problematic due to related discomfort and difficulties with further expansion of cells, particularly those derived from aging people. Allogeneic primary human hepatocytes meeting quality standards are also in short supply. Alternatively, autologous hepatocytes can be produced by reprogramming of differentiated cells through the stage of induced pluripotent stem cells. In addition, fibroblasts and mesenchymal stromal cells can be directly induced to undergo advanced stage hepatogenic differentiation. Reprogramming of cells derived from elderly people is accompanied by the reversal of age-associated changes at the cellular level manifesting itself by telomere elongation and the U-turn of DNA methylation. Cell reprogramming can provide high quality rejuvenated hepatocytes for cell therapy and liver tissue engineering. Further technological advancements and establishment of national and global registries of

  17. Current status of accelerator-based boron neutron capture therapy

    International Nuclear Information System (INIS)

    Kreiner, A. J.; Bergueiro, J.; Di Paolo, H.; Castell, W.; Vento, V. Thatar; Cartelli, D.; Kesque, J.M.; Valda, A.A.; Ilardo, J.C.; Baldo, M.; Erhardt, J.; Debray, M.E.; Somacal, H.R.; Estrada, L.; Sandin, J.C. Suarez; Igarzabal, M.; Huck, H.; Padulo, J.; Minsky, D.M.

    2011-01-01

    The direct use of proton and heavy ion beams for radiotherapy is a well established cancer treatment modality, which is becoming increasingly widespread due to its clear advantages over conventional photon-based treatments. This strategy is suitable when the tumor is spatially well localized. Also the use of neutrons has a long tradition. Here Boron Neutron Capture Therapy (BNCT) stands out, though on a much smaller scale, being a second-generation promising alternative for tumors which are diffuse and infiltrating. On this sector, so far only nuclear reactors have been used as neutron sources. In this paper we describe the current situation worldwide as far as the use of accelerator-based neutron sources for BNCT is concerned (so-called Accelerator-Based (AB)-BNCT). In particular we discuss the present status of an ongoing project to develop a folded Tandem-ElectroStatic-Quadrupole (TESQ) accelerator at the Atomic Energy Commission of Argentina. The project goal is a machine capable of delivering 30 mA of 2.4 MeV protons to be used in conjunction with a neutron production target based on the 7 Li(p,n) 7 Be reaction. These are the specifications needed to produce sufficiently intense and clean epithermal neutron beams to perform BNCT for deep-seated tumors in less than an hour. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Stagni, Venturina; Santini, Simonetta; Barilà, Daniela, E-mail: daniela.barila@uniroma2.it [Department of Biology, University of Tor Vergata, Rome 00133 (Italy); Laboratory of Cell Signaling, Santa Lucia Foundation-IRCCS, Rome 00179 (Italy)

    2012-04-05

    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.

  19. Incretin-based therapy and type 2 diabetes

    DEFF Research Database (Denmark)

    Hare, Kristine J; Knop, Filip Krag

    2010-01-01

    This chapter focuses on the incretin hormones, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP), and their therapeutic potential in treating patients with type 2 diabetes. Type 2 diabetes is characterized by insulin resistance, impaired glucose-induced insulin...... secretion, and inappropriately regulated glucagon secretion which in combination eventually result in hyperglycemia and in the longer term microvascular and macrovascular diabetic complications. Traditional treatment modalities--even multidrug approaches--for type 2 diabetes are often unsatisfactory....... Two new drug classes based on the actions of the incretin hormones have been approved for therapy of type 2 diabetes: injectable long-acting stable analogs of GLP-1, incretin mimetics, and orally available inhibitors of dipeptidyl peptidase 4 (DPP4; the enzyme responsible for the rapid degradation...

  20. Biomarker Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?

    Science.gov (United States)

    Krantz, Benjamin A; O'Reilly, Eileen M

    2017-12-21

    Over the last decade many of the major solid organ cancers have seen improvements in survival due to development of novel therapeutics and corresponding biomarkers that predict treatment efficacy or resistance. In contrast, in pancreatic ductal adenocarcinoma (PDAC) favorable outcomes remain challenging, in part related to the lack of validated biomarkers for patient and treatment selection and thus optimal clinical decision-making. Nonetheless, increasingly therapeutic development for PDAC is accompanied by bioassays to evaluate response and study mechanism of actions with a corresponding increase in the number of trials in mid to late-stage with integrated biomarkers. Additionally, blood based biomarkers that provide a measure of disease activity and allow for minimally invasive tumor analyses are emerging, including circulating tumor DNA, exosomes and circulating tumor cells. In this article, we will review potential biomarkers for currently approved therapies as well as emerging biomarkers for therapeutics under development. Copyright ©2017, American Association for Cancer Research.

  1. Do Biologic Therapies for Rheumatoid Arthritis Offset Treatment-Related Resource Utilization and Cost? A Review of the Literature and an Instrumental Variable Analysis.

    Science.gov (United States)

    Bansback, Nick; Fu, Eric; Sun, Huiying; Guh, Daphne; Zhang, Wei; Lacaille, Diane; Milbers, Katherine; Anis, Aslam H

    2017-09-01

    One justification for using expensive biologic therapy in rheumatoid arthritis (RA) has been that it can reduce future healthcare utilization such as joint surgeries and physician visits. However, the evidence to support this assertion is unclear. We conducted a review of the literature for studies which have analyzed the trends in resource use of RA patients, and then undertook a retrospective observational analysis of a Canadian administrative database using instrumental variable methods. Our review found a trend in reduced resource utilization prior to the introduction of biologics and no evidence that biologic therapies have specifically contributed to this reduction. Our observational analysis, which overcame some of the epidemiological challenges with determining the influence of biologics on resource utilization, found a possible reduction in other medications but possible increases rather than decreases in physician visits and hospitalizations. However, our sample was not sufficiently large to make definitive conclusions. Over 15 years since the introduction of biologics for RA, no evidence exists supporting the assumption that biologic therapies reduce future healthcare utilization. While such a question is challenging to generate evidence for, and so an absence of evidence does not suggest that the hypothesis is incorrect, an instrumental variable analysis using sufficient data could provide definitive evidence.

  2. 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

  3. Robotic, MEMS-based Multi Utility Sample Preparation Instrument for ISS Biological Workstation, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop a multi-functional, automated sample preparation instrument for biological wet-lab workstations on the ISS. The instrument is based on a...

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

    Science.gov (United States)

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

    2011-05-01

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

  5. Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy.

    Science.gov (United States)

    do Amaral, Ronaldo J F C; Almeida, Henrique V; Kelly, Daniel J; O'Brien, Fergal J; Kearney, Cathal J

    2017-01-01

    The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP) have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

  6. Infrapatellar Fat Pad Stem Cells: From Developmental Biology to Cell Therapy

    Directory of Open Access Journals (Sweden)

    Ronaldo J. F. C. do Amaral

    2017-01-01

    Full Text Available The ideal cell type to be used for cartilage therapy should possess a proven chondrogenic capacity, not cause donor-site morbidity, and should be readily expandable in culture without losing their phenotype. There are several cell sources being investigated to promote cartilage regeneration: mature articular chondrocytes, chondrocyte progenitors, and various stem cells. Most recently, stem cells isolated from joint tissue, such as chondrogenic stem/progenitors from cartilage itself, synovial fluid, synovial membrane, and infrapatellar fat pad (IFP have gained great attention due to their increased chondrogenic capacity over the bone marrow and subcutaneous adipose-derived stem cells. In this review, we first describe the IFP anatomy and compare and contrast it with other adipose tissues, with a particular focus on the embryological and developmental aspects of the tissue. We then discuss the recent advances in IFP stem cells for regenerative medicine. We compare their properties with other stem cell types and discuss an ontogeny relationship with other joint cells and their role on in vivo cartilage repair. We conclude with a perspective for future clinical trials using IFP stem cells.

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

    Science.gov (United States)

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

    2010-06-26

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

  8. Glaucoma: Biological Trabecular and Neuroretinal Pathology with Perspectives of Therapy Innovation and Preventive Diagnosis

    Directory of Open Access Journals (Sweden)

    Raffaele Nuzzi

    2017-09-01

    Full Text Available Glaucoma is a common degenerative disease affecting retinal ganglion cells (RGC and optic nerve axons, with progressive and chronic course. It is one of the most important reasons of social blindness in industrialized countries. Glaucoma can lead to the development of irreversible visual field loss, if not treated. Diagnosis may be difficult due to lack of symptoms in early stages of disease. In many cases, when patients arrive at clinical evaluation, a severe neuronal damage may have already occurred. In recent years, newer perspective in glaucoma treatment have emerged. The current research is focusing on finding newer drugs and associations or better delivery systems in order to improve the pharmacological treatment and patient compliance. Moreover, the application of various stem cell types with restorative and neuroprotective intent may be found appealing (intravitreal autologous cellular therapy. Advances are made also in terms of parasurgical treatment, characterized by various laser types and techniques. Moreover, recent research has led to the development of central and peripheral retinal rehabilitation (featuring residing cells reactivation and replacement of defective elements, as well as innovations in diagnosis through more specific and refined methods and inexpensive tests.

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

    Directory of Open Access Journals (Sweden)

    Benjamin L. Franc

    2003-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Jorge Quesada

    2012-01-01

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

  11. To grab the stroma by the horns: from biology to cancer therapy with mesenchymal stem cells.

    Science.gov (United States)

    Droujinine, Ilia A; Eckert, Mark A; Zhao, Weian

    2013-05-01

    Mesenchymal stem or stromal cells (MSCs) are precursor cells that play important roles in tumorigenesis. MSCs are recruited to tumors from local and distant sources to form part of the tumor microenvironment. MSCs influence tumor progression by interacting with cancer cells, endothelial cells, immune cells, and cancer stem cells, in a context-dependent network. This review aims to synthesize this emerging yet controversial field to identify key questions regarding the mechanisms of MSC mobilization and survival in blood; homing to tumors, metastases, and premetastatic sites; spatiotemporal organization and differentiation; and interaction with immune cells and cancer stem cells. Understanding the fundamental biology underlying mesenchymal stem cell and tumor interactions has the potential to inform our knowledge of cancer initiation and progression as well as lead to novel therapeutics for cancer. Furthermore, knowledge of endogenous mechanisms can be used to "program" exogenous MSCs for targeted chemotherapeutic delivery to tumors and metastases. Emerging studies will provide crucial insight into the mechanisms of tumor interactions with the whole organism including MSCs.

  12. Cancer stem cells: a systems biology view of their role in prognosis and therapy.

    Science.gov (United States)

    Mertins, Susan D

    2014-04-01

    Evidence has accumulated that characterizes highly tumorigenic cancer cells residing in heterogeneous populations. The accepted term for such a subpopulation is cancer stem cells (CSCs). While many questions still remain about their precise role in the origin, progression, and drug resistance of tumors, it is clear they exist. In this review, a current understanding of the nature of CSC, their potential usefulness in prognosis, and the need to target them will be discussed. In particular, separate studies now suggest that the CSC is plastic in its phenotype, toggling between tumorigenic and nontumorigenic states depending on both intrinsic and extrinsic conditions. Because of this, a static view of gene and protein levels defined by correlations may not be sufficient to either predict disease progression or aid in the discovery and development of drugs to molecular targets leading to cures. Quantitative dynamic modeling, a bottom up systems biology approach whereby signal transduction pathways are described by differential equations, may offer a novel means to overcome the challenges of oncology today. In conclusion, the complexity of CSCs can be captured in mathematical models that may be useful for selecting molecular targets, defining drug action, and predicting sensitivity or resistance pathways for improved patient outcomes.

  13. Biology Based Lung Cancer Model for Chronic Low Radon Exposures

    International Nuclear Information System (INIS)

    Truta-Popa, Lucia-Adina; Hofmann, Werner; Fakir, Hatim; Cosma, Constantin

    2008-01-01

    Low dose effects of alpha particles at the tissue level are characterized by the interaction of single alpha particles, affecting only a small fraction of the cells within that tissue. Alpha particle intersections of bronchial target cells during a given exposure period were simulated by an initiation-promotion model, formulated in terms of cellular hits within the cycle time of the cell (dose-rate) and then integrated over the whole exposure period (dose). For a given average number of cellular hits during the lifetime of bronchial cells, the actual number of single and multiple hits was selected from a Poisson distribution. While oncogenic transformation is interpreted as the primary initiation step, stimulated mitosis by killing adjacent cells is assumed to be the primary radiological promotion event. Analytical initiation and promotion functions were derived from experimental in vitro data on oncogenic transformation and cellular survival.To investigate the shape of the lung cancer risk function at chronic, low level exposures in more detail, additional biological factors describing the tissue response and operating specifically at low doses were incorporated into the initiation-promotion model. These mechanisms modifying the initial response at the cellular level were: adaptive response, genomic instability, induction of apoptosis by surrounding cells, and detrimental as well as protective bystander mechanisms. To quantify the effects of these mechanisms as functions of dose, analytical functions were derived from the experimental evidence presently available. Predictions of lung cancer risk, including these mechanisms, exhibit a distinct sublinear dose-response relationship at low exposures, particularly for very low exposure rates

  14. Risk for hepatitis B and C virus reactivation in patients with psoriasis on biologic therapies: A retrospective cohort study and systematic review of the literature.

    Science.gov (United States)

    Snast, Igor; Atzmony, Lihi; Braun, Marius; Hodak, Emmilia; Pavlovsky, Lev

    2017-07-01

    Patients with psoriasis on biologic therapies and a history of viral hepatitis carry a risk for reactivation. We evaluated safety of biologic therapies in psoriasis patients seropositive for hepatitis B or C viruses (HBV, HCV). A retrospective cohort study design was used. Clinical and laboratory data for 30 patients undergoing biologic therapy who were seropositive for HBV or HCV were evaluated. Next, a systematic review was performed. Primary outcomes were hepatitis and viral reactivation during therapy. Treatment duration and antiviral prophylaxis were also recorded. Serology indicated HCV infection in 4 patients, past HBV infection in 17 patients, isolated core antibody in 8 patients, and chronic HBV infection in 1 patient. During follow-up (mean 4.85 ± 3.1 years), no patients experienced hepatitis or viral reactivation. The systematic review of the literature included 49 studies comprising 312 patients followed for a mean of 30.9 months. Viral reactivation occurred in 2/175 patients who were seropositive for core antibody and 3/97 with HCV infection (yearly rates, 0.32% and 2.42%, respectively) compared with 8/40 patients with chronic HBV infection (yearly rate, 13.92%). Three of these 8 patients with reactivated HBV infection received antiviral prophylaxis. We pooled heterogeneous studies evaluating different biologic therapies. Biologic therapies pose minimal risk for viral reactivation in low-risk patients without hepatitis seropositive for HCV or HBV core antibody but are a considerable risk in patients with chronic HBV infection, highlighting the necessity of antiviral prophylaxis. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  15. 'Third wave' cognitive therapy versus mentalization-based therapy for major depressive disorder. A protocol for a randomised clinical trial

    DEFF Research Database (Denmark)

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

    2012-01-01

    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...

  16. A new era in blood and lymphatic cancer biology and therapy

    Directory of Open Access Journals (Sweden)

    David Dingli

    2011-03-01

    Full Text Available David DingliDivision of Hematology and Department of Internal Medicine, Mayo Clinic, Rochester, MN, USATumors derived from the transformation of hematopoietic or lymphoid cells are increasing in incidence1 and with improvements in therapy, their prevalence is also growing. The increasing availability of more sophisticated molecular tools is refining the definition of these diseases2 and now more than ever, we are on the verge of ‘personalized medicine’. No disease is as personal as cancer. The current view of tumorigenesis is that somatic cells serially acquire mutations that lead to the malignant phenotype,3,4 a state characterized by loss of cell cycle regulation, resistance to apoptosis, unbridled cellular proliferation, angiogenesis, evasion of the immune response, and ultimately, invasion of other tissues.5,6 Although many somatic mutations probably do not provide a reproductive advantage to cells or can even be deleterious, some mutations enhance the reproductive fitness of the cell enabling it to expand into a clone where additional mutations may lead to the full malignant phenotype. Given that evolution is the result of reproduction, mutation and selection, cancer is a natural consequence, especially in large multicellular organisms that can live for many years.7 Exposure to genotoxic agents (chemicals, viruses, radiation or the response to chronic injury increases the risk of transformation since at some level, the risk is related to the number of cells that are dividing and how often they divide. It is not yet clear how many mutations are required to lead to the cancer phenotype but perhaps with very few exceptions, one mutation is not enough to lead to neoplastic transformation and disease.

  17. Mood disorders and biological rhythms in young adults: A large population-based study.

    Science.gov (United States)

    M