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Sample records for progression therapy response

  1. Baseline characteristics predict risk of progression and response to combined medical therapy for benign prostatic hyperplasia (BPH).

    Science.gov (United States)

    Kozminski, Michael A; Wei, John T; Nelson, Jason; Kent, David M

    2015-02-01

    To better risk stratify patients, using baseline characteristics, to help optimise decision-making for men with moderate-to-severe lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH) through a secondary analysis of the Medical Therapy of Prostatic Symptoms (MTOPS) trial. After review of the literature, we identified potential baseline risk factors for BPH progression. Using bivariate tests in a secondary analysis of MTOPS data, we determined which variables retained prognostic significance. We then used these factors in Cox proportional hazard modelling to: i) more comprehensively risk stratify the study population based on pre-treatment parameters and ii) to determine which risk strata stood to benefit most from medical intervention. In all, 3047 men were followed in MTOPS for a mean of 4.5 years. We found varying risks of progression across quartiles. Baseline BPH Impact Index score, post-void residual urine volume, serum prostate-specific antigen (PSA) level, age, American Urological Association Symptom Index score, and maximum urinary flow rate were found to significantly correlate with overall BPH progression in multivariable analysis. Using baseline factors permits estimation of individual patient risk for clinical progression and the benefits of medical therapy. A novel clinical decision tool based on these analyses will allow clinicians to weigh patient-specific benefits against possible risks of adverse effects for a given patient. © 2014 The Authors. BJU International © 2014 BJU International.

  2. Response: Progress Takes Time.

    Science.gov (United States)

    Rist, Marilee C.

    1984-01-01

    Although declining enrollment and administrative seniority have hampered efforts to eliminate sex discrimination in employment practices in three Long Island, New York, school systems (Commack, Smithtown, and Bay Shore), progress is being made. Because of the Reagan administration's lack of support for affirmative action, however, litigation…

  3. Arts Therapies and Progressive Illness: Nameless Dread

    OpenAIRE

    Waller, Diane E.

    2002-01-01

    Arts Therapies and Progressive Illness is a guide to the use of arts therapies in the treatment of patients with diseases such as Parkinson's and Alzheimer's. In the last few years arts therapies have been used in an increasingly wide range of applications with new groups of patients, such as patients in palliative care, or with learning disabilities - Diane Waller has been a driving force behind this expansion.\\ud This book covers treatment such as art therapy, dance movement therapy and mus...

  4. Non-invasive imaging provides spatiotemporal information on disease progression and response to therapy in a murine model of multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Simone S Riedel

    Full Text Available Multiple myeloma (MM is a B-cell malignancy, where malignant plasma cells clonally expand in the bone marrow of older people, causing significant morbidity and mortality. Typical clinical symptoms include increased serum calcium levels, renal insufficiency, anemia, and bone lesions. With standard therapies, MM remains incurable; therefore, the development of new drugs or immune cell-based therapies is desirable. To advance the goal of finding a more effective treatment for MM, we aimed to develop a reliable preclinical MM mouse model applying sensitive and reproducible methods for monitoring of tumor growth and metastasis in response to therapy.A mouse model was created by intravenously injecting bone marrow-homing mouse myeloma cells (MOPC-315.BM that expressed luciferase into BALB/c wild type mice. The luciferase in the myeloma cells allowed in vivo tracking before and after melphalan treatment with bioluminescence imaging (BLI. Homing of MOPC-315.BM luciferase+ myeloma cells to specific tissues was examined by flow cytometry. Idiotype-specific myeloma protein serum levels were measured by ELISA. In vivo measurements were validated with histopathology.Strong bone marrow tropism and subsequent dissemination of MOPC-315.BM luciferase(+ cells in vivo closely mimicked the human disease. In vivo BLI and later histopathological analysis revealed that 12 days of melphalan treatment slowed tumor progression and reduced MM dissemination compared to untreated controls. MOPC-315.BM luciferase(+ cells expressed CXCR4 and high levels of CD44 and α4β1 in vitro which could explain the strong bone marrow tropism. The results showed that MOPC-315.BM cells dynamically regulated homing receptor expression and depended on interactions with surrounding cells.This study described a novel MM mouse model that facilitated convenient, reliable, and sensitive tracking of myeloma cells with whole body BLI in living animals. This model is highly suitable for monitoring

  5. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  6. Responsible Canadian energy progress report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2010-07-01

    The Canadian Association of Petroleum Producers (CAPP) represents oil and gas companies throughout Canada; its members produce over 90% of Canada's natural gas and crude oil output. The aim of the Association is to improve the economics of the Canadian upstream petroleum sector in an environmentally and socially responsible way. The aim of this Responsible Canadian Energy report is to present the performance data of CAPP's members for the year 2009. Data, trends, and performance analyses are provided throughout the document. This analysis makes it possible to determine where progress has been made and where performance improvement is necessary. It also presents success stories and best practices so that other companies can learn from them how to improve their own performance. This paper provides useful information on the performance of the upstream petroleum industry in Canada and highlights where the focus should be for further improvement in its performance.

  7. Music Therapy and Music Therapy Research. Response

    DEFF Research Database (Denmark)

    Pedersen, Inge Nygaard

    2002-01-01

    This response to Keynote by Prof. Even Ruud (N)"Music Education and Music Therapy seeks to define these two areas with specific focus on tools and methods for analysis of music as these methods are developed in music therapy. This includes that the music therapist, the music and the client create...

  8. Progress in Gene Therapy for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Kamran A.; Davis, Brian J. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States); Wilson, Torrence M. [Department of Urology, Mayo Clinic, Rochester, MN (United States); Wiseman, Gregory A. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States); Federspiel, Mark J. [Department of Molecular Medicine, Mayo Clinic, Rochester, MN (United States); Morris, John C., E-mail: davis.brian@mayo.edu [Division of Endocrinology, Mayo Clinic, Rochester, MN (United States)

    2012-11-19

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  9. Progress in Gene Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Ahmed, Kamran A.; Davis, Brian J.; Wilson, Torrence M.; Wiseman, Gregory A.; Federspiel, Mark J.; Morris, John C.

    2012-01-01

    Gene therapy has held promise to correct various disease processes. Prostate cancer represents the second leading cause of cancer death in American men. A number of clinical trials involving gene therapy for the treatment of prostate cancer have been reported. The ability to efficiently transduce tumors with effective levels of therapeutic genes has been identified as a fundamental barrier to effective cancer gene therapy. The approach utilizing gene therapy in prostate cancer patients at our institution attempts to address this deficiency. The sodium-iodide symporter (NIS) is responsible for the ability of the thyroid gland to transport and concentrate iodide. The characteristics of the NIS gene suggest that it could represent an ideal therapeutic gene for cancer therapy. Published results from Mayo Clinic researchers have indicated several important successes with the use of the NIS gene and prostate gene therapy. Studies have demonstrated that transfer of the human NIS gene into prostate cancer using adenovirus vectors in vitro and in vivo results in efficient uptake of radioactive iodine and significant tumor growth delay with prolongation of survival. Preclinical successes have culminated in the opening of a phase I trial for patients with advanced prostate disease which is currently accruing patients. Further study will reveal the clinical promise of NIS gene therapy in the treatment of prostate as well as other malignancies.

  10. Achieving efficient RNAi therapy: progress and challenges

    Directory of Open Access Journals (Sweden)

    Kun Gao

    2013-07-01

    Full Text Available RNA interference (RNAi has been harnessed to produce a new class of drugs for treatment of various diseases. This review summarizes the most important parameters that govern the silencing efficiency and duration of the RNAi effect such as small interfering RNA (siRNA stability and modification, the type of delivery system and particle sizing methods. It also discusses the predominant barriers for siRNA delivery, such as off-target effects and introduces internalization, endosomal escape and mathematical modeling in RNAi therapy and combinatorial RNAi. At present, effective delivery of RNAi therapeutics in vivo remains a challenge although significant progress has been made in this field.

  11. A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Black Esther P

    2009-05-01

    Full Text Available Abstract Background The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC, and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy. Methods Microarray data from 80 metastatic CRC patients subsequently treated with cetuximab were extracted from the study by Khambata-Ford et al. The study included KRAS status, response, and PFS for each patient. The gene expression data were scaled and analyzed using our predictive model. An improved predictive model of response was identified by removing features in the 180-gene predictor that introduced noise. Results Forty-three of eighty patients were identified as harboring wildtype-KRAS. When the model was applied to these patients, the predicted-sensitive group had significantly longer PFS than the predicted-resistant group (median 88 days vs. 56 days; mean 117 days vs. 63 days, respectively, p = 0.008. Kaplan-Meier curves were also significantly improved in the predicted-sensitive group (p = 0.0059, HR = 0.4109. The model was simplified to 26 of the original 180 genes and this further improved stratification of PFS (median 147 days vs. 56.5 days in the predicted sensitive and resistant groups, respectively, p Conclusion Our model of sensitivity to EGFR inhibition stratified PFS following cetuximab in KRAS-wildtype CRC patients. This study represents the first true external validation of a molecular predictor of response to cetuximab in KRAS-WT metastatic CRC. Our model may hold clinical utility for identifying patients responsive

  12. Research progress in antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    YU Guoying

    2015-04-01

    Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

  13. Role of the functional MNS16A VNTR-243 variant of the human telomerase reverse transcriptase gene in progression and response to therapy of patients with non-Hodgkin's B-cell lymphomas.

    Science.gov (United States)

    Wysoczanska, B; Wrobel, T; Dobrzynska, O; Mazur, G; Bogunia-Kubik, K

    2015-04-01

    MNS16A is a functional polymorphic tandem repeat within the human telomerase reverse transcriptase (hTERT) gene. To investigate whether any of the MNS16A repeats represents a genetic risk factor for NHL susceptibility, progression of or response to therapy in 75 patients with non-Hodgkin's lymphomas (NHLs) and 126 healthy individuals were genotyped using the PCR-VNTR technique. A slightly higher frequency of the MNS16A VNTR-243 variant was detected among patients who did not respond to treatment (NR) as compared to patients with complete or partial remission (0.83 vs. 0.51, P = 0.055). NR patients more frequently developed aggressive than indolent type of the disease (0.92 vs. 0.41, P = 0.001). The VNTR-243 allele was more frequently detected among patients with an intermediate-high/high International Prognostic Index (IPI 3-4) score (P = 0.063), especially in patients with advanced age and IPI 3-4 (P = 0.040). In multivariate analysis, higher IPI 3-4 score (OR = 11.364, P = 0.051) and aggressive type of the disease (OR = 18.182, P = 0.012) were found to be independent genetic markers associated with nonresponse to treatment. Presence of the MNS16A VNTR-243 variant also strongly tended to affect the risk of a less favourable response to therapy and was more frequently present among nonresponders (OR = 5.848, P = 0.059). Genetic variation within the hTERT gene may affect the progression and treatment of lymphoproliferative disorders. © 2015 John Wiley & Sons Ltd.

  14. Lipid-Altering Therapies and the Progression of Atherosclerotic Disease

    International Nuclear Information System (INIS)

    Wierzbicki, Anthony S.

    2007-01-01

    Lipids play a key role in the progression of atherosclerosis, and lipid-lowering therapies have been studied for 30 years in coronary disease. Measurement of the progression of atherosclerosis through carotid intima-media thickness, coronary mean lumen diameter, and, mostly recently, intravascular ultrasound is generally accepted. This article reviews the role of lipid-lowering therapies in changing the rate of atherosclerosis progression in the coronary and carotid circulations. Statins are the primary therapy used to reduce atherosclerosis and cardiovascular events, including strokes and transient ischemic attacks, and have benefits in reducing events in patients undergoing carotid endarterectomy. In contrast, data for other agents, including fibrates and nicotinic acid, in reducing the progression of atherosclerosis are less extensive and not as well known. There is increasing interest in optimizing the whole lipid profile, as this might deliver extra benefits over and above statin therapy alone. Initial proof of this concept has recently come from studies that measured the progression of atherosclerosis and showed that adding nicotinic acid to statin therapy and, more directly, infusion of high-density lipoprotein-like particles reduced progression and indeed might induce regression of the disease. It is likely that the management of significant carotid stenosis will become ever more drug focused and will be customized to the lipid profile of each patient with intervention reserved only for late-stage symptomatic disease

  15. Progress of assessment and rehabilitation therapy of cognitive impairment

    Directory of Open Access Journals (Sweden)

    Yuan-yuan TAO

    2017-07-01

    Full Text Available  Cognitive impairment is one of major disorders after brain injury. With the rapid development of rehabilitation medicine in China, more and more attention was focused on it. The methods of assessment and rehabilitation therapy of cognitive impairment are more widely used in clinic. Based on traditional methods of assessment and rehabilitation therapy, driven by the development of computer, Internet and Internet of Things, more and more new methods emerged. This article intends to review the commonly used assessment and rehabilitation therapy of cognitive impairment and their progress. DOI: 10.3969/j.issn.1672-6731.2017.05.002

  16. Nanoscale theranostics for physical stimulus-responsive cancer therapies.

    Science.gov (United States)

    Chen, Qian; Ke, Hengte; Dai, Zhifei; Liu, Zhuang

    2015-12-01

    Physical stimulus-responsive therapies often employing multifunctional theranostic agents responsive to external physical stimuli such as light, magnetic field, ultra-sound, radiofrequency, X-ray, etc., have been widely explored as novel cancer therapy strategies, showing encouraging results in many pre-clinical animal experiments. Unlike conventional cancer chemotherapy which often accompanies with severe toxic side effects, physical stimulus-responsive agents usually are non-toxic by themselves and would destruct cancer cells only under specific external stimuli, and thus could offer greatly reduced toxicity and enhanced treatment specificity. In addition, physical stimulus-responsive therapies can also be combined with other traditional therapeutics to achieve synergistic anti-tumor effects via a variety of mechanisms. In this review, we will summarize the latest progress in the development of physical stimulus-responsive therapies, and discuss the important roles of nanoscale theranostic agents involved in those non-conventional therapeutic strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Progress toward Gene Therapy for Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Chamberlain, Joel R; Chamberlain, Jeffrey S

    2017-05-03

    Duchenne muscular dystrophy (DMD) has been a major target for gene therapy development for nearly 30 years. DMD is among the most common genetic diseases, and isolation of the defective gene (DMD, or dystrophin) was a landmark discovery, as it was the first time a human disease gene had been cloned without knowledge of the protein product. Despite tremendous obstacles, including the enormous size of the gene and the large volume of muscle tissue in the human body, efforts to devise a treatment based on gene replacement have advanced steadily through the combined efforts of dozens of labs and patient advocacy groups. Progress in the development of DMD gene therapy has been well documented in Molecular Therapy over the past 20 years and will be reviewed here to highlight prospects for success in the imminent human clinical trials planned by several groups. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  18. Audit in the therapy professions: some constraints on progress.

    Science.gov (United States)

    Robinson, S

    1996-12-01

    To ascertain views about constraints on the progress of audit experienced by members of four of the therapy professions: physiotherapy, occupational therapy, speech and language therapy, and clinical psychology. Interviews in six health service sites with a history of audit in these professions. 62 interviews were held with members of the four professions and 60 with other personnel with relevant involvement. Five main themes emerged as the constraints on progress: resources; expertise; relations between groups; organisational structures; and overall planning of audit activities. Concerns about resources focused on lack of time, insufficient finance, and lack of access to appropriate systems of information technology. Insufficient expertise was identified as a major constraint on progress. Guidance on designing instruments for collection of data was the main concern, but help with writing proposals, specifying and keeping to objectives, analysing data, and writing reports was also required. Although sources of guidance were sometimes available, more commonly this was not the case. Several aspects of relations between groups were reported as constraining the progress of audit. These included support and commitment, choice of audit topics, conflicts between staff, willingness to participate and change practice, and concerns about confidentiality. Organisational structures which constrained audit included weak links between heads of professional services and managers of provider units, the inhibiting effect of change, the weakening of professional coherence when therapists were split across directorates, and the ethos of regarding audit findings as business secrets. Lack of an overall plan for audit meant that while some resources were available, others equally necessary for successful completion of projects were not. Members of four of the therapy professions identified a wide range of constraints on the progress of audit. If their commitment to audit is to be

  19. Technological progress in radiation therapy for brain tumors

    LENUS (Irish Health Repository)

    Vernimmen, Frederik Jozef

    2014-01-01

    To achieve a good therapeutic ratio the radiation dose to the tumor should be as high as possible with the lowest possible dose to the surrounding normal tissue. This is especially the case for brain tumors. Technological ad- vancements in diagnostic imaging, dose calculations, and radiation delivery systems, combined with a better un- derstanding of the pathophysiology of brain tumors have led to improvements in the therapeutic results. The widely used technology of delivering 3-D conformal therapy with photon beams (gamma rays) produced by Li-near Accelerators has progressed into the use of Intensity modulated radiation therapy (IMRT). Particle beams have been used for several decades for radiotherapy because of their favorable depth dose characteristics. The introduction of clinically dedicated proton beam therapy facilities has improved the access for cancer patients to this treatment. Proton therapy is of particular interest for pediatric malignancies. These technical improvements are further enhanced by the evolution in tumor physiology imaging which allows for improved delineation of the tumor. This in turn opens the potential to adjust the radiation dose to maximize the radiobiological effects. The advances in both imaging and radiation therapy delivery will be discussed.

  20. Desmoid fibromatosis: MRI features of response to systemic therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sheth, Pooja J.; Subhawong, Ty K. [University of Miami Miller School of Medicine/Jackson Memorial Hospital, Department of Radiology, Miami, FL (United States); Del Moral, Spencer; Wilky, Breelyn A.; Trent, Jonathan C. [University of Miami Miller School of Medicine/Sylvester Comprehensive Cancer Center, Division of Hematology/Oncology, Department of Medicine, Miami, FL (United States); Cohen, Jonathan [Oncology and Radiation Associates, Miami, FL (United States); Rosenberg, Andrew E. [University of Miami Miller School of Medicine, Department of Pathology, Miami, FL (United States); Temple, H.T. [Center for Orthopedic Innovations, Miami, FL (United States)

    2016-10-15

    Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (D{sub max}), approximate tumor volume (V{sub Tumor}), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. D{sub max} decreased more in responders (mean -11.0 %) than in stable/progressive lesions (mean -3.6 and 0 % respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were ''stable,'' including the 3 progressive lesions. In responders, V{sub Tumor} change averaged -29.4 %, but -19.2 % and +32.5 % in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54 % in partial response/stable disease, but only by 10 % in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23 % to 0 %, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically

  1. Progressive pituitary hormone deficiency following radiation therapy in adults

    International Nuclear Information System (INIS)

    Loureiro, Rafaela A.; Vaisman, Mario

    2004-01-01

    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

  2. Response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Schiffer, Angélique A; Widdershoven, Jos W

    2009-01-01

    Cardiac resynchronization therapy (CRT) is a promising treatment for a subgroup of patients with advanced congestive heart failure and a prolonged QRS interval. Despite the majority of patients benefiting from CRT, 10-40% of patients do not respond to this treatment and are labeled as nonresponders...

  3. Ecology, Ethics, and Responsibility in Family Therapy.

    Science.gov (United States)

    Maddock, James W.

    1993-01-01

    Notes that working with marital and family problems complicates the concept of therapeutic responsibility. Discusses several societal contributors to ethical dilemmas in contemporary family therapy and summarizes an ecological framework for therapy on the basis of which a profile of the ethical family therapist is derived. (Author/NB)

  4. Fibrocytes: A Novel Stromal Cells to Regulate Resistance to Anti-Angiogenic Therapy and Cancer Progression.

    Science.gov (United States)

    Goto, Hisatsugu; Nishioka, Yasuhiko

    2017-12-29

    An adequate blood supply is essential for cancer cells to survive and grow; thus, the concept of inhibiting tumor angiogenesis has been applied to cancer therapy, and several drugs are already in clinical use. It has been shown that treatment with those anti-angiogenic drugs improved the response rate and prolonged the survival of patients with various types of cancer; however, it is also true that the effect was mostly limited. Currently, the disappointing clinical results are explained by the existence of intrinsic or acquired resistance to the therapy mediated by both tumor cells and stromal cells. This article reviews the mechanisms of resistance mediated by stromal cells such as endothelial cells, pericytes, fibroblasts and myeloid cells, with an emphasis on fibrocytes, which were recently identified as the cell type responsible for regulating acquired resistance to anti-angiogenic therapy. In addition, the other emerging role of fibrocytes as mediator-producing cells in tumor progression is discussed.

  5. Progressive multifocal leukoencephalopathy. Epidemiology, clinical pictures, diagnosis and therapy

    International Nuclear Information System (INIS)

    Kishida, Shuji

    2007-01-01

    Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by the reactivation of a ubiquitous polyomavirus JC (JCV). PML was for many years a rare disease occurring only in patients with underlying severe impaired immunity. Over the past three decades, the incidence of PML has significantly increased related to the AIDS (acquired immunodeficiency syndrome) pandemic and, more recently, to the growing use of immunosuppressive drugs. The clinical presentation of PML is variable with neurological symptoms corresponding to affected cerebral areas. Usually, the clinical outcome of patients with PML is poor with an inexorable progression to death within 6 months of symptom onset. Although PML usually requires a brain biopsy or autopsy for confirmation, radiological imaging and a demonstration of JCV-DNA in the CSF (cerebrospinal fluid) provide supportive evidence for the diagnosis. Although there is no proven effective therapy for PML, patients with HIV (human immunodeficeincy virus)-related PML may benefit significantly from HAART (highly active antiretroviral therapy). In this article the author reviews the epidemiology, especially in Japan, current challenges in the diagnosis and the treatment guidelines of patients with PML based on recent advances in the understanding of the JC virus biology. (author)

  6. Sirolimus therapy to halt the progression of ADPKD.

    Science.gov (United States)

    Perico, Norberto; Antiga, Luca; Caroli, Anna; Ruggenenti, Piero; Fasolini, Giorgio; Cafaro, Mariateresa; Ondei, Patrizia; Rubis, Nadia; Diadei, Olimpia; Gherardi, Giulia; Prandini, Silvia; Panozo, Andrea; Bravo, Rodolfo Flores; Carminati, Sergio; De Leon, Felipe Rodriguez; Gaspari, Flavio; Cortinovis, Monica; Motterlini, Nicola; Ene-Iordache, Bogdan; Remuzzi, Andrea; Remuzzi, Giuseppe

    2010-06-01

    Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.

  7. Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Mark W., E-mail: mmcdona2@iuhealth.org [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Indiana University Health Proton Therapy Center, Bloomington, Indiana (United States); Linton, Okechuckwu R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana (United States); Shah, Mitesh V. [Department of Neurosurgery, Indiana University School of Medicine, Indianapolis, Indiana (United States)

    2013-12-01

    Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm{sup 3} (range, 0-701 cm{sup 3}). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional

  8. Proton Therapy for Reirradiation of Progressive or Recurrent Chordoma

    International Nuclear Information System (INIS)

    McDonald, Mark W.; Linton, Okechuckwu R.; Shah, Mitesh V.

    2013-01-01

    Purpose: To report the results in patients reirradiated with proton therapy for recurrent or progressive chordoma, with or without salvage surgery. Methods and Materials: A retrospective review of 16 consecutive patients treated from 2005 to 2012 was performed. All patients had received at least 1 prior course of radiation therapy to the same area, and all but 1 patient had at least 1 surgical resection for disease before receiving reirradiation. At the time of recurrence or progression, half of the patients underwent additional salvage surgery before receiving reirradiation. The median prior dose of radiation was 75.2 Gy (range, 40-79.2 Gy). Six patients had received prior proton therapy, and the remainder had received photon radiation. The median gross tumor volume at the time of reirradiation was 71 cm 3 (range, 0-701 cm 3 ). Reirradiation occurred at a median interval of 37 months after prior radiation (range, 12-129 months), and the median dose of reirradiation was 75.6 Gy (relative biological effectiveness [RBE]) (range. 71.2-79.2 Gy [RBE]), given in standard daily fractionation (n=14) or hyperfractionation (n=2). Results: The median follow-up time was 23 months (range, 6-63 months); it was 26 months in patients alive at the last follow-up visit (range, 12-63 months). The 2-year estimate for local control was 85%, overall survival 80%, chordoma-specific survival 88%, and development of distant metastases 20%. Four patients have had local progression: 3 in-field and 1 marginal. Late toxicity included grade 3 bitemporal lobe radionecrosis in 1 patient that improved with hyperbaric oxygen, a grade 4 cerebrospinal fluid leak with meningitis in 1 patient, and a grade 4 ischemic brainstem stroke (out of radiation field) in 1 patient, with subsequent neurologic recovery. Conclusions: Full-dose proton reirradiation provided encouraging initial disease control and overall survival for patients with recurrent or progressive chordoma, although additional toxicities may

  9. Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

    Science.gov (United States)

    Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

    2014-01-01

    Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  10. Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

    Directory of Open Access Journals (Sweden)

    Solène Coisy

    2014-04-01

    Full Text Available Introduction: Progressive outer retinal necrosis (PORN is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV and responsible for severe visual loss. Case Report: A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion: VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

  11. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics.

    Science.gov (United States)

    de la Monte, Suzanne M

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol . 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease.

  12. Analysis of interventional therapy for progressing stage gastric cancer

    International Nuclear Information System (INIS)

    Zhu Mingde; Zhang Zijing; Ji Hongsheng; Ge Chenlin; Hao Gang; Wei Kongming; Yuan Yuhou; Zhao Xiuping

    2008-01-01

    Objective: To investigate the interventional therapy and its curative effect for progressing stage gastric cancer. Methods: two hundred and twelve patients with progressing stage gastric cancer were treated with arterial perfusion and arterial embolization. Gastric cardia cancer was treated through the left gastric artery and the left inferior phrenic artery or splenic artery. Cancers of lesser and greater gastric curvature was treated either through the left and right gastric arteries or common hepatic artery or through gastroduodenal artery, right gastroomental artery or splenic artery. Gastric antrum cancers were perfused through gastroduodenal artery or after the middle segmental embolization of right gastroomental artery. Results: One hundred and ninety three cases undergone interventional management were followed up. The CR + PR of gastric cardia cancer was 53.13%; gastric body cancer 44.44%; gastric antrum cancer 10%; recurrent cancer and remnant gastric cancer 0. There was no significant difference in outcome between gastric cardia cancer and gastric body cancer (P>0.05) but significant differences were shown both between gastric cardia cancer and gastric antrum cancer, and between gastric body cancer and gastric antrum cancer (P<0.05), with 1 year and 2 years survival rates of 81% and 56% respectively. Conclusion: The interventional therapeutic effect of progressing stage gastric cancers is different due to the different sites of the lesions in the gastric tissue. The curative effect of gastric cardia cancer and gastric body cancer is better than that of gastric antrum cancer, recurrent cancer and remnant gastric cancer. (authors)

  13. Non-response to (statin) therapy

    DEFF Research Database (Denmark)

    Trompet, S; Postmus, I; Slagboom, P E

    2016-01-01

    PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p levels (p ... that non-adherence is investigated instead of non-responsiveness....

  14. Stereotactic body radiation therapy for liver oligo-recurrence and oligo-progression from various tumors

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Yu Jin; Kim, Mi Sook; Jang, Won Il; Seo, Young Seok; Cho, Chul Koo; Yoo, Hyung Jun; Paik, Eun Kyung [Dept. of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2017-06-15

    To evaluate the outcomes of stereotactic body radiation therapy (SBRT) for patients with liver oligo-recurrence and oligo-progression from various primary tumors. Between 2002 and 2013, 72 patients with liver oligo-recurrence (oligo-metastasis with a controlled primary tumor) and oligo-progression (contradictory progression of a few sites of disease despite an overall tumor burden response to therapy) underwent SBRT. Of these, 9 and 8 patients with uncontrollable distant metastases and patients immediate loss to follow-up, respectively, were excluded. The total planning target volume was used to select the SBRT dose (median, 48 Gy; range, 30 to 60 Gy, 3–4 fractions). Toxicity was evaluated using the Common Toxicity Criteria for Adverse Events v4.0. We evaluated 55 patients (77 lesions) treated with SBRT for liver metastases. All patients had controlled primary lesions, and 28 patients had stable lesions at another site (oligo-progression). The most common primary site was the colon (36 patients), followed by the stomach (6 patients) and other sites (13 patients). The 2-year local control and progression-free survival rates were 68% and 22%, respectively. The 2- and 5-year overall survival rates were 56% and 20%, respectively. The most common adverse events were grade 1–2 fatigue, nausea, and vomiting; no grade ≥3 toxicities were observed. Univariate analysis revealed that oligo-progression associated with poor survival. SBRT for liver oligo-recurrence and oligo-progression appears safe, with similar local control rates. For liver oligo-progression, criteria are needed to select patients in whom improved overall survival can be expected through SBRT.

  15. Predicting response to epigenetic therapy

    DEFF Research Database (Denmark)

    Treppendahl, Marianne B; Sommer Kristensen, Lasse; Grønbæk, Kirsten

    2014-01-01

    of good pretreatment predictors of response is of great value. Many clinical parameters and molecular targets have been tested in preclinical and clinical studies with varying results, leaving room for optimization. Here we provide an overview of markers that may predict the efficacy of FDA- and EMA...

  16. Progressive necrotic encephalopathy following tacrolimus therapy for liver transplantation.

    Science.gov (United States)

    Aridon, Paolo; Ragonese, Paolo; Di Benedetto, Norma; Grasso, Giovanni; Conaldi, Pier Giulio; D'Amelio, Marco; Savettieri, Giovanni

    2009-12-01

    Previously described neurologic damage induced by immunosuppressive treatments includes transient or reversible central nervous system involvement. We describe a 57-year-old man who underwent liver transplantation and was started on immunosuppressive therapy with tacrolimus (FK506). Six months later, he started complaining of a progressive motor and sensory impairment of the left side, together with cognitive impairment. Brain MRI showed an enlarging lesion of the white matter with peripheral contrast enhancement. PET study indicated severe hypometabolism in the right hemisphere and spectroscopic MRI showed a peak of choline and relative reduction of other metabolites. Findings of CSF examinations and cultures, serology, and molecular techniques were normal. Tacrolimus treatment was stopped. A cerebral biopsy of the lesion showed a sub acute necrotizing process. In the following months, cognitive status of the patient tended to improve although he remained hemiplegic, while serial MRI confirmed the tendency to the recovery of the lesion that was still present 1 year after. The present observation describes a progressive encephalopathy associated with immune suppression with an unusual feature and permanent brain damage.

  17. Progress in the diagnosis of and therapy for MDS.

    Science.gov (United States)

    Nannya, Yasuhito

    2016-01-01

    The WHO classification system of MDS 4 th edition was recently updated. This revision includes nomenclature changes, reflecting the policy of the revision team to emphasize morphological features over cytopenias. Other changes are 1) taking SF3B1 mutation status into account for the definition criteria of MDS-RS (ring sideroblasts), 2) allowing for one additional cytogenetic abnormality (excluding -7/del (7q)) to be diagnosed as 'MDS with isolated del (5q)', 3) sub-classifying MDS-U according to the reasons for being included in this category, and 4) changing the diagnostic rules for myeloid neoplasms with erythroid blast predominance. This session also deals with recent topics in hematopoietic stem cell transplantation (HSCT) as an example of progress in therapy for MDS. Although HSCT is the only curative therapy for MDS, high treatment related mortality precludes its applicability especially for elderly patients, for whom demethylating agents are an alternative. Recently, reports on both well-designed retrospective or prospective studies have validated the advantage of HSCT over demethylating agents for patients of comparatively advanced age with higher risk MDS. Optimal intensity of conditioning regimens for HSCT is another controversial topic for which preliminary results of randomized controlled trials have been released and will be introduced in this session.

  18. Therapy response evaluation with positron emission tomography-computed tomography.

    Science.gov (United States)

    Segall, George M

    2010-12-01

    Positron emission tomography-computed tomography with F-18-fluorodeoxyglucose is widely used for evaluation of therapy response in patients with solid tumors but has not been as readily adopted in clinical trials because of the variability of acquisition and processing protocols and the absence of universal response criteria. Criteria proposed for clinical trials are difficult to apply in clinical practice, and gestalt impression is probably accurate in individual patients, especially with respect to the presence of progressive disease and complete response. Semiquantitative methods of determining tissue glucose metabolism, such as standard uptake value, can be a useful descriptor for levels of tissue glucose metabolism and changes in response to therapy if technical quality control measures are carefully maintained. The terms partial response, complete response, and progressive disease are best used in clinical trials in which the terms have specific meanings and precise definitions. In clinical practice, it may be better to use descriptive terminology agreed upon by imaging physicians and clinicians in their own practice. Copyright © 2010. Published by Elsevier Inc.

  19. Immune response in pemphigus and beyond: progresses and emerging concepts.

    Science.gov (United States)

    Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

    2016-01-01

    Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.

  20. Imaging response during therapy with radium-223 for castration-resistant prostate cancer with bone metastases

    DEFF Research Database (Denmark)

    Keizman, D; Fosboel, M O; Reichegger, H

    2017-01-01

    BACKGROUND: The imaging response to radium-223 therapy is at present poorly described. We aimed to describe the imaging response to radium-223 treatment. METHODS: We retrospectively evaluated the computed tomography (CT) and bone scintigraphy response of metastatic castration-resistant prostate c....../or radiological) may be noted during the first 3 months, and should not be confused with progression. Imaging by CT scan should be considered after three and six doses of radium-223 to rule out extraskeletal disease progression....

  1. Progression of retinal pigment epithelial atrophy in antiangiogenic therapy of neovascular age-related macular degeneration.

    Science.gov (United States)

    Schütze, Christopher; Wedl, Manuela; Baumann, Bernhard; Pircher, Michael; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2015-06-01

    To monitor retinal pigment epithelial (RPE) atrophy progression during antiangiogenic therapy of neovascular age-related macular degeneration (AMD) over 2 years using polarization-sensitive optical coherence tomography (OCT). Prospective interventional case series. setting: Clinical practice. Thirty patients (31 eyes) with treatment-naïve neovascular AMD. Standard intravitreal therapy (0.5 mg ranibizumab) was administered monthly during the first year and pro re nata (PRN; as-needed) during the second year. Spectral-domain (SD) OCT and polarization-sensitive OCT (selectively imaging the RPE) examinations were performed at baseline and at 1, 3, 6, 12, and 24 months using a standardized protocol. RPE-related changes were evaluated using a semi-automated polarization-sensitive OCT segmentation algorithm and correlated with SD OCT and fundus autofluorescence (FAF) findings. RPE response, geographic atrophy (GA) progression. Atrophic RPE changes included RPE thinning, RPE porosity, focal RPE atrophy, and development of GA. Early RPE loss (ie, RPE porosity, focal atrophy) increased progressively during initial monthly treatment and remained stable during subsequent PRN-based therapy. GA developed in 61% of eyes at month 24. Mean GA area increased from 0.77 mm(2) at 12 months to 1.10 mm(2) (standard deviation = 1.09 mm(2)) at 24 months. Reactive accumulation of RPE-related material at the lesion borders increased until month 3 and subsequently decreased. Progressive RPE atrophy and GA developed in the majority of eyes. RPE migration signifies certain RPE plasticity. Polarization-sensitive OCT specifically images RPE-related changes in neovascular AMD, contrary to conventional imaging methods. Polarization-sensitive OCT allows for precisely monitoring the sequence of RPE-related morphologic changes. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Biomarkers of evasive resistance predict disease progression in cancer patients treated with antiangiogenic therapies

    Science.gov (United States)

    Pircher, Andreas; Jöhrer, Karin; Kocher, Florian; Steiner, Normann; Graziadei, Ivo; Heidegger, Isabel; Pichler, Renate; Leonhartsberger, Nicolai; Kremser, Christian; Kern, Johann; Untergasser, Gerold; Gunsilius, Eberhard; Hilbe, Wolfgang

    2016-01-01

    Numerous antiangiogenic agents are approved for the treatment of oncological diseases. However, almost all patients develop evasive resistance mechanisms against antiangiogenic therapies. Currently no predictive biomarker for therapy resistance or response has been established. Therefore, the aim of our study was to identify biomarkers predicting the development of therapy resistance in patients with hepatocellular cancer (n = 11), renal cell cancer (n = 7) and non-small cell lung cancer (n = 2). Thereby we measured levels of angiogenic growth factors, tumor perfusion, circulating endothelial cells (CEC), circulating endothelial progenitor cells (CEP) and tumor endothelial markers (TEM) in patients during the course of therapy with antiangiogenic agents, and correlated them with the time to antiangiogenic progression (aTTP). Importantly, at disease progression, we observed an increase of proangiogenic factors, upregulation of CEC/CEP levels and downregulation of TEMs, such as Robo4 and endothelial cell-specific chemotaxis regulator (ECSCR), reflecting the formation of torturous tumor vessels. Increased TEM expression levels tended to correlate with prolonged aTTP (ECSCR high = 275 days vs. ECSCR low = 92.5 days; p = 0.07 and for Robo4 high = 387 days vs. Robo4 low = 90.0 days; p = 0.08). This indicates that loss of vascular stabilization factors aggravates the development of antiangiogenic resistance. Thus, our observations confirm that CEP/CEC populations, proangiogenic cytokines and TEMs contribute to evasive resistance in antiangiogenic treated patients. Higher TEM expression during disease progression may have clinical and pathophysiological implications, however, validation of our results is warranted for further biomarker development. PMID:26956051

  3. Discontinuing disease-modifying therapy in progressive multiple sclerosis: can we stop what we have started?

    LENUS (Irish Health Repository)

    Lonergan, Roisin

    2012-02-01

    Disease-modifying therapy is ineffective in disabled patients (Expanded Disability Status Scale [EDSS] > 6.5) with secondary progressive multiple sclerosis (MS) without relapses, or in primary progressive MS. Many patients with secondary progressive MS who initially had relapsing MS continue to use disease-modifying therapies. The enormous associated costs are a burden to health services. Regular assessment is recommended to guide discontinuation of disease-modifying therapies when no longer beneficial, but this is unavailable to many patients, particularly in rural areas. The objectives of this study are as follows: 1. To observe use of disease-modifying therapies in patients with progressive multiple sclerosis and EDSS > 6.5. 2. To examine approaches used by a group of international MS experts to stopping-disease modifying therapies in patients with secondary progressive MS without relapses. During an epidemiological study in three regions of Ireland (southeast Dublin city, and Wexford and Donegal Counties), we recorded details of disease-modifying therapies in patients with progressive MS and EDSS > 6.5. An e-questionnaire was sent to 26 neurologists with expert knowledge of MS, asking them to share their approach to stopping disease-modifying therapies in patients with secondary progressive MS. Three hundred and thirty-six patients were studied: 88 from southeast Dublin, 99 from Wexford and 149 from Donegal. Forty-four had EDSS > 6.5: 12 were still using disease-modifying therapies. Of the surveyed neurologists, 15 made efforts to stop disease-modifying therapies in progressive multiple sclerosis, but most did not insist. A significant proportion (12 of 44 patients with progressive MS and EDSS > 6.5) was considered to be receiving therapy without benefit. Eleven of the 12 were from rural counties, reflecting poorer access to neurology services. The costs of disease-modifying therapies in this group (>170,000 euro yearly) could be re-directed towards development

  4. Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

    International Nuclear Information System (INIS)

    Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

    2011-01-01

    Ovarian cancer is the most deadly gynecological cancer with a very poor prognosis. Xenograft mouse models have proven to be one very useful tool in testing candidate therapeutic agents and gene function in vivo. In this study we identify genes and gene networks important for the efficacy of a pre-clinical anti-tumor therapeutic, MT19c. In order to understand how ovarian xenograft tumors may be growing and responding to anti-tumor therapeutics, we used genome-wide mRNA expression and DNA copy number measurements to identify key genes and pathways that may be critical for SKOV-3 xenograft tumor progression. We compared SKOV-3 xenografts treated with the ergocalciferol derived, MT19c, to untreated tumors collected at multiple time points. Cell viability assays were used to test the function of the PPARγ agonist, Rosiglitazone, on SKOV-3 cell growth. These data indicate that a number of known survival and growth pathways including Notch signaling and general apoptosis factors are differentially expressed in treated vs. untreated xenografts. As tumors grow, cell cycle and DNA replication genes show increased expression, consistent with faster growth. The steroid nuclear receptor, PPARγ, was significantly up-regulated in MT19c treated xenografts. Surprisingly, stimulation of PPARγ with Rosiglitazone reduced the efficacy of MT19c and cisplatin suggesting that PPARγ is regulating a survival pathway in SKOV-3 cells. To identify which genes may be important for tumor growth and treatment response, we observed that MT19c down-regulates some high copy number genes and stimulates expression of some low copy number genes suggesting that these genes are particularly important for SKOV-3 xenograft growth and survival. We have characterized the time dependent responses of ovarian xenograft tumors to the vitamin D analog, MT19c. Our results suggest that PPARγ promotes survival for some ovarian tumor cells. We propose that a combination of regulated expression and copy number

  5. Description of load progression and pain response during progressive resistance training early after total hip arthroplasty

    DEFF Research Database (Denmark)

    Mikkelsen, Lone R; Petersen, Annemette K; Mechlenburg, Inger

    2016-01-01

    events during the initial four weeks of training. RESULTS: The majority of patients experienced only moderate hip pain during exercise (range in median across exercises and sessions: 5-35 mm Visual Analog Scale) and mild pain at rest (median: 1-18 mm Visual Analog Scale), both of which decreased over...... time ( p training load (67%-166 % across exercises, p training sessions, short term pain response (an increase >20 mm Visual Analog Scale) occurred in 13 patients in 24 training sessions. CONCLUSION: Progressive resistance......OBJECTIVE: To describe a progressive resistance training intervention implemented shortly after total hip arthroplasty, including a detailed description of load progression, pain response and adverse events to the training. DESIGN: Secondary analyses of data from the intervention group...

  6. Bicarbonate therapy for prevention of chronic kidney disease progression.

    Science.gov (United States)

    Łoniewski, Igor; Wesson, Donald E

    2014-03-01

    Kidney injury in chronic kidney disease (CKD) is likely multifactorial, but recent data support that a component is mediated by mechanisms used by the kidney to increase acidification in response to an acid challenge to systemic acid-base status. If so, systemic alkalization might attenuate this acid-induced component of kidney injury. An acid challenge to systemic acid-base status increases nephron acidification through increased production of endothelin, aldosterone, and angiotensin II, each of which can contribute to kidney inflammation and fibrosis that characterizes CKD. Systemic alkalization that ameliorates an acid challenge might attenuate the contributions of angiotensin II, endothelin, and aldosterone to kidney injury. Some small clinical studies support the efficacy of alkalization in attenuating kidney injury and slowing glomerular filtration rate decline in CKD. This review focuses on the potential that orally administered NaHCO₃ prevents CKD progression and additionally addresses its mechanism of action, side effects, possible complications, dosage, interaction, galenic form description, and contraindications. Current National Kidney Foundation guidelines recommend oral alkali, including NaHCO₃(-), in CKD patients with serum HCO₃(-) <22 mmol/l. Although oral alkali can be provided by other medications and by base-inducing dietary constituents, oral NaHCO₃ will be the focus of this review because of its relative safety and apparent efficacy, and its comparatively low cost.

  7. CAR-T therapy for leukemia: progress and challenges.

    Science.gov (United States)

    Wang, Xin; Xiao, Qing; Wang, Zhe; Feng, Wen-Li

    2017-04-01

    Despite the rapid development of therapeutic strategies, leukemia remains a type of difficult-to-treat hematopoietic malignancy that necessitates introduction of more effective treatment options to improve life expectancy and quality of patients. Genetic engineering in adoptively transferred T cells to express antigen-specific chimeric antigen receptors (CARs) has proved highly powerful and efficacious in inducing sustained responses in patients with refractory malignancies, as exemplified by the success of CD19-targeting CAR-T treatment in patients with relapsed acute lymphoblastic leukemia. Recent strategies, including manipulating intracellular activating domains and transducing viral vectors, have resulted in better designed and optimized CAR-T cells. This is further facilitated by the rapid identification of an accumulating number of potential leukemic antigens that may serve as therapeutic targets for CAR-T cells. This review will provide a comprehensive background and scrutinize recent important breakthrough studies on anti-leukemia CAR-T cells, with focus on recently identified antigens for CAR-T therapy design and approaches to overcome critical challenges. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Adult Stem Cell Therapy for Stroke: Challenges and Progress

    Science.gov (United States)

    Bang, Oh Young; Kim, Eun Hee; Cha, Jae Min; Moon, Gyeong Joon

    2016-01-01

    Stroke is one of the leading causes of death and physical disability among adults. It has been 15 years since clinical trials of stem cell therapy in patients with stroke have been conducted using adult stem cells like mesenchymal stem cells and bone marrow mononuclear cells. Results of randomized controlled trials showed that adult stem cell therapy was safe but its efficacy was modest, underscoring the need for new stem cell therapy strategies. The primary limitations of current stem cell therapies include (a) the limited source of engraftable stem cells, (b) the presence of optimal time window for stem cell therapies, (c) inherited limitation of stem cells in terms of growth, trophic support, and differentiation potential, and (d) possible transplanted cell-mediated adverse effects, such as tumor formation. Here, we discuss recent advances that overcome these hurdles in adult stem cell therapy for stroke. PMID:27733032

  9. Research progress in combination therapy with pegylated interferon and nucleos(tide analogues in treatment of chronic hepatitis B

    Directory of Open Access Journals (Sweden)

    YU Yiqi

    2015-09-01

    Full Text Available Current antiviral treatment strategy for chronic hepatitis B (CHB includes pegylated interferon (PEG-IFN and nucleos(tide analogues (NAs. Whether combination therapy with PEG-IFN and NAs improve therapeutic efficacy has become the key question regarding the antiviral therapy for CHB. This article reviews the recent progress in combination therapy for the management of CHB. The results indicate that the efficacy of simultaneous combination of PEG-IFN and NAs is not superior to that of PEG-IFN monotherapy in terms of HBeAg seroconversion and response after drug withdrawal. Sequential combination or switching therapy in PEG-IFN- or NAs-treated patients, as well as combination with immune cell therapy, is a promising treatment strategy.

  10. Investigation progress of imaging techniques monitoring stem cell therapy

    International Nuclear Information System (INIS)

    Wu Jun; An Rui

    2006-01-01

    Recently stem cell therapy has showed potential clinical application in diabetes mellitus, cardiovascular diseases, malignant tumor and trauma. Efficient techniques of non-invasively monitoring stem cell transplants will accelerate the development of stem cell therapies. This paper briefly reviews the clinical practice of stem cell, in addition, makes a review of monitoring methods including magnetic resonance and radionuclide imaging which have been used in stem cell therapy. (authors)

  11. Integrative modeling of transcriptional regulation in response to antirheumatic therapy

    Directory of Open Access Journals (Sweden)

    Thiesen Hans-Juergen

    2009-08-01

    Full Text Available Abstract Background The investigation of gene regulatory networks is an important issue in molecular systems biology and significant progress has been made by combining different types of biological data. The purpose of this study was to characterize the transcriptional program induced by etanercept therapy in patients with rheumatoid arthritis (RA. Etanercept is known to reduce disease symptoms and progression in RA, but the underlying molecular mechanisms have not been fully elucidated. Results Using a DNA microarray dataset providing genome-wide expression profiles of 19 RA patients within the first week of therapy we identified significant transcriptional changes in 83 genes. Most of these genes are known to control the human body's immune response. A novel algorithm called TILAR was then applied to construct a linear network model of the genes' regulatory interactions. The inference method derives a model from the data based on the Least Angle Regression while incorporating DNA-binding site information. As a result we obtained a scale-free network that exhibits a self-regulating and highly parallel architecture, and reflects the pleiotropic immunological role of the therapeutic target TNF-alpha. Moreover, we could show that our integrative modeling strategy performs much better than algorithms using gene expression data alone. Conclusion We present TILAR, a method to deduce gene regulatory interactions from gene expression data by integrating information on transcription factor binding sites. The inferred network uncovers gene regulatory effects in response to etanercept and thus provides useful hypotheses about the drug's mechanisms of action.

  12. Recent Progress in the Medical Therapy of Pituitary Tumors

    Directory of Open Access Journals (Sweden)

    Fabienne Langlois

    2017-05-01

    Full Text Available Management of pituitary tumors is multidisciplinary, with medical therapy playing an increasingly important role. With the exception of prolactin-secreting tumors, surgery is still considered the first-line treatment for the majority of pituitary adenomas. However, medical/pharmacological therapy plays an important role in controlling hormone-producing pituitary adenomas, especially for patients with acromegaly and Cushing disease (CD. In the case of non-functioning pituitary adenomas (NFAs, pharmacological therapy plays a minor role, the main objective of which is to reduce tumor growth, but this role requires further studies. For pituitary carcinomas and atypical adenomas, medical therapy, including chemotherapy, acts as an adjuvant to surgery and radiation therapy, which is often required to control these aggressive tumors. In the last decade, knowledge about the pathophysiological mechanisms of various pituitary adenomas has increased, thus novel medical therapies that target specific pathways implicated in tumor synthesis and hormonal over secretion are now available. Advancement in patient selection and determination of prognostic factors has also helped to individualize therapy for patients with pituitary tumors. Improvements in biochemical and “tumor mass” disease control can positively affect patient quality of life, comorbidities and overall survival. In this review, the medical armamentarium for treating CD, acromegaly, prolactinomas, NFA, and carcinomas/aggressive atypical adenomas will be presented. Pharmacological therapies, including doses, mode of administration, efficacy, adverse effects, and use in special circumstances are provided. Medical therapies currently under clinical investigation are also briefly discussed.

  13. Clinical Report of Oriental Medicine Treatment with Bee Venom Therapy of Progressive muscle atrophy 1 Patient

    Directory of Open Access Journals (Sweden)

    Kim Young-Ho

    2000-07-01

    Full Text Available The authors reports in order to study the effect of Bee Venom therapy of progressive muscle atrophy. The authors investigated 1 patient who is treated at Woosuk University Oriental Medical Hospital. The patient diagnosed by MRI EMG Hematology Muscle biopsy as progressive muscle atrophy is administered by Bee Venom therapy for 4 months. Bee Venom therapy is operated by 2 times per a week(every 3 days, 0.1cc per one operation, 0.05cc per one acupuncture point. The authors checked changes of this patient's chief symptoms by comparing before and after Bee Venom therapy is operated at 30 times. After Bee Venom therapy, the patient increased motor power & ROM, decreased general cooling sense & swallowing disorder. As above, the authors conclude that better results can be obtained Oriental Medical Treatment with Bee Venom therapy in progressive muscle atrophy

  14. Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential antifibrotic therapy

    DEFF Research Database (Denmark)

    Karsdal, Morten A; Henriksen, Kim; Nielsen, Mette Juul

    2016-01-01

    There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic t...

  15. Progresses towards safe and efficient gene therapy vectors.

    Science.gov (United States)

    Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

    2015-10-13

    The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

  16. Progress toward cell-directed therapy for phenylketonuria

    Science.gov (United States)

    Harding, CO

    2009-01-01

    Phenylketonuria (PKU) is one of the most common inborn errors of metabolism with an annual incidence of approximately 1:16,000 live births in North America. Contemporary therapy relies upon lifelong dietary protein restriction and supplementation with phenylalanine-free medical foods. This therapy is expensive and unpalatable; dietary compliance is difficult to maintain throughout life. Non-adherence to the diet is associated with learning disabilities, adult-onset neurodegenerative disease, and maternal PKU syndrome. The fervent dream of many individuals with PKU is a more permanent cure for this disease. This paper will review ongoing efforts to develop viable cell-directed therapies, in particular cell transplantation and gene therapy, for the treatment of PKU. PMID:18498375

  17. Progress of assessment and rehabilitation therapy of cognitive impairment

    OpenAIRE

    Yuan-yuan TAO; Rong SUN; Lu-ping SONG

    2017-01-01

     Cognitive impairment is one of major disorders after brain injury. With the rapid development of rehabilitation medicine in China, more and more attention was focused on it. The methods of assessment and rehabilitation therapy of cognitive impairment are more widely used in clinic. Based on traditional methods of assessment and rehabilitation therapy, driven by the development of computer, Internet and Internet of Things, more and more new methods emerged. This article intends to revie...

  18. 18F-FDG-PET detects complete response to PD1-therapy in melanoma patients two weeks after therapy start

    Energy Technology Data Exchange (ETDEWEB)

    Seith, Ferdinand; Schmidt, Holger; Pfannenberg, Christina; Gueckel, Brigitte; Schwenzer, Nina [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); Forschner, Andrea; Garbe, Claus [Eberhard Karls University, Department of Dermatology, Tuebingen (Germany); Nikolaou, Konstantin [Eberhard Karls University, Diagnostic and Interventional Radiology, Department of Radiology, Tuebingen (Germany); German Cancer Consortium (DKTK), Heidelberg (Germany); La Fougere, Christian [German Cancer Consortium (DKTK), Heidelberg (Germany); Eberhard Karls University, Nuclear Medicine and Clinical Molecular Imaging, Department of Radiology, Tuebingen (Germany)

    2018-01-15

    The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t{sub 0}, base-line), two weeks (t{sub 1}, study examination) and three months after treatment initiation (t{sub 2}, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t{sub 1} turned out to have complete response at t{sub 2}. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t{sub 2}, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t{sub 1}. OS in patients with PMD at t{sub 2} varied between 148 and 814 days. SMD at both t{sub 1} and t{sub 2} was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future. (orig.)

  19. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    International Nuclear Information System (INIS)

    Flanagan, Louise; Whyte, Lorna; Chatterjee, Namita; Tenniswood, Martin

    2010-01-01

    Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis. To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells

  20. Effects of clusterin over-expression on metastatic progression and therapy in breast cancer

    Directory of Open Access Journals (Sweden)

    Chatterjee Namita

    2010-03-01

    Full Text Available Abstract Background Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s of the secretory isoform in breast tumor progression and metastasis. Methods To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU that over-expresses clusterin. We have measured the in vitro effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression. Results In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs. Conclusions These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.

  1. Therapeutic responses in systematic targeted alpha therapy trial for melanoma

    International Nuclear Information System (INIS)

    Raja, C.; Rizvi, S.M.A.; Song, E.Y.; Graham, P.; Kearsley, J.H.; Goldsmith, H.; Bosserhoff, A.; Morgenstern, A.; Apostolidis, C.; Reisfeld, R.

    2006-01-01

    Full text: The therapeutic response of melanoma patients after systemic alpha therapy has been investigated in an open-labeled Phase 1 dose escalation study to establish the effective dose of alpha-immunoconjugate 2l3 Bi-cDTPA-9.2.27 mAb (AIC). The tools used to investigate the effects were physical examination; the images of the tumours, pathology comparisons over 12 weeks; CT comparisons and changes in tumour marker over 8 weeks. The physical examination indicated varied tumour responses. One patient showed complete response at 12 weeks post-TAT, with 20 of 21 tumours completely regressing, the last reduced by 80%. The tumour beds were biopsied for staining; S l OO was negative and no viable cells were observed. Most patients showed stable disease at 2 weeks. In one patient the CT comparison of 8 weeks with baseline showed marked reduction in three lung lesions. At least 4/21 patients showed partial response at 4 to 8 weeks and the same number showed stable disease. The disease progressed in 7 patients. The tumour marker melanoma inhibitory activity protein (MIA) showed reductions over 8 weeks, and was consistent with observations in most patients. Complete and partial responses were observed in systemic TAT for stage IV melanoma, but there was no dose-response relationship

  2. Predicting response to incretin-based therapy

    Directory of Open Access Journals (Sweden)

    Agrawal N

    2011-04-01

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

  3. Tumour therapy with radionuclides: assessment of progress and problems

    International Nuclear Information System (INIS)

    Carlsson, Joergen; Forssell Aronsson, Eva; Hietala, Sven-Ola; Stigbrand, Torgny; Tennvall, Jan

    2003-01-01

    Radionuclide therapy is a promising modality for treatment of tumours of haematopoietic origin while the success for treatment of solid tumours so far has been limited. The authors consider radionuclide therapy mainly as a method to eradicate disseminated tumour cells and small metastases while bulky tumours and large metastases have to be treated surgically or by external radiation therapy. The promising therapeutic results for haematological tumours give hope that radionuclide therapy will have a breakthrough also for treatment of disseminated cells from solid tumours. New knowledge related to this is continuously emerging since new molecular target structures are being characterised and the knowledge on pharmacokinetics and cellular processing of different types of targeting agents increases. There is also improved understanding of the factors of importance for the choice of appropriate radionuclides with respect to their decay properties and the therapeutic applications. Furthermore, new methods to modify the uptake of radionuclides in tumour cells and normal tissues are emerging. However, we still need improvements regarding dosimetry and treatment planning as well as an increased knowledge about the tolerance doses for normal tissues and the radiobiological effects on tumour cells. This is especially important in targeted radionuclide therapy where the dose rates often are lower than 1 Gy/h

  4. Neck Vibration Proprioceptive Postural Response Intact in Progressive Supranuclear Palsy unlike Idiopathic Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Stefan Kammermeier

    2017-12-01

    Full Text Available Progressive supranuclear palsy (PSP and late-stage idiopathic Parkinson’s disease (IPD are neurodegenerative movement disorders resulting in different postural instability and falling symptoms. IPD falls occur usually forward in late stage, whereas PSP falls happen in early stages, mostly backward, unprovoked, and with high morbidity. Postural responses to sensory anteroposterior tilt illusion by bilateral dorsal neck vibration were probed in both groups versus healthy controls on a static recording posture platform. Three distinct anteroposterior body mass excursion peaks (P1–P3 were observed. 18 IPD subjects exhibited well-known excessive response amplitudes, whereas 21 PSP subjects’ responses remained unaltered to 22 control subjects. Neither IPD nor PSP showed response latency deficits, despite brainstem degeneration especially in PSP. The observed response patterns suggest that PSP brainstem pathology might spare the involved proprioceptive pathways and implies viability of neck vibration for possible biofeedback and augmentation therapy in PSP postural instability.

  5. Progressive Hypertrophic Genital Herpes in an HIV-Infected Woman despite Immune Recovery on Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mark H. Yudin

    2008-01-01

    Full Text Available Most HIV-infected individuals are coinfected by Herpes simplex virus type 2 (HSV-2. HSV-2 reactivates more frequently in HIV-coinfected individuals with advanced immunosuppression, and may have very unusual clinical presentations, including hypertrophic genital lesions. We report the case of a progressive, hypertrophic HSV-2 lesion in an HIV-coinfected woman, despite near-complete immune restoration on antiretroviral therapy for up to three years. In this case, there was prompt response to topical imiquimod. The immunopathogenesis and clinical presentation of HSV-2 disease in HIV-coinfected individuals are reviewed, with a focus on potential mechanisms for persistent disease despite apparent immune reconstitution. HIV-infected individuals and their care providers should be aware that HSV-2 may cause atypical disease even in the context of near-comlpete immune reconstitution on HAART.

  6. Stem Cell Therapies for Treating Diabetes: Progress and Remaining Challenges.

    Science.gov (United States)

    Sneddon, Julie B; Tang, Qizhi; Stock, Peter; Bluestone, Jeffrey A; Roy, Shuvo; Desai, Tejal; Hebrok, Matthias

    2018-06-01

    Restoration of insulin independence and normoglycemia has been the overarching goal in diabetes research and therapy. While whole-organ and islet transplantation have become gold-standard procedures in achieving glucose control in diabetic patients, the profound lack of suitable donor tissues severely hampers the broad application of these therapies. Here, we describe current efforts aimed at generating a sustainable source of functional human stem cell-derived insulin-producing islet cells for cell transplantation and present state-of-the-art efforts to protect such cells via immune modulation and encapsulation strategies. Copyright © 2018. Published by Elsevier Inc.

  7. Plutonium Reclamation Facility incident response project progress report

    International Nuclear Information System (INIS)

    Austin, B.A.

    1997-01-01

    This report provides status of Hanford activities in response to process deficiencies highlighted during and in response to the May 14, 1997, explosion at the Plutonium Reclamation Facility. This report provides specific response to the August 4, 1997, memorandum from the Secretary which requested a progress report, in 120 days, on activities associated with reassessing the known and evaluating new vulnerabilities (chemical and radiological) at facilities that have been shut down, are in standby, are being deactivated or have otherwise changed their conventional mode of operation in the last several years. In addition, this report is intended to provide status on emergency response corrective activities as requested in the memorandum from the Secretary on August 28, 1997. Status is also included for actions requested in the second August 28, 1997, memorandum from the Secretary, regarding timely notification of emergencies

  8. Plutonium Reclamation Facility incident response project progress report

    Energy Technology Data Exchange (ETDEWEB)

    Austin, B.A.

    1997-11-25

    This report provides status of Hanford activities in response to process deficiencies highlighted during and in response to the May 14, 1997, explosion at the Plutonium Reclamation Facility. This report provides specific response to the August 4, 1997, memorandum from the Secretary which requested a progress report, in 120 days, on activities associated with reassessing the known and evaluating new vulnerabilities (chemical and radiological) at facilities that have been shut down, are in standby, are being deactivated or have otherwise changed their conventional mode of operation in the last several years. In addition, this report is intended to provide status on emergency response corrective activities as requested in the memorandum from the Secretary on August 28, 1997. Status is also included for actions requested in the second August 28, 1997, memorandum from the Secretary, regarding timely notification of emergencies.

  9. Remodeling of Tumor Stroma and Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Johansson, Anna; Ganss, Ruth, E-mail: ganss@waimr.uwa.edu.au [Western Australian Institute for Medical Research, Centre for Medical Research, University of Western Australia, Perth 6000 (Australia)

    2012-03-27

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy.

  10. Remodeling of Tumor Stroma and Response to Therapy

    International Nuclear Information System (INIS)

    Johansson, Anna; Ganss, Ruth

    2012-01-01

    Solid tumors are intrinsically resistant to therapy. Cancer progression occurs when tumor cells orchestrate responses from diverse stromal cell types such as blood vessels and their support cells, inflammatory cells, and fibroblasts; these cells collectively form the tumor microenvironment and provide direct support for tumor growth, but also evasion from cytotoxic, immune and radiation therapies. An indirect result of abnormal and leaky blood vessels in solid tumors is high interstitial fluid pressure, which reduces drug penetration, but also creates a hypoxic environment that further augments tumor cell growth and metastatic spread. Importantly however, studies during the last decade have shown that the tumor stroma, including the vasculature, can be modulated, or re-educated, to allow better delivery of chemotherapeutic drugs or enhance the efficiency of active immune therapy. Such remodeling of the tumor stroma using genetic, pharmacological and other therapeutic approaches not only enhances selective access into tumors but also reduces toxic side effects. This review focuses on recent novel concepts to modulate tumor stroma and thus locally increase therapeutic efficacy

  11. Slower Fibrosis Progression Among Liver Transplant Recipients With Sustained Virological Response After Hepatitis C Treatment

    Science.gov (United States)

    Habib, Shahid; Meister, Edward; Habib, Sana; Murakami, Traci; Walker, Courtney; Rana, Abbas; Shaikh, Obaid S.

    2015-01-01

    Background The natural course of hepatic fibrosis in HCV allograft recipients with sustained virological response (SVR) after anti-HCV therapy remains debatable. The aim of this study was to examine the progression of fibrosis in a cohort of patients who achieved SVR compared with those without treatment. Methods The 167 patients who met the inclusion and exclusion criteria were chosen from a transplant database. All patients were required to have histological evidence of recurrent HCV infection post-liver transplantation and a follow-up biopsy. The 140 of these patients had received anti-viral therapy. Twenty-seven patients were identified as controls and were matched with the treatment group in all respects. The patients were categorized into four groups based on treatment response: 1) no treatment (control) (n = 27); 2) non-responders (n = 81); 3) relapsers (n = 32); and 4) SVR (n = 27). The endpoint was the stage of fibrosis on the follow-up liver biopsy. Results The treated and untreated groups were similar in clinical characteristics at the time of transplantation and prior to the initiation of treatment. The 72% of the cohort showed a fibrosis progression of ≥ 1 stage; this change did not significantly differ between the patient groups. Nonetheless, the fibrosis progression rate was the highest in the untreated group and lowest in the patients who achieved SVR. A coefficient of determination was used. Improvements in fibrosis scores were found with greater treatment duration. These improvements were most evident with the achievement of SVR. Conclusions In conclusion, SVR after anti-viral therapy for recurrent hepatitis C infection post-transplantation was associated with slower fibrosis progression and significantly improved graft survival. PMID:27785303

  12. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    OpenAIRE

    El-Badri, Nagwa; Ghoneim, Mohamed A.

    2013-01-01

    Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy...

  13. Mesenchymal Stem Cell Therapy in Diabetes Mellitus: Progress and Challenges

    Directory of Open Access Journals (Sweden)

    Nagwa El-Badri

    2013-01-01

    Full Text Available Advanced type 2 diabetes mellitus is associated with significant morbidity and mortality due to cardiovascular, nervous, and renal complications. Attempts to cure diabetes mellitus using islet transplantation have been successful in providing a source for insulin secreting cells. However, limited donors, graft rejection, the need for continued immune suppression, and exhaustion of the donor cell pool prompted the search for a more sustained source of insulin secreting cells. Stem cell therapy is a promising alternative for islet transplantation in type 2 diabetic patients who fail to control hyperglycemia even with insulin injection. Autologous stem cell transplantation may provide the best outcome for those patients, since autologous cells are readily available and do not entail prolonged hospital stays or sustained immunotoxic therapy. Among autologous adult stem cells, mesenchymal stem cells (MSCs therapy has been applied with varying degrees of success in both animal models and in clinical trials. This review will focus on the advantages of MSCs over other types of stem cells and the possible mechanisms by which MSCs transplant restores normoglycemia in type 2 diabetic patients. Sources of MSCs including autologous cells from diabetic patients and the use of various differentiation protocols in relation to best transplant outcome will be discussed.

  14. Abnormal language-related oscillatory responses in primary progressive aphasia

    Directory of Open Access Journals (Sweden)

    A. Kielar

    Full Text Available Patients with Primary Progressive Aphasia (PPA may react to linguistic stimuli differently than healthy controls, reflecting degeneration of language networks and engagement of compensatory mechanisms. We used magnetoencephalography (MEG to evaluate oscillatory neural responses in sentence comprehension, in patients with PPA and age-matched controls. Participants viewed sentences containing semantically and syntactically anomalous words that evoke distinct oscillatory responses. For age-matched controls, semantic anomalies elicited left-lateralized 8–30 Hz power decreases distributed along ventral brain regions, whereas syntactic anomalies elicited bilateral power decreases in both ventral and dorsal regions. In comparison to controls, patients with PPA showed altered patterns of induced oscillations, characterized by delayed latencies and attenuated amplitude, which were correlated with linguistic impairment measured offline. The recruitment of right hemisphere temporo-parietal areas (also found in controls was correlated with preserved semantic processing abilities, indicating that preserved neural activity in these regions was able to support successful semantic processing. In contrast, syntactic processing was more consistently impaired in PPA, regardless of neural activity patterns, suggesting that this domain of language is particularly vulnerable to the neuronal loss. In addition, we found that delayed peak latencies of oscillatory responses were associated with lower accuracy for detecting semantic anomalies, suggesting that language deficits observed in PPA may be linked to delayed or slowed information processing. Keywords: MEG oscillations, Primary progressive aphasia (PPA, Sentence comprehension

  15. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy

    Directory of Open Access Journals (Sweden)

    Mohit Dogra

    2018-01-01

    Full Text Available We report a case of progressive outer retinal necrosis (PORN in a patient of microscopic polyangitis (MPA, being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  16. Progressive outer retinal necrosis after rituximab and cyclophosphamide therapy.

    Science.gov (United States)

    Dogra, Mohit; Bajgai, Priya; Kumar, Ashok; Sharma, Aman

    2018-04-01

    We report a case of progressive outer retinal necrosis (PORN) in a patient of microscopic polyangitis (MPA), being treated with immunosuppressive drugs such as cyclophosphamide and rituximab. Her aqueous tap was positive for Varicella Zoster virus and she was treated with oral and intravitreal antivirals, along with discontinuation of one of the immunosuppressive agents, i.e. rituximab, which might have led to reactivation of the virus causing necrotizing retinitis lesions. Rituximab and cyclophosphamide are extremely potent drugs, which are necessary to manage immunological disorders such as MPA. However, they may predispose the patient to serious complications like viral infections, including PORN.

  17. DRUG THERAPY IN THE PROGRESSED CML PATIENT WITH MULTI-TKI FAILURE

    Directory of Open Access Journals (Sweden)

    Ibrahim C. Haznedaroglu

    2015-02-01

    Full Text Available The aim of this paper is to outline pharmacotherapy of the ‘third-line management of CML’ (progressive disease course after sequential TKI drugs. Current management of CML with multi-TKI failure is reviewed. TKI (bosutinib, ponatinib, dasatinib, nilotinib and non-TKI (omacetaxine mepussecinate, IFN or PEG-IFN drugs are available. The literature search was made in PubMed with particular focus on the clinical trials, recommendations, guidelines and expert opinions, as well as international recommendations. Progressing CML disease with multi-TKI failure should be treated with alloSCT based on the availability of the donor and EBMT transplant risk scores. The TKI and non-TKI drugs shall be used to get best promising (hematological, cytogenetic, molecular response. During the CP-CML phase of multi-TKI failure, 2nd generation TKIs (nilotinib or dasatinib are used if they remained. Bosutinib and ponatinib (3rd generation TKIs can be administered in triple-TKI failed (imatinib and nilotinib and dasatinib patients. The presence of T315I mutation at any phase requires ponatinib or omacetaxine mepussecinate therapy before allografting. During the AP/BC-CML phase of multi-TKI failure, the most powerful TKI available (ponatinib or dasatinib if remained together with chemotherapy should be given before alloSCT. Monitoring of CML disease and drug off-target risks (particularly vascular thrombotic events are vital.

  18. Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

    Science.gov (United States)

    Coutre, Steven; Choi, Michael; Furman, Richard R; Eradat, Herbert; Heffner, Leonard; Jones, Jeffrey A; Chyla, Brenda; Zhou, Lang; Agarwal, Suresh; Waskiewicz, Tina; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Wierda, William G; Davids, Matthew S

    2018-04-12

    B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282. © 2018 by The American Society of Hematology.

  19. Research progress on criteria for discontinuation of EGFR inhibitor therapy

    Directory of Open Access Journals (Sweden)

    Zhuang HQ

    2012-10-01

    Full Text Available Hong-qing Zhuang, Zhi-yong Yuan, Jun Wang, Ping Wang, Lu-jun Zhao, Bai-lin ZhangDepartment of Radiotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Lung Cancer Center, Tianjin, People's Republic of ChinaAbstract: The clinical success of the epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKI as therapeutic agents has prompted great interest in their further development and clinical testing for a wide variety of malignancies. However, most studies have focused on the efficacy of TKI, and few studies have been done on the criteria for their discontinuation. The current standard for drug discontinuation is “until progression”, based on change in tumor size. However, tumor size is not related to the gene expression which determines the efficacy of TKI in the final analysis, and it is also difficult to make a thorough and correct prediction based on tumor size when the TKI is discontinued. Nevertheless, clinical evaluation of the criteria for TKI discontinuation is still in its early days. Some promising findings have started to emerge. With the improving knowledge of EGFR and its inhibitors, it is expected that the criteria for discontinuation of EGFR inhibitor therapy will become clearer.Keywords: epidermal growth factor receptor, drug discontinuation, acquired drug-resistance

  20. Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression

    Science.gov (United States)

    Medina-Navarro, Rafael; Corona-Candelas, Itzia; Barajas-González, Saúl; Díaz-Flores, Margarita; Durán-Reyes, Genoveva

    2014-01-01

    Background A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. Methods/Principal Findings Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, palbumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy. PMID:25187963

  1. Towards personalized therapy for multiple sclerosis: prediction of individual treatment response.

    Science.gov (United States)

    Kalincik, Tomas; Manouchehrinia, Ali; Sobisek, Lukas; Jokubaitis, Vilija; Spelman, Tim; Horakova, Dana; Havrdova, Eva; Trojano, Maria; Izquierdo, Guillermo; Lugaresi, Alessandra; Girard, Marc; Prat, Alexandre; Duquette, Pierre; Grammond, Pierre; Sola, Patrizia; Hupperts, Raymond; Grand'Maison, Francois; Pucci, Eugenio; Boz, Cavit; Alroughani, Raed; Van Pesch, Vincent; Lechner-Scott, Jeannette; Terzi, Murat; Bergamaschi, Roberto; Iuliano, Gerardo; Granella, Franco; Spitaleri, Daniele; Shaygannejad, Vahid; Oreja-Guevara, Celia; Slee, Mark; Ampapa, Radek; Verheul, Freek; McCombe, Pamela; Olascoaga, Javier; Amato, Maria Pia; Vucic, Steve; Hodgkinson, Suzanne; Ramo-Tello, Cristina; Flechter, Shlomo; Cristiano, Edgardo; Rozsa, Csilla; Moore, Fraser; Luis Sanchez-Menoyo, Jose; Laura Saladino, Maria; Barnett, Michael; Hillert, Jan; Butzkueven, Helmut

    2017-09-01

    Timely initiation of effective therapy is crucial for preventing disability in multiple sclerosis; however, treatment response varies greatly among patients. Comprehensive predictive models of individual treatment response are lacking. Our aims were: (i) to develop predictive algorithms for individual treatment response using demographic, clinical and paraclinical predictors in patients with multiple sclerosis; and (ii) to evaluate accuracy, and internal and external validity of these algorithms. This study evaluated 27 demographic, clinical and paraclinical predictors of individual response to seven disease-modifying therapies in MSBase, a large global cohort study. Treatment response was analysed separately for disability progression, disability regression, relapse frequency, conversion to secondary progressive disease, change in the cumulative disease burden, and the probability of treatment discontinuation. Multivariable survival and generalized linear models were used, together with the principal component analysis to reduce model dimensionality and prevent overparameterization. Accuracy of the individual prediction was tested and its internal validity was evaluated in a separate, non-overlapping cohort. External validity was evaluated in a geographically distinct cohort, the Swedish Multiple Sclerosis Registry. In the training cohort (n = 8513), the most prominent modifiers of treatment response comprised age, disease duration, disease course, previous relapse activity, disability, predominant relapse phenotype and previous therapy. Importantly, the magnitude and direction of the associations varied among therapies and disease outcomes. Higher probability of disability progression during treatment with injectable therapies was predominantly associated with a greater disability at treatment start and the previous therapy. For fingolimod, natalizumab or mitoxantrone, it was mainly associated with lower pretreatment relapse activity. The probability of

  2. Research progress in nanographene oxide with tumor imaging and therapy

    Directory of Open Access Journals (Sweden)

    YOU Peihong

    2015-04-01

    Full Text Available Nanographene oxide,one of graphene oxide derivatives and a novel two-dimensional carbon nanomaterial,has become a popular research topic in nanomedicine due to its unique properties such as ultra-high surface-to-volume ratio and great photo-thermal effect.It contains a large amount of reactive chemical groups,including carboxy group,carbonyl group,hydroxyl group and epoxy group,which enable its easy biological and chemical functionalization and excellent biocompatibility.Therefore,it has potential applications in biomedical field.This paper briefly describes the preparation and functionalization of nanographeme oxide,and then mainly focuses on its application studies in the biomedical field,including in vitro and in vivo toxicity tests and advanced research progress of tumor imaging and treatment.

  3. Progress in sensorimotor rehabilitative physical therapy programs for stroke patients

    Science.gov (United States)

    Chen, Jia-Ching; Shaw, Fu-Zen

    2014-01-01

    Impaired motor and functional activity following stroke often has negative impacts on the patient, the family and society. The available rehabilitation programs for stroke patients are reviewed. Conventional rehabilitation strategies (Bobath, Brunnstrom, proprioception neuromuscular facilitation, motor relearning and function-based principles) are the mainstream tactics in clinical practices. Numerous advanced strategies for sensory-motor functional enhancement, including electrical stimulation, electromyographic biofeedback, constraint-induced movement therapy, robotics-aided systems, virtual reality, intermittent compression, partial body weight supported treadmill training and thermal stimulation, are being developed and incorporated into conventional rehabilitation programs. The concept of combining valuable rehabilitative procedures into “a training package”, based on the patient’s functional status during different recovery phases after stroke is proposed. Integrated sensorimotor rehabilitation programs with appropriate temporal arrangements might provide great functional benefits for stroke patients. PMID:25133141

  4. Physico-technical progress in neutron-capture therapy method

    International Nuclear Information System (INIS)

    Kanda, Keiji; Furubayashi, Toru; Aoki, Kazuhiko

    1985-01-01

    This paper describes mainly development studies on the determination method of in vivo 10 B for the purpose of employment for neutron capture therapy for malignant melanoma and other tumors. To darify the efficacy of the neutron capture therapy, it is necessary to determine 10 B concentration in the diseased part. This study aimed at in vivo 10 B concention determination in living sample to the level of ppm order with 10 % of analytical error within 1 hour, and these determination conditions were satified by prompt γ-ray (478 keV) determination of 10 B (n, αγ) 7 Li reaction. This method required no sample pretreatment. Further, data normalization by γ-ray of H(n, γ)D reaction permitted no disturbance by sample shape or size. Lower limit of detection of the proposed method was estimated in terms of measuring time and statistical error by the equations of 10 B concentration and error analysis derived by the authors. As for the effect of prompt γ-rays of 23 Na(n, γ) 24 Na and 6 Li(n, γ) 7 Li reactions, it was clarified that the former showed no disturbance but some correction was necessary in case of less than 0.1 g of smaple size owing to the latter reaction. In vivo sample determination showed the proposed method was practical. In this paper some results of phantom experiment for in vivo non-destructive 10 B measurement and related simulation calculation, and examination of effect of (γ, n) reaction in heavy water of biomedical irradiation equipment on radiation quality were also described. (Takagi, S.)

  5. Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer’s disease therapeutics

    OpenAIRE

    de la Monte, Suzanne M.

    2012-01-01

    Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer’s disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer’s, subsequent neurodegeneration might be prevented. ...

  6. Progressing a human embryonic stem-cell-based regenerative medicine therapy towards the clinic.

    Science.gov (United States)

    Whiting, Paul; Kerby, Julie; Coffey, Peter; da Cruz, Lyndon; McKernan, Ruth

    2015-10-19

    Since the first publication of the derivation of human embryonic stem cells in 1998, there has been hope and expectation that this technology will lead to a wave of regenerative medicine therapies with the potential to revolutionize our approach to managing certain diseases. Despite significant resources in this direction, the path to the clinic for an embryonic stem-cell-based regenerative medicine therapy has not proven straightforward, though in the past few years progress has been made. Here, with a focus upon retinal disease, we discuss the current status of the development of such therapies. We also highlight some of our own experiences of progressing a retinal pigment epithelium cell replacement therapy towards the clinic. © 2015 The Author(s).

  7. [Progress of researches on the mechanism of cupping therapy].

    Science.gov (United States)

    Cui, Shuai; Cui, Jin

    2012-12-01

    Cupping therapy of Chinese medicine is able to relieve a variety of diseases or clinical conditions, which results from the comprehensive effects of multiple types of stimulation exerted onto the regional acupoint areas. Among the stimuli, the negative pressure from cupping is one of the main factors inducing therapeutic effects. In the present paper, the authors review development of researches on the underlying mechanism of therapeutic effects of cupping-negative pressure from 1) the factor of intra-cup negative pressure; 2) influence of intra-cup negative pressure on cup-blackspot formation; 3) influence of cupping on regional blood vessels and blood flow; 4) effect of cupping on regional ultrastructure of the capillary in the raw-surface tissue; 5) effect of cupping-negative pressure on regional endothelial cells; and 6) biological effects of negative pressure drainage. Generally, cupping induced negative pressure can dilate local blood vessels to improve microcirculation, promote capillary endothelial cells repair, accelerate granulation and angiogenesis, etc., in the regional tissues, normalizing the patients' functional state at last.

  8. Progress in psoriasis therapy via novel drug delivery systems

    Directory of Open Access Journals (Sweden)

    Nitha Vincent

    2014-09-01

    Full Text Available Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.

  9. Patient predictors of response to cognitive behaviour therapy and schema therapy for depression.

    Science.gov (United States)

    Carter, Janet D; McIntosh, Virginia Vw; Jordan, Jennifer; Porter, Richard J; Douglas, Katie; Frampton, Christopher M; Joyce, Peter R

    2018-01-01

    Few studies have examined differential predictors of response to psychotherapy for depression. Greater understanding about the factors associated with therapeutic response may better enable therapists to optimise response by targeting therapy for the individual. The aim of the current exploratory study was to examine patient characteristics associated with response to cognitive behaviour therapy and schema therapy for depression. Participants were 100 outpatients in a clinical trial randomised to either cognitive behaviour therapy or schema therapy. Potential predictors of response examined included demographic, clinical, functioning, cognitive, personality and neuropsychological variables. Individuals with chronic depression and increased levels of pre-treatment negative automatic thoughts had a poorer response to both cognitive behaviour therapy and schema therapy. A treatment type interaction was found for verbal learning and memory. Lower levels of verbal learning and memory impairment markedly impacted on response to schema therapy. This was not the case for cognitive behaviour therapy, which was more impacted if verbal learning and memory was in the moderate range. Study findings are consistent with the Capitalisation Model suggesting that therapy that focuses on the person's strengths is more likely to contribute to a better outcome. Limitations were that participants were outpatients in a randomised controlled trial and may not be representative of other depressed samples. Examination of a variety of potential predictors was exploratory and requires replication.

  10. Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

    International Nuclear Information System (INIS)

    Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh; Myerson, Robert J.; Fleshman, James W.; Grigsby, Perry W.

    2008-01-01

    Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDG uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer

  11. Progress in research on combination treatment of cancer with radiation therapy and immunotherapy

    International Nuclear Information System (INIS)

    Wang Hao; Jia Rui; Yan Jinqi; Yu Jiyun

    2007-01-01

    Radiation therapy (RT) is an important local treatment for tumors, and immunotherapy is a systematic treatment. Combination of RT with immunotherapy may bring about an obvious synergistic anti-tumor effort. Here the research progress in this aspect is reviewed. (authors)

  12. Correlating HIV tropism with immunological response under combination antiretroviral therapy.

    Science.gov (United States)

    Bader, J; Schöni-Affolter, F; Böni, J; Gorgievski-Hrisoho, M; Martinetti, G; Battegay, M; Klimkait, T

    2016-09-01

    A significant percentage of patients infected with HIV-1 experience only suboptimal CD4 cell recovery while treated with combination therapy (cART). It is still unclear whether viral properties such as cell tropism play a major role in this incomplete immune response. This study therefore intended to follow the tropism evolution of the HIV-1 envelope during periods of suppressive cART. Viruses from two distinct patient groups, one with good and another one with poor CD4 recovery after 5 years of suppressive cART, were genotypically analysed for viral tropism at baseline and at the end of the study period. Patients with CCR5-tropic CC-motif chemokine receptor 5 viruses at baseline tended to maintain this tropism to the study end. Patients who had a CXCR4-tropic CXC-motif chemokine receptor 4 virus at baseline were overrepresented in the poor CD4 recovery group. Overall, however, the majority of patients presented with CCR5-tropic viruses at follow-up. Our data lend support to the hypothesis that tropism determination can be used as a parameter for disease progression even if analysed long before the establishment of a poorer immune response. Moreover, the lasting predominating CCR5-tropism during periods of full viral control suggests the involvement of cellular mechanisms that preferentially reduce CXCR4-tropic viruses during cART. © 2016 British HIV Association.

  13. A responsive evaluation of mental health treatment in Cambodia: Intentionally addressing poverty to increase cultural responsiveness in therapy.

    Science.gov (United States)

    Seponski, Desiree M; Lewis, Denise C; Megginson, Maegan C

    2014-01-01

    Mental health issues are significant contributors to the global burden of disease with the highest incidence in resource poor countries; 90% of those in need of mental health treatment reside in low resource countries but receive only 10% of the world's resources. Cambodia, the eighth least developed country in the world, serves as one example of the need to address mental health concerns in low-income, resource poor countries. The current study utilises responsive evaluation methodology to explore how poverty-stricken Cambodian clients, therapists and supervisors experience Western models of therapy as culturally responsive to their unique needs. Quantitative and qualitative data were triangulated across multiple stakeholders using numerous methods including a focus group, interviews, surveys, case illustrations and live supervision observation and analysed using constant comparative analysis. Emerging findings suggest that poverty, material needs, therapy location and financial situations greatly impact the daily lives and mental health conditions of Cambodians and hinder clients' therapeutic progress. The local community needs and context of poverty greatly hinder clients' therapeutic progress in therapy treatment and when therapy does not directly address the culture of poverty, clients did not experience therapy as valuable despite some temporary decreases in mental health symptoms.

  14. Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Hisao Imai

    2015-01-01

    Full Text Available Objectives: The effects of first-line chemotherapy on overall survival (OS might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC. We examined whether progression-free survival (PFS, post-progression survival (PPS, and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data. Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94, PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24, and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13. The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05. Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.

  15. Scientific progress without increasing verisimilitude: In response to Niiniluoto.

    Science.gov (United States)

    Rowbottom, Darrell P

    2015-06-01

    First, I argue that scientific progress is possible in the absence of increasing verisimilitude in science's theories. Second, I argue that increasing theoretical verisimilitude is not the central, or primary, dimension of scientific progress. Third, I defend my previous argument that unjustified changes in scientific belief may be progressive. Fourth, I illustrate how false beliefs can promote scientific progress in ways that cannot be explicated by appeal to verisimilitude. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Perspectives of the Nrf-2 signaling pathway in cancer progression and therapy

    Directory of Open Access Journals (Sweden)

    Priyanka Basak

    Full Text Available The Nuclear factor erythroid2-related factor2 (Nrf2, a master regulator of redox homoeostasis, is a key transcription factor regulating a wide array of genes for antioxidant and detoxification enzymes. It protects organs from various kinds of toxic insults. On the other hand, activation of Nrf2 is also correlated with cancer progression and chemoresistance. Downregulation of Nrf2 activity has attracted an increasing amount of attention as it may provide an alternative cancer therapy. In this review, we examine recent studies on roles of Nrf2 in several pathophysiological conditions emphasising cancer. We discuss elaborately the current knowledge on Nrf2 regulation including KEAP1-dependent and KEAP1-independent cascades. KEAP1/Nrf2 system is a master regulator of cellular response against a variety of environmental stresses. We also highlight several tightly controlled regulations of Nrf2 by numerous proteins, small molecules, toxic metals, etc. In addition, we evaluate the possible therapeutic approaches of increasing chemosensitivity via modulating Nrf2 signaling. Keywords: Nrf2, Transcription factor, KEAP1, Oxidative stress, Cell proliferation, Carcinogenesis, Chemoprevention

  17. Response to combination antiretroviral therapy: variation by age

    DEFF Research Database (Denmark)

    Lundgren, Jens

    2008-01-01

    -naive individuals starting combination antiretroviral therapy from 1998 to 2006. OUTCOME MEASURES: Time from combination antiretroviral therapy initiation to HIV RNA less than 50 copies/ml (virological response), CD4 increase of more than 100 cells/microl (immunological response) and new AIDS/death were analysed...... response. The probability of virological response was lower in those aged 6-12 (adjusted hazard ratio: 0.87) and 13-17 (0.78) years, but was higher in those aged 50-54 (1.24), 55-59 (1.24) and at least 60 (1.18) years. The probability of immunological response was higher in children and younger adults...... and reduced in those 60 years or older. Those aged 55-59 and 60 years or older had poorer clinical outcomes after adjusting for the latest CD4 cell count. CONCLUSION: Better virological responses but poorer immunological responses in older individuals, together with low precombination antiretroviral therapy...

  18. Progress on gene therapy, cell therapy, and pharmacological strategies toward the treatment of oculopharyngeal muscular dystrophy.

    Science.gov (United States)

    Harish, Pradeep; Malerba, Alberto; Dickson, George; Bachtarzi, Houria

    2015-05-01

    Oculopharyngeal muscular dystrophy (OPMD) is a muscle-specific, late-onset degenerative disorder whereby muscles of the eyes (causing ptosis), throat (leading to dysphagia), and limbs (causing proximal limb weakness) are mostly affected. The disease is characterized by a mutation in the poly(A)-binding protein nuclear-1 (PABPN1) gene, resulting in a short GCG expansion in the polyalanine tract of PABPN1 protein. Accumulation of filamentous intranuclear inclusions in affected skeletal muscle cells constitutes the pathological hallmark of OPMD. This review highlights the current translational research advances in the treatment of OPMD. In vitro and in vivo disease models are described. Conventional and experimental therapeutic approaches are discussed with emphasis on novel molecular therapies including the use of intrabodies, gene therapy, and myoblast transfer therapy.

  19. The Initial Response To Corticosteroid Therapy in Childhood ...

    African Journals Online (AJOL)

    Background: Nephrotic syndrome (NS) in African children is associated with poor response to corticosteroids. There is disparity in treatment response on the African continent. The aim of this present study was to describe the initial response to corticosteroid therapy of childhood NS in Côte d'ivoire. Materials and methods: ...

  20. Inadequate Response to Therapy as a Predictor of Suicide.

    Science.gov (United States)

    Dahlsgaard, Katherine K.; Beck, Aaron T.; Brown, Gregory K.

    1998-01-01

    The role of response to cognitive therapy as a predictor of suicide was investigated by comparing 17 outpatients with mood disorders who committed suicide with 17 matched patients who did not commit suicide. Significant differences were found on several variables including higher levels of hopelessness at termination of therapy. (Author/EMK)

  1. Phase II study of radiopeptide {sup 177}Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Claringbold, Phillip G. [Fremantle Hospital, Department of Oncology, Fremantle, WA (Australia); Brayshaw, Paul A.; Turner, J.H. [University of Western Australia, Department of Nuclear Medicine, Fremantle Hospital, Fremantle, WA (Australia); Price, Richard A. [Fremantle Hospital, Department of Radiology, Fremantle, WA (Australia)

    2011-02-15

    In this phase II study we investigated the safety and efficacy of combination capecitabine and {sup 177}Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). Enrolled in the study were 33 patients with biopsy-proven NETs, positive {sup 111}In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq {sup 177}Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m{sup 2} capecitabine per day. Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of {sup 177}Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients. (orig.)

  2. Retinoblastoma loss modulates DNA damage response favoring tumor progression.

    Directory of Open Access Journals (Sweden)

    Marcos Seoane

    Full Text Available Senescence is one of the main barriers against tumor progression. Oncogenic signals in primary cells result in oncogene-induced senescence (OIS, crucial for protection against cancer development. It has been described in premalignant lesions that OIS requires DNA damage response (DDR activation, safeguard of the integrity of the genome. Here we demonstrate how the cellular mechanisms involved in oncogenic transformation in a model of glioma uncouple OIS and DDR. We use this tumor type as a paradigm of oncogenic transformation. In human gliomas most of the genetic alterations that have been previously identified result in abnormal activation of cell growth signaling pathways and deregulation of cell cycle, features recapitulated in our model by oncogenic Ras expression and retinoblastoma (Rb inactivation respectively. In this scenario, the absence of pRb confers a proliferative advantage and activates DDR to a greater extent in a DNA lesion-independent fashion than cells that express only HRas(V12. Moreover, Rb loss inactivates the stress kinase DDR-associated p38MAPK by specific Wip1-dependent dephosphorylation. Thus, Rb loss acts as a switch mediating the transition between premalignant lesions and cancer through DDR modulation. These findings may have important implications for the understanding the biology of gliomas and anticipate a new target, Wip1 phosphatase, for novel therapeutic strategies.

  3. Pre-treatment amygdala volume predicts electroconvulsive therapy response

    NARCIS (Netherlands)

    ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

    2014-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and

  4. Multimodal OCT for complex assessment of tumors response to therapy

    Science.gov (United States)

    Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

    2017-07-01

    Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

  5. Research progress of rehabilitation therapy in Parkinson's disease and its mechanism

    Directory of Open Access Journals (Sweden)

    Jin LIU

    2017-07-01

    Full Text Available Parkinson's disease (PD is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rehabilitation therapy can delay the development of disease, improve motor symptoms and non - motor symptoms (NMS, and consequently improve the activities of daily living (ADL in patients with PD. The mechanism of rehabilitation improving the symptoms of PD is very complex, involving a variety of molecular mechanisms. Thus, this review will focus on the effect of rehabilitation therapy on PD and the underlying molecular mechanism including neurotransmitters, trophic factors, synaptic plasticity and immune system. DOI: 10.3969/j.issn.1672-6731.2017.06.003

  6. Asthma: non-responsiveness to conventional therapy.

    Science.gov (United States)

    Rebuck, A S

    1986-01-01

    Despite regular inhalation of beta-agonists, topical steroids and anticholinergic aerosols and the achievement of therapeutic blood levels of theophylline, some asthmatics have rapidly fluctuating levels of peak flow measurements throughout the day. Often little or no improvement is obtained with larger doses of corticosteroids. Before embarking on more intense drug therapy, attention should be paid to conscientious adherence to the prescribed regimen and avoidance of aspirin and tartrazine, as well as to exposure to allergens such as those associated with household pets. A number of newer therapeutic options are related to the use of air jet or ultrasonic nebulizers, that allow liquid forms of inhalation agents to be taken slowly in the home environment. In this regard, combination therapy with a beta-agonist and the anticholinergic ipratropium has been shown to have bronchodilating properties superior to either agent used alone. Secondly, sodium cromoglycate in its liquid form appears to have bronchodilator properties; taken on a regular basis, four times per day, it appears to have a steroid-sparing effect. Two alternatives are available for increasing the intensity of corticosteroid therapy, other than by prolonged, high-dose prednisone. The first is that of high-dose inhaled beclomethasone (up to 2000 micrograms/day) using the 250 micrograms/puff inhaler. The second is that of intravenous therapy with methylprednisolone, recently shown to have lung permeability superior to that of prednisolone. Office patients can be treated with occasional or even regular 'pulse' doses of methylprednisolone, an approach that is now finding acceptance in the management of the inflammatory alveolitides.

  7. The Effectiveness of the Progression of Widex Zen Tinnitus Therapy: A Pilot Study.

    Science.gov (United States)

    Tyler, Richard S; Deshpande, Aniruddha K; Lau, Chi C; Kuk, Francis

    2017-09-18

    The aim of this study was to measure the progression of benefits to individuals with tinnitus from providing informational counseling, hearing aids, a brief tinnitus activities treatment and Zen therapy. Several magnitude estimation scales and tinnitus handicap scales were administered for the duration of the study to 20 participants. Results indicated that all participants benefited from this sequential approach of providing different components of this tinnitus treatment. Large benefits were observed following the tinnitus activities treatment and the Zen treatments. We conclude that the progressive approach of treatment demonstrated here should be of benefit to most individuals with tinnitus and that the Widex Zen sound therapy is a worthwhile treatment for many tinnitus sufferers.

  8. Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

    Science.gov (United States)

    Mikhaylova, Irina N; Shubina, Irina Zh; Chkadua, George Z; Petenko, Natalia N; Morozova, Lidia F; Burova, Olga S; Beabelashvili, Robert Sh; Parsunkova, Kermen A; Balatskaya, Natalia V; Chebanov, Dmitrii K; Pospelov, Vadim I; Nazarova, Valeria V; Vihrova, Anastasia S; Cheremushkin, Evgeny A; Molodyk, Alvina A; Kiselevsky, Mikhail V; Demidov, Lev V

    2018-05-11

    Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

  9. Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.

    Directory of Open Access Journals (Sweden)

    Ahmed A Alkhateeb

    Full Text Available Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml or CRP (>7.25 mg/l was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.

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

    Directory of Open Access Journals (Sweden)

    Li Kuiyuan

    2009-04-01

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

  11. Progress toward overcoming hypoxia-induced resistance to solid tumor therapy

    International Nuclear Information System (INIS)

    Karakashev, Sergey V; Reginato, Mauricio J

    2015-01-01

    Hypoxic tumors are associated with poor clinical outcome for multiple types of human cancer. This may be due, in part, to hypoxic cancer cells being resistant to anticancer therapy, including radiation therapy, chemotherapy, and targeted therapy. Hypoxia inducible factor 1, a major regulator of cellular response to hypoxia, regulates the expression of genes that are involved in multiple aspects of cancer biology, including cell survival, proliferation, metabolism, invasion, and angiogenesis. Here, we review multiple pathways regulated by hypoxia/hypoxia inducible factor 1 in cancer cells and discuss the latest advancements in overcoming hypoxia-mediated tumor resistance

  12. Stereotactic Body Radiation Therapy for Locally Progressive and Recurrent Pancreatic Cancer after Prior Radiation

    Directory of Open Access Journals (Sweden)

    Philip Sutera

    2018-03-01

    Full Text Available IntroductionPancreatic adenocarcinoma is an aggressive malignancy that has consistently demonstrated poor outcomes despite aggressive treatments. Despite multimodal treatment, local disease progression and local recurrence are common. Management of recurrent or progressive pancreatic carcinomas proves a further challenge. In patients previously treated with radiation therapy, stereotactic body radiation therapy (SBRT is a promising modality capable of delivering high dose to the tumor while limiting dose to critical structures. We aimed to determine the feasibility and tolerability of SBRT for recurrent or local pancreatic cancer in patients previously treated with external beam radiation therapy (EBRT.Materials and methodsPatients treated with EBRT who developed recurrent or local pancreatic ductal adenocarcinoma treated with SBRT reirradiation at our institution, from 2004 to 2014 were reviewed. Our primary endpoints included overall survival (OS, local control, regional control, and late grade 3+ radiation toxicity. Endpoints were analyzed with the Kaplan–Meier method. The association of these survival endpoints with risk factors was studied with univariate Cox proportional hazards models.ResultsWe identified 38 patients with recurrent/progressive pancreatic cancer treated with SBRT following prior radiation therapy. Prior radiation was delivered to a median dose of 50.4 Gy in 28 fractions. SBRT was delivered to a median dose of 24.5 Gy in 1–3 fractions. Surgical resection was performed on 55.3% of all patients. Within a median follow-up of 24.4 months (inter-quartile range, 14.9–32.7 months, the median OS from diagnosis for the entire cohort was 26.6 months (95% CI: 20.3–29.8 with 2-year OS of 53.0%. Median survival from SBRT was 9.7 months (95% CI, 5.5–13.8. The 2-year freedom from local progression and regional progression was 58 and 82%, respectively. For the entire cohort, 18.4 and 10.5% experienced late grade 2

  13. Acceptance and commitment therapy and contextual behavioral science: examining the progress of a distinctive model of behavioral and cognitive therapy.

    Science.gov (United States)

    Hayes, Steven C; Levin, Michael E; Plumb-Vilardaga, Jennifer; Villatte, Jennifer L; Pistorello, Jacqueline

    2013-06-01

    A number of recent authors have compared acceptance and commitment therapy (ACT) and traditional cognitive behavior therapy (CBT). The present article describes ACT as a distinct and unified model of behavior change, linked to a specific strategy of scientific development, which we term "contextual behavioral science." We outline the empirical progress of ACT and describe its distinctive development strategy. A contextual behavioral science approach is an inductive attempt to build more adequate psychological systems based on philosophical clarity; the development of basic principles and theories; the development of applied theories linked to basic ones; techniques and components linked to these processes and principles; measurement of theoretically key processes; an emphasis on mediation and moderation in the analysis of applied impact; an interest in effectiveness, dissemination, and training; empirical testing of the research program across a broad range of areas and levels of analysis; and the creation of a more effective scientific and clinical community. We argue that this is a reasonable approach, focused on long-term progress, and that in broad terms it seems to be working. ACT is not hostile to traditional CBT, and is not directly buoyed by whatever weaknesses traditional CBT may have. ACT should be measured at least in part against its own goals as specified by its own developmental strategy. Copyright © 2011. Published by Elsevier Ltd.

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

    Directory of Open Access Journals (Sweden)

    Ponich E.S.

    2015-09-01

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

  15. The Effects of Music Therapy on the Physiological Response of Asthmatic Children Receiving Inhalation Therapy.

    Science.gov (United States)

    Roslita, Riau; Nurhaeni, Nani; Wanda, Dessie

    The clinical manifestation of asthma in children can interfere with their daily activities. Music therapy may become one of the alternative approaches to making children feel comfortable during inhalation therapy. The aim of the study was to identify the effects of music therapy on the physiological response of asthmatic preschool and school-age children receiving inhalation therapy. This study used a quasi-experimental, nonequivalent control group with a pre-test-post-test design. The 44 respondents consisted of preschool and school-age children assigned to intervention and control groups. The results showed a significant difference in average oxygen saturation, heart rate, and respiratory rate between the control and intervention groups before and after intervention (p Music therapy can be used as a nursing intervention to improve the physiological response of children with breathing problems.

  16. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.

    2014-11-11

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  17. HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer

    KAUST Repository

    Boulbes, Delphine R.; Arold, Stefan T.; Chauhan, Gaurav B.; Blachno, Korina V.; Deng, Nanfu; Chang, Wei-Chao; Jin, Quanri; Huang, Tzu-Hsuan; Hsu, Jung-Mao; Brady, Samuel W.; Bartholomeusz, Chandra; Ladbury, John E.; Stone, Steve; Yu, Dihua; Hung, Mien-Chie; Esteva, Francisco J.

    2014-01-01

    Resistance to HER2-targeted therapies remains a major obstacle in the treatment of HER2-overexpressing breast cancer. Understanding the molecular pathways that contribute to the development of drug resistance is needed to improve the clinical utility of novel agents, and to predict the success of targeted personalized therapy based on tumor-specific mutations. Little is known about the clinical significance of HER family mutations in breast cancer. Because mutations within HER1/EGFR are predictive of response to tyrosine kinase inhibitors (TKI) in lung cancer, we investigated whether mutations in HER family kinase domains are predictive of response to targeted therapy in HER2-overexpressing breast cancer. We sequenced the HER family kinase domains from 76 HER2-overexpressing invasive carcinomas and identified 12 missense variants. Patients whose tumors carried any of these mutations did not respond to HER2 directed therapy in the metastatic setting. We developed mutant cell lines and used structural analyses to determine whether changes in protein conformation could explain the lack of response to therapy. We also functionally studied all HER2 mutants and showed that they conferred an aggressive phenotype and altered effects of the TKI lapatinib. Our data demonstrate that mutations in the finely tuned HER kinase domains play a critical function in breast cancer progression and may serve as prognostic and predictive markers.

  18. Phase II study of cabozantinib in patients with progressive glioblastoma: subset analysis of patients naive to antiangiogenic therapy

    Science.gov (United States)

    Drappatz, Jan; de Groot, John; Prados, Michael D; Reardon, David A; Schiff, David; Chamberlain, Marc; Mikkelsen, Tom; Desjardins, Annick; Holland, Jaymes; Ping, Jerry; Weitzman, Ron; Cloughesy, Timothy F

    2018-01-01

    Abstract Background Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors. This open-label, phase II trial evaluated cabozantinib in patients with recurrent or refractory glioblastoma (GBM). Methods Patients were initially enrolled at a starting dose of 140 mg/day, but the starting dose was amended to 100 mg/day because of toxicity. Treatment continued until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed by an independent radiology facility using modified Response Assessment in Neuro-Oncology criteria. Additional endpoints included duration of response, 6-month and median progression-free survival, overall survival, and safety. Results Among 152 patients naive to prior antiangiogenic therapy, the objective response rate was 17.6% and 14.5% in the 140 mg/day and 100 mg/day groups, respectively, which did not meet the predefined statistical target for success. The proportions of patients alive and progression free at 6 months were 22.3% and 27.8%, respectively. Median progression-free survival was 3.7 months in both groups, and median overall survival was 7.7 months and 10.4 months, respectively. The incidence of grade 3/4 adverse events (AEs) was 79.4% and 84.7% in the 140 mg/day and 100 mg/day groups, respectively, and dose reductions due to AEs were experienced by 61.8% and 72.0%, respectively. Common grade 3/4 AEs included fatigue, diarrhea, and palmar-plantar erythrodysesthesia syndrome. Conclusions Cabozantinib showed evidence of clinical activity in patients with recurrent GBM naive to antiangiogenic therapy, although the predefined statistical target for success was not met. At the starting doses assessed, AEs were frequently managed with dose reductions. Clinical Trials Registration Number NCT00704288 (https://www.clinicaltrials.gov/ct2/show/NCT00704288) PMID

  19. Effect of lipid-lowering therapy on the progression of intracranial arterial stenosis.

    Science.gov (United States)

    Tan, Teng-Yeow; Kuo, Yeh-Lin; Lin, Wei-Che; Chen, Ting-Yao

    2009-02-01

    Intracranial arterial stenosis (IAS) is a severe disease with a high recurrent stroke rate even under the best medical treatment. Statins have been demonstrated to prevent stroke and to slow or halt atherosclerosis progression. This study was performed to observe the effect of atorvastatin on the progression of IAS, explore the factors associated with atherosclerosis regression and the recurrent rate of stroke. A hospital-base observation study enrolled 40 stroke patients with middle cerebral artery (MCA) or/and basilar artery (BA) stenosis. All participants had hyperlipidemia and were given atorvastatin 40 mg per day for at least six months. IAS was assessed by magnetic resonance angiogram (MRA) at the time of enrollment and then at least six months later. The primary outcome was the progression of IAS. All patients were also given antiplatelet agents for stroke prevention. At the end of the study, 23 (58 %), 15 (38 %) and 2 (4 %) patients had regressed, stationary and progressed IAS, respectively. Females were likely to have regressed IAS. The recurrent stroke rate was 18 %. Among the 54 stenotic vessels, 29 (54 %) vessels were assessed as improvement in stenosis. Compared with other studies, more regressed, stationary IAS and less progressed IAS were found in our study. Female gender was likely to have regressed IAS after statin treatment. Further clinical outcome trials are required to assess the effects of such therapy on morbidity and mortality in this particular group of patients.

  20. The progress reports on the development of therapies of Duchenne muscular dystrophy

    Science.gov (United States)

    Scheuerbrandt, G

    2009-01-01

    Summary The roots of the progress reports on the development of therapies for Duchenne muscular dystrophy (DMD) that since 2000 have been produced at Breitnau/Germany and distributed to the parents of DMD patients cover over 30 years of continual occupation with this disease. The beginning was marked by the development of an early detection programme for the genetic disposition for DMD in infant boys. The next step was the organisation of workshops on the management of DMD and the writing of progress reports on these and other relevant conferences. Getting acquainted with the ideas of the protagonists in the research field by holding interviews was a decisive prerequisite for this activity. This took place in tandem with the development of a new kind of multiplex “family letters” that attempted to answer frequently asked questions to many DMD families at the same time. When – with the beginning of the new millennium – the endeavours towards gene therapies for DMD started to boom all over the scientific world, progress reports designed to keep the families informed about research on DMD treatment were added to the family letters. These reports that give an account of the latest state of the research are written in a plain language that can be understood by laypersons. In the meantime the reports have adopted the character of reviews that are updated annually. They are written in English and German and translated into Spanish and many other languages. PMID:20128138

  1. Epigenetic Modifications and Head and Neck Cancer: Implications for Tumor Progression and Resistance to Therapy

    Directory of Open Access Journals (Sweden)

    Rogerio M. Castilho

    2017-07-01

    Full Text Available Head and neck squamous carcinoma (HNSCC is the sixth most prevalent cancer and one of the most aggressive malignancies worldwide. Despite continuous efforts to identify molecular markers for early detection, and to develop efficient treatments, the overall survival and prognosis of HNSCC patients remain poor. Accumulated scientific evidences suggest that epigenetic alterations, including DNA methylation, histone covalent modifications, chromatin remodeling and non-coding RNAs, are frequently involved in oral carcinogenesis, tumor progression, and resistance to therapy. Epigenetic alterations occur in an unsystematic manner or as part of the aberrant transcriptional machinery, which promotes selective advantage to the tumor cells. Epigenetic modifications also contribute to cellular plasticity during tumor progression and to the formation of cancer stem cells (CSCs, a small subset of tumor cells with self-renewal ability. CSCs are involved in the development of intrinsic or acquired therapy resistance, and tumor recurrences or relapse. Therefore, the understanding and characterization of epigenetic modifications associated with head and neck carcinogenesis, and the prospective identification of epigenetic markers associated with CSCs, hold the promise for novel therapeutic strategies to fight tumors. In this review, we focus on the current knowledge on epigenetic modifications observed in HNSCC and emerging Epi-drugs capable of sensitizing HNSCC to therapy.

  2. Quality assurance in proton therapy: a systematic approach in progress at Orsay

    International Nuclear Information System (INIS)

    Mazal, A.; Habrand, J.L.; Laforture, F.; Breteau, N.; Mazal, A.; Habrand, J.L.; Breteau, N.

    1996-01-01

    The degree of accuracy and reliability required in proton therapy can only be guaranteed of a comprehensive quality assurance (QA) programme is established. Such a programme obviously has common features with general QA in radiotherapy, but some aspects are specific to the use of protons and particularly to the characteristics of each facility. A study is in progress at Orsay to convert a series of quality controls into a systematic quality assurance programme. It includes some basic steps on organisation, setting up a QA committee and QA task groups, organizing meetings, policies, procedures, records qualifications, and determining some examples of tolerance in controls. Among some critical and specific points identified in this process are the combined treatment with photons at different institutions, the specificity of a non-hospital and complex facility, the high degree of precision required for the patient setup, and the need to develop in-house basic tools such as the treatment planning system. The inclusion of all the patients in prospective well-defined clinical trials, the comparison with alternative techniques and the radiobiological studies are considered as fundamentals for the QA programme. Present dosimetric and radiobiological intercomparisons between proton-therapy centres are considered as partial audits. A study is in progress to establish common dosimetric and clinical protocols, radiological models and dose and volume specifications. In spite of the differences between the existing facilities, it should be possible to obtain international consensus on general guidelines for a QA programme in proton therapy. (author)

  3. Using Response Times to Assess Learning Progress: A Joint Model for Responses and Response Times

    Science.gov (United States)

    Wang, Shiyu; Zhang, Susu; Douglas, Jeff; Culpepper, Steven

    2018-01-01

    Analyzing students' growth remains an important topic in educational research. Most recently, Diagnostic Classification Models (DCMs) have been used to track skill acquisition in a longitudinal fashion, with the purpose to provide an estimate of students' learning trajectories in terms of the change of fine-grained skills overtime. Response time…

  4. Effect of cellular therapy in progression of Becker’s muscular dystrophy: a case study

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2016-03-01

    Full Text Available Becker muscular dystrophy (BMD is an inherited disorder due to deletions of the dystrophin gene that leads to muscle weakness. Effects of bone marrow mononuclear cell (BMMNC transplantation in Muscular Dystrophy have shown to be safe and beneficial. We treated a 20-year-old male suffering from BMD with autologous BMMNC transplantation followed by multidisciplinary rehabilitation. He presented with muscle weakness and had difficulty in performing his activities. The BMMNCs were transplanted via intrathecal and intramuscular routes. The effects were measured on clinical and functional changes. Over 9 months, gradual improvement was noticed in muscle strength, respiratory functions and North Star Ambulatory Assessment Scale. Functional Independence Measure, Berg Balance Score, Brooke and Vignos Scale remained stable indicating halting of the progression. The case report suggests that cellular therapy combined with rehabilitation may have possibility of repairing and regenerating muscle fibers and decreasing the rate of progression of BMD.

  5. Cutaneous progressive angiomatosis on the muzzle of a dog, treated by laser photocoagulation therapy.

    Science.gov (United States)

    Olivieri, Lara; Nardini, Giordano; Pengo, Graziano; Abramo, Francesca

    2010-10-01

    A 10-year old, female, cocker spaniel was presented with a bleeding lesion on the muzzle and nasal planum observed initially as a small raised nodule at 1 year of age. This became clinically more pronounced at 5 years of age, progressively enlarged thereafter and was diagnosed initially as a vascular tumour. On clinical examination, multiple confluent nodules of variable diameter (0.5-1.5 cm) deformed the outline of the nose. Histological examination revealed a progressive angiomatosis with multifocal infiltrative growth of increased dermal vascularization with different sized and type of anastomosing vessels lined by a monolayer of reactive endothelium, often arranged as papillary projections into the lumina. Partial nosectomy, the first therapeutic approach, was unsuccessful and the lesion relapsed within 6 months. However, subsequent laser photocoagulation therapy provided a good cosmetic outcome, no relapse 1 year later, and appeared to provide an effective alternative to ablation surgery. © 2010 The Authors. Journal compilation © 2010 ESVD and ACVD.

  6. 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

  7. Progress and challenges in the development of a cell-based therapy for hemophilia A.

    Science.gov (United States)

    Fomin, M E; Togarrati, P P; Muench, M O

    2014-12-01

    Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review, we discuss the possibilities, progress, and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific induced pluripotent stem cells. © 2014 International Society on Thrombosis and Haemostasis.

  8. Progress and challenges in the development of a cell-based therapy for hemophilia A

    Science.gov (United States)

    Fomin, Marina E.; Togarrati, Padma Priya; Muench, Marcus O.

    2015-01-01

    Hemophilia A results from an insufficiency of factor VIII (FVIII). Although replacement therapy with plasma-derived or recombinant FVIII is a life-saving therapy for hemophilia A patients, such therapy is a life-long treatment rather than a cure for the disease. In this review we discuss the possibilities, progress and challenges that remain in the development of a cell-based cure for hemophilia A. The success of cell therapy depends on the type and availability of donor cells, the age of the host and method of transplantation, and the levels of engraftment and production of FVIII by the graft. Early therapy, possibly even prenatal transplantation, may yield the highest levels of engraftment by avoiding immunological rejection of the graft. Potential cell sources of FVIII include a specialized subset of endothelial cells known as liver sinusoidal endothelial cells (LSECs) present in the adult and fetal liver, or patient-specific endothelial cells derived from induced pluripotent stem cells (iPSCs) that have undergone gene editing to produce FVIII. Achieving sufficient engraftment of transplanted LSECs is one of the obstacles to successful cell therapy for hemophilia A. We discuss recent results from transplants performed in animals that show production of functional and clinically relevant levels of FVIII obtained from donor LSECs. Hence, the possibility of treating hemophilia A can be envisioned through persistent production of FVIII from transplanted donor cells derived from a number of potential cell sources or through creation of donor endothelial cells from patient-specific iPSCs. PMID:25297648

  9. The Preclinical Research Progress of Stem Cells Therapy in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-01-01

    Full Text Available Parkinson’s disease (PD is a type of degenerative disorder of the basal ganglia, causing tremor at rest, muscle rigidity hypokinesia, and dementia. The effectiveness of drug treatments gradually diminishes because the conversion to dopamine within the brain is increasingly disrupted by the progressive degeneration of the dopaminergic terminals. After long-term treatment, most patients with PD suffer from disability that cannot be satisfactorily controlled. To solve these issues, stem cells have recently been used for cell therapy of PD. In this review, the characteristics of different stem cells and their therapeutic effects on PD treatment will be discussed.

  10. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  11. The role and progress of interventional therapy in the prevention and treatment of postoperative hepatocellular carcinoma recurrence

    International Nuclear Information System (INIS)

    Xiao Yunping; Xiao Enhua

    2008-01-01

    The articles concerning intensive effect and progress of interventional therapy for hepatocellular carcinoma (HCC) recurrence were comprehensively reviewed. Along with unceasing abundance of all interventional methods (including transcatheter arterial chemoemblization (TACE), percutaneous dehydrated ethanol injection, radio frequency ablation, percutaneous microwave therapy, argon-helium cryoablation, high-intensity focused ultrasound and radionuclide interventional therapy, etc), combined interventional therapies mainly TACE were increasingly appreciated in postoperative HCC recurrence, but still have to be further standardized. With further emerging and maturing of new technologies, such as antiangiogenesis, gene therapy and targeted therapy on HCC metastatic and recurrence specific cycle; the effect of combined therapy will be further promoted. Interventional therapy will play an important role in the prevention and treatment of postoperative HCC recurrence in the foreseen furture. (authors)

  12. Immune Profiles to Predict Response to Desensitization Therapy in Highly HLA-Sensitized Kidney Transplant Candidates.

    Science.gov (United States)

    Yabu, Julie M; Siebert, Janet C; Maecker, Holden T

    2016-01-01

    Kidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy. Measuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize

  13. Overview of the MGH-Northeast Proton Therapy Center plans and progress

    International Nuclear Information System (INIS)

    Flanz, J.; Durlacher, S.; Goitein, M.; Levine, A.; Reardon, P.; Smith, A.

    1995-01-01

    The Northeast Proton Therapy Center (NPTC) is currently being designed and is scheduled for completion in 1998. The goal of the project is to provide the northeast region of the United States with a first class proton therapy facility which has the capabilities needed for the conduct of innovative research, and proven treatments using proton therapy. The NPTC will be built on the Massachusetts General Hospital (MGH) campus. MGH has contracted Bechtel Corporation to coordinate the design and building of the civil construction. Ion Beam Applications (IBA) who is teamed with General Atomics, is responsible for the equipment. The specifications for the facility are written in terms of the clinical performance requirements and will be presented. Aspects of the facility design, status and plans will also be presented. (orig.)

  14. Progress of stem/progenitor cell-based therapy for retinal degeneration.

    Science.gov (United States)

    Tang, Zhimin; Zhang, Yi; Wang, Yuyao; Zhang, Dandan; Shen, Bingqiao; Luo, Min; Gu, Ping

    2017-05-10

    Retinal degeneration (RD), such as age-related macular degeneration (AMD) and retinitis pigmentosa, is one of the leading causes of blindness. Presently, no satisfactory therapeutic options are available for these diseases principally because the retina and retinal pigmented epithelium (RPE) do not regenerate, although wet AMD can be prevented from further progression by anti-vascular endothelial growth factor therapy. Nevertheless, stem/progenitor cell approaches exhibit enormous potential for RD treatment using strategies mainly aimed at the rescue and replacement of photoreceptors and RPE. The sources of stem/progenitor cells are classified into two broad categories in this review, which are (1) ocular-derived progenitor cells, such as retinal progenitor cells, and (2) non-ocular-derived stem cells, including embryonic stem cells, induced pluripotent stem cells, and mesenchymal stromal cells. Here, we discuss in detail the progress in the study of four predominant stem/progenitor cell types used in animal models of RD. A short overview of clinical trials involving the stem/progenitor cells is also presented. Currently, stem/progenitor cell therapies for RD still have some drawbacks such as inhibited proliferation and/or differentiation in vitro (with the exception of the RPE) and limited long-term survival and function of grafts in vivo. Despite these challenges, stem/progenitor cells represent the most promising strategy for RD treatment in the near future.

  15. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Directory of Open Access Journals (Sweden)

    Glen J Weiss

    Full Text Available Small cell lung cancer (SCLC that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50% received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration. The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  16. A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy.

    Science.gov (United States)

    Weiss, Glen J; Byron, Sara A; Aldrich, Jessica; Sangal, Ashish; Barilla, Heather; Kiefer, Jeffrey A; Carpten, John D; Craig, David W; Whitsett, Timothy G

    2017-01-01

    Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients. Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by MLH1 alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated. Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.

  17. Alanine EPR dosimeter response in proton therapy beams

    International Nuclear Information System (INIS)

    Gall, K.; Serago, C.; Desrosiers, M.; Bensen, D.

    1997-01-01

    We report a series of measurements directed to assess the suitability of alanine as a mailable dosimeter for dosimetry quality assurance of proton radiation therapy beams. These measurements include dose-response of alanine at 140 MeV, and comparison of response vs energy with a parallel plate ionization chamber. All irradiations were made at the Harvard Cyclotron Laboratory, and the dosimeters were read at NIST. The results encourage us that alanine could be expected to serve as a mailable dosimeter with systematic error due to differential energy response no greater than 3% when doses of 25 Gy are used. (Author)

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

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2013-01-01

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

  19. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

    Science.gov (United States)

    Mora, Ana L.; Rojas, Mauricio; Pardo, Annie; Selman, Moises

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. PMID:29081515

  20. Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy

    DEFF Research Database (Denmark)

    Mikkelsen, Marta Kramer; Thomsen, Frederik Birkebæk; Berg, Kasper Drimer

    2017-01-01

    between statin use and risk of progression, HR 0.98 (95% CI: 0.72-1.32). In competing risk analyses the 5-year cumulative incidence of progression was 55% (95% CI: 46-64%) for statin users and 62% (95% CI: 57-67%) for non-statin users, p = 0.11. CONCLUSION: In the current study, statin use at time of PCa......INTRODUCTION: In several observational studies, statin use has been associated with reduced risk of progression and mortality in men with prostate cancer (PCa). The study aim was to investigate the association between statin use at time of PCa diagnosis and time to PCa progression in men...... with advanced or metastatic PCa receiving androgen deprivation therapy (ADT) as primary treatment. PATIENTS AND METHODS: The study population consisted of all men receiving ADT as primary therapy at two Danish Urological Departments in 2007-2013. The primary outcome was time to progression defined as castration...

  1. Family Policy: The Conservative Challenge and the Progressive Response.

    Science.gov (United States)

    Cherlin, Andrew

    1983-01-01

    Examines the question of how family professionals should respond to the conservative pro-family movement. Argues that the response of liberal family professionals to date--consisting largely of a defense of pluralism--has been inadequate and should concentrate on the most important issues facing families currently. (JAC)

  2. Challenges and progress in predicting biological responses to incorporated radioactivity

    International Nuclear Information System (INIS)

    Howell, R. W.; Neti, P. V. S. V.; Pinto, M.; Gerashchenko, B. I.; Narra, V. R.; Azzam, E. I.

    2006-01-01

    Prediction of risks and therapeutic outcome in nuclear medicine largely rely on calculation of the absorbed dose. Absorbed dose specification is complex due to the wide variety of radiations emitted, non-uniform activity distribution, biokinetics, etc. Conventional organ absorbed dose estimates assumed that radioactivity is distributed uniformly throughout the organ. However, there have been dramatic improvements in dosimetry models that reflect the substructure of organs as well as tissue elements within them. These models rely on improved nuclear medicine imaging capabilities that facilitate determination of activity within voxels that represent tissue elements of ∼0.2-1 cm 3 . However, even these improved approaches assume that all cells within the tissue element receive the same dose. The tissue element may be comprised of a variety of cells having different radiosensitivities and different incorporated radioactivity. Furthermore, the extent to which non-uniform distributions of radioactivity within a small tissue element impact the absorbed dose distribution is strongly dependent on the number, type, and energy of the radiations emitted by the radionuclide. It is also necessary to know whether the dose to a given cell arises from radioactive decays within itself (self-dose) or decays in surrounding cells (cross-dose). Cellular response to self-dose can be considerably different than its response to cross-dose from the same radiopharmaceutical. Bystander effects can also play a role in the response. Evidence shows that even under conditions of 'uniform' distribution of radioactivity, a combination of organ dosimetry, voxel dosimetry and dosimetry at the cellular and multicellular levels can be required to predict response. (authors)

  3. Systems responses to progressive water stress in durum wheat.

    Directory of Open Access Journals (Sweden)

    Dimah Z Habash

    Full Text Available Durum wheat is susceptible to terminal drought which can greatly decrease grain yield. Breeding to improve crop yield is hampered by inadequate knowledge of how the physiological and metabolic changes caused by drought are related to gene expression. To gain better insight into mechanisms defining resistance to water stress we studied the physiological and transcriptome responses of three durum breeding lines varying for yield stability under drought. Parents of a mapping population (Lahn x Cham1 and a recombinant inbred line (RIL2219 showed lowered flag leaf relative water content, water potential and photosynthesis when subjected to controlled water stress time transient experiments over a six-day period. RIL2219 lost less water and showed constitutively higher stomatal conductance, photosynthesis, transpiration, abscisic acid content and enhanced osmotic adjustment at equivalent leaf water compared to parents, thus defining a physiological strategy for high yield stability under water stress. Parallel analysis of the flag leaf transcriptome under stress uncovered global trends of early changes in regulatory pathways, reconfiguration of primary and secondary metabolism and lowered expression of transcripts in photosynthesis in all three lines. Differences in the number of genes, magnitude and profile of their expression response were also established amongst the lines with a high number belonging to regulatory pathways. In addition, we documented a large number of genes showing constitutive differences in leaf transcript expression between the genotypes at control non-stress conditions. Principal Coordinates Analysis uncovered a high level of structure in the transcriptome response to water stress in each wheat line suggesting genome-wide co-ordination of transcription. Utilising a systems-based approach of analysing the integrated wheat's response to water stress, in terms of biological robustness theory, the findings suggest that each durum

  4. Study Progress of Physiological Responses in High Temperature Environment

    Science.gov (United States)

    Li, K.; Zheng, G. Z.; Bu, W. T.; Wang, Y. J.; Lu, Y. Z.

    2017-10-01

    Certain workers are exposed to high temperatures for a long time. Heat stress will result in a series of physiological responses, and cause adverse effects on the health and safety of workers. This paper summarizes the physiological changes of cardiovascular system, core temperature, skin temperature, water-electrolyte metabolism, alimentary system, neuroendocrine system, reaction time and thermal fatigue in high temperature environments. It can provide a theoretical guidance for labor safety in high temperature environment.

  5. Progress in study of a medical reactor for boron neutron capture therapy

    International Nuclear Information System (INIS)

    Sasaki, Makoto; Hirota, Jitsuya; Tamao, Shigeo; Kanda, Keiji; Mishima, Yutaka.

    1993-01-01

    A design study of a medical reactor for Boron Neutron Capture Therapy has made progress. Main specifications of the reactor are as follows; thermal power of 2 MW, water cooling by natural convection, semitight core of hexagonal lattice, UO 2 fuel rod of 9.5 mm diameter and no refueling in the reactor-life. Three horizontal and one vertical neutron beam holes are to be provided for simultaneous treatments by thermal and epithermal neutrons and for further biomedical research. The design objectives for the beam holes are to deliver the therapeutic doses in a modest time (30 to 60 min) with minimal fast neutron and gamma contaminants. The n-γ coupling Sn transport calculations have been carried out using n-21 and γ-9 group cross sections on 2-dim. practical models. The calculated results indicate that the design objectives will be achievable even if the thermal power of the reactor is reduced to 1 MW. (author)

  6. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    Science.gov (United States)

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

  7. [Immune response in therapy with allergens and allergoids].

    Science.gov (United States)

    Kalveram, C M; Kalveram, K J; Kästner, H; Forck, G

    1986-02-01

    We report on the patterns of specific IgE, IgG, and IgA antibodies during different kinds of hyposensitization. Whereas sIgE antibodies may even be influenced by environmental stimulants, the production of sIgG antibodies depends on the amount of antigens injected for therapy. There is some evidence that patients who do not reveal sIgG response have increased sIgA antibody titers, instead.

  8. Molecular Mechanisms of Disease Progression in Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type during Ibrutinib Therapy

    Directory of Open Access Journals (Sweden)

    Lucy C. Fox

    2018-06-01

    Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is one of the well-recognized extranodal lymphomas commonly addicted to the B-cell receptor-MYD88 superpathway. We aimed to describe the genomic changes in a patient who progressed through treatment with ibrutinib, a Bruton’s tyrosine kinase (BTK inhibitor. An 80-year-old woman presented with multiply relapsed PCDLBCL-LT after multiple lines of chemoimmunotherapy and radiotherapy. Pre-treatment testing of the localized cutaneous tumor lesion on a lymphoid amplicon panel demonstrated an MYD88 p.L265P mutation. Ibrutinib therapy was subsequently commenced, resulting in complete resolution of the skin disease. Despite an ongoing skin response, the patient developed progressive nodal disease at two months. Genomic analysis of the cutaneous tumor sample at baseline was compared to that of the inguinal lymph node upon progression, and revealed the acquisition of multiple genomic changes. These included several aberrations expected to bypass BTK inhibition, including two CARD11-activating mutations, and a deleterious mutation in the nuclear factor kappa B (NF-κB negative regulator, NFKBIE. In addition, an IgH-IRF8 translocation was detected (which brings the IRF8 transcription factor under control of the immunoglobulin heavy chain locus, representing a third plausible mechanism contributing to ibrutinib resistance. Several copy-number changes occurred in both samples, including an amplification of 18q, which encodes the anti-apoptotic protein BCL2. We describe the first case of novel genomic changes of PCDLBCL-LT that occurred while on ibrutinib, providing important mechanistic insights into both pathogenesis and drug resistance.

  9. Locoregional Tumor Progression After Radiation Therapy Influences Overall Survival in Pediatric Patients With Neuroblastoma

    International Nuclear Information System (INIS)

    Pai Panandiker, Atmaram S.; McGregor, Lisa; Krasin, Matthew J.; Wu Shengjie; Xiong Xiaoping; Merchant, Thomas E.

    2010-01-01

    Purpose: There is renewed attention to primary site irradiation and local control for patients with high-risk neuroblastoma (NB). We conducted a retrospective review to identify factors that might predict for locoregional tumor control and its impact on overall survival. Methods and Materials: Between July 2000 through August 2006, a total of 44 pediatric patients with NB received radiation therapy (RT) with curative intent using computed tomography (CT)-based treatment planning. The median age was 3.4 years and the median cumulative dose was 23.4 Gy. Overall survival and locoregional tumor control were measured from the start of RT to the date of death or event as determined by CT/magnetic resonance imaging/meta-iodobenzylguanidine. The influence of age at irradiation, gender, race, cumulative radiation dose, International Neuroblastoma Staging System stage, treatment protocol and resection status was determined with respect to locoregional tumor control. Results: With a median follow-up of 34 months ± 21 months, locoregional tumor progression was observed in 11 (25%) and was evenly divided between primary site and adjacent nodal/visceral site failure. The influence of locoregional control reached borderline statistical significance (p = 0.06). Age (p = 0.5), dose (p = 0.6), resection status (p = 0.7), and International Neuroblastoma Staging System stage (p = 0.08) did not influence overall survival. Conclusions: Overall survival in high-risk neuroblastoma is influenced by locoregional tumor control. Despite CT-based planning, progression in adjacent nodal/visceral sites appears to be common; this requires further investigation regarding target volume definitions, dose, and the effects of systemic therapy.

  10. A model for predicting lung cancer response to therapy

    International Nuclear Information System (INIS)

    Seibert, Rebecca M.; Ramsey, Chester R.; Hines, J. Wesley; Kupelian, Patrick A.; Langen, Katja M.; Meeks, Sanford L.; Scaperoth, Daniel D.

    2007-01-01

    Purpose: Volumetric computed tomography (CT) images acquired by image-guided radiation therapy (IGRT) systems can be used to measure tumor response over the course of treatment. Predictive adaptive therapy is a novel treatment technique that uses volumetric IGRT data to actively predict the future tumor response to therapy during the first few weeks of IGRT treatment. The goal of this study was to develop and test a model for predicting lung tumor response during IGRT treatment using serial megavoltage CT (MVCT). Methods and Materials: Tumor responses were measured for 20 lung cancer lesions in 17 patients that were imaged and treated with helical tomotherapy with doses ranging from 2.0 to 2.5 Gy per fraction. Five patients were treated with concurrent chemotherapy, and 1 patient was treated with neoadjuvant chemotherapy. Tumor response to treatment was retrospectively measured by contouring 480 serial MVCT images acquired before treatment. A nonparametric, memory-based locally weight regression (LWR) model was developed for predicting tumor response using the retrospective tumor response data. This model predicts future tumor volumes and the associated confidence intervals based on limited observations during the first 2 weeks of treatment. The predictive accuracy of the model was tested using a leave-one-out cross-validation technique with the measured tumor responses. Results: The predictive algorithm was used to compare predicted verse-measured tumor volume response for all 20 lesions. The average error for the predictions of the final tumor volume was 12%, with the true volumes always bounded by the 95% confidence interval. The greatest model uncertainty occurred near the middle of the course of treatment, in which the tumor response relationships were more complex, the model has less information, and the predictors were more varied. The optimal days for measuring the tumor response on the MVCT images were on elapsed Days 1, 2, 5, 9, 11, 12, 17, and 18 during

  11. Assessment of Microbiology Students’ Progress With an Audience Response System

    Directory of Open Access Journals (Sweden)

    M. Ahmad Chaudhry

    2011-09-01

    Full Text Available The development of new approaches to teaching of large lecture courses is needed. Today’s classroom has a wide range of students including high-achieving motivated learners, students struggling to understand basic concepts, and learning-challenged students. Many of these students can be lost in large classes under the shadow of the high-achieving extroverted students who dominate classroom question-and-answer sessions. Measuring a student’s understanding and achievement of content standards becomes difficult until an assessment has been done. To close this gap, an audience response system was introduced in an introductory Principles of Microbiology course. This technology specifically addressed the goal of individualizing instruction to the needs of the students. The evaluation of this project indicated an overall positive impact on student learning.

  12. Assessment of microbiology students' progress with an audience response system.

    Science.gov (United States)

    Chaudhry, M Ahmad

    2011-01-01

    The development of new approaches to teaching of large lecture courses is needed. Today's classroom has a wide range of students including high-achieving motivated learners, students struggling to understand basic concepts, and learning-challenged students. Many of these students can be lost in large classes under the shadow of the high-achieving extroverted students who dominate classroom question-and-answer sessions. Measuring a student's understanding and achievement of content standards becomes difficult until an assessment has been done. To close this gap, an audience response system was introduced in an introductory Principles of Microbiology course. This technology specifically addressed the goal of individualizing instruction to the needs of the students. The evaluation of this project indicated an overall positive impact on student learning.

  13. Gallium-67 scintigraphy for monitoring therapy response and follow-up of paracoccidioidomycosis

    International Nuclear Information System (INIS)

    Yamaga, L.Y.; Watanabe, T.; Hironaka, F.; Buchpiguel, C.; Cerri, G.; Benard, G.; Shikanai-Yasuda, M.A.

    2002-01-01

    Objectives: The current tools to evaluate patients' therapy response in paracoccidioidomycosis (PCM) are based on clinical, immunological and radiological data. However, these criteria may be of limited value in the follow-up of asymptomatic lesions, negative pre-treatment serological tests and in severe pulmonary involvement whose chest radiography usually doesn't differentiate active from fibrotic lesions. The purpose of this study was to determine the value of Ga imaging for monitoring therapy response and follow-up of PCM patients. Methods: We studied 45 patients with confirmed PCM. Each patient underwent 2 to 7 Ga scintigraphies (total:147 scans) during a follow-up period of 4 months to 8,5 years. The Ga findings were compared to the clinical outcome and serum specific antibody levels. Results: Most patients showed improvement in the sequential Ga scans during the treatment with progressive decrease in number and intensity of sites with active infectious process. Ga scan was performed in nine patients with clinical cure and negative or persistently low levels of serum antibody following prolonged treatment. The scintigraphy confirmed the absence of inflammatory disease in all of these cases. Three patients with clinically suspected recurrence after irregular treatment showed positive Ga scans, confirming disease reactivation. Conclusion: Ga imaging is helpful in monitoring therapy response of PCM patients. Moreover, this method may be used to evaluate disease activity by confirming apparent cure and clinical recurrence

  14. Therapy of chronic hepatitis C: Virologic response monitoring

    Directory of Open Access Journals (Sweden)

    Kuljić-Kapulica Nada

    2010-01-01

    Full Text Available Background/Aim. Virological testing is considered to be essential in the management of hepatitis C virus (HCV infection in order to diagnose infection, and, most importantly, as a quide for treatment decisions and assess the virological response to antiviral therapy. The aim of this study was to determine the rate of a sustained virological response (SVR and various factors associated with response rates in chronic hepatitis C infected patients treated with pegiinterferon alpha (PEGINF and ribavirin (RBV combination therapy. Methods. A total of 34 patients, treated with PEG-IFN and RBV were studied. Serum HCV-RNA was measured before the treatment, 12 weeks following the start of the therapy and 6 weeks after the treatment cessation. SVR was defined as undetectable serum HCV-RNA 6 months of post-treatment follow-up, virologic relapse (VR as relapse of HCV-RNA during the post-treatment follow-up. Serum HCV-RNA was measured with the Cobas Amplicor test. Results. At the end of post-treatment follow-up 19 (55.8% patients demonstrated a SVR. The majority of the patients were genotype 1 (27, and the other were genotype 3 (5 patients and genotype 4 (2 patients. There was VR in 6 patients 6 months after the therapy. In 9 patients HCV-RNA was positive after 12 weeks. Conclusion. We demonstrated that patients with chronic HCV infection can be successfully treated with combination of PEG-INF and RBV. This result emphasizes also that post-treatment follow-up to identify patients with SVR or VR could be important.

  15. Molecular events basic to cellular radiation response. Progress report

    International Nuclear Information System (INIS)

    Kolodny, G.M.

    1974-01-01

    Work during the past year has been focused on three areas related to the cellular effects of radiation. Radiation effects on RNA and the regulation of gene expression and amino acid-nucleic acid interactions were studied. Studies on the radiation response of RNA in growing and confluent cells were continued. We have derived radiation survival curves and demonstrated repair of potentially lethal damage in 3T3 cells. Studies of giant cell formation and turnover of ribosomal RNA in irradiated cells has demonstrated differences in growing and confluent cells. We have sought evidence consistent with our hypothesis for regulation of eukaryotic gene expression with segments of RNA reutilized to prime new RNA synthesis. Data derived from the turnover of ribosomal RNA and the methylation pattern of ribosomal RNA during turnover are consistent with the possibility that a segment of 18s ribosomal RNA is being conserved during new RNA synthesis. We were unable to show reutilization of the 5' trinucleotide of 18s and 28s ribosomal RNA but did find a ribonuclease resistant oligonucleotide in 18s RNA which appeared to be reutilized. In studies of amino acid nucleic-acid interactions using nuclear magnetic resonance spectroscopy we have been able to successfully synthesize an amidate and begin an examination of the intramolecular interactions. We have also studied intermolecular interactions betweentryptophan and nucleoside monophosphates and found upfield shifts which provide evidence for preferential stacking of the 6-membered ring of tryptophan with adenine and evidence for specific geometry of interactions of tryptophan with cytosine. (U.S.)

  16. Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.

    Science.gov (United States)

    Loibl, Sibylle; Turner, Nicholas C; Ro, Jungsil; Cristofanilli, Massimo; Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Loi, Sherene; André, Fabrice; Harbeck, Nadia; Verma, Sunil; Folkerd, Elizabeth; Puyana Theall, Kathy; Hoffman, Justin; Zhang, Ke; Bartlett, Cynthia Huang; Dowsett, Mitchell

    2017-09-01

    study to include premenopausal women in a trial investigating a CDK4/6 inhibitor combined with endocrine therapy, has the largest premenopausal cohort reported in an endocrine-resistant setting. In pretreated premenopausal women with hormone receptor-positive advanced breast cancer, palbociclib plus fulvestrant and goserelin (luteinizing hormone-releasing hormone [LHRH] agonist) treatment almost doubled median progression-free survival (PFS) and significantly increased the objective response rate versus endocrine monotherapy, achieving results comparable to those reported for chemotherapy without apparently interfering with LHRH agonist-induced ovarian suppression. The significant PFS gain and tolerable safety profile strongly support use of this regimen in premenopausal women with endocrine-resistant disease who could possibly delay chemotherapy. © AlphaMed Press 2017.

  17. Optimal dose-response relationships in voice therapy.

    Science.gov (United States)

    Roy, Nelson

    2012-10-01

    Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".

  18. Childhood asthma clusters and response to therapy in clinical trials.

    Science.gov (United States)

    Chang, Timothy S; Lemanske, Robert F; Mauger, David T; Fitzpatrick, Anne M; Sorkness, Christine A; Szefler, Stanley J; Gangnon, Ronald E; Page, C David; Jackson, Daniel J

    2014-02-01

    Childhood asthma clusters, or subclasses, have been developed by computational methods without evaluation of clinical utility. To replicate and determine whether childhood asthma clusters previously identified computationally in the Severe Asthma Research Program (SARP) are associated with treatment responses in Childhood Asthma Research and Education (CARE) Network clinical trials. A cluster assignment model was determined by using SARP participant data. A total of 611 participants 6 to 18 years old from 3 CARE trials were assigned to SARP pediatric clusters. Primary and secondary outcomes were analyzed by cluster in each trial. CARE participants were assigned to SARP clusters with high accuracy. Baseline characteristics were similar between SARP and CARE children of the same cluster. Treatment response in CARE trials was generally similar across clusters. However, with the caveat of a smaller sample size, children in the early-onset/severe-lung function cluster had best response with fluticasone/salmeterol (64% vs 23% 2.5× fluticasone and 13% fluticasone/montelukast in the Best ADd-on Therapy Giving Effective Responses trial; P = .011) and children in the early-onset/comorbidity cluster had the least clinical efficacy to treatments (eg, -0.076% change in FEV1 in the Characterizing Response to Leukotriene Receptor Antagonist and Inhaled Corticosteroid trial). In this study, we replicated SARP pediatric asthma clusters by using a separate, large clinical trials network. Early-onset/severe-lung function and early-onset/comorbidity clusters were associated with differential and limited response to therapy, respectively. Further prospective study of therapeutic response by cluster could provide new insights into childhood asthma treatment. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  19. Theory and Practice of Positive Feminist Therapy: A Culturally Responsive Approach to Divorce Therapy with Chinese Women

    Science.gov (United States)

    Tzou, Jean Yuh-Jin; Kim, Eunha; Waldheim, Kim

    2012-01-01

    Positive Feminist Therapy (PFT) is a strength-based culturally responsive therapy model specifically designed for helping Chinese women facing marital conflicts and divorce, integrating Empowerment Feminist Therapy, systems theory, and positive psychology. To help clients become change agents, PFT uses clients' existing strengths to develop…

  20. The effect of conditional probability of chord progression on brain response: an MEG study.

    Directory of Open Access Journals (Sweden)

    Seung-Goo Kim

    Full Text Available BACKGROUND: Recent electrophysiological and neuroimaging studies have explored how and where musical syntax in Western music is processed in the human brain. An inappropriate chord progression elicits an event-related potential (ERP component called an early right anterior negativity (ERAN or simply an early anterior negativity (EAN in an early stage of processing the musical syntax. Though the possible underlying mechanism of the EAN is assumed to be probabilistic learning, the effect of the probability of chord progressions on the EAN response has not been previously explored explicitly. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, the empirical conditional probabilities in a Western music corpus were employed as an approximation of the frequencies in previous exposure of participants. Three types of chord progression were presented to musicians and non-musicians in order to examine the correlation between the probability of chord progression and the neuromagnetic response using magnetoencephalography (MEG. Chord progressions were found to elicit early responses in a negatively correlating fashion with the conditional probability. Observed EANm (as a magnetic counterpart of the EAN component responses were consistent with the previously reported EAN responses in terms of latency and location. The effect of conditional probability interacted with the effect of musical training. In addition, the neural response also correlated with the behavioral measures in the non-musicians. CONCLUSIONS/SIGNIFICANCE: Our study is the first to reveal the correlation between the probability of chord progression and the corresponding neuromagnetic response. The current results suggest that the physiological response is a reflection of the probabilistic representations of the musical syntax. Moreover, the results indicate that the probabilistic representation is related to the musical training as well as the sensitivity of an individual.

  1. The role of stereotactic body radiation therapy in oligometastatic colorectal cancer: Clinical case report of a long-responder patient treated with regorafenib beyond progression.

    Science.gov (United States)

    Roberto, Michela; Falcone, Rosa; Mazzuca, Federica; Archibugi, Livia; Castaldi, Nadia; Botticelli, Andrea; Osti, Mattia Falchetto; Marchetti, Paolo

    2017-12-01

    Regorafenib is the new standard third-line therapy in metastatic colorectal cancer (mCRC). However, the reported 1-year overall survival rate does not exceed 25%. A 55-year-old man affected by mCRC, treated with regorafenib combined with stereotactic body radiotherapy (SBRT), showing a durable response. After 6 months of regorafenib, a PET/CT scan revealed a focal uptake in a solid lung nodule which was treated with SBRT, whereas continuing regorafenib administration. Fourteen months later, the patient had further progression in a parasternal lymph node, but treatment with regorafenib was continued. The regorafenib-associated side effects, such us the hand-foot syndrome, were favorable managed by reducing the dose from 160 to 120 mg/day. Patient-reported outcome was characterized by a progression-free survival of approximately 3 years. in presence of oligometastatic progression, a local SBRT while retaining the same systemic therapy may be a better multidisciplinary approach. Moreover, disease progression is no longer an absolute contraindication for continuing the regorafenib treatment.

  2. Emotional responses to music: towards scientific perspectives on music therapy.

    Science.gov (United States)

    Suda, Miyuki; Morimoto, Kanehisa; Obata, Akiko; Koizumi, Hideaki; Maki, Atsushi

    2008-01-08

    Neurocognitive research has the potential to identify the relevant effects of music therapy. In this study, we examined the effect of music mode (major vs. minor) on stress reduction using optical topography and an endocrinological stress marker. In salivary cortisol levels, we observed that stressful conditions such as mental fatigue (thinking and creating a response) was reduced more by major mode music than by minor mode music. We suggest that music specifically induces an emotional response similar to a pleasant experience or happiness. Moreover, we demonstrated the typical asymmetrical pattern of stress responses in upper temporal cortex areas, and suggested that happiness/sadness emotional processing might be related to stress reduction by music.

  3. Primary intestinal and thoracic lymphangiectasia: a response to antiplasmin therapy.

    Science.gov (United States)

    MacLean, Joanna E; Cohen, Eyal; Weinstein, Michael

    2002-06-01

    Lymphangiectasia is a congenital or acquired disorder characterized by abnormal, dilated lymphatics with a variable age of presentation. We describe a case of lymphangiectasia with intestinal and pulmonary involvement in an adolescent female, who presented with many of the classic features including chylous pleural effusions, lymphopenia, hypogammaglobinemia, and a protein-losing enteropathy. She also presented with recurrent lower gastrointestinal bleeding, which is infrequently described. The patient did not improve with bowel rest and a low-fat medium-chain triglyceride diet and had little improvement with octreotide acetate therapy. However, she had a clinical response to antiplasmin therapy, trans-4-aminothylcyclohexamine carboxylic acid (tranexamic acid) in terms of serum albumin and gastrointestinal bleeding. She continues to have exacerbations of her condition, as well as persistent lymphopenia and chronic pleural effusions.

  4. Vinorelbine-based salvage therapy in HER2-positive metastatic breast cancer patients progressing during trastuzumab-containing regimens: a retrospective study

    Directory of Open Access Journals (Sweden)

    Viale Giuseppe

    2008-07-01

    Full Text Available Abstract Background The vinka-alkaloyd vinorelbine is a potentially valuable treatment in patients with HER2-positive, trastuzumab-resistant advanced breast cancer. We sought to document the clinical activity of vinorelbine-based salvage treatments in this clinical setting. Methods We analyzed a cohort of 424 consecutive women receiving trastuzumab-based therapy for HER2-positive advanced breast cancer. Of these, 299 were identified as progressing during the initial trastuzumab-based treatment, and 77 received vinorelbine-based therapy as first salvage treatment. Central review of pathological specimens revealed that 70 patients had HER2-amplification detected by FISH. For these patients we determined overall response rate (ORR = complete-CR + partial-PR and clinical benefit (CB = CR+PR+ Stable disease lasting at least 6 months, time to progression (TTP and overall survival (OS from the initiation of vinorelbine-based salvage therapy. Results In 60 patients who were evaluable for tumor response, ORR and CB rates were 28% (95% C.I. 18%-41% and 50% (95% C.I. 38%-62%, respectively. Median follow-up from the initiation of salvage therapy was 15 months (range 1–63 months. Median TTP and OS were 7.1 months (95% C.I. 6.6–7.7 months and 21 months (95% C.I. 14.3–27.7 months, respectively. No differences in clinical outcomes were observed according to whether vinorelbine was administered as a single agent or in combination with other cytostatics, or whether trastuzumab was stopped or continued beyond disease progression. Conclusion our findings suggests that vinorelbine-based combinations are active and should be further evaluated in studies conducted in trastuzumab-resistant patients, including those evaluating newer HER2-targeting agents.

  5. Lymphocytic Colitis: Pathologic predictors of response to therapy.

    Science.gov (United States)

    Setia, Namrata; Alpert, Lindsay; van der Sloot, Kimberley Wj; Colussi, Dora; Stewart, Kathleen O; Misdraji, Joseph; Khalili, Hamed; Lauwers, Gregory Y

    2018-02-13

    While the presence of intraepithelial lymphocytosis with surface epithelial damage is a unifying feature of lymphocytic colitis, there are non-classical features that create morphologic heterogeneity between cases. Limited data are available on the significance of these secondary histologic features. Cases of lymphocytic colitis diagnosed between 2002 and 2013 were identified using the Research Patient Data Registry of a tertiary referral center. Diagnostic biopsy slides were reviewed and evaluated for histologic features of lymphocytic colitis. Clinical data including type of therapy and response to treatment were collected. Chi-square (or Fischer's exact test) and logistic regression analysis were used where appropriate. Thirty-two cases of lymphocytic colitis with complete clinical data and slides available for review were identified. The mean age was 56.4 years, and the female-to-male ratio was 3:2. Eleven (11) patients improved with minimal intervention (Group 1), 14 patients responded to steroid therapy (Group 2), and 7 patients responded to mesalamine, bismuth subsalicylate and/or cholestyramine therapy (Group 3). Histologic differences in the characteristics of the subepithelial collagen table (p=0.018), the severity of lamina propria inflammation (p=0.042) and the presence of eosinophil clusters (p=0.016) were seen between groups 2 and 3. Patients in group 1 were more likely to have mild crypt architectural distortion in their biopsies than patients in groups 2 and 3. Lymphocytic colitis is a heterogeneous disease and the evaluation of histologic factors may help identify various subtypes and predict therapy response. Copyright © 2018. Published by Elsevier Inc.

  6. A national multicenter phase 2 study of prostate-specific antigen (PSA) pox virus vaccine with sequential androgen ablation therapy in patients with PSA progression: ECOG 9802.

    Science.gov (United States)

    DiPaola, Robert S; Chen, Yu-Hui; Bubley, Glenn J; Stein, Mark N; Hahn, Noah M; Carducci, Michael A; Lattime, Edmund C; Gulley, James L; Arlen, Philip M; Butterfield, Lisa H; Wilding, George

    2015-09-01

    E9802 was a phase 2 multi-institution study conducted to evaluate the safety and effectiveness of vaccinia and fowlpox prostate-specific antigen (PSA) vaccine (step 1) followed by combination with androgen ablation therapy (step 2) in patients with PSA progression without visible metastasis. To test the hypothesis that vaccine therapy in this early disease setting will be safe and have a biochemical effect that would support future studies of immunotherapy in patients with minimal disease burden. Patients who had PSA progression following local therapy were treated with PROSTVAC-V (vaccinia)/TRICOM on cycle 1 followed by PROSTVAC-F (fowlpox)/TRICOM for subsequent cycles in combination with granulocyte-macrophage colony-stimulating factor (step 1). Androgen ablation was added on progression (step 2). Step 1 primary end points included progression at 6 mo and characterization of change in PSA velocity pretreatment to post-treatment. Step 2 end points included PSA response with combined vaccine and androgen ablation. In step 1, 25 of 40 eligible patients (63%) were progression free at 6 mo after registration (90% confidence interval [CI], 48-75). The median pretreatment PSA velocity was 0.13 log(PSA)/mo, in contrast to median postregistration velocity of 0.09 log(PSA)/mo (p=0.02), which is an increase in median PSA doubling time from 5.3 mo to 7.7 mo. No grade ≥4 treatment-related toxicity was observed. In the 27 patients eligible and treated for step 2, 20 patients achieved a complete response (CR) at 7 mo (CR rate: 74%; 90% CI, 57-87). Although supportive of larger studies in the cooperative group setting, this study is limited by the small number of patients and the absence of a control group as in a phase 3 study. A viral PSA vaccine can be administered safely in the multi-institutional cooperative group setting to patients with minimal disease volume alone and combined with androgen ablation, supporting the feasibility of future phase 3 studies in this

  7. Cell therapy companies make strong progress from October 2012 to March 2013 amid mixed stock market sentiment.

    Science.gov (United States)

    Mason, Chris; Mason, Julian; Culme-Seymour, Emily J; Bonfiglio, Gregory A; Reeve, Brock C

    2013-06-06

    During Q4 2012 and Q1 2013, the cell therapy industry made strong progress in translation and commercialization. Continued development of the companies included in a dedicated stock market index suggests emergence of this industry as a distinct healthcare sector. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Occupational therapy for patients with chronic diseases: CVA, rheumatoid arthritis and progressive diseases of the central nervous system.

    NARCIS (Netherlands)

    Driessen, M.J.; Dekker, J.; Lankhorst, G.; Zee, J. van der

    1997-01-01

    A substantial proportion of the patients treated by occupational therapists have a chronic disease. The aim of this study was to describe the outlines of occupational therapy treatment for three specific groups of chronic diseases: progressive neurological diseases, cerebrovascular accident and

  9. A Canine Audience: The Effect of Animal-Assisted Therapy on Reading Progress among Students Identified with Learning Disabilities

    Science.gov (United States)

    Griess, Julie Omodio

    2010-01-01

    This study explored the use of animal-assisted therapy with students identified with a learning disability and limited reading success. Initially, reading progress was defined as the participants' comprehension rate obtained from an oral Informal Reading Inventory (IRI) passage. The nature of the Informal Reading Inventory requires the…

  10. Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a man with AIDS

    Directory of Open Access Journals (Sweden)

    Yoganathan K

    2012-04-01

    Full Text Available Katie Yoganathan1, David Brown2, Kathir Yoganathan31Cardiff Medical School, Cardiff, Wales, UK; 2Virus Reference Department, Microbiology Services, Health Protection Agency, London, UK; 3Singleton Hospital, Abertawe Bro Morgannwg University Health Board, Swansea, UKAbstract: A 43-year-old Caucasian homosexual man with AIDS presented with blurring of vision, change of personality, and memory loss in March 1999. He had first been admitted 2 months previously for treatment of Pneumocystis jiroveci pneumonia. A magnetic resonance imaging scan on admission showed multiple white matter lesions involving both subcortical cerebral hemispheres and cerebellar regions, with no mass effect or surrounding edema. JC virus was detected by nested polymerase chain reaction in the cerebrospinal fluid. These findings were diagnostic of progressive multifocal leukoencephalopathy (PML. His CD4 count was 34 cells/mL, and his HIV ribonucleic acid level was 800,789 copies/mL. He was treated with a combination antiretroviral therapy. He was last reviewed in October 2011. He was fully independent socially and mentally, but he still had some residual neurologic signs with right-sided homonymous hemianopia and visual agnosia. His HIV ribonucleic acid level was undetectable, and his CD4 count was 574 cells/mm3. Although the median survival of patients with PML was poor before the antiretroviral therapy era, our patient, who is now aged 55 years, is still alive 12 years after the diagnosis. The diagnosis of PML and differential diagnosis of focal neurologic signs in HIV-positive patients are discussed in this case report.Keywords: HIV, focal neurologic signs, cerebral toxoplasmosis, primary brain lymphoma, ischaemic stroke

  11. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Directory of Open Access Journals (Sweden)

    Bruno Scarpellini

    Full Text Available We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR, before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD] was detected.Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  12. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Science.gov (United States)

    Scarpellini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

    2016-01-01

    We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  13. PET/CT for therapy response assessment in lymphoma

    DEFF Research Database (Denmark)

    Hutchings, Martin; Barrington, Sally F

    2009-01-01

    PET with (18)F-FDG is a standard staging procedure for most lymphoma subtypes. Performed during and after therapy for Hodgkin lymphoma (HL) and aggressive non-Hodgkin lymphoma (NHL), (18)F-FDG PET results have a high prognostic value and correlate with survival. (18)F-FDG PET has been incorporated...... into revised response criteria for aggressive lymphomas, and several ongoing trials are under way to investigate the value of treatment adaptation based on early (18)F-FDG PET results for HL and aggressive NHL. There is little evidence to support the use of (18)F-FDG PET for monitoring of the treatment...... of indolent lymphomas and for routine use in the surveillance setting. So that trial results can be compared and translated easily into clinical practice, uniform and evidence-based guidelines for the interpretation and reporting of response monitoring scans are warranted. Because it is still not proven...

  14. PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

    Science.gov (United States)

    Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

    2015-10-01

    To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

  15. Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer.

    Science.gov (United States)

    Janjigian, Yelena Y; Sanchez-Vega, Francisco; Jonsson, Philip; Chatila, Walid K; Hechtman, Jaclyn F; Ku, Geoffrey Y; Riches, Jamie C; Tuvy, Yaelle; Kundra, Ritika; Bouvier, Nancy; Vakiani, Efsevia; Gao, Jianjiong; Heins, Zachary J; Gross, Benjamin E; Kelsen, David P; Zhang, Liying; Strong, Vivian E; Schattner, Mark; Gerdes, Hans; Coit, Daniel G; Bains, Manjit; Stadler, Zsofia K; Rusch, Valerie W; Jones, David R; Molena, Daniela; Shia, Jinru; Robson, Mark E; Capanu, Marinela; Middha, Sumit; Zehir, Ahmet; Hyman, David M; Scaltriti, Maurizio; Ladanyi, Marc; Rosen, Neal; Ilson, David H; Berger, Michael F; Tang, Laura; Taylor, Barry S; Solit, David B; Schultz, Nikolaus

    2018-01-01

    The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability-high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein-Barr virus-positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance. Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49-58. ©2017 AACR. See related commentary by Sundar and Tan, p. 14 See related article by Pectasides et al., p. 37 This article is highlighted in the In This Issue feature, p. 1 . ©2017 American Association for Cancer Research.

  16. Early response to therapy and survival in multiple myeloma.

    Science.gov (United States)

    Schaar, C G; Kluin-Nelemans, J C; le Cessie, S; Franck, P F H; te Marvelde, M C; Wijermans, P W

    2004-04-01

    Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan-prednisone therapy (MP: melphalan 0.25 mg/kg, prednisone 1.0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease (n = 18), immunoglobulin M (IgM)-MM (n = 1) and no immunotyping (n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM.

  17. Adaptive T cell responses induced by oncolytic Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor therapy expanded by dendritic cell and cytokine-induced killer cell adoptive therapy.

    Science.gov (United States)

    Ren, Jun; Gwin, William R; Zhou, Xinna; Wang, Xiaoli; Huang, Hongyan; Jiang, Ni; Zhou, Lei; Agarwal, Pankaj; Hobeika, Amy; Crosby, Erika; Hartman, Zachary C; Morse, Michael A; H Eng, Kevin; Lyerly, H Kim

    2017-01-01

    Purpose : Although local oncolytic viral therapy (OVT) may enhance tumor lysis, antigen release, and adaptive immune responses, systemic antitumor responses post-therapy are limited. Adoptive immunotherapy with autologous dendritic cells (DC) and cytokine-induced killer cells (DC-CIK) synergizes with systemic therapies. We hypothesized that OVT with Herpes Simplex Virus-granulocyte macrophage-colony-stimulating factor (HSV-GM-CSF) would induce adaptive T cell responses that could be expanded systemically with sequential DC-CIK therapy. Patients and Methods : We performed a pilot study of intratumoral HSV-GM-CSF OVT followed by autologous DC-CIK cell therapy. In addition to safety and clinical endpoints, we monitored adaptive T cell responses by quantifying T cell receptor (TCR) populations in pre-oncolytic therapy, post-oncolytic therapy, and after DC-CIK therapy. Results : Nine patients with advanced malignancy were treated with OVT (OrienX010), of whom seven experienced stable disease (SD). Five of the OVT treated patients underwent leukapheresis, generation, and delivery of DC-CIKs, and two had SD, whereas three progressed. T cell receptor sequencing of TCR β sequences one month after OVT therapy demonstrates a dynamic TCR repertoire in response to OVT therapy in the majority of patients with the systematic expansion of multiple T cell clone populations following DC-CIK therapy. This treatment was well tolerated and long-term event free and overall survival was observed in six of the nine patients. Conclusions : Strategies inducing the local activation of tumor-specific immune responses can be combined with adoptive cellular therapies to expand the adaptive T cell responses systemically and further studies are warranted.

  18. Survival in Response to Multimodal Therapy in Anaplastic Thyroid Cancer.

    Science.gov (United States)

    Prasongsook, Naiyarat; Kumar, Aditi; Chintakuntlawar, Ashish V; Foote, Robert L; Kasperbauer, Jan; Molina, Julian; Garces, Yolanda; Ma, Daniel; Wittich, Michelle A Neben; Rubin, Joseph; Richardson, Ronald; Morris, John; Hay, Ian; Fatourechi, Vahab; McIver, Bryan; Ryder, Mabel; Thompson, Geoffrey; Grant, Clive; Richards, Melanie; Sebo, Thomas J; Rivera, Michael; Suman, Vera; Jenkins, Sarah M; Smallridge, Robert C; Bible, Keith C

    2017-12-01

    Historical outcomes in anaplastic thyroid cancer (ATC) have been dismal. To determine whether an initial intensive multimodal therapy (MMT) is associated with improved ATC survival. MMT was offered to all patients with newly diagnosed ATC treated at the Mayo Clinic from 2003 through 2015; MMT vs care with palliative intent (PI) was individualized considering clinical status and patient preferences. Outcomes were retrospectively analyzed by American Joint Committee on Cancer stage and treatments compared with patient cohort data from 1949 through 1999. Forty-eight patients (60% male; median age, 62 years); 18 treated with PI, 30 with MMT. Overall survival (OS) and progression-free survival determined by Kaplan-Meier method. Median OS and 1-year survival for the later cohort were 9 months [95% confidence interval (CI), 4 to 22 months] and 42% (95% CI, 28% to 56%) vs 3 months and 10% for the earlier cohort. Median OS was 21 months compared with 3.9 months in the pooled MMT vs PI groups for the later cohort [hazard ratio (HR), 0.32; P = 0.0006]. Among only patients in the later cohort who had stage IVB disease, median OS was 22.4 vs 4 months (HR, 0.12; 95% CI, 0.03 to 0.44; P = 0.0001), with 68% vs 0% alive at 1 year (MMT vs PI). Among patients with stage IVC cancer, OS did not differ by therapy. MMT appears to convey longer survival in ATC among patients with stage IVA/B disease. Copyright © 2017 Endocrine Society

  19. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids

    Science.gov (United States)

    2008-08-01

    SUBJECT TERMS Cancer therapy by localized immune response, Magneto -rehological Fluids 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...Metastasized Breast Cancer by Localized Therapy utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit Evrensel...2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy utilizing

  20. Progress in Global Surveillance and Response Capacity 10 Years After Severe Acute Respiratory Syndrome

    Centers for Disease Control (CDC) Podcasts

    2013-04-10

    Dr. Mike Miller reads an abridged version of the Emerging Infectious Diseases' synopsis, Progress in Global Surveillance and Response Capacity 10 Years after Severe Acute Respiratory Syndrome.  Created: 4/10/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/11/2013.

  1. The Shortened Raven Standard Progressive Matrices: Item Response Theory-Based Psychometric Analyses and Normative Data

    Science.gov (United States)

    Van der Elst, Wim; Ouwehand, Carolijn; van Rijn, Peter; Lee, Nikki; Van Boxtel, Martin; Jolles, Jelle

    2013-01-01

    The purpose of the present study was to evaluate the psychometric properties of a shortened version of the Raven Standard Progressive Matrices (SPM) under an item response theory framework (the one- and two-parameter logistic models). The shortened Raven SPM was administered to N = 453 cognitively healthy adults aged between 24 and 83 years. The…

  2. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

    Directory of Open Access Journals (Sweden)

    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  3. Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

    Directory of Open Access Journals (Sweden)

    Kikkawa Ryuichi

    2004-12-01

    Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

  4. Dermatomyositis Leading to Necrotizing Vasculitis: A Perfect Response to Applied Therapy.

    Science.gov (United States)

    Akbaryan, Mahmood; Darabi, Farideh; Soltani, Zahra

    2016-12-01

    Dermatomyositis is an idiopathic inflammatory myopathy that cause skin and muscle complications. The ethiology is not understood well yet. Released cytokines including interferon and interleukins are suggested to make inflammatory responses in the skin or muscle. Muscle weakness and skin lesions including heliotrope rash, shawl sign and Gottron's papules are the most common symptoms. A biopsy (muscle or skin) is always the most reliable method for diagnosis. Corticosteroids in association with immunosuppressive agents are used as standard treatment. The patient was a 30 years old woman who got involved with dermatomyositis for 10 years. She has been under therapy with Methotrexate, Prednisolon and Azathioprine until she came to us suffering from progressive skin lesions. Experiments and examinations were normal except the lesions and detected lipoatrophy. Because of immune cells infiltration and observations necrotizing vasculitis was diagnosed. After three month of high dose prednisolon and intravenous cyclophosphamide therapy the lesions vanished remarkable. True and immediate diagnosis gives physicians the chance not only to assess the best treatment but have adequate time to apply the procedure. However shortening the therapy and diminishing morbidity of the disease need more investigations and efforts.

  5. PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Daphne Gschwantler-Kaulich

    Full Text Available Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN. This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS and overall survival (OS with a median follow-up of 60 months.Eighty patients were PTEN positive (69.6% and 35 patients PTEN negative (30.4%. We found a significant association of the expression of PTEN and p53 (p = 0.041, while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018, while there was no significant correlation with PFS or OS.In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.

  6. Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

    Science.gov (United States)

    Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

    2017-01-01

    The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  7. Prediction of response to interferon therapy in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, F; Søndergaard, Helle Bach; Koch-Henriksen, N

    2014-01-01

    OBJECTIVE: Single nucleotide polymorphisms (SNPs) in the genes encoding interferon response factor (IRF)-5, IRF-8 and glypican-5 (GPC5) have been associated with disease activity in multiple sclerosis (MS) patients treated with interferon (IFN)-β. We analysed whether SNPs in the IRF5, IRF8 and GPC5...... genes are associated with clinical disease activity in MS patients beginning de novo treatment with IFN-β. METHODS: The SNPs rs2004640, rs3807306 and rs4728142 in IRF5, rs13333054 and rs17445836 in IRF8 and rs10492503 in GPC5 were genotyped in 575 patients with relapsing-remitting MS followed...... prospectively after the initiation of their first treatment with IFN-β. RESULTS: 62% of patients experienced relapses during the first 2 years of treatment, and 32% had disability progression during the first 5 years of treatment. Patients with a pretreatment annualized relapse rate >1 had an increased risk...

  8. Response to pediatric physical therapy in infants with positional preference and skull deformation

    NARCIS (Netherlands)

    Wijk, R.M. van; Pelsma, M.; Groothuis-Oudshoorn, C.G.; IJzerman, M.J.; Vlimmeren, L.A. van; Boere-Boonekamp, M.M.

    2014-01-01

    BACKGROUND: Pediatric physical therapy seems to reduce skull deformation in infants with positional preference. However, not all infants show improvement. OBJECTIVE: The study objective was to determine which infant and parent characteristics were related to responses to pediatric physical therapy

  9. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  10. Fibromyalgia with severe forms of progression in a multidisciplinary therapy setting with emphasis on hyperthermia therapy – a prospective controlled study

    Directory of Open Access Journals (Sweden)

    Romeyke T

    2014-12-01

    Full Text Available Tobias Romeyke, Hans Christoph Scheuer, Harald Stummer Department of Public Health and Health Technology Assessment, Division for Organizational Behavior Research and Workplace Health Promotion, University for Health Sciences, Medical Informatics and Technology, Vienna, Austria Introduction: Fibromyalgia syndrome (FMS is a multi-factorial disease involving physiological as well as psychological factors. The aim of the study was to investigate a multidisciplinary inpatient treatment with emphasis on hyperthermia therapy by patients with widespread pain.Materials and methods: The study involved 104 patients suffering from severely progressive FMS. A convenience sample and a prospective cohort design were used. The patients were treated in an acute hospital focusing on rheumatologic pain therapy and multidisciplinary complementary medicine. One patient group was treated with inclusion of hyperthermia therapy and the other group without. The therapy density (number of performed therapies per patient was determined for every patient. Functional capacity measured by the Hannover functional status questionnaire (Funktionsfragebogen Hannover and symptoms (von Zerssen complaint list were analyzed for both groups on admission and on discharge.Results: On admission, no significant difference could be established between control group (CG; multimodal without hyperthermia and hyperthermia group (HG; multimodal with hyperthermia (functional capacity, P=0.936. Functional capacity improved for the CG and the HG. On discharge, there was a significant difference between the two groups (functional capacity, P=0.039. There were no significant differences in fibromyalgia symptoms between CG (mean 41.8 and HG (mean 41.8 on their admission to hospital (P=0.988. On discharge, there was a significant difference (P=0.024 between the two groups (HG, mean 30.6; CG, mean 36.6. The inpatient therapy of patients with severely progressive fibromyalgia is characterized by a

  11. [Partial response of solar urticaria to omalizumab therapy].

    Science.gov (United States)

    Kowalzick, L; Thiel, W; C Bielfeld; Ziegler, H; Eickenscheidt, L

    2017-06-01

    The treatment of solar urticaria is regarded as difficult. In some cases good responses to the anti-IgE antibody omalizumab (Xolair®), approved for treatment of chronic spontaneous urticaria, have been reported. We report on a 50-year-old Caucasian woman who for the last 5 years has developed localized itching and stinging erythemas following exposure to sunlight accompanied sometimes by anaphylactic reactions. Oral antihistamines in three- to four-fold doses and a topical sun screen had been only partially effective in long-term use. Positive immediate-type reactions with whealing appeared in phototesting with low doses of UVB and UVA. Three weeks after s. c. injection of 300 mg omalizumab, the minimal urticarial dose (MUD) for UVB was increased at least 20-fold (from omalizumab administration to 14 points in weeks two and three. Overall, a partial response of solar urticaria to omalizumab therapy could be observed in the present case.

  12. The Impact of Combination Therapy with a-Blockers and 5ARIs on the Progression of BPH.

    Science.gov (United States)

    Sountoulides, Petros; Gravas, Stavros

    2015-01-01

    Benign prostatic hyperplasia (BPH) can be a progressive disease for some men with significant impact on their quality of life due to worsening of symptoms, risk of acute urinary retention (AUR) and surgery. Certain clinical parameters such as age, prostate volume and PSA are able to predict those patients with BPH-associated LUTS that are at risk of disease progression. These patients will likely benefit most from medical therapy that provides symptom relief while at the same time may prevent disease progression. Studies have shown that a-blockers, although able to rapidly alleviate symptoms, have no effect on prostate volume, risk for AUR and BPH-related surgery. On the other hand 5ARIs have proven their efficacy in reducing prostate size, the risk of AUR and prostate surgery. Therefore combination therapy with an a-blocker and a 5ARI can be the mainstay of treatment for those patients at risk of BPH progression. Patients' perspective and their needs and expectations from treatment are other crucial parameters to consider in order selecting the optimal management of BPH. Therefore physicians should take into consideration the drug properties and also the patients' preferences before deciding on the optimal pharmacological treatment for BPH-associated LUTS.

  13. Longitudinal Changes in Depressive Circuitry in Response to Neuromodulation Therapy

    Directory of Open Access Journals (Sweden)

    Yagna Pathak

    2016-07-01

    Full Text Available Background: Major Depressive Disorder (MDD is a public health problem worldwide. There is increasing interest in using non-invasive therapies such as repetitive transcranial magnetic stimulation (rTMS to treat MDD. However, the changes induced by rTMS on neural circuits remain poorly characterized. The present study aims to test whether the brain regions previously targeted by deep brain stimulation (DBS in the treatment of MDD respond to rTMS, and whether functional connectivity measures can predict clinical response.Methods: rTMS (20 sessions was administered to five MDD patients at the left-dorsolateral prefrontal cortex (L-DLPFC over 4 weeks. Magnetoencephalography (MEG recordings and Montgomery-Asberg Depression Rating Scale (MADRS assessments were acquired before, during and after treatment. Our primary measures, obtained with MEG source imaging, were changes in power spectral density (PSD and changes in functional connectivity as measured using coherence.Results: Of the five patients, four met the clinical response criterion (40% or greater decrease in MADRS after four weeks of treatment. An increase in gamma power at the L-DLPFC was correlated with improvement in symptoms. We also found that increases in delta band connectivity between L-DLPFC/amygdala and L-DLPFC/pregenual anterior cingulate cortex (pACC, and decreases in gamma band connectivity between L-DLPFC/subgenual anterior cingulate cortex (sACC, were correlated with improvements in depressive symptoms. Conclusions: Our results suggest that non-invasive intervention techniques, such as rTMS, modulate the ongoing activity of depressive circuits targeted for DBS, and that MEG can capture these changes. Gamma oscillations may originate from GABA-mediated inhibition, which increases synchronization of large neuronal populations, possibly leading to increased long-range functional connectivity. We postulate that responses to rTMS could provide valuable insights into early evaluation

  14. Applying Item Response Theory methods to design a learning progression-based science assessment

    Science.gov (United States)

    Chen, Jing

    Learning progressions are used to describe how students' understanding of a topic progresses over time and to classify the progress of students into steps or levels. This study applies Item Response Theory (IRT) based methods to investigate how to design learning progression-based science assessments. The research questions of this study are: (1) how to use items in different formats to classify students into levels on the learning progression, (2) how to design a test to give good information about students' progress through the learning progression of a particular construct and (3) what characteristics of test items support their use for assessing students' levels. Data used for this study were collected from 1500 elementary and secondary school students during 2009--2010. The written assessment was developed in several formats such as the Constructed Response (CR) items, Ordered Multiple Choice (OMC) and Multiple True or False (MTF) items. The followings are the main findings from this study. The OMC, MTF and CR items might measure different components of the construct. A single construct explained most of the variance in students' performances. However, additional dimensions in terms of item format can explain certain amount of the variance in student performance. So additional dimensions need to be considered when we want to capture the differences in students' performances on different types of items targeting the understanding of the same underlying progression. Items in each item format need to be improved in certain ways to classify students more accurately into the learning progression levels. This study establishes some general steps that can be followed to design other learning progression-based tests as well. For example, first, the boundaries between levels on the IRT scale can be defined by using the means of the item thresholds across a set of good items. Second, items in multiple formats can be selected to achieve the information criterion at all

  15. Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

    Directory of Open Access Journals (Sweden)

    Southey Bruce R

    2011-06-01

    Full Text Available Abstract Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively or with other cancers (10, 19, and 15 genes, respectively and the rest (16, 4, and 10 genes, respectively are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96% were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations

  16. Response to ovarian stimulation in patients facing gonadotoxic therapy.

    Science.gov (United States)

    Johnson, Lauren N C; Dillon, Katherine E; Sammel, Mary D; Efymow, Brenda L; Mainigi, Monica A; Dokras, Anuja; Gracia, Clarisa R

    2013-04-01

    Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility preservation (FP) were assessed for response to ovarian stimulation. Fifty FP patients facing gonadotoxic therapy were matched by age, race, cycle number, date of stimulation and fertilization method to patients undergoing IVF for infertility or oocyte donation. There were no differences in baseline FSH, anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no differences in numbers of oocytes retrieved, mature oocytes or fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve, response to stimulation and oocyte and embryo yield compared to controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole. With improvement in cancer survival rates, there has been a shift in attention toward management of long-term consequences of cancer therapy, including infertility. Many young women with cancer, particularly those who will be treated with chemotherapy, pursue fertility preservation (FP) strategies for the purpose of banking oocytes or embryos for future use. We examined patients with no prior exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP. Fifty FP patients were identified and matched to healthy controls by age, race, cycle number, date of stimulation and fertilization

  17. High-response hybrid quantum dots- 2D conductor phototransistors: recent progress and perspectives

    Science.gov (United States)

    Sablon, Kimberly A.; Sergeev, Andrei; Najmaei, Sina; Dubey, Madan

    2017-03-01

    Having been inspired by the tremendous progress in material nanoscience and device nanoengineering, hybrid phototransistors combine solution processed colloidal semiconductor quantum dots (QDs) with graphene or two-dimensional (2D) semiconductor materials. Novel detectors demonstrate ultrahigh photoconductive gain, high and selective photoresponse, low noise, and very high responsivity in visible- and near-infrared ranges. The outstanding performance of phototransistors is primarily due to the strong, selective, and size tunable absorption of QDs and fast charge transfer in 2D high mobility conductors. However, the relatively small mobility of QD nanomaterials was a technological barrier, which limited the operating rate of devices. Very recent innovations in detector design and significant progress in QD ligand engineering provide effective tools for further qualitative improvements. This article reviews the recent progress in material science, nanophysics, and device engineering related to hybrid phototransistors. Detectors based on various QD nanomaterials and several 2D conductors are compared, and advantages and disadvantages of various nanomaterials for applications in hybrid phototransistors are identified. We also benchmark the experimental characteristics with model results that establish interrelations and tradeoffs between detector characteristics, such as responsivity, dark and noise currents, the photocarrier lifetime, response, and noise bandwidths. We have shown that the most recent phototransistors demonstrate performance limited by the fundamental generation recombination noise in high gain devices. Interrelation between the dynamic range of the detector and the detector sensitivity is discussed. The review is concluded with a brief discussion of the remaining challenges and possible significant improvements in the performance of hybrid phototransistors.

  18. A comparison of the ventilatory response of sleeping newborn lambs to step and progressive hypoxaemia.

    Science.gov (United States)

    Cohen, G; Malcolm, G; Henderson-Smart, D

    1997-01-01

    1. Slight variations in the rate at which hypoxaemia develops may significantly alter the ventilatory response (VR) elicited. Here we have developed a technique to compare the VRs elicited from sleeping newborn lambs by specific (step versus progressive), short-duration ( or = 9 days (10 +/- 0.3 days) were also compared. There was an upward shift in the position of step and progressive response curves of older lambs, reflecting primarily the increased vigour of the initial hyperpnoea elicited by step (delta Vi at 1 min = +20 +/- 4% at 4 days vs. +40 +/- 11% at 10 days) as well as progressive (delta Vi at 1 min = +6 +/- 2% at 4 days vs. +17 +/- 5% at 10 days) hypoxaemia. 5. Qualitatively different VRs may be elicited from the newborn, depending upon the specific hypoxaemic profile administered. Therefore, to evaluate the significance of VRs elicited in response to classical, steady-state hypoxia at different postnatal ages properly, the stimulus must be accurately described. PMID:9288688

  19. Manipulation of biliary lipids by gene therapy: potential consequences for patients with progressive familial intrahepatic cholestasis

    NARCIS (Netherlands)

    Oude Elferink, Ronald P. J.

    2005-01-01

    Gene therapy constitutes a great promise for the treatment of inherited diseases as well as cancer. Although the principle is extremely elegant, reality proves that several important problems remain to be solved before gene therapy becomes a standard application for these conditions. Meanwhile, and

  20. Cognitive-behavioral therapy as continuation treatment to sustain response after electroconvulsive therapy in depression: a randomized controlled trial.

    Science.gov (United States)

    Brakemeier, Eva-Lotta; Merkl, Angela; Wilbertz, Gregor; Quante, Arnim; Regen, Francesca; Bührsch, Nicole; van Hall, Franziska; Kischkel, Eva; Danker-Hopfe, Heidi; Anghelescu, Ion; Heuser, Isabella; Kathmann, Norbert; Bajbouj, Malek

    2014-08-01

    Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response. In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months. Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm. These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Possible genetic implications in the response to cardiac resynchronisation therapy in a patient affected by heart failure

    Directory of Open Access Journals (Sweden)

    Natalia Pezzali

    2011-06-01

    Full Text Available This report presents a case of a patient with idiopathic dilated cardiomyopathy and severe left ventricular systolic dysfunction who underwent cardiac resynchronisation therapy (CRT. During the follow-up a progressive increase in left ventricular ejection fraction was observed, as well as clinical improvement. No cardiovascular events occurred during the follow-up, except for appropriate Implantable Cardioverter Defibrillator (ICD bursts for fast ventricular tachycardia. Genotyping for adrenoceptor gene polymorphisms detected that the patient was Glu27Glu homozygous carrier. There’s a large interindividual variability in response to CRT. Despite attempts to identify factors having an impact on this therapy, only QRS duration is accepted according to guidelines. Beta-adrenoceptors polymorphisms, modulating sympathetic drive in heart failure and left ventricular remodelling, may have a role in identifying patients with a better response to CRT, in order to target and individualise the patients’ treatment.

  2. Molecular study of the dentin-pulp complex responses to caries progression

    Directory of Open Access Journals (Sweden)

    Yani Corvianindya Rahayu

    2007-03-01

    Full Text Available The dentin-pulp complex exhibits various responses to caries, including events of injury, defense, and repair. The overall responses dependent on pulp cell activity and the signaling processes, which regulate the behavior of these cells. The signals for tissue repair are thought to be mediated by dentin-bound growth factors released during caries progression. Growth factors are a key of molecules responsible for signaling a variety of cellular process following dental injury. The endogenous proteolytic enzymes (Matrix metalloproteinases, MMPs present in dentin matrix might also participate in releasing bioactive molecule. Several members of the MMP family are found in the soft and hard tissue compartment of dentin-pulp complex. Their presumed role in many physiological process during the development and maintenance of the dentin-pulp complex, they may also contribute to the pathogenesis of dentin caries and the responses elicited by caries.

  3. Synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression: analysis of a proof-of-concept randomised clinical trial of cytokine blockade.

    LENUS (Irish Health Repository)

    Rooney, Terence

    2012-02-01

    OBJECTIVES: To evaluate synovial tissue and serum biomarkers of disease activity, therapeutic response and radiographic progression during biological therapy for rheumatoid arthritis (RA). METHODS: Patients with active RA entered a randomised study of anakinra 100 mg\\/day, administered as monotherapy or in combination with pegsunercept 800 microg\\/kg twice a week. Arthroscopic synovial tissue biopsies were obtained at baseline and two further time points. Following immunohistochemical staining, selected mediators of RA pathophysiology were quantified using digital image analysis. Selected mediators were also measured in the serum. RESULTS: Twenty-two patients were randomly assigned: 11 received monotherapy and 11 combination therapy. American College of Rheumatology 20, 50 and 70 response rates were 64%, 64% and 46% with combination therapy and 36%, 9% and 0% with monotherapy, respectively. In synovial tissue, T-cell infiltration, vascularity and transforming growth factor beta (TGFbeta) expression demonstrated significant utility as biomarkers of disease activity and therapeutic response. In serum, interleukin 6 (IL-6), matrix metalloproteinase (MMP) 1, MMP-3 and tissue inhibitor of metalloproteinase 1 (TIMP-1) were most useful in this regard. An early decrease in serum levels of TIMP-1 was predictive of the later therapeutic outcome. Pretreatment tissue levels of T-cell infiltration and the growth factors vascular endothelial growth factor\\/TGFbeta, and serum levels of IL-6, IL-8, MMP-1, TIMP-1, soluble tumour necrosis factor receptor types I and II and IL-18 correlated with radiographic progression. CONCLUSIONS: Synovial tissue analysis identified biomarkers of disease activity, therapeutic response and radiographic progression. Biomarker expression in tissue was independent of the levels measured in the serum.

  4. Current status of gene therapy for breast cancer: progress and challenges

    Directory of Open Access Journals (Sweden)

    McCrudden CM

    2014-11-01

    Full Text Available Cian M McCrudden, Helen O McCarthySchool of Pharmacy, Queen’s University Belfast, Belfast, UKAbstract: Breast cancer is characterized by a series of genetic mutations and is therefore ideally placed for gene therapy intervention. The aim of gene therapy is to deliver a nucleic acid-based drug to either correct or destroy the cells harboring the genetic aberration. More recently, cancer gene therapy has evolved to also encompass delivery of RNA interference technologies, as well as cancer DNA vaccines. However, the bottleneck in creating such nucleic acid pharmaceuticals lies in the delivery. Deliverability of DNA is limited as it is prone to circulating nucleases; therefore, numerous strategies have been employed to aid with biological transport. This review will discuss some of the viral and nonviral approaches to breast cancer gene therapy, and present the findings of clinical trials of these therapies in breast cancer patients. Also detailed are some of the most recent developments in nonviral approaches to targeting in breast cancer gene therapy, including transcriptional control, and the development of recombinant, multifunctional bio-inspired systems. Lastly, DNA vaccines for breast cancer are documented, with comment on requirements for successful pharmaceutical product development.Keywords: breast cancer, gene therapy, nonviral, clinical trial

  5. Clinical Response to Gefitinib Retreatment of Lung Adenocarcinoma Patients Who Benefited from An Initial Gefitinib Therapy: A Retrospective Analysis

    Directory of Open Access Journals (Sweden)

    Junling LI

    2012-01-01

    Full Text Available Background and objective Gefitinib is an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI that has been widely used for the treatment of non-small cell lung cancer (NSCLC. It is most effective in women, as well as in patients who have never smoked, have pulmonary adenocarcinomas, or are of Asian origin. Several treatment options are available for NSCLC patients who responded to initial gefitinib therapy but demonstrated tumor progression, of which gefitinib readministration is the chosen therapeutic option. The present study aims to evaluate the efficacy and toxicity of gefitinib readministration. Methods The clinical data of 18 patients with NSCLC who had shown partial response (PR or achieved a stable disease (SD status after gefitinib administration and were retreated with gefitinib due to failure of the initial therapy were reviewed and retrospectively analyzed. Results Of the 18 patients studied, 1 (6% showed partial remission (PR, 11 (61% achieved SD, and 6 (33% experienced disease progression. The disease control rate was 67%, and the median progression-free survival was 5.16 months (range, 1 to 24.8 months. The median overall survival from the start of the gefitinib therapy was 39.4 months (range, 15.38 to 52.44 months. Moreover, the median overall survival from the beginning of the 2nd therapy was 12.41 months (range, 3.98 to 38.24 months. Mild toxicity was observed with the 2nd gefitinib therapy. Conclusion The results of the present study indicate that patients with NSCLC may still be expected to achieve prolonged survival through gefitinib readministration if they initially responded to gefitinib and underwent various subsequent treatments.

  6. A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

    DEFF Research Database (Denmark)

    Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

    2012-01-01

    The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

  7. Progress in the Full-Text Publication Rate of Orthopaedic and Sport Physical Therapy Abstracts Presented at the American Physical Therapy Association's Combined Sections Meeting.

    Science.gov (United States)

    Warden, Stuart J; Fletcher, Jacquelyn M; Barker, Rick G; Guildenbecher, Elizabeth A; Gorkis, Colleen E; Thompson, William R

    2017-10-07

    Study Design Descriptive study. Background Professional meetings, such as the American Physical Therapy Association's (APTA's) Combined Sections Meeting (CSM), provide forums for sharing information. However, it was reported that only one-quarter of orthopaedic and sports physical therapy abstracts presented at the CSM between 2000 and 2004 went on to full-text publication. This low conversion rate raises a number of concerns regarding the full dissemination of work within the profession. Objectives The purpose of this study was to determine the full-text publication rate of work presented in abstract form at subsequent CSMs and investigate factors influencing the rate. Methods A systematic search was undertaken to locate full-text publications of orthopaedic and sports physical therapy abstracts presented at CSMs between 2005 and 2011. Eligible publications were published within 5 years following abstract presentation. The influences of year of abstract presentation, APTA section, presentation type, institution of origin, study design, and study significance were assessed. Results Over one-third (38.6%) of presented abstracts progressed to full-text publication. Odds of full-text publication increased if the abstract was presented as a platform presentation, originated from a doctorate-granting institution, reported findings of an experimental study, or reported a statistically significant finding. Conclusion The full-text publication rate for orthopaedic and sports physical therapy abstracts presented at recent CSMs has increased by over 50% compared to that reported for the preceding period. The rate is now in the range of that reported in comparable clinical disciplines, demonstrating important progress in the full dissemination of work within the profession. J Orthop Sports Phys Ther, Epub 7 Oct 2017. doi:10.2519/jospt.2018.7581.

  8. P13.10 Intracranial response to nivolumab in NSCLC patients with untreated or progressing CNS metastases

    Science.gov (United States)

    Yust-Katz, S.; Dudnik, E.; Perlov, E.; Zer, A.; Flex, D.; Peled, N.; Siegal, T.

    2016-01-01

    Abstract Background: Central nervous system (CNS) metastases occur in about 30% of patients (pts) with advanced non-small cell lung cancer (NSCLC). Local treatment strategies (e.g., radiotherapy or surgery) result in delays in systemic therapy administration and are frequently associated with neurocognitive impairment. Nivolumab is an anti-PD1 immune check-point inhibitor which has been recently approved by the FDA as a second line treatment of NSCLC. Data regarding its intracranial activity is lacking. Methods: We retrospectively reviewed efficacy and safety of nivolumab administered intravenously at a dose of 3mg/kg q2 weeks in five pts with advanced NSCLC and new or progressing intracranial metastases which were diagnosed before or within 1 month after starting the treatment. Results: Pt baseline characteristics were as follows: median age 78y (range, 52–84); 2 males; 4 smokers; ECOG PS 0/1/2 - 2 pts/1 pt/2 pts; histological subtype: adenocarcinoma/ squamous-cell carcinoma/NSCLC NOS 3 pts /1 pt/1 pt; EGFR WT/ALK neg/KRAS M all/all/2 pts. Four pts had parenchymal brain metastases, three pts had leptomeningeal disease. All pts were asymptomatic and did not require corticosteroids or immediate brain irradiation. Dramatic response in the brain was observed in two pts (including 1 pt with leptomeningeal spread demonstrating a complete response in the CNS); time-to-response comprised 5 weeks and 9 weeks; all responses are still ongoing at the time of the report (18+ weeks, 19+ weeks). In one pt stabilization of leptomeningeal carcinomatosis for 10 weeks was achieved. Systemic responses and intracranial responses were largely concordant. No treatment-related or CNS-metastases related grade ≥ 3 adverse events were observed. Conclusions: Nivolumab has a promising intracranial activity and favorable safety profile in pts with NSCLC and untreated/progressing CNS metastases. Nivolumab CNS activity warrants further evaluation.

  9. Molecular Imaging and Precision Medicine: PET/Computed Tomography and Therapy Response Assessment in Oncology.

    Science.gov (United States)

    Sheikhbahaei, Sara; Mena, Esther; Pattanayak, Puskar; Taghipour, Mehdi; Solnes, Lilja B; Subramaniam, Rathan M

    2017-01-01

    A variety of methods have been developed to assess tumor response to therapy. Standardized qualitative criteria based on 18F-fluoro-deoxyglucose PET/computed tomography have been proposed to evaluate the treatment effectiveness in specific cancers and these allow more accurate therapy response assessment and survival prognostication. Multiple studies have addressed the utility of the volumetric PET biomarkers as prognostic indicators but there is no consensus about the preferred segmentation methodology for these metrics. Heterogeneous intratumoral uptake was proposed as a novel PET metric for therapy response assessment. PET imaging techniques will be used to study the biological behavior of cancers during therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Dynamic microbubble contrast-enhanced US to measure tumor response to targeted therapy: a proposed clinical protocol with results from renal cell carcinoma patients receiving antiangiogenic therapy.

    Science.gov (United States)

    Williams, Ross; Hudson, John M; Lloyd, Brendan A; Sureshkumar, Ahthavan R; Lueck, Gordon; Milot, Laurent; Atri, Mostafa; Bjarnason, Georg A; Burns, Peter N

    2011-08-01

    To develop and implement an evidence-based protocol for characterizing vascular response of renal cell carcinoma (RCC) to targeted therapy by using dynamic contrast material-enhanced (DCE) ultrasonography (US). The study was approved by the institutional research ethics board; written informed consent was obtained from all patients. Seventeen patients (four women; median age, 58 years; range, 42-72 years; 13 men, median age, 62 years; range, 45-81 years) with metastatic RCC were examined by using DCE US before and after 2 weeks of treatment with sunitinib (May 2007 to October 2009). Two contrast agent techniques--bolus injection and disruption-replenishment infusion of microbubbles--were compared. Changes in tumor blood velocity and fractional blood volume were measured with both methods, together with reproducibility and effect of compensation for respiratory motion. Tumor changes were assessed with computed tomography, by using the best response with the Response Evaluation Criteria in Solid Tumors (RECIST) and progression-free survival (PFS). Follow-up RECIST measurements were performed at 6-week intervals until progressive disease was detected. In response to treatment, median tumor fractional blood volume measured with the disruption-replenishment infusion method decreased by 73.2% (interquartile range, 46%-87%) (P protocol is a flexible method suitable for many tumor types, but further studies are needed to assess whether this protocol may be predictive of patient outcome. © RSNA, 2011.

  11. Early pneumothorax as a feature of response to crizotinib therapy in a patient with ALK rearranged lung adenocarcinoma

    International Nuclear Information System (INIS)

    Gennatas, Spyridon; Stanway, Susana J; Thomas, Robert; Min, Toon; Shah, Riyaz; O’Brien, Mary ER; Popat, Sanjay

    2013-01-01

    Single arm phase 1 and 2 studies on Crizotinib in ALK-positive patients so far have shown rapid and durable responses. Spontaneous pneumothoraces as a result of response to anti-cancer therapy are rare in oncology but have been documented in a number of tumour types including lung cancer. This includes cytotoxic chemotherapy as well as molecular targeted agents such as gefitinib and Bevacizumab. These often require chest drain insertion or surgical intervention with associated morbidity and mortality. They have also been associated with response to treatment. This is the first report we are aware of documenting pneumothorax as response to crizotinib therapy. A 48-year-old Caucasian male presented with a Stage IV, TTF1 positive, EGFR wild-type adenocarcinoma of the lung. He received first line chemotherapy with three cycles of cisplatin-pemetrexed chemotherapy with a differential response, and then second-line erlotinib for two months before further radiological evidence of disease progression. Further analysis of his diagnostic specimen identified an ALK rearrangement by fluorescence in situ hybridization (FISH). He was commenced on crizotinib therapy 250 mg orally twice daily. At his 4-week assessment he had a chest radiograph that identified a large left-sided pneumothorax with disease response evident on the right. Chest CT confirmed a 50% left-sided pneumothorax on a background of overall disease response. A chest tube was inserted with complete resolution of the pneumothorax that did not recur following its removal. Our case demonstrates this potential complication of crizotinib therapy and we therefore recommend that pneumothorax be considered in patients on crizotinib presenting with high lung metastatic burden and with worsening dyspnoea

  12. The proton therapy system for MGH's NPTC: equipment description and progress report

    International Nuclear Information System (INIS)

    Jongen, Y.; Beeckman, W.; Cohilis, P.

    1996-01-01

    At the beginning of 1994, the Massachusetts General Hospital (MGH) of the Harvard Medical School in Boston (MA, USA) a pioneer in proton therapy since 1959, selected a team led by Ion Beam Applications SA (IBA) to supply the proton therapy equipment of its new Northeast Proton Therapy Centre (NPTC),. The IBA integrated system includes a compact 235 MeV isochronous cyclotron, a short energy selection transforming the fixed energy beam extracted form the cyclotron into a variable energy beam, one or more isocentric gantries fitted with a nozzle, a system consisting of one or more horizontal beam lines, a global control system including an accelerator control unit and several independent but networked therapy control stations, a global safety management system, and a robotic patient positioning system. The present paper presents the equipment being built for the NPTC. (author)

  13. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    Science.gov (United States)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  15. Importance of Heart Rate During Exercise for Response to Cardiac Resynchronization Therapy

    NARCIS (Netherlands)

    Maass, Alexander H.; Buck, Sandra; Nieuwland, Wybe; Bruegemann, Johan; Van Veldhuisen, Dirk J.; Van Gelder, Isabelle C.

    Background: Cardiac resynchronization therapy (CRT) is an established therapy for patients with severe heart failure and mechanical dyssynchrony. Response is only achieved in 60-70% of patients. Objectives: To study exercise-related factors predicting response to CRT. Methods: We retrospectively

  16. Neurocysticercosis as an important differential of paradoxical response during antituberculosis therapy in HIV-negative patient

    Directory of Open Access Journals (Sweden)

    Rivonirina Andry Rakotoarivelo

    2011-12-01

    Full Text Available Neurocysticercosis can simulate a paradoxical response during antituberculosis therapy with neurological ailments. We report the case of a 31 year-old-man, treated for tuberculous meningitis who developed neurological deficit after nine weeks of early antituberculous therapy. The diagnosis of neurocysticercosis was confirmed by CT scan and cerebrospinal fluid analysis. Neurocysticercosis should be sought as an important differential of paradoxical response during antituberculosis therapy.

  17. Influence of Immune Responses in Gene/Stem Cell Therapies for Muscular Dystrophies

    Directory of Open Access Journals (Sweden)

    Andrea Farini

    2014-01-01

    Full Text Available Muscular dystrophies (MDs are a heterogeneous group of diseases, caused by mutations in different components of sarcolemma, extracellular matrix, or enzymes. Inflammation and innate or adaptive immune response activation are prominent features of MDs. Various therapies under development are directed toward rescuing the dystrophic muscle damage using gene transfer or cell therapy. Here we discussed current knowledge about involvement of immune system responses to experimental therapies in MDs.

  18. Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiaopeng Ma

    2017-01-01

    Full Text Available Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.

  19. Progress in nonviral gene therapy for breast cancer and what comes next?

    Science.gov (United States)

    Bottai, Giulia; Truffi, Marta; Corsi, Fabio; Santarpia, Libero

    2017-05-01

    The possibility of correcting defective genes and modulating gene expression through gene therapy has emerged as a promising treatment strategy for breast cancer. Furthermore, the relevance of tumor immune microenvironment in supporting the oncogenic process has paved the way for novel immunomodulatory applications of gene therapy. Areas covered: In this review, the authors describe the most relevant delivery systems, focusing on nonviral vectors, along with the description of the major approaches used to modify target cells, including gene transfer, RNA interference (RNAi), and epigenetic regulation. Furthermore, they highlight innovative therapeutic strategies and the application of gene therapy in clinical trials for breast cancer. Expert opinion: Gene therapy has the potential to impact breast cancer research. Further efforts are required to increase the clinical application of RNAi-based therapeutics, especially in combination with conventional treatments. Innovative strategies, including genome editing and stem cell-based systems, may contribute to translate gene therapy into clinical practice. Immune-based approaches have emerged as an attractive therapeutic opportunity for selected breast cancer patients. However, several challenges need to be addressed before considering gene therapy as an actual option for the treatment of breast cancer.

  20. Progress in the understanding and utilization of biologic response modifiers in the treatment of uveitis.

    Science.gov (United States)

    Maleki, Arash; Meese, Halea; Sahawneh, Haitham; Foster, C Stephen

    2016-07-01

    Uveitis is the third most common cause of blindness in developed countries. Considering the systemic and local complications of long-term corticosteroid therapy and the intolerance due to side effects and ineffectiveness of conventional chemotherapy, use of biologic response modifiers is a reasonable alternative in the treatment of non-infectious uveitis and persistent uveitic macular edema. The majority of the evidence presented here comes from open uncontrolled analyses. Based on these studies, tumor necrosis factor alpha inhibitors, especially infliximab and adalimumab, have been shown to be effective in the treatment of non-infectious uveitis in numerous studies. More research is necessary, particularly multi-center randomized clinical trials, to address the choice of biologic response modifier agent and the length of treatment as we employ biologic response modifiers in different types of uveitis and persistent uveitic macular edema.

  1. Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study

    International Nuclear Information System (INIS)

    Mortazavi-Jehanno, Nina; Giraudet, Anne-Laure; Champion, Laurence; Edeline, Veronique; Madar, Olivier; Pecking, Alain Paul; Lerebours, Florence; Stanc, Elise Le; Bellet, Dominique; Alberini, Jean-Louis

    2012-01-01

    The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by 18 F-FDG PET/CT. The study group comprised 22 patients with breast cancer (age 58 ± 11 years, mean ± SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 ± 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV max between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS. (orig.)

  2. Assessment of response to endocrine therapy using FDG PET/CT in metastatic breast cancer: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Mortazavi-Jehanno, Nina; Giraudet, Anne-Laure; Champion, Laurence; Edeline, Veronique; Madar, Olivier; Pecking, Alain Paul [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Lerebours, Florence [Institut Curie, Hopital Rene Huguenin, Service d' Oncologie Medicale, Saint-Cloud (France); Stanc, Elise Le [Hopital Foch, Service de Medecine Nucleaire, Suresnes (France); Bellet, Dominique [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Paris Descartes, Pharmacologie Chimique et Genetique and Imagerie, Inserm U1022 CNRS UMR 8151, Faculte des sciences pharmaceutiques et biologiques, Paris (France); Alberini, Jean-Louis [Institut Curie, Hopital Rene Huguenin, Service de Medecine Nucleaire, Saint-Cloud (France); Universite Versailles Saint-Quentin, Faculte de Medecine, Versailles (France)

    2012-03-15

    The purpose of this pilot study was to assess whether outcome in metastatic or recurrent breast cancer patients is related to metabolic response to endocrine therapy determined by {sup 18}F-FDG PET/CT. The study group comprised 22 patients with breast cancer (age 58 {+-} 11 years, mean {+-} SD) who were scheduled to receive endocrine therapy. They were systematically assessed by PET/CT at baseline and after a mean of 10 {+-} 4 weeks for evaluation of response after induction. All patients demonstrated FDG-avid lesions on the baseline PET/CT scan. The metabolic response was assessed according to EORTC criteria and based on the mean difference in SUV{sub max} between the two PET/CT scans, and the patients were classified into four groups: complete or partial metabolic response, or stable or progressive metabolic disease (CMR, PMR, SMD and PMD, respectively). All patients were followed in our institution. Metastatic sites were localized in bone (n = 15), lymph nodes (n = 11), chest wall (n = 3), breast (n = 5), lung (n = 3), soft tissue (n = 1) and liver (n = 1). PMR was observed in 11 patients (50%), SMD in 5 (23%) and PMD in 6 (27%). The median progression-free survival (PFS) times were 20, 27 and 6 months in the PMR, SMD and PMD groups, respectively. PFS in the SMD group differed from that in the PMR and SMD groups (p < 0.0001). Metabolic response assessed by FDG PET/CT imaging in patients with metastatic breast cancer treated with endocrine therapy is predictive of the patients' PFS. (orig.)

  3. Progressive pituitary hormone deficiency following radiation therapy in adults; Deficiencia progressiva dos hormonios adeno-hipofisarios apos radioterapia em adultos

    Energy Technology Data Exchange (ETDEWEB)

    Loureiro, Rafaela A.; Vaisman, Mario [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil). Servico de Endocrinologia]. E-mail: rafaela_loureiro@hotmail.com

    2004-10-01

    Hypopituitarism can be caused by radiation therapy, even when it is not directly applied on the hypothalamic-pituitary axis, and can lead to anterior pituitary deficiency mainly due to hypothalamic damage. The progressive loss of the anterior pituitary hormones usually occurs in the following order: growth hormone, gonadotropin hormones, adrenocorticotropic hormone and thyroid-stimulating hormone. Although there are several different tests available to confirm anterior pituitary deficiency, this paper will focus on the gold standard tests for patients submitted to radiation therapy. We emphasize that the decline of anterior pituitary function is time- and dose-dependent with some variability among the different axes. Therefore, awareness of the need of a joint management by endocrinologists and oncologists is essential to improve treatment and quality of life of the patients. (author)

  4. The Soluble Plasminogen Activator Receptor as a Biomarker on Monitoring the Therapy Progress of Pulmonary TB-AFB(+ Patients

    Directory of Open Access Journals (Sweden)

    Tri Yudani Mardining Raras

    2010-01-01

    P=.0001<.05, R2=.890 after 2 months (median 8.019?ng/mL and 4 months (median 5.771?ng/mL of treatment, respectively. However, only slightly declined after 6 months therapy (median 5.009?ng/mL, near control group level (median 4.772?ng/mL. Interestingly, the significant reduced of suPAR level was parallel to treatment efficacy and correlated with other clinical and laboratory parameters, that is, decreasing of patients' complaints, increasing of BMI (r=-0.281, thoracic imaging improvement, sputum conversion, decreasing of ESR (r=0.577 and monocytes count (r=0.536 with exception the width of lesion in thoracic imaging. In conclusion, the suPAR level in could reflect the progress of TB therapy.

  5. Metformin use and improved response to therapy in rectal cancer

    International Nuclear Information System (INIS)

    Skinner, Heath D.; Crane, Christopher H.; Garrett, Christopher R.; Eng, Cathy; Chang, George J.; Skibber, John M.; Rodriguez-Bigas, Miguel A.; Kelly, Patrick; Sandulache, Vlad C.; Delclos, Marc E.; Krishnan, Sunil; Das, Prajnan

    2013-01-01

    Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8–63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study

  6. Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

    Science.gov (United States)

    Ferrari, Linda; Fichera, Alessandro

    2015-01-01

    The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

  7. Magnetic resonance imaging may simulate progressive multifocal leucoencephalopathy in a patient with chronic lymphocytic leukemia after fludarabine therapy

    Directory of Open Access Journals (Sweden)

    Kalita J

    2008-01-01

    Full Text Available A 60-year-old male with chronic lymphatic leukemia (CLL after 6 months of fludarabine therapy was admitted with status epilepticus and developed left hemiplegia. His magnetic resonance imaging revealed multiple T2 hyperintense lesions in the right frontal and left parieto-occipital lesion, simulating progressive multifocal leucoencephalopathy (PML. Cerebrospinal fluid Polymerase Chain Reaction (PCR for JC virus was negative. We suggest the possible role of fludarabine in producing PML-like lesions in patients with Chronic Lymphocytic Leukemia (CLL.

  8. Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice.

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Giao Ly, Nancy Ngoc; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-06-01

    The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of preinvasive foci. We investigated the effects of radiation therapy in p48(Cre);LSL-Kras(G12D) (KC) and p48(Cre);LSLKras(G12D);LSL-Trp53(R172H) (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony-stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2 to 12 Gy and analyzed by flow cytometry. Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from radiation treated invasive and preinvasive pancreatic tumors had an immune-suppressive, M2-like phenotype compared with control mice. Pancreata from mice exposed to radiation had fewer CD8(+) T cells than controls, and greater numbers of CD4(+) T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. A neutralizing antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Radiation treatment causes macrophages

  9. Associations of hormonal contraceptive use with measures of HIV disease progression and antiretroviral therapy effectiveness.

    Science.gov (United States)

    Whiteman, Maura K; Jeng, Gary; Samarina, Anna; Akatova, Natalia; Martirosyan, Margarita; Kissin, Dmitry M; Curtis, Kathryn M; Marchbanks, Polly A; Hillis, Susan D; Mandel, Michele G; Jamieson, Denise J

    2016-01-01

    To examine the associations between hormonal contraceptive use and measures of HIV disease progression and antiretroviral treatment (ART) effectiveness. A prospective cohort study of women with prevalent HIV infection in St. Petersburg, Russia, was conducted. After contraceptive counseling, participants chose to use combined oral contraceptives (COCs), depot-medroxyprogesterone acetate (DMPA), a copper intrauterine device (IUD) or male condoms for pregnancy prevention. Among participants not using ART at enrollment, we used multivariate Cox regression to assess the association between current (time-varying) contraceptive use and disease progression, measured by the primary composite outcome of CD4 decline to contraceptive method. During a total of 5233 months follow-up among participants not using ART with enrollment CD4 ≥350 cells/mm(3) (n=315), 97 experienced disease progression. Neither current use of COCs [adjusted hazard ratio (aHR) 0.91, 95% confidence interval (CI) 0.56-1.48] nor DMPA (aHR 1.28, 95% CI 0.71-2.31) was associated with a statistically significant increased risk for disease progression compared with use of nonhormonal methods (IUD or condoms). Among participants using ART at enrollment (n=77), we found no statistically significant differences in the predicted mean changes in CD4 cell count comparing current use of COCs (p=.1) or DMPA (p=.3) with nonhormonal methods. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Hormonal contraceptive use was not significantly associated with measures of HIV disease progression or ART effectiveness among women with prevalent HIV infection. Published by Elsevier Inc.

  10. High-response hybrid quantum dots- 2D conductor phototransistors: recent progress and perspectives

    Directory of Open Access Journals (Sweden)

    Sablon Kimberly A.

    2017-03-01

    Full Text Available Having been inspired by the tremendous progress in material nanoscience and device nanoengineering, hybrid phototransistors combine solution processed colloidal semiconductor quantum dots (QDs with graphene or two-dimensional (2D semiconductor materials. Novel detectors demonstrate ultrahigh photoconductive gain, high and selective photoresponse, low noise, and very high responsivity in visible- and near-infrared ranges. The outstanding performance of phototransistors is primarily due to the strong, selective, and size tunable absorption of QDs and fast charge transfer in 2D high mobility conductors. However, the relatively small mobility of QD nanomaterials was a technological barrier, which limited the operating rate of devices. Very recent innovations in detector design and significant progress in QD ligand engineering provide effective tools for further qualitative improvements. This article reviews the recent progress in material science, nanophysics, and device engineering related to hybrid phototransistors. Detectors based on various QD nanomaterials and several 2D conductors are compared, and advantages and disadvantages of various nanomaterials for applications in hybrid phototransistors are identified. We also benchmark the experimental characteristics with model results that establish interrelations and tradeoffs between detector characteristics, such as responsivity, dark and noise currents, the photocarrier lifetime, response, and noise bandwidths. We have shown that the most recent phototransistors demonstrate performance limited by the fundamental generation recombination noise in high gain devices. Interrelation between the dynamic range of the detector and the detector sensitivity is discussed. The review is concluded with a brief discussion of the remaining challenges and possible significant improvements in the performance of hybrid phototransistors.

  11. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide

    DEFF Research Database (Denmark)

    Dresemann, G.; Weller, M.; Ostenfeld-Rosenthal, Ann Maria

    2010-01-01

    A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor...

  12. Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review.

    Science.gov (United States)

    Botella, Cristina; Fernández-Álvarez, Javier; Guillén, Verónica; García-Palacios, Azucena; Baños, Rosa

    2017-07-01

    This review is designed to systematically examine the available evidence about virtual reality exposure therapy's (VRET) efficacy for phobias, critically describe some of the most important challenges in the field and discuss possible directions. Evidence reveals that virtual reality (VR) is an effective treatment for phobias and useful for studying specific issues, such as pharmacological compounds and behavioral manipulations, that can enhance treatment outcomes. In addition, some variables, such as sense of presence in virtual environments, have a significant influence on outcomes, but further research is needed to better understand their role in therapeutic outcomes. We conclude that VR is a useful tool to improve exposure therapy and it can be a good option to analyze the processes and mechanisms involved in exposure therapy and the ways this strategy can be enhanced. In the coming years, there will be a significant expansion of VR in routine practice in clinical contexts.

  13. Northern European trees show a progressively diminishing response to increasing atmospheric carbon dioxide concentrations

    CSIR Research Space (South Africa)

    Waterhouse, JS

    2004-04-01

    Full Text Available Reviews 23 (2004) 803?810 Northern European trees show a progressively diminishing response to increasing atmospheric carbon dioxide concentrations J.S. Waterhousea,*, V.R. Switsura,b, A.C. Barkera, A.H.C. Cartera,b,{, D.L. Hemmingc, N.J. Loaderd, I..., V.R., Waterhouse, J.S., Heaton, T.H.E., Carter, A.H.C., 1998. Climatic variation andthe stable carbon isotope composition of tree ring cellulose: an intercomparison of Quercus robur, Fagus sylvatica and Pinus silvestris. Tellus 50B, 25?33. J.ggi, M...

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

    Science.gov (United States)

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

    2009-01-01

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

  15. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

    2010-01-01

    The aim of this clinical trial was to investigate safety and efficacy when combining cetuximab with bevacizumab and irinotecan in patients with recurrent primary glioblastoma multiforme (GBM). Patients were included with recurrent primary GBM and progression within 6 months of ending standard tre...

  16. Unidentified angular recurrent ulceration responsive to antiviral therapy

    Directory of Open Access Journals (Sweden)

    Rahmi Amtha

    2013-03-01

    Full Text Available Background: Recurrent ulcer on angular area is usually called stomatitis angularis. It is caused by many factors such as vertical dimension reduce, vitamin B12, and immune system deficiency, C. albicans and staphylococcus involvement. Clinically is characterized by painful fissure with erythematous base without fever. Purpose: to describe an unidentified angular ulcer proceeded by recurrent ulcers with no response of topical therapy. Case: An 18-years old male came to Oral Medicine clinic in RSCM who complained of angular recurrent ulcers since 3 years ago which developed on skin and bleed easily on mouth opening. Patient had fever before the onset of ulcers. Large, painful, irregular ulcers covered by red crustae on angular area bilaterally. Patient has been treated with various drugs without improvement and lead to mouth opening limitation. Intra oral shows herpetiformtype of ulcer and swollen of gingival. Case management: Provisional diagnosis was established as viral infection thus acyclovir 200 mg five times daily for two weeks and topical anti inflammation gel were administered. Blood test for IgG/IgM of HSV1 and HSV2 were non reactive, however ulceration showed a remarkable improvement. The ulcers healed completely after next 2 weeks with acyclovir. Conclusion: The angular ulceration on above patient failed to fulfill the criteria of stomatitis angularis or herpes labialis lesion. However it showed a good response to antiviral. Therefore, unidentified angular ulceration was appointed, as the lesion might be triggered by other type of human herpes virus or types of virus that response to acyclovir.Latar belakang: ulser rekuren pada sudut mulut biasanya disebut stomatitis angularis. Kelainan ini disebabkan oleh banyak faktor seperti berkurangnya dimensi vertikal, defisiensi vitamin B12 dan sistem kekebalan tubuh, infeksi C. albicans serta staphylococcus. Secara klinis kelainan ini ditandai dengan fisur sakit pada sudut mulut dengan dasar

  17. Escherichia coli DinB inhibits replication fork progression without significantly inducing the SOS response.

    Science.gov (United States)

    Mori, Tetsuya; Nakamura, Tatsuro; Okazaki, Naoto; Furukohri, Asako; Maki, Hisaji; Akiyama, Masahiro Tatsumi

    2012-01-01

    The SOS response is readily triggered by replication fork stalling caused by DNA damage or a dysfunctional replicative apparatus in Escherichia coli cells. E. coli dinB encodes DinB DNA polymerase and its expression is upregulated during the SOS response. DinB catalyzes translesion DNA synthesis in place of a replicative DNA polymerase III that is stalled at a DNA lesion. We showed previously that DNA replication was suppressed without exogenous DNA damage in cells overproducing DinB. In this report, we confirm that this was due to a dose-dependent inhibition of ongoing replication forks by DinB. Interestingly, the DinB-overproducing cells did not significantly induce the SOS response even though DNA replication was perturbed. RecA protein is activated by forming a nucleoprotein filament with single-stranded DNA, which leads to the onset of the SOS response. In the DinB-overproducing cells, RecA was not activated to induce the SOS response. However, the SOS response was observed after heat-inducible activation in strain recA441 (encoding a temperature-sensitive RecA) and after replication blockage in strain dnaE486 (encoding a temperature-sensitive catalytic subunit of the replicative DNA polymerase III) at a non-permissive temperature when DinB was overproduced in these cells. Furthermore, since catalytically inactive DinB could avoid the SOS response to a DinB-promoted fork block, it is unlikely that overproduced DinB takes control of primer extension and thus limits single-stranded DNA. These observations suggest that DinB possesses a feature that suppresses DNA replication but does not abolish the cell's capacity to induce the SOS response. We conclude that DinB impedes replication fork progression in a way that does not activate RecA, in contrast to obstructive DNA lesions and dysfunctional replication machinery.

  18. Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy.

    Science.gov (United States)

    Sandri, Sara; De Sanctis, Francesco; Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T; Nishimura, Michael I; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

    2017-10-20

    Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.

  19. Mild angle early onset idiopathic scoliosis children avoid progression under FITS method (Functional Individual Therapy of Scoliosis).

    Science.gov (United States)

    Białek, Marianna

    2015-05-01

    Physiotherapy for stabilization of idiopathic scoliosis angle in growing children remains controversial. Notably, little data on effectiveness of physiotherapy in children with Early Onset Idiopathic Scoliosis (EOIS) has been published.The aim of this study was to check results of FITS physiotherapy in a group of children with EOIS.The charts of the patients archived in a prospectively collected database were retrospectively reviewed. The inclusion criteria were:diagnosis of EOIS based on spine radiography, age below 10 years, both girls and boys, Cobb angle between 118 and 308, Risser zero, FITS therapy, no other treatment (bracing), and a follow-up at least 2 years from the initiation of the treatment. The criterion for curve progression were as follows: the Cobb angle increase of 68 or more, for curve stabilization; the Cobb angle was 58 comparing to the initial radiograph,for curve correction; and the Cobb angle decrease of 68 or more at the final follow-up radiograph.There were 41 children with EOIS, 36 girls and 5 boys, mean age 7.71.3 years (range 4 to 9 years) who started FITS therapy. The curve pattern was single thoracic (5 children), single thoracolumbar (22 children) or double thoracic/thoracolumbar (14 children), totally 55 structural curvatures. The minimum follow-up was 2 years after initiation of the FITS treatment, maximum was 16 years, mean 4.8 years). At follow-up the mean age was 12.53.4 years. Out of 41 children, 10 passed pubertal growth spurt at the final follow-up and 31 were still immature and continued FITS therapy. Out of 41 children, 27 improved, 13 were stable, and one progressed. Out of 55 structural curves, 32 improved, 22 were stable and one progressed. For the 55 structural curves, the Cobb angle significantly decreased from 18.085.48 at first assessment to 12.586.38 at last evaluation,pphysiotherapy was effective in preventing curve progression in children with EOIS. Final postpubertal follow-up data is needed.

  20. Heterogeneity of the cytokinome in undifferentiated arthritis progressing to rheumatoid arthritis and its change in the course of therapy. Move toward personalized medicine.

    Science.gov (United States)

    Brzustewicz, Edyta; Bzoma, Izabella; Daca, Agnieszka; Szarecka, Maria; Bykowska, Malgorzata Sochocka; Witkowski, Jacek M; Bryl, Ewa

    2017-09-01

    To conduct a comprehensive analysis of cytokine concentrations in sera and mononuclear cell supernatants in order to examine inter- and intra-individual cytokine variations in undifferentiated arthritis progressing to rheumatoid arthritis and healthy control groups. Patients with UA (undifferentiated arthritis) developing RA (rheumatoid arthritis) (UA→RA) (n=16) and healthy controls (n=16) were enrolled into the study. UA→RA patients were followed up for six months since the final RA diagnosis. Cytokines IFN-γ, IL-10, TNF, IL-17A, IL-6, IL-1β, IL-2 in sera and mononuclear cell supernatants in 72h and 120h culture variants with- and without anti-CD3 stimulations were assayed using flow cytometric bead array. The cytokine profile of UA→RA differs from the healthy individual cytokine profile. It is possible to observe specific cytokine pattern characterizing each patient, which alters during course of disease. Specifically, we can distinguish three UA→RA cohorts: the group of patients susceptible to the therapy, characterized by the drop of cytokine levels between 1st and 3rd visit with visible decrease of cytokines in 2nd visit and then secondary slighter increase in 3rd visit; the group of patients refractory or clinically worsening on the therapy, characterized by the highest cytokine levels at 2nd visit with secondary decrease in 3rd visit; and the group of patients with variable responses to the therapy without any specific common cytokine pattern. The cytokine patterns in supernatants of PBMC stimulated anti-CD3 for 72h and 120h are very similar. The personal profile including multiplexed cytokine patterns in serum and supernatant may be potentially used for optimization of therapy introduction and monitoring. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Ke-Sin Yan

    2017-05-01

    Full Text Available Enhancer of zeste homolog 2 (EZH2, a histone methyltransferase, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3 to regulate gene expression through epigenetic machinery. EZH2 functions as a double-facet molecule in regulation of gene expression via repression or activation mechanisms, depending on the different cellular contexts. EZH2 interacts with both histone and non-histone proteins to modulate diverse physiological functions including cancer progression and malignancy. In this review article, we focused on the updated information regarding microRNAs (miRNAs and long non coding RNAs (lncRNAs in regulation of EZH2, the oncogenic and tumor suppressive roles of EZH2 in cancer progression and malignancy, as well as current pre-clinical and clinical trials of EZH2 inhibitors.

  2. Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: Comparison of RECIST, Choi and volumetric criteria

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, N., E-mail: Nicolai.schramm@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Englhart, E., E-mail: Elisabeth.Englhart@gmx.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Schlemmer, M., E-mail: Marcus.Schlemmer@med.uni-muenchen.de [Department of Medicine III, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Hittinger, M., E-mail: Markus.Hittinger@uksh.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Übleis, C., E-mail: Christopher.Uebleis@med.uni-muenchen.de [Department of Nuclear Medicine, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Becker, C.R., E-mail: Christoph.becker@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Reiser, M.F., E-mail: Maximilian.Reiser@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany); Berger, F., E-mail: Frank.Berger@med.uni-muenchen.de [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistrasse 15, 81377 Munich (Germany)

    2013-06-15

    Purpose: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). Patients and methods: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan–Meier statistics. Results: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20) 20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. Conclusion: One year after modification of therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated.

  3. Tumor response and clinical outcome in metastatic gastrointestinal stromal tumors under sunitinib therapy: Comparison of RECIST, Choi and volumetric criteria

    International Nuclear Information System (INIS)

    Schramm, N.; Englhart, E.; Schlemmer, M.; Hittinger, M.; Übleis, C.; Becker, C.R.; Reiser, M.F.; Berger, F.

    2013-01-01

    Purpose: Purpose of the study was to compare radiological treatment response according to RECIST, Choi and volumetry in GIST-patients under 2nd-line-sunitinib-therapy and to correlate the results of treatment response assessment with disease-specific survival (DSS). Patients and methods: 20 patients (mean: 60.7 years; 12 male/8 female) with histologically proven GIST underwent baseline-CT of the abdomen under imatinib and follow-up-CTs 3 months and 1 year after change to sunitinib. 68 target lesions (50 hepatic, 18 extrahepatic) were investigated. Therapy response (partial response (PR), stable disease (SD), progressive disease (PD)) was evaluated according to RECIST, Choi and volumetric criteria. Response according to the different assessment systems was compared and correlated to the DSS of the patients utilizing Kaplan–Meier statistics. Results: The mean DSS (in months) of the response groups 3 months after therapy change was: RECIST: PR (0/20); SD (17/20): 30.4 (months); PD (3/20) 11.6. Choi: PR (10/20) 28.6; SD (8/20) 28.1; PD (2/20) 13.5. Volumetry: PR (4/20) 29.6; SD (11/20) 29.7; PD (5/20) 17.2. Response groups after 1 year of sunitinib showed the following mean DSS: RECIST: PR (3/20) 33.6; SD (9/20) 29.7; PD (8/20) 20.3. Choi: PR (10/20) 21.5; SD (4/20) 42.9; PD (6/20) 23.9. Volumetry: PR (6/20) 27.3; SD (5/20) 38.5; PD (9/20) 19.3. Conclusion: One year after modification of therapy, only partial response according to RECIST indicated favorable survival in patients with GIST. The value of alternate response assessment strategies like Choi criteria for prediction of survival in molecular therapy still has to be demonstrated

  4. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG)

    DEFF Research Database (Denmark)

    Rustin, Gordon John Sampson; Vergote, Ignace; Eisenhauer, Elizabeth

    2011-01-01

    . Thus, we recommend that the definitions described later in detail are incorporated into clinical trial protocols to maintain consistency. The criteria for defining progression are now acceptable in clinical trials of recurrent disease as they have since been validated (Pujade-Lauraine, personal...... communication, 2010). The GCIG requests that data from all clinical trials using these definitions are made available to GCIG trial centers so that continual validation and improvement can be accomplished. These definitions were developed from analyzing patients receiving cytotoxic chemotherapy and have not yet......The Gynecological Cancer Intergroup (GCIG) has previously reached consensus regarding the criteria that should be used in clinical trial protocols to define progression-free survival after first-line therapy as well as the criteria to define response to treatment in recurrent disease using...

  5. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

    Science.gov (United States)

    Morille, Marie; Passirani, Catherine; Vonarbourg, Arnaud; Clavreul, Anne; Benoit, Jean-Pierre

    2008-01-01

    Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection and for multi-located tumor sites, i.e. metastases. Non-viral vectors based on the use of cationic lipids or polymers appear to have promising potential, given the problems of safety encountered with viral vectors. Using these non-viral vectors, the current challenge is to obtain a similarly effective transfection to viral ones. Based on the advantages and disadvantages of existing vectors and on the hurdles encountered with these carriers, the aim of this review is to describe the "perfect vector" for systemic gene therapy against cancer.

  6. Progress in developing cationic vectors for non-viral systemic gene therapy against cancer.

    OpenAIRE

    Morille , Marie; Passirani , Catherine; Vonarbourg , Arnaud; Clavreul , Anne; Benoit , Jean-Pierre

    2008-01-01

    International audience; Initially, gene therapy was viewed as an approach for treating hereditary diseases, but its potential role in the treatment of acquired diseases such as cancer is now widely recognized. The understanding of the molecular mechanisms involved in cancer and the development of nucleic acid delivery systems are two concepts that have led to this development. Systemic gene delivery systems are needed for therapeutic application to cells inaccessible by percutaneous injection...

  7. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson’s disease

    Science.gov (United States)

    Rittman, Timothy; Nombela, Cristina; Fois, Alessandro; Coyle-Gilchrist, Ian; Barker, Roger A.; Hughes, Laura E.; Rowe, James B.

    2016-01-01

    Abstract Progressive supranuclear palsy and Parkinson’s disease have distinct underlying neuropathology, but both diseases affect cognitive function in addition to causing a movement disorder. They impair response inhibition and may lead to impulsivity, which can occur even in the presence of profound akinesia and rigidity. The current study examined the mechanisms of cognitive impairments underlying disinhibition, using horizontal saccadic latencies that obviate the impact of limb slowness on executing response decisions. Nineteen patients with clinically diagnosed progressive supranuclear palsy (Richardson’s syndrome), 24 patients with clinically diagnosed Parkinson’s disease and 26 healthy control subjects completed a saccadic Go/No-Go task with a head-mounted infrared saccadometer. Participants were cued on each trial to make a pro-saccade to a horizontal target or withhold their responses. Both patient groups had impaired behavioural performance, with more commission errors than controls. Mean saccadic latencies were similar between all three groups. We analysed behavioural responses as a binary decision between Go and No-Go choices. By using Bayesian parameter estimation, we fitted a hierarchical drift–diffusion model to individual participants’ single trial data. The model decomposes saccadic latencies into parameters for the decision process: decision boundary, drift rate of accumulation, decision bias, and non-decision time. In a leave-one-out three-way classification analysis, the model parameters provided better discrimination between patients and controls than raw behavioural measures. Furthermore, the model revealed disease-specific deficits in the Go/No-Go decision process. Both patient groups had slower drift rate of accumulation, and shorter non-decision time than controls. But patients with progressive supranuclear palsy were strongly biased towards a pro-saccade decision boundary compared to Parkinson’s patients and controls. This

  8. Different decision deficits impair response inhibition in progressive supranuclear palsy and Parkinson's disease.

    Science.gov (United States)

    Zhang, Jiaxiang; Rittman, Timothy; Nombela, Cristina; Fois, Alessandro; Coyle-Gilchrist, Ian; Barker, Roger A; Hughes, Laura E; Rowe, James B

    2016-01-01

    Progressive supranuclear palsy and Parkinson's disease have distinct underlying neuropathology, but both diseases affect cognitive function in addition to causing a movement disorder. They impair response inhibition and may lead to impulsivity, which can occur even in the presence of profound akinesia and rigidity. The current study examined the mechanisms of cognitive impairments underlying disinhibition, using horizontal saccadic latencies that obviate the impact of limb slowness on executing response decisions. Nineteen patients with clinically diagnosed progressive supranuclear palsy (Richardson's syndrome), 24 patients with clinically diagnosed Parkinson's disease and 26 healthy control subjects completed a saccadic Go/No-Go task with a head-mounted infrared saccadometer. Participants were cued on each trial to make a pro-saccade to a horizontal target or withhold their responses. Both patient groups had impaired behavioural performance, with more commission errors than controls. Mean saccadic latencies were similar between all three groups. We analysed behavioural responses as a binary decision between Go and No-Go choices. By using Bayesian parameter estimation, we fitted a hierarchical drift-diffusion model to individual participants' single trial data. The model decomposes saccadic latencies into parameters for the decision process: decision boundary, drift rate of accumulation, decision bias, and non-decision time. In a leave-one-out three-way classification analysis, the model parameters provided better discrimination between patients and controls than raw behavioural measures. Furthermore, the model revealed disease-specific deficits in the Go/No-Go decision process. Both patient groups had slower drift rate of accumulation, and shorter non-decision time than controls. But patients with progressive supranuclear palsy were strongly biased towards a pro-saccade decision boundary compared to Parkinson's patients and controls. This indicates a prepotency of

  9. Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Alastair G Kerr

    2016-01-01

    Full Text Available Familial hypercholesterolemia (FH is a life-threatening genetic disorder characterized by elevated levels of plasma low-density lipoprotein cholesterol (LDL-cholesterol. Current attempts at gene therapy for FH have been limited by the use of strong heterologous promoters which lack genomic DNA elements essential for regulated expression. Here, we have combined a minigene vector expressing the human LDLR cDNA from a 10 kb native human LDLR locus genomic DNA promoter element, with an efficient miRNA targeting 3-hydroxy-3-methylgutaryl-coenzyme A reductase (Hmgcr, to further enhance LDLR expression. We show that the combined vector suppresses endogenous Hmgcr transcripts in vivo, leading to an increase in LDLR transgene expression. In a diet-induced Ldlr-/- mouse model of FH, we show that administration of the combined vector reduces atherogenic plasma lipids by ≃32%. Finally, we demonstrate that our episomal nonviral vectors are able to reduce atherosclerosis by ≃40% after 12 weeks in vivo. Taken together, the vector system we describe exploits the normal cellular regulation of the LDLR to provide prolonged expression of LDLR through targeted knockdown of Hmgcr. This novel gene therapy system could act alone, or in synergy with current therapies that modulate intracellular cholesterol, such as statins, greatly enhancing its therapeutic application for FH.

  10. Research progress in animal models and stem cell therapy for Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Han F

    2014-12-01

    Full Text Available Fabin Han,1,2 Wei Wang1, Chao Chen1 1Centre for Stem Cells and Regenerative Medicine, 2Department of Neurology, Liaocheng People’s Hospital/The Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People’s Republic of China Abstract: Alzheimer’s disease (AD causes degeneration of brain neurons and leads to memory loss and cognitive impairment. Since current therapeutic strategies cannot cure the disease, stem cell therapy represents a powerful tool for the treatment of AD. We first review the advances in molecular pathogenesis and animal models of AD and then discuss recent clinical studies using small molecules and immunoglobulins to target amyloid-beta plaques for AD therapy. Finally, we discuss stem cell therapy for AD using neural stem cells, olfactory ensheathing cells, embryonic stem cells, and mesenchymal stem cell from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific induced pluripotent stem cells are proposed as a future treatment for AD. Keywords: amyloid-beta plaque, neurofibrillary tangle, neural stem cell, olfactory ensheathing cell, mesenchymal stem cell, induced pluripotent stem cell

  11. High cortisol awakening response is associated with an impairment of the effect of bright light therapy

    DEFF Research Database (Denmark)

    Martiny, Klaus Per Juul; Lunde, Marianne Anita; Undén, M

    2009-01-01

    OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63...... patients, as an awakening profile, before medication and light therapy started. The CAR was calculated by using three time-points: awakening and 20 and 60 min after awakening. RESULTS: Patients with low CAR had a very substantial effect of bright light therapy compared with dim light therapy, whereas...... patients with a high CAR had no effect of bright light therapy compared with dim light therapy. CONCLUSION: High CAR was associated with an impairment of the effect of bright light therapy. This result raises the question of whether bright light acts through a mechanism different from...

  12. Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice

    Science.gov (United States)

    Seifert, Lena; Werba, Gregor; Tiwari, Shaun; Ly, Nancy Ngoc Giao; Nguy, Susanna; Alothman, Sara; Alqunaibit, Dalia; Avanzi, Antonina; Daley, Donnele; Barilla, Rocky; Tippens, Daniel; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R.; Hajdu, Cristina; Pellicciotta, Ilenia; Oh, Philmo; Du, Kevin; Miller, George

    2016-01-01

    Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcome, compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the therapeutic effects of radiation on invasive PDAs and accelerates progression of pre-invasive foci. Methods We investigated the effects of radiation in p48Cre;LSL-KrasG12D (KC) and p48Cre;LSLKrasG12D;LSL-Trp53R172H (KPC) mice, as well as in C57BL/6 mice with orthotopic tumors grown from FC1242 cells derived from KPC mice. Some mice were given neutralizing antibodies against macrophage colony stimulating factor 1 (CSF1 or MCSF) or F4/80. Pancreata were exposed to doses of radiation ranging from 2–12 Gy and analyzed by flow cytometry. Results Pancreata of KC mice exposed to radiation had a higher frequency of advanced pancreatic intraepithelial lesions and more foci of invasive cancer than pancreata of unexposed mice (controls); radiation reduced survival time by more than 6 months. A greater proportion of macrophages from invasive and pre-invasive pancreatic tumors had an immune-suppressive, M2-like phenotype, compared with control mice. Pancreata from mice exposed to radiation had fewer CD8+ T cells than controls and greater numbers of CD4+ T cells of T-helper 2 and T-regulatory cell phenotypes. Adoptive transfer of T cells from irradiated PDA to tumors of control mice accelerated tumor growth. Radiation induced production of MCSF by PDA cells. An antibody against MCSF prevented radiation from altering the phenotype of macrophages in tumors, increasing the anti-tumor T-cell response and slowing tumor growth. Conclusions Radiation exposure causes macrophages in PDAs

  13. Stage progression and need for renal replacement therapy in a renal protection programme in Colombia. A cohort study.

    Science.gov (United States)

    Yepes Delgado, Carlos Enrique; Pérez Dávila, Sara; Montoya Jaramillo, Marcela; Orrego Orozco, Beatriz Elena

    Due to the global burden represented by chronic kidney disease (CKD), the World Health Organization encouraged the implementation of renal protection programmes (RPP) to affect its incidence through prevention and control measures. To assess the effectiveness of a Colombian RPP in terms of its effect on the stage progression of CKD and the need for renal replacement therapy (RRT). An analytical study that monitored 2cohorts of patients diagnosed with CKD. The study compares the behaviour of clinical and renal impairment indicators from patients exposed to a RPP with that of patients following conventional treatment (CT). The population of both intervention groups was considered when determining the sample size. The incidence rate was calculated as well as patient survival (Kaplan Meier). In addition, a multivariate analysis (Cox) was used to calculate the influence that exposure to the RPP had on the outcomes of the patients following the RPP and those following CT. The patients exposed to the RPP took longer to advance to the next CKD stage and require RRT. The incidence rate for progression is higher for the patients following CT (0.050, IC 95%: 0.040-0.064) compared to those in the RPP (0.034, IC 95%: 0.030-0.039). The ratio of incidence rates was 1.480 (IC 95% 1.21-1.90). The hazard of progression was lower for the RPP (HR: 0.855, IC 95%: 0.74- 0.98), as was the hazard of requiring RRT (HR: 0.797, IC 95%: 0.606-1.049). The RPP is a secondary prevention strategy against CKD which has an effect on the stage progression of CKD and the need for RRT. Early patient detection has a positive effect on the outcomes studied. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Swallowing therapy and progressive resistance training in head and neck cancer patients undergoing radiotherapy treatment

    DEFF Research Database (Denmark)

    Hajdú, Sara F; Wessel, Irene; Johansen, Christoffer

    2017-01-01

    BACKGROUND: Head and neck cancer (HNC) patients are often challenged by treatment induced dysphagia and trismus. Traditionally, rehabilitation is initiated when loss of function has already occurred. There is increasing evidence that it is of benefit to patients to initiate an early rehabilitation...... process before and during treatment. HNC patients have a unique set of functional challenges such as pre- and post-treatment dysphagia, pain and weight loss. The aim of the trial is to investigate the effects of swallowing and mouth-opening exercises combined with progressive resistance training (PRT...

  15. A Commentary on the Social Responsibility of Occupational Therapy Education

    Science.gov (United States)

    Sakellariou, Dikaios; Pollard, Nick

    2013-01-01

    As one of the allied health professions, occupational therapy has adopted a primarily clinical focus on human occupation (or the process of daily life) and this is reflected in education, which has until recently tended to overlook contextual social factors such as poverty, marginalisation, exclusion, unemployment, incarceration and immigration.…

  16. Dimentions of Counselee Responses over Several Therapy Sessions

    Science.gov (United States)

    Zimmer, Jules M.; And Others

    1972-01-01

    The results of the current study, as well as the Zimmer and Cowles (1972) study using quite different procedures, involved a comparison of client-centered, gestalt, and rational therapies and do not support the conclusion that therapeutic relationships tend to be characteristically the same. Theoretical orientation as operationalized by…

  17. Stimuli-responsive biodegradable polymeric micelles for targeted cancer therapy

    NARCIS (Netherlands)

    Talelli, M.A.

    2011-01-01

    Thermosensitive and biodegradable polymeric micelles based on mPEG-b-pHPMAmLacn have shown very promising results during the past years. The results presented in this thesis illustrate the high potential of these micelles for anticancer therapy and imaging and fully justify further pharmaceutical

  18. Gender Differences in the Maintenance of Response to Cognitive Behavior Therapy for Posttraumatic Stress Disorder

    Science.gov (United States)

    Felmingham, Kim L.; Bryant, Richard A.

    2012-01-01

    Objective: To examine potential differential responses in men and women to cognitive behavior therapy for posttraumatic stress disorder (PTSD). Method: Fifty-two men and 56 women diagnosed with PTSD participated in randomized controlled trials of cognitive behavior therapy for PTSD. Participants were randomly allocated to either (a) exposure-only…

  19. Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids. Addendum

    Science.gov (United States)

    2009-08-01

    Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible Magnetic Fluids PRINCIPAL INVESTIGATOR: Cahit A. Evrensel...AND SUBTITLE 5a. CONTRACT NUMBER Immune Response Augmentation in Metastasized Breast Cancer by Localized Therapy Utilizing Biocompatible... Magneto -rheological Fluid (MRF) iron nano-particles were synthesized using the reverse micelle technique and coated with poly(NIPAAm). The size

  20. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Bartalena, L.; Marcocci, C.; Bogazzi, F.; Panicucci, M.; Lepri, A.; Pinchera, A. (Univ. of Pisa (Italy))

    1989-11-16

    We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.

  1. Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Bartalena, L.; Marcocci, C.; Bogazzi, F.; Panicucci, M.; Lepri, A.; Pinchera, A.

    1989-01-01

    We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment

  2. High flow nasal cannula oxygen therapy, work in progress in respiratory critical care.

    Science.gov (United States)

    Schreiber, Annia; DI Marco, Fabiano; Braido, Fulvio; Solidoro, Paolo

    2016-12-01

    After a planned extubation, the re-occurrence of acute respiratory distress needing the restoration of invasive mechanical support is a severe phenomenon associated with several important consequences, including increased morbidity, Intensive Care Unit mortality, and an enormous financial burden. So far, the most commonly used techniques to ameliorate gas exchange in the postextubation period were low-flow oxygen therapy and non-invasive ventilation (NIV). High flows through nasal cannulae (HFNC) is a system which allows increased CO2 wash-out of anatomical dead space, positive nasopharyngeal pressure, a relatively constant FiO2, and an improvement of mucociliary function. In a recently published paper by Hernandez et al. HFNC therapy, compared in the postextubation period to standard oxygen in patients at low risk of re-intubation, was associated with a lower re-intubation rate within 72 hours of extubation, with no evidence of any delays in re-intubation which may prove fatal, as previously reported in the context of NIV. Despite yielding some useful starting points and positive results with HFNC, some discrepancies have emerged in the findings of the studies in this field. As we await further more homogeneous and enlightening studies, at present we can only affirm that HFNC seems to be a useful means to prevent and treat postextubation hypoxemia. In fact no harmful or adverse effects related to HFNC emerged in any of the studies and globally, it was associated with better comfort and tolerance compared with NIV, which justifies its use as a first alternative to standard oxygen therapy.

  3. Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Freedland, Stephen J., E-mail: steve.freedland@duke.edu [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Gerber, Leah [Department of Surgery, Durham VA Medical Center, Durham, North Carolina (United States); Department of Surgery (Urology), Duke University School of Medicine, Durham, North Carolina (United States); Department of Pathology, Duke University School of Medicine, Durham, North Carolina (United States); Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S. [Myriad Genetics, Inc, Salt Lake City, Utah (United States); Salama, Joseph K. [Department of Radiation Oncology, Durham VA Medical Center, Durham, North Carolina (United States); Department of Radiation Oncology, Duke University School of Medicine, Durham, North Carolina (United States); Stone, Steven [Myriad Genetics, Inc, Salt Lake City, Utah (United States)

    2013-08-01

    Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy.

  4. Prognostic Utility of Cell Cycle Progression Score in Men With Prostate Cancer After Primary External Beam Radiation Therapy

    International Nuclear Information System (INIS)

    Freedland, Stephen J.; Gerber, Leah; Reid, Julia; Welbourn, William; Tikishvili, Eliso; Park, Jimmy; Younus, Adib; Gutin, Alexander; Sangale, Zaina; Lanchbury, Jerry S.; Salama, Joseph K.; Stone, Steven

    2013-01-01

    Purpose: To evaluate the prognostic utility of the cell cycle progression (CCP) score, a RNA signature based on the average expression level of 31 CCP genes, for predicting biochemical recurrence (BCR) in men with prostate cancer treated with external beam radiation therapy (EBRT) as their primary curative therapy. Methods and Materials: The CCP score was derived retrospectively from diagnostic biopsy specimens of men diagnosed with prostate cancer from 1991 to 2006 (n=141). All patients were treated with definitive EBRT; approximately half of the cohort was African American. Outcome was time from EBRT to BCR using the Phoenix definition. Median follow-up for patients without BCR was 4.8 years. Association with outcome was evaluated by Cox proportional hazards survival analysis and likelihood ratio tests. Results: Of 141 patients, 19 (13%) had BCR. The median CCP score for patient samples was 0.12. In univariable analysis, CCP score significantly predicted BCR (P=.0017). The hazard ratio for BCR was 2.55 for 1-unit increase in CCP score (equivalent to a doubling of gene expression). In a multivariable analysis that included Gleason score, prostate-specific antigen, percent positive cores, and androgen deprivation therapy, the hazard ratio for CCP changed only marginally and remained significant (P=.034), indicating that CCP provides prognostic information that is not provided by standard clinical parameters. With 10-year censoring, the CCP score was associated with prostate cancer-specific mortality (P=.013). There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: Among men treated with EBRT, the CCP score significantly predicted outcome and provided greater prognostic information than was available with clinical parameters. If validated in a larger cohort, CCP score could identify high-risk men undergoing EBRT who may need more aggressive therapy

  5. Recent progress of applying mesenchymal stem cells in therapy of urgent radiation damage

    International Nuclear Information System (INIS)

    Liu Jiangong; Guo Wanlong; Zhang Shuxian; Duan Zhikai

    2010-01-01

    At present, Cytokine therapy is the main strategy capable of preventing and reducing the acute radiation syndrome (ARS). With the problem of difficult match and severe graft versus host disease, haemopoietic stem cells can be used to find some effective approaches to treat acute radiation damage. Mesenchymal stem cells are of great therapeutic potential due to their particular characteristics including secretion of hematopoietic cytokine, reconstruction hemopoietic microenvironment, poor-immunogenicity, ease of reception ectogenic gene transfection and expression. This paper is to summarize the studies of biological characteristics of MSC and its application prospects in urgent radiation damage. (authors)

  6. Response of the oral mucosa to porphyrin mediated boron neutron capture therapy

    International Nuclear Information System (INIS)

    Morris, G.M.

    2003-01-01

    Pre-clinical studies are now in progress to develop boron neutron capture therapy (BNCT) modalities for the treatment of head and neck carcinomas. BNCT is a bimodal therapy which involves the administration of a boron-10 enriched compound, that accumulates preferentially in tumours, prior to irradiation with low energy neutrons. These neutrons are captured by boron-10 atoms to produce a highly localised radiation exposure. More recently, it has been demonstrated that various boronated porphyrins can target a variety of tumours. Of the porphyrins evaluated to date, copper tetracarboranylphenyl porphyrin (CuTCPH) is a strong candidate for potential clinical evaluation. It has extremely high specificity for a variety of tumour models. Therapeutic efficacy of CuTCPH mediated BNCT has been demonstrated in pre-clinical studies using the murine EMT-6 carcinoma model. In the present investigation the response of the oral mucosa to CuTCPH mediated boron neutron capture (BNC) irradiation was assessed using a standard rat model (ventral tongue). Single exposure irradiation was carried out on the thermal neutron beam at the Brookhaven Medical Research Reactor, at 3 days after the final injection of the boronated porphyrin. The impact of CuTCPH mediated BNC irradiation on oral mucosa at therapeutically effective exposure times, assessed using the ventral tongue model, was minimal. This was primarily due to the fact that blood boron levels (from CuTCPH) were very low at the time of irradiation. Analysis of the dose-effect data for CuTCPH gave a compound biological effectiveness (CBE) factor of 2.5. It can be concluded that, although, the CBE factor (calculated using blood boron concentrations) was relatively high, CuTCPH mediated BNC irradiation should not cause significant damage at clinically relevant radiation doses. This is because blood boron levels would be very low at the time of irradiation

  7. Progressive tumefactive fibroinflammatory lesion of the infratemporal fossa treated by radiation therapy

    Directory of Open Access Journals (Sweden)

    Brian O’Sullivan

    2012-01-01

    Full Text Available Tumefactive fibroinflammatory lesion (TFIL is a rare benign tumor in the head and neck region. We present a case of a 40-year-old female with a benign but progressive lesion of the infratemporal fossa, which was diagnosed as TFIL. Patient responded briefly to a course of steroid treatment but eventually showed progression and was unresponsive to further steroids. She was then treated with external beam radiation to a dose of 60 Gy in 30 fractions. After radiation a slow, gradual decrease in tumor size was noted over the course of years and she is free of disease after more than 11 years of follow-up. The major longterm side effect this patient developed was an expected unilateral radiation-induced retinopathy, due to the close proximity of the lesion to the orbit. The dilemma of treatment of benign disease with radiation with potential long-term complications is discussed and a review of the literature on TFIL is presented.

  8. Progress and Challenges in the Design and Clinical Development of Antibodies for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Juan C. Almagro

    2018-01-01

    Full Text Available The remarkable progress in engineering and clinical development of therapeutic antibodies in the last 40 years, after the seminal work by Köhler and Milstein, has led to the approval by the United States Food and Drug Administration (FDA of 21 antibodies for cancer immunotherapy. We review here these approved antibodies, with emphasis on the methods used for their discovery, engineering, and optimization for therapeutic settings. These methods include antibody engineering via chimerization and humanization of non-human antibodies, as well as selection and further optimization of fully human antibodies isolated from human antibody phage-displayed libraries and immunization of transgenic mice capable of generating human antibodies. These technology platforms have progressively led to the development of therapeutic antibodies with higher human content and, thus, less immunogenicity. We also discuss the genetic engineering approaches that have allowed isotype switching and Fc modifications to modulate effector functions and bioavailability (half-life, which together with the technologies for engineering the Fv fragment, have been pivotal in generating more efficacious and better tolerated therapeutic antibodies to treat cancer.

  9. Emotional, motivational and interpersonal responsiveness of children with autism in improvisational music therapy

    DEFF Research Database (Denmark)

    Kim, Jinah; Wigram, Tony; Gold, Christian

    2009-01-01

    Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint attention ep...

  10. Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R. P.; Przetak, C. [Zentralklinik Bad Berka, Clinic of Nuclear Medicine, Center for PET, Bad Berka (Germany)

    2001-09-01

    Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these.

  11. Evaluation of therapy response in breast and ovarian cancer patients by positron emission tomography (PET)

    International Nuclear Information System (INIS)

    Baum, R. P.; Przetak, C.

    2001-01-01

    Positron emission tomography (PET) has the potential to contribute significantly to treatment planning and to the evaluation of response to therapy in patients with cancer. For disease recurrence PET imaging provides information non-invasively. The final goal is to biologically characterize an individual patients' tumor and to predict the response to treatment at the earliest possible time. Quantitative and/or semi-quantitative PET studies yield valuable information in breast cancer regarding prognosis and response to chemohormontherapy in a timely fashion. In ovarian cancer, up to now only few studies have been performed applying PET techniques for the evaluation of treatment response. These preliminary studies indicate that serial assessment of tumor metabolism by FDG-PET early during effective chemotherapy may predict subsequent response to such therapy. PET studies can be repeated without any side-effects and with low radiation exposure and results can be directly correlated with clinical laboratory data and histology. Therapy monitoring by PET could help to optimize neoadjuvant therapy protocols and to avoid ineffective preoperative therapy in non-responders, but this has to be proven in a larger number of patients and in different neoadjuvant settings such as chemotherapy, radiation therapy, hormone therapy or a combination of these

  12. Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

    Science.gov (United States)

    Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

    2017-12-01

    The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival

  13. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    DEFF Research Database (Denmark)

    Appelt, A. L.; Ploen, J.; Vogelius, I. R.

    2013-01-01

    estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...

  14. D-T neutron generator development for cancer therapy. 1980 annual progress report

    International Nuclear Information System (INIS)

    Bacon, F.M.; Walko, R.J.; Bickes, R.W. Jr.; Cowgill, D.F.; Riedel, A.A.; O'Hagan, J.B.

    1980-05-01

    This report summarizes the work completed during the first year of a two-year grant by NCI/HEW to investigate the feasibility of developing a D-T neutron generator for use in cancer therapy. Experiments have continued on the Target Test Facility (TTF) developed during a previous grant to investigate high-temperature metal hydrides for use as target materials. The high voltage reliability of the TTF has been improved so that 200 kV, 200 mA operation is now routine. In recent target tests, the D-D neutron production rate was measured to be > 1 x 10 11 /s, a rate that corresponds to a D-T neutron production rate of > 1 x 10 13 /s - the desired rate for use in cancer therapy. Deuterium concentration depth profiles in the target, measured during intense ion beam bombardment, show that deuterium is depleted near the surface of the target due to impurities implanted by the ion beam. Recent modifications of the duopigatron ion source to reduce secondary electron damage to the electrodes also improved the ion source efficiency by about 40%. An ultra high vacuum version of the TTF is now being constructed to determine if improved vacuum conditions will reduce ion source impurities to a sufficiently low level that the deuterium near the surface of the target is not depleted. Testing will begin in June 1980

  15. Progression of puberty after initiation of androgen therapy in patients with idiopathic hypogonadotropic hypogonadism

    Directory of Open Access Journals (Sweden)

    Bindu Kulshreshtha

    2013-01-01

    Full Text Available Background: Onset of puberty in boys usually occurs by 14 years of age. Some boys may exhibit delayed sexual maturation till about 17-18 years of age. However, pubertal onset beyond 18 years of age is exceedingly rare. Materials and Methods: Patients diagnosed as idiopathic hypogonadotropic hypogonadism (IHH who had onset of puberty (increase in testicular volume >10 ml while on androgen therapy were studied. These patients were evaluated prospectively. Results: There were nine subjects that were included in the study. The pre-therapy testicular volumes ranged from 3 to 6 ml. Luteinizing hormone (LH levels increased from 1.2 ± 0.96 to 2.8 ± 1.0 IU/L, follicular stimulating hormone (FSH levels increased from 1.5 ± 0.79 to 3.5 ± 1.9 IU/L, and testosterone increased from 0.36 ± 0.16 to 3.4 ± 2.1 ng/ml. Three out of nine patients had testosterone levels below 3 ng/ml. Conclusion: Our present study indicates that pubertal development can occur in patients presenting with hypogonadotropic hypogonadism after 18 years of age. However, acquired pubertal status may be subnormal

  16. Image-guided macular laser therapy: design considerations and progress toward implementation

    Science.gov (United States)

    Berger, Jeffrey W.; Shin, David S.

    1999-06-01

    Laser therapy is currently the only treatment of proven benefit for exudative age related macular degeneration and diabetic retinopathy. To guide treatment for macular diseases, investigations were initiated to permit overlay of previously-stored angiographic images and image sequences superimposed onto the real-time biomicroscopic fundus image. Prior to treatment, a set of partially overlapping fundus images is acquired and montaged in order to provide a map for subsequent tracking operations. A binocular slit-lamp biomicroscope interfaced to a CCD camera, framegrabber board, and PC permits acquisition and rendering of retinal images. Computer-vision algorithms facilitate robust tracking, registration, and near-video-rate image overlay of previously-stored retinal photographic and angiographic images onto the real-time fundus image. Laser treatment is guided in this augmented reality environment where the borders of the treatment target--for example, the boundaries of a choroidal neovascularization complex--are easily identified through overlay of angiographic information superimposed on, and registered with, the real-time fundus image. During periods of misregistration as judged by the amplitude of the tracking similarity metric, laser function is disabled, affording additional safety. Image-guided macular laser therapy should facilitate accurate targeting of treatable lesions and less unintentional retinal injury when compared with standard techniques.

  17. Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males

    Directory of Open Access Journals (Sweden)

    H Çakır-Atabek

    2015-11-01

    Full Text Available The relationship between oxidative stress and some exercise components of resistance exercise (e.g. intensity, exercise volume has not been clearly defined. Additionally, the oxidative stress markers may respond differently in various conditions. This study aims to determine the effects of progressive intensity of resistance exercise (RE on oxidative stress and antioxidants in trained and untrained men, and also to investigate the possible threshold intensity required to evoke oxidative stress. RE trained (N=8 and untrained (N=8 men performed the leg extension RE at progressive intensities standardized for total volume: 1x17 reps at 50% of one-repetition maximum (1RM; 1x14 reps at 60% of 1RM; 1x12 reps at 70% of 1RM; 2x5 reps at 80% of 1RM; and 3x3 reps at 90% of 1RM. Blood samples were drawn before (PRE and immediately after each intensity, and after 30 minutes, 60 minutes and 24 hours following the RE. Lipid-hydroperoxide (LHP significantly increased during the test and then decreased during the recovery in both groups (p0.05. Standardized volume of RE increased oxidative stress responses. Our study suggests that lower intensity (50% is enough to increase LHP, whereas higher intensity (more than 80% is required to evoke protein oxidation.

  18. Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses.

    Science.gov (United States)

    Kim, S B; Bozeman, R G; Kaisani, A; Kim, W; Zhang, L; Richardson, J A; Wright, W E; Shay, J W

    2016-06-30

    Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA.

  19. Is serum neopterin level a marker of responsiveness to interferon beta-1a therapy in multiple sclerosis?

    Science.gov (United States)

    Casoni, F; Merelli, E; Bedin, R; Sola, P; Bertolotto, A; Faglioni, P

    2004-01-01

    Interferon beta (INFbeta) may induce the expression of several proteins, including neopterin, considered a biological marker of INFbeta activity. The aim of this study was to determine the serum neopterin concentration at the beginning of, and during, IFNbeta-1a therapy in relapsing-remitting multiple sclerosis (r-r MS) patients, and to look for a possible correlation between protein synthesis and the clinical course of the disease. Thirteen r-r MS patients were treated with INFbeta-1a (i.m. 6 MIU/week) for 2 years. Blood samples for neopterin determinations were taken daily over a period of 1 week at the end of each 6 months of therapy, and tested for neutralizing antibodies (NABs). Neopterin levels peaked 24-48 h post-injection and returned to baseline after 120 h. After 1 year of therapy, four patients dropped out of the study because of progression of the disease: in these subjects a significant decrement of neopterin was observed. Neopterin baseline values were not found to decrease over the 2 years of therapy, and neopterin may be considered to be a useful marker of responsiveness to IFNbeta.

  20. Optimization of Progressive Freeze Concentration on Apple Juice via Response Surface Methodology

    Science.gov (United States)

    Samsuri, S.; Amran, N. A.; Jusoh, M.

    2018-05-01

    In this work, a progressive freeze concentration (PFC) system was developed to concentrate apple juice and was optimized by response surface methodology (RSM). The effects of various operating conditions such as coolant temperature, circulation flowrate, circulation time and shaking speed to effective partition constant (K) were investigated. Five different level of central composite design (CCD) was employed to search for optimal concentration of concentrated apple juice. A full quadratic model for K was established by using method of least squares. A coefficient of determination (R2) of this model was found to be 0.7792. The optimum conditions were found to be coolant temperature = -10.59 °C, circulation flowrate = 3030.23 mL/min, circulation time = 67.35 minutes and shaking speed = 30.96 ohm. A validation experiment was performed to evaluate the accuracy of the optimization procedure and the best K value of 0.17 was achieved under the optimized conditions.

  1. Epigenetics of Estrogen Receptor Signaling: Role in Hormonal Cancer Progression and Therapy

    International Nuclear Information System (INIS)

    Mann, Monica; Cortez, Valerie; Vadlamudi, Ratna K.

    2011-01-01

    Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα -mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications

  2. Epigenetics of Estrogen Receptor Signaling: Role in Hormonal Cancer Progression and Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mann, Monica; Cortez, Valerie [Department of Cellular and Structural Biology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229 (United States); Vadlamudi, Ratna K., E-mail: vadlamudi@uthscsa.edu [Department of Obstetrics and Gynecology, UTHSCSA, 7703 Floyd Curl Drive, San Antonio, TX 78229 (United States)

    2011-03-29

    Estrogen receptor (ERα) signaling plays a key role in hormonal cancer progression. ERα is a ligand-dependent transcription factor that modulates gene transcription via recruitment to the target gene chromatin. Emerging evidence suggests that ERα signaling has the potential to contribute to epigenetic changes. Estrogen stimulation is shown to induce several histone modifications at the ERα target gene promoters including acetylation, phosphorylation and methylation via dynamic interactions with histone modifying enzymes. Deregulation of enzymes involved in the ERα -mediated epigenetic pathway could play a vital role in ERα driven neoplastic processes. Unlike genetic alterations, epigenetic changes are reversible, and hence offer novel therapeutic opportunities to reverse ERα driven epigenetic changes. In this review, we summarize current knowledge on mechanisms by which ERα signaling potentiates epigenetic changes in cancer cells via histone modifications.

  3. Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial

    DEFF Research Database (Denmark)

    Hasselbalch, Benedikte; Lassen, Ulrik; Hansen, Steinbjørn

    2010-01-01

    complete responses and 9 patients had partial responses. The 6-month progression-free survival probability was 30% and median overall survival was 29 weeks (95% CI: 23-37 weeks). One patient had lacunar infarction, 1 patient had multiple pulmonary embolisms, and 3 patients had grade 3 skin toxicity......, for which 1 patient needed plastic surgery. One patient was excluded due to suspicion of interstitial lung disease. Three patients had deep-vein thrombosis; all continued on study after adequate treatment. Cetuximab in combination with bevacizumab and irinotecan in recurrent GBM is well tolerated except...... for skin toxicity, with an encouraging response rate. However, the efficacy data do not seem to be superior compared with results with bevacizumab and irinotecan alone....

  4. Governing therapy choices: Power/Knowledge in the treatment of progressive renal failure

    Directory of Open Access Journals (Sweden)

    Perron Amélie M

    2006-12-01

    Full Text Available Abstract This article outlines the struggle between the power of the health care professional and the rights of the individual to choose freely a modality of treatment. Nurses are instrumental in assisting patients in making the best decision for a therapy they will have to assume for the rest of their lives. In guiding patients' decision, nurses must take into account these unavoidable contingencies: changes in lifestyle, nutritional restrictions, level of acceptance, compliance issues, ease of training and availability of support/facilities. Ensuring that the patient makes an informed decision is therefore an ongoing challenge for nurses as they are taking part in a delicate balancing act between not directly influencing the patient's decision while making sure the patient is accurately informed.

  5. [Intrathecal baclofen therapy for spastic paraparesis due to aortic dissecting aneurysm; recent progress in treatment strategy].

    Science.gov (United States)

    Nakajima, T; Akagawa, H; Ochiai, T; Hayashi, M; Goto, S; Taira, T; Okada, Y

    2009-11-01

    A 48-year-old man suffered from acute dissection of thoracic aortic aneurysm which eventually led to replacement of the ascending aorta with a tube graft. During this clinical course, circulatory failure in intercostal artery resulted in spinal cord infarction followed by moto-sensory disturbance below Th7 dermatomic area. Seven months later, spasticity with pain in both lower extremities became conspicuous that was uncontrollable by any oral medication. Eventually the patient underwent the implantation of continuous infusion pump for intrathecal baclofen therapy (ITB). The clinical condition was remarkably improved and now has been well controlled. ITB, authorized by Japanese Ministry of Health Labour and Welfare in 2006, has notable therapeutic effects on spasticity derived from any sort of central nervous disorder. More promotive enlightenment if ITB is indispensable for enhancement of its medical benefit in Japan.

  6. Deep postoperative spine infection treated by negative pressure therapy in patients with progressive spinal deformities.

    Science.gov (United States)

    Canavese, Federico; Marengo, Lorenza; Corradin, Marco; Mansour, Mounira; Samba, Antoine; Andreacchio, Antonio; Rousset, Marie; Dimeglio, Alain

    2018-04-01

    The aim of the study is to review the outcome of using the VAC system in children and adolescents who have developed postoperative spinal infection after posterior instrumented spinal fusion, and to evaluate whether this technique is also feasible in patients treated with posterior instrumented fusion with polyester sublaminar bands. A total of 11 out of 118 consecutive children and adolescents (5 males) with deep postoperative spinal infection were identified; infections were categorised as early (acute), delayed (subacute) or late (chronic) according to time of onset. Irrespective of the etiology and the onset, all the deep infections were managed with the reported technique. All the patients had regular clinical and radiological follow-up. Eight out of 11 patients developed an early (72.7%), 2 a delayed (18.2%) and 1 a late deep postoperative infection (9.1%); 7 out of 11 (63.6%) showed severe mental compromise. No statistically significant differences were observed for mean number of VAC dressing changes (p = 0.81) and mean length of hospitalisation comparing patients with early infection versus patients with delayed or late infections (p = 0.32). Mean number of VAC dressing changes (p = 0.02) and mean number of hospitalisation days (p = 0.05) were higher in patients with underlying neurological disorders than in those without, while mean length of hospitalisation was longer in neuromuscular patients. The application of the VAC system, as an adjunct to surgical debridement and adequate antibiotic therapy, is a reliable method for the treatment of postoperative infection in children and adolescents undergoing spinal instrumentation and fusion. It can reduce the need for further complex soft-tissue procedure, removal of hardware with consequent loss of correction, and pseudoarthrosis. Finally, the use of VAC therapy is not contraindicated in patients treated with hybrid constructs with sublaminar bands. III.

  7. Progression of Treated versus Untreated Liver Imaging Reporting and Data System Category 4 Masses after Transcatheter Arterial Embolization Therapy.

    Science.gov (United States)

    Ronald, James; Gupta, Rajan T; Marin, Daniele; Wang, Qi; Durocher, Nicholas S; Suhocki, Paul V; Kim, Charles Y

    2018-05-01

    To compare outcomes of treated vs untreated Liver Imaging Reporting and Data System category 4 (LR-4) masses after transcatheter arterial embolization. In 167 patients undergoing embolization for HCC from January 2005 to December 2012, LR-4 masses were retrospectively identified on CT and MR imaging examinations performed before embolization. In 149 patients undergoing embolization from January 2013 to December 2016, masses prospectively classified as LR-4 were identified. In total, there were 81 LR-4 masses in 62 patients (16 women; mean age 62 y; range 29-83 y). Procedures were reviewed to determine whether LR-4 masses were within or outside the liver volume that received embolization during treatment of dominant masses. Time to progression to LR-5 and by modified Response Evaluation Criteria in Solid Tumors (mRECIST) was estimated for treated vs untreated LR-4 masses using the Kaplan-Meier method and compared using the log rank test. LR-4 masses averaged 1.8 cm; 88%, 60%, 14%, and 14% demonstrated arterial phase hyperenhancement, washout, a capsule, and growth. Of LR-4 masses, 62 were within the liver volume that received embolization and considered treated, and 19 were outside and considered untreated. Response rates according to mRECIST were 37% vs 21% for treated vs untreated masses (P = .27). The 6- and 12-month rates of progression to LR-5 were 7% and 26% for treated masses vs 27% and 75% for untreated masses (P = .001). According to mRECIST, 7% and 27% of treated masses progressed vs 30% and 65% of untreated masses (P = .001). LR-4 masses that receive embolization in the setting of dominant masses elsewhere show lower rates of progression compared with untreated masses. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

  8. Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.

    Science.gov (United States)

    Traboulsi, Wael; Sergent, Frédéric; Boufettal, Houssine; Brouillet, Sophie; Slim, Rima; Hoffmann, Pascale; Benlahfid, Mohammed; Zhou, Qun Y; Balboni, Gianfranco; Onnis, Valentina; Bolze, Pierre A; Salomon, Aude; Sauthier, Philippe; Mallet, François; Aboussaouira, Touria; Feige, Jean J; Benharouga, Mohamed; Alfaidy, Nadia

    2017-11-15

    Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy. Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control ( n = 20) and in distinctive CHM ( n = 38) and CC ( n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice. Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions. Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR . ©2017 American Association for Cancer Research.

  9. Gemcitabine plus nedaplatin as salvage therapy is a favorable option for patients with progressive metastatic urothelial carcinoma after two lines of chemotherapy.

    Science.gov (United States)

    Matsumoto, Kazumasa; Mochizuki, Kohei; Hirayama, Takahiro; Ikeda, Masaomi; Nishi, Morihiro; Tabata, Ken-ichi; Okazaki, Miyoko; Fujita, Tetsuo; Taoka, Yoshinori; Iwamura, Masatsugu

    2015-01-01

    This study was conducted to evaluate the effectiveness of a combination of gemcitabine and nedaplatin therapy among patients with metastatic urothelial carcinoma previously treated with two lines of chemotherapy. Between February 2009 and August 2013, 30 patients were treated with gemcitabine and paclitaxel as a second-line chemotherapy. All had received a first-line chemotherapy consisting of methotrexate, vinblastine, doxorubicin and cisplatin. Ten patients who had measurable histologically proven advanced or metastatic urothelial carcinoma of the urinary bladder and upper urinary tract received gemcitabine 1,000 mg/m2 on days 1, 8 and 15 and nedaplatin 70 mg/m2 on day 2 as a third-line chemotherapy. Tumors were assessed by imaging every two cycles. The median number of treatment cycles was 3.5. One patient had partial response and three had stable disease. The disease-control rate was 40%, the median overall survival was 8.8 months and the median progression-free survival was 5.0 months. The median overall survival times for the first-line and second-line therapies were 29.1 and 13.9 months, respectively. Among disease-controlled patients (n=4), median overall survival was 14.2 months. Myelosuppression was the most common toxicity. There were no therapy-related deaths. Gemcitabine and nedaplatin chemotherapy is a favorable third-line chemotherapeutic option for patients with metastatic urothelial carcinoma. Given the safety and benefit profile seen in this study, further prospective trials are warranted given the implications of our results with regard to strategic chemotherapy for patients with advanced or metastatic urothelial carcinoma.

  10. Clinical implications of heterogeneity of tumor response to radiation therapy

    International Nuclear Information System (INIS)

    Suit, H.; Skates, S.; Taghian, A.; Okunieff, P.; Efird, J.T.

    1992-01-01

    Heterogeneity of response of tumor tissue to radiation clearly exists. Major parameters include histopathologic type, size (number of tumor rescue units (TRUs)), hemoglobin concentration, cell proliferation kinetics and immune rejection reaction by host. Further, normal and presumably tumor tissue response is altered in certain genetic diseases, e.g. ataxia telangiectasia. Any assessment of response of tumor tissue to a new treatment method or the testing of a new clinical response predictor is optimally based upon a narrow strata, viz., uniform with respect to known parameters of response, e.g. size, histological type. Even among tumors of such a clinical defined narrow strata, there will be residual heterogeneity with respect to inherent cellular radiation sensitivity, distributions of pO 2 , (SH), cell proliferation, etc. (author). 39 refs., 7 figs., 3 tabs

  11. Rates and Durability of Response to Salvage Radiation Therapy Among Patients With Refractory or Relapsed Aggressive Non-Hodgkin Lymphoma

    International Nuclear Information System (INIS)

    Tseng, Yolanda D.; Chen, Yu-Hui; Catalano, Paul J.; Ng, Andrea

    2015-01-01

    Purpose: To evaluate the response rate (RR) and time to local recurrence (TTLR) among patients who received salvage radiation therapy for relapsed or refractory aggressive non-Hodgkin lymphoma (NHL) and investigate whether RR and TTLR differed according to disease characteristics. Methods and Materials: A retrospective review was performed for all patients who completed a course of salvage radiation therapy between January 2001 and May 2011 at Brigham and Women's Hospital/Dana-Farber Cancer Institute. Separate analyses were conducted for patients treated with palliative and curative intent. Predictors of RR for each subgroup were assessed using a generalized estimating equation model. For patients treated with curative intent, local control (LC) and progression-free survival were estimated with the Kaplan-Meier method; predictors for TTLR were evaluated using a Cox proportional hazards regression model. Results: Salvage radiation therapy was used to treat 110 patients to 121 sites (76 curative, 45 palliative). Salvage radiation therapy was given as part of consolidation in 18% of patients treated with curative intent. Median dose was 37.8 Gy, with 58% and 36% of curative and palliative patients, respectively, receiving 39.6 Gy or higher. The RR was high (86% curative, 84% palliative). With a median follow-up of 4.8 years among living patients, 5-year LC and progression-free survival for curative patients were 66% and 34%, respectively. Refractory disease (hazard ratio 3.3; P=.024) and lack of response to initial chemotherapy (hazard ratio 4.3; P=.007) but not dose (P=.93) were associated with shorter TTLR. Despite doses of 39.6 Gy or higher, 2-year LC was only 61% for definitive patients with refractory disease or disease that did not respond to initial chemotherapy. Conclusions: Relapsed or refractory aggressive NHL is responsive to salvage radiation therapy, and durable LC can be achieved in some cases. However, refractory disease is associated with a

  12. Do chronic myeloid leukemia patients with late "warning" responses benefit from "watch and wait" or switching therapy to a second generation tyrosine kinase inhibitor?

    Science.gov (United States)

    García-Gutiérrez, Valentin; Puerta, Jose Manuel; Maestro, Begoña; Casado Montero, Luis Felipe; Muriel, Alfonso; Molina Hurtado, Jose Ramon; Perez-Encinas, Manuel; Moreno Romero, Maria Victoria; Suñol, Pere Barba; Sola Garcia, Ricardo; De Paz, Raquel; Ramirez Sanchez, Maria Jose; Osorio, Santiago; Mata Vazquez, Maria Isabel; Martinez López, Joaquin; Sastre, Jose Luis; Portero, Maria de Los Angles; Bautista, Guiomar; Duran Nieto, Maria Soledad; Giraldo, Pilar; Jimenez Jambrina, Margarita; Burgaleta, Carmen; Ruiz Aredondo, Joaquin; Peñarrubia, Maria Jesús; Requena, Maria José; Fernández Valle, María Del Carmen; Calle, Carmen; Paz Coll, Antonio; Hernández-Rivas, Jose Ángel; Franco Osorio, Rafael; Cano, Pilar; Tallón Pérez, David; Fernández de la Mata, Margarita; Garrido, Pilar López; Steegmann, Juan Luis

    2014-11-01

    In the latest recommendations for the management of chronic-phase chronic myeloid leukemia suboptimal responses have been reclassified as "warning responses." In contrast to previous recommendations current guidance advises close monitoring without changing therapy. We have identified 198 patients treated with first-line imatinib, with a warning response after 12 months of treatment (patients with a complete cytogenetic response but no major molecular response [MMR]). One hundred and forty-six patients remained on imatinib, while 52 patients changed treatment to a second generation tyrosine kinase inhibitor (2GTKI). Changing therapy did not correlate with an increase in overall survival or progression-free survival. Nevertheless, a significant improvement was observed in the probability of a MMR: 24% vs. 42% by 12 months and 43% vs. 64% by 24 months (P = 0.002); as well as the probability of achieving a deep molecular responses (MR(4.5) ): 1% vs. 17% and 7% vs. 23% by 12 and 24 months, respectively (P = molecular responses after changing treatment to 2GTKI in patients with late suboptimal response treated with imatinib first line. However, these benefits were not correlated with an improvement of progression free survival or overall survival. © 2014 Wiley Periodicals, Inc.

  13. Progression of hydroxychloroquine toxic effects after drug therapy cessation: new evidence from multimodal imaging.

    Science.gov (United States)

    Mititelu, Mihai; Wong, Brandon J; Brenner, Marie; Bryar, Paul J; Jampol, Lee M; Fawzi, Amani A

    2013-09-01

    Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. Retinal toxic effects. Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). Preservation of the external limiting membrane carries a positive prognostic value in

  14. Rapid response of breast cancer to neoadjuvant intramammary testosterone-anastrozole therapy: neoadjuvant hormone therapy in breast cancer.

    Science.gov (United States)

    Glaser, Rebecca L; Dimitrakakis, Constantine

    2014-06-01

    Experimental and clinical data support the inhibitory effect of testosterone on breast tissue and breast cancer. However, testosterone is aromatized to estradiol, which exerts the opposite effect. The aim of this study was to determine the effect of testosterone, combined with the aromatase inhibitor anastrozole, on a hormone receptor positive, infiltrating ductal carcinoma in the neoadjuvant setting. To determine clinical response, we obtained serial ultrasonic measurements and mammograms before and after therapy. Three combination implants-each containing 60 mg of testosterone and 4 mg of anastrozole-were placed anterior, superior, and inferior to a 2.4-cm tumor in the left breast. Three additional testosterone-anastrozole implants were again placed peritumorally 48 days later. By day 46, there was a sevenfold reduction in tumor volume, as measured on ultrasound. By week 13, we documented a 12-fold reduction in tumor volume, demonstrating a rapid logarithmic response to intramammary testosterone-anastrozole implant therapy, equating to a daily response rate of 2.78% and a tumor half-life of 23 days. Therapeutic systemic levels of testosterone were achieved without elevation of estradiol, further demonstrating the efficacy of anastrozole combined with testosterone. This novel therapy, delivered in the neoadjuvant setting, has the potential to identify early responders and to evaluate the effectiveness of therapy in vivo. This may prove to be a new approach to both local and systemic therapies for breast cancer in subgroups of patients. In addition, it can be used to reduce tumor volume, allowing for less surgical intervention and better cosmetic oncoplastic results.

  15. Progress of Shenqi Fuzheng Injection as Adjuvant Therapy for Malignant Tumors

    Directory of Open Access Journals (Sweden)

    Jing WANG

    2017-09-01

    Full Text Available Tumor is a kind of common and frequently-occurring disease that severely impaires human lives and health. As is proposed in Required Readings for Medical Professions, “Accumulation of virus causes insuffcient healthy qi, and then results in invasion of evil qi into the body”. Tumor is caused by interaction of exogenous evil qi and pathogenic products in the body such as phlegm and blood stasis on the basis of healthy qi defciency and disharmony of viscera. Therefore, the condition of healthy qi is not only the key of the occurrence of tumor, but a decisive factor of the development and prognosis of the disease. At present, the main therapeutic approaches for malignant tumors are radiotherapy and chemotherapy. However, during the disease process, the healthy qi gradually decreases due to the consumption of malignant tumors and the injury caused by radiotherapy and chemotherapy. In recent years, taking advantages of traditional Chinese drugs such as Shenqi Fuzheng Injection in combination with radiotherapy or chemotherapy is an important approach for many clinical physicians to improve therapeutic effects and alleviate toxic and side effects induced by radiotherapy and chemotherapy. This study mainly reviewed the progress of mechanisms and application of Shenqi Fuzhen Injection in malignant tumors in recent years.

  16. Synchronized Progression of Prestin Expression and Auditory Brainstem Response during Postnatal Development in Rats

    Directory of Open Access Journals (Sweden)

    Jianfeng Hang

    2016-01-01

    Full Text Available Prestin is the motor protein expressed in the cochlear outer hair cells (OHCs of mammalian inner ear. The electromotility of OHCs driven by prestin is responsible for the cochlear amplification which is required for normal hearing in adult animals. Postnatal expression of prestin and activity of OHCs may contribute to the maturation of hearing in rodents. However, the temporal and spatial expression of prestin in cochlea during the development is not well characterized. In the present study, we examined the expression and function of prestin from the OHCs in apical, middle, and basal turns of the cochleae of postnatal rats. Prestin first appeared at postnatal day 6 (P6 for basal turn, P7 in middle turn, and P9 for apical turn of cochlea. The expression level increased progressively over the next few days and by P14 reached the mature level for all three segments. By comparison with the time course of the development of auditory brainstem response for different frequencies, our data reveal that prestin expression synchronized with the hearing development. The present study suggests that the onset time of hearing may require the expression of prestin and is determined by the mature function of OHCs.

  17. Fuselage Versus Subcomponent Panel Response Correlation Based on ABAQUS Explicit Progressive Damage Analysis Tools

    Science.gov (United States)

    Gould, Kevin E.; Satyanarayana, Arunkumar; Bogert, Philip B.

    2016-01-01

    Analysis performed in this study substantiates the need for high fidelity vehicle level progressive damage analyses (PDA) structural models for use in the verification and validation of proposed sub-scale structural models and to support required full-scale vehicle level testing. PDA results are presented that capture and correlate the responses of sub-scale 3-stringer and 7-stringer panel models and an idealized 8-ft diameter fuselage model, which provides a vehicle level environment for the 7-stringer sub-scale panel model. Two unique skin-stringer attachment assumptions are considered and correlated in the models analyzed: the TIE constraint interface versus the cohesive element (COH3D8) interface. Evaluating different interfaces allows for assessing a range of predicted damage modes, including delamination and crack propagation responses. Damage models considered in this study are the ABAQUS built-in Hashin procedure and the COmplete STress Reduction (COSTR) damage procedure implemented through a VUMAT user subroutine using the ABAQUS/Explicit code.

  18. Temporal Progression of Retinal Progenitor Cell Identity: Implications in Cell Replacement Therapies

    Directory of Open Access Journals (Sweden)

    Awais Javed

    2017-12-01

    Full Text Available Retinal degenerative diseases, which lead to the death of rod and cone photoreceptor cells, are the leading cause of inherited vision loss worldwide. Induced pluripotent or embryonic stem cells (iPSCs/ESCs have been proposed as a possible source of new photoreceptors to restore vision in these conditions. The proof of concept studies carried out in mouse models of retinal degeneration over the past decade have highlighted several limitations for cell replacement in the retina, such as the low efficiency of cone photoreceptor production from stem cell cultures and the poor integration of grafted cells in the host retina. Current protocols to generate photoreceptors from stem cells are largely based on the use of extracellular factors. Although these factors are essential to induce the retinal progenitor cell (RPC fate from iPSCs/ESCs, developmental studies have shown that RPCs alter fate output as a function of time (i.e., their temporal identity to generate the seven major classes of retinal cell types, rather than spatial position. Surprisingly, current stem cell differentiation protocols largely ignore the intrinsic temporal identity of dividing RPCs, which we argue likely explains the low efficiency of cone production in such cultures. In this article, we briefly review the mechanisms regulating temporal identity in RPCs and discuss how they could be exploited to improve cone photoreceptor production for cell replacement therapies.

  19. Recent progress in studying curcumin and its nano-preparations for cancer therapy.

    Science.gov (United States)

    Liu, Jieying; Chen, Siyuan; Lv, Li; Song, Lei; Guo, Shengrong; Huang, Shengtang

    2013-01-01

    A hydrophobic polyphenol compound extracted from turmeric, curcumin has been widely utilized as traditional medicines for centuries in China and India. Over the last decades, because of its low toxicity, extensive studies have been focused on its physicochemical properties and pharmacological activities on various diseases, such as cancer, cardio-vascular disease, inflammatory bowel, wound healing, Alzheimer's disease, rheumatoid arthritis, and diabetes. In particular, bioactivities of curcumin as an effective chemopreventive agent, chemo-/radio-sensitizer for tumor cells, and chemo-/radio-protector for normal organs, are of extraordinary research interests in the literature. Despite these advantages, applications of curcumin are limited in clinical trials because of its poor water solubility and low oral bioavailability. Nano-preparations as an emerging platform for the efficient delivery of anti-cancer drugs should overcome these problems. In this review, we at first briefly revisit important properties of curcumin as well as its uses in cancer treatments, and then overview various nano-preparations of curcumin for cancer therapy, including nanoparticles, liposomes, micelles, nanoemulsions, cyclodextrin complexes, nanodisks, nanofibres, solid lipid nanoparticles, and curcumin conjugates.

  20. Impact of hepatitis B virus infection on HIV response to antiretroviral therapy in a Chinese antiretroviral therapy center

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    Rongrong Yang

    2014-11-01

    Conclusions: HBV co-infection can affect late immunological and virological responses to ART and increase the risk of hepatotoxicity. Mortality due to liver disease was high among HIV/HBV co-infected individuals in this study, despite HBV-active ART. As long as HIV/HBV co-infected persons need anti-HBV therapy, they should be recommended ART that includes agents with activity against both HIV and HBV, regardless of the CD4 cell count level.

  1. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

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    Ilaria eSciamanna

    2016-02-01

    Full Text Available In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1 retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT, which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  2. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Science.gov (United States)

    Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

    2016-02-01

    In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  3. Dynamics of the Intratumoral Immune Response during Progression of High-Grade Serous Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Mandy Stanske

    2018-03-01

    Full Text Available PURPOSE: Tumor-infiltrating lymphocytes (TILs have an established impact on the prognosis of high-grade serous ovarian carcinoma (HGSOC, however, their role in recurrent ovarian cancer is largely unknown. We therefore systematically investigated TIL densities and MHC class I and II (MHC1, 2 expression in the progression of HGSOC. EXPERIMENTAL DESIGN: CD3+, CD4+, CD8+ TILs and MHC1, 2 expression were evaluated by immunohistochemistry on tissue microarrays in 113 paired primary and recurrent HGSOC. TILs were quantified by image analysis. All patients had been included to the EU-funded OCTIPS FP7 project. RESULTS: CD3+, CD4+, CD8+ TILs and MHC1 and MHC2 expression showed significant correlations between primary and recurrent tumor levels (Spearman rho 0.427, 0.533, 0.361, 0.456, 0.526 respectively; P<.0001 each. Paired testing revealed higher CD4+ densities and MHC1 expression in recurrent tumors (Wilcoxon P=.034 and P=.018. There was also a shift towards higher CD3+ TILs levels in recurrent carcinomas when analyzing platinum-sensitive tumors only (Wilcoxon P=.026 and in pairs with recurrent tumor tissue from first relapse only (Wilcoxon P=.031. High MHC2 expression was the only parameter to be significantly linked to prolonged progression-free survival after first relapse (PFS2, log-rank P=.012. CONCLUSIONS: This is the first study that analyzed the development of TILs density and MHC expression in paired primary and recurrent HGSOC. The level of the antitumoral immune response in recurrent tumors was clearly dependent on the one in the primary tumor. Our data contribute to the understanding of temporal heterogeneity of HGSOC immune microenvironment and have implications for selection of samples for biomarker testing in the setting of immune-targeting therapeutics.

  4. Influence of combined therapy with prospidin and methotrexate on radiological progression, functional status and quality of life in pts with rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    O. V. Simonova

    2004-01-01

    Full Text Available Objective. To evaluate influence of combination therapy with prospidin (P and methotrexate (MTX on X-ray progression, functional status (FS and quality of life (QL in patients with rheumatoid arthritis (RA in comparison with MTX monotherapy. Material and methods. 143 RA pts (129 female and 14 male were studied. Of them, there were. Mean age was 45.5±5.l years. Average duration of the disease was 4.5 years. 20 pts had II and 123 - 111 degree of RA activity. The second X-ray stage according to Steinbroker dominated. 72 pts of group I received P+MTX combination therapy. The therapy included intravenous drip-feed of P 200-300 mg per week in 200ml of 5% glucose and MTX 10 mg per week 1M. The maintaining therapy included P 100-200 mg per week IM and MTX 10 mg per week. 71 patients of group II received MTX monotherapy 10 mg per week. X-ray progression assessment was performed according to Sharp method. FS was evaluated with the HAQ questionnaire, Lee test. QL was evaluated with SF-36 scale. Pts were examined before and after I, 2, 3, 6 and 12 months of treatment. Results. There was no increase of X-ray progression of the disease in case of P+MTX therapy as compared with MTX monotherapy. Both methods resulted in improvement of FS parameters and physical health. Combination therapy significantly improved psychological health as well.

  5. Histologic response of soft tissue sarcoma to radiation therapy

    International Nuclear Information System (INIS)

    Willett, C.G.; Schiller, A.L.; Suit, H.D.; Mankin, H.J.; Rosenberg, A.

    1987-01-01

    Twenty-seven patients with soft tissue sarcoma had preoperative radiotherapy, limb-sparing marginal surgical resection and whole-mount tumor histologic analysis. Incisional biopsy specimens before radiotherapy were reviewed for tumor type, grade, and extent of necrosis. Preoperative radiotherapy was given in either of two regimens: 13 patients received a mean total dose of 5250 cGy in one daily 180 to 200 cGy fractions and 14 patients a mean total dose of 4770 cGy in two daily fractions of 180 to 200 cGy separated by 4 hours. Twenty-one specimens had at least 80% necrosis or severely altered cells, a 3+ to 4+ response. Grade and size of the tumor appeared to be indicators of response to treatment rather than histologic type. Three of five patients (60%) with Grade 1, eight of 11 patients (73%) with Grade 2 lesions, and ten of 11 patients (91%) with Grade 3 tumors had 80% or greater necrosis or severely altered cells. For tumors 10 cm or less in greatest diameter, the 3+ to 4+ histologic response was seen in 12 of 14 patients (86%) whereas for lesions greater than 10 cm, this response was observed in nine of 13 patients (69%). For patients with Grade 2 or 3 soft tissue sarcoma, 13 of 14 patients (93%) treated with two fractions per day and two of four patients (50%) receiving one fraction per day exhibited significant response. All six patients treated twice daily for lesions greater than 10 cm had 3+ to 4+ histologic response compared to three of seven (43%) patients treated once per day. Therefore, grade and size of soft tissue sarcoma are important predictors of response to radiotherapy and preoperative twice daily radiotherapy may more likely permit the conservative surgical excision of sarcomas of borderline resectability

  6. Predictive value of early viriological response for sustained viriological response in chronic hepatitis c with conventional interferon therapy

    International Nuclear Information System (INIS)

    Awan, A.; Umar, M.; Khaar, H.T.B.; Kulsoom, A.; Minhas, Z.; Ambreen, S.; Habib, N.; Mumtaz, W.; Habib, F.

    2016-01-01

    Background: Hepatitis is a major public health problem in Pakistan due to its strong association with liver failure and hepatocellular carcinoma. In Pakistan, conventional interferon therapy along with Ribavirin is favoured especially in Government funded programs for treatment of Hepatitis C, over the more expensive Pegylated Interferon and Ribavirin combination therapy as recommended by Pakistan society of Gastroenterology and GI endoscopy due to its favourable results observed in genotype 3 which is the dominant genotype of this region. Objective of our study was to assess the viriological responses with standard interferon therapy and to determine the predictive values of early viriological response (EVR) for Sustained Viriological Response (SVR) in chronic hepatitis C patients treated with standard interferon therapy. Methods: A cross sectional study was conducted on patients with chronic hepatitis C having received standard interferon and ribavirin therapy for six months. EVR and SVR were noted for analysis. Positive and negative predictive values of EVR on SVR were calculated. Results: Out of the total sample (N=3075), 1946 (63.3 percentage) patients were tested for EVR. 1386 (71.2 percentage) were positive while 560 (28.8 percentage) were negative while 516 (16.8 percentage) were tested for SVR. Two hundred and eighty-five (55.2 percentage) were positive while 231 (44.8 percentage) were negative. EVR and SVR tested were N=117. Positive predictive value of EVR on SVR was 67.1 percentage and negative predictive value was 65.8 percentage. Statistically significant association between EVR and SVR was determined with Chi square statistic of 11.8 (p-value <0.0001). Conclusion: EVR is a good predictor of response of patients to standard interferon and ribavirin therapy. In the absence of an EVR, it seems imperative to stop further treatment. Virilogical responses with conventional interferon therapy are comparable to those of pegylated interferon therapy so

  7. The host immunological response to cancer therapy: An emerging concept in tumor biology

    International Nuclear Information System (INIS)

    Voloshin, Tali; Voest, Emile E.; Shaked, Yuval

    2013-01-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome

  8. The host immunological response to cancer therapy: An emerging concept in tumor biology

    Energy Technology Data Exchange (ETDEWEB)

    Voloshin, Tali [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel); Voest, Emile E. [Department of Medical Oncology, University Medical Center Utrecht, Utrecht (Netherlands); Shaked, Yuval, E-mail: yshaked@tx.technion.ac.il [Department of Molecular Pharmacology, Rappaport Faculty of Medicine and the Rappaport Institute, Technion—Israel Institute of Technology, 1 Efron Street, Bat Galim, Haifa 31096 (Israel)

    2013-07-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction—both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. -- Highlights: • Cancer therapy induces host molecular and cellular pro-tumorigenic effects. • Host effects in response to therapy may promote tumor relapse and metastasis. • The reactive host consists of immunological mediators promoting tumor re-growth. • Blocking therapy-induced host mediators may improve outcome.

  9. Prediction of electroconvulsive therapy response and remission in major depression: Meta-analysis

    NARCIS (Netherlands)

    Van Diermen, L. (Linda); Van Den Ameele, S. (Seline); A.M. Kamperman (Astrid); Sabbe, B.C.G. (Bernard C.G.); Vermeulen, T. (Tom); Schrijvers, D. (Didier); T.K. Birkenhäger (Tom)

    2018-01-01

    textabstractElectroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate

  10. Effect of cobalt-60 radiation on response to endodontic therapy in monkeys

    International Nuclear Information System (INIS)

    Matson, J.E.; Patterson, S.S.; Kafrawy, A.H.; Hornback, N.B.; Shidnia, H.

    1978-01-01

    Response of teeth that had received therapeutic doses of Cobalt-60 radiation to endodontic therapy were investigated in three monkeys. The results indicated no appreciable effect of the irradiation on the response to root canal treatment aside from reduction in osteoblastic activity

  11. Prediction of Response to Medication and Cognitive Therapy in the Treatment of Moderate to Severe Depression

    Science.gov (United States)

    Fournier, Jay C.; DeRubeis, Robert J.; Shelton, Richard C.; Hollon, Steven D.; Amsterdam, Jay D.; Gallop, Robert

    2009-01-01

    A recent randomized controlled trial found nearly equivalent response rates for antidepressant medications and cognitive therapy in a sample of moderate to severely depressed outpatients. In this article, the authors seek to identify the variables that were associated with response across both treatments as well as variables that predicted…

  12. Counter-responses as organizers in adolescent analysis and therapy.

    Science.gov (United States)

    Richmond, M Barrie

    2004-01-01

    The author introduces Counter-response as a phenomological term to replace theory-burdened terms like counter-transference, counter-identification, and counter-resistance. He discusses the analyst's use of self (drawing on the comparison with Winnicott's use of the object) in processing the expectable destabilizing counter-reactions that occur in working therapeutically with disturbed adolescents and their parents. Further; he discusses the counter-reaction to the patient's narrative, acting-out, and how re-enactments can serve as an organizer for understanding the patient's inner life when the analyst formulates his/her counter-response. Emphasis is placed on the therapist forming his or her own narrative with the adolescent that takes into account the evoked counter-reaction. For this purpose, the author recommends the use of a combined counter-response and metaphor-orienting perspective to acknowledge and work with the denial, illusions, reversal of perspective, and catastrophic anxieties experienced with these adolescents. The counter-response perspective permits the emergence of the disturbed adolescent's novel narrative; however, since these experiences can be destabilizing or disruptive, the author also recommends the use of a personal metaphor to anticipate the reluctance to examining, processing, and formulating the analyst's dysphoric counter-reaction. With the use of the counter-response, the analyst's therapeutic ideal is to achieve a more optimal balance between using accepted narrative theories and exploring novel enactment experiences. His swimming metaphor stratagem is designed to keep the analyst in these difficult encounters.

  13. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifies. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement required from a response modifier to effect significant improvements in tumor cure rates

  14. Modifiers of radiation response in tumor therapy: strategies and expectations

    International Nuclear Information System (INIS)

    Elkind, M.M.

    1982-01-01

    The administration of two (or more) cytotoxic agents to widen the differential between the responses of tumor and normal tissues depends upon the biological properties of the agents in the cells and tissues, their interactive potential, and the strategy employed in their administration. Assuming that one agent is ionizing radiation, and considering response modification in broad terms, the qualitative features of various strategies are developed for physical as well as chemical modifiers. The heterogeneity of human tumor cells and the compensatory mechanisms of normal tissues following injury are identified as topical areas requiring sustained research effort. Finally, estimates are developed for the degree of improvement from a response modifier to effect significant improvements in tumor cure rates

  15. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS mouse model.

    Directory of Open Access Journals (Sweden)

    Csilla Ari

    Full Text Available Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG, the main ingredient of the DP, and the ketogenic diet (KD, would increase motor function and survival in a mouse model of ALS (SOD1-G93A. ALS mice were fed standard rodent diet (SD, KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001 and 4.2% (p = 0.006, respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which

  16. Metabolic therapy with Deanna Protocol supplementation delays disease progression and extends survival in amyotrophic lateral sclerosis (ALS) mouse model.

    Science.gov (United States)

    Ari, Csilla; Poff, Angela M; Held, Heather E; Landon, Carol S; Goldhagen, Craig R; Mavromates, Nicholas; D'Agostino, Dominic P

    2014-01-01

    Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and eventual death from respiratory failure. There is currently no cure or effective treatment for ALS. Besides motor neuron degeneration, ALS is associated with impaired energy metabolism, which is pathophysiologically linked to mitochondrial dysfunction and glutamate excitotoxicity. The Deanna Protocol (DP) is a metabolic therapy that has been reported to alleviate symptoms in patients with ALS. In this study we hypothesized that alternative fuels in the form of TCA cycle intermediates, specifically arginine-alpha-ketoglutarate (AAKG), the main ingredient of the DP, and the ketogenic diet (KD), would increase motor function and survival in a mouse model of ALS (SOD1-G93A). ALS mice were fed standard rodent diet (SD), KD, or either diets containing a metabolic therapy of the primary ingredients of the DP consisting of AAKG, gamma-aminobutyric acid, Coenzyme Q10, and medium chain triglyceride high in caprylic triglyceride. Assessment of ALS-like pathology was performed using a pre-defined criteria for neurological score, accelerated rotarod test, paw grip endurance test, and grip strength test. Blood glucose, blood beta-hydroxybutyrate, and body weight were also monitored. SD+DP-fed mice exhibited improved neurological score from age 116 to 136 days compared to control mice. KD-fed mice exhibited better motor performance on all motor function tests at 15 and 16 weeks of age compared to controls. SD+DP and KD+DP therapies significantly extended survival time of SOD1-G93A mice by 7.5% (p = 0.001) and 4.2% (p = 0.006), respectively. Sixty-three percent of mice in the KD+DP and 72.7% of the SD+DP group lived past 125 days, while only 9% of the control animals survived past that point. Targeting energy metabolism with metabolic therapy produces a therapeutic effect in ALS mice which may prolong

  17. Tracking the progress of HIV: the impact of point-of-care tests on antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Reid SD

    2013-09-01

    Full Text Available Steven D Reid, Sarah J Fidler, Graham S Cooke Department of Infectious Diseases, St Mary's Hospital, Imperial College London, London, UK Abstract: It is now around 30 years since the discovery of HIV, the virus that causes AIDS. More than 70 million people have been infected in that time and around 35 million have died. The majority of those currently living with HIV/AIDS are in low- and middle-income countries, with sub-Saharan Africa bearing a disproportionate burden of the global disease. In high-income countries, the introduction of antiretroviral therapy (ART has drastically reduced the morbidity and mortality associated with HIV. Patients on ART are now predicted to have near-normal life expectancy and the role of treatment is increasingly recognized in preventing new infections. In low- and middle-income countries, treatment is now more widely available and around half of those who need ART are currently receiving it. Early diagnosis of HIV is essential if ART is to be optimally implemented. Lab-based diagnostics for screening, diagnosis, treatment initiation, and the monitoring of treatment efficacy are critical in managing the disease and reducing the number of new infections each year. The introduction of point-of-care HIV rapid tests has transformed the epidemic, particularly in low- and middle-income countries. For the first time, these point-of-care tests allow for the rapid identification of infected individuals outside the laboratory who can undergo counseling and treatment and, in the case of pregnant women, allow the timely initiation of ART to reduce the risk of vertical transmission. Although survival is markedly improved with ART even in the absence of laboratory monitoring, long-term management of people living with HIV on ART, and their partners, is essential to ensure successful viral suppression. The burden of disease in many resource-poor settings with high HIV prevalence has challenged the ability of local laboratories

  18. Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Xuemei; Zhai, Tingting; Ma, Ruixia; Luo, Congjuan; Wang, Huifang; Liu, Liqiu

    2018-11-01

    Whether uric acid levels were associated with the progression of chronic kidney disease (CKD) remained controversial. This meta-analysis was aimed to assess the effect of lowering serum uric acid therapy on the progression of CKD to clarify the role of uric acid in the progression of CKD indirectly. Pubmed, Embase, the Cochrane library, CBM were searched for randomized controlled trials (RCTs) that assessed the efficiency of lowering serum uric acid therapy on the progression of CKD without language restriction. Summary estimates of weighted mean differences (WMDs) and relative risk (RR) were obtained by using random-effect or fixed-effect models. Sensitivity analyses were performed to identify the source of heterogeneity. A total of 12 randomized controlled trials with 832 CKD participants were included in the analysis. Pooled estimate for eGFR was in favor of lowering serum uric acid therapy with a mean difference (MD) of 3.88 ml/min/1.73 m 2 , 95% CI 1.26-6.49 ml/min/1.73 m 2 , p = .004 and this was consistent with results for serum creatinine. The risk of worsening of kidney function or ESRD or death was significantly decreased in the treatment group compared to the control group (RR 0.39, 95% CI 0.28-0.52, pUric acid-lowering therapy may be effective in retarding the progression of CKD. Further randomized controlled trials should be performed to confirm the effect of lowering serum uric acid therapy on the progression of CKD.

  19. Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy. AIDS Clinical Trials Group Protocol 915 Team.

    Science.gov (United States)

    Holland, G N; Levinson, R D; Jacobson, M A

    1995-05-01

    A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression. This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates, which reflects the amount of retina destroyed when progression occurs. Patients were randomly given one of two foscarnet maintenance therapy doses (90 mg/kg of body weight/day [FOS-90 group] or 120 mg/kg of body weight/day [FOS-120 group] after induction therapy. Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis, posterior progression rates and foveal proximity rates for individual lesions, selected by prospectively defined criteria, were calculated in each patient. Rates were compared between groups. The following median rates were greater for the FOS-90 group (N = 8) than for the FOS-120 group (N = 10): greatest maximum rate at which lesions enlarged in a posterior direction (43.5 vs 12.5 microns/day; P = .002); posterior progression rate for lesions closest to the fovea (42.8 vs 5.5 microns/day; P = .010); and maximum foveal proximity rate for either eye (32.3 vs 3.4 microns/day; P = .031). Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy. A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy.

  20. Pretreatment with betamethasone of patients with Graves' disease given radioiodine therapy: thyroid autoantibody responses and outcome of therapy

    International Nuclear Information System (INIS)

    Gamstedt, A.; Karlsson, A.

    1991-01-01

    The effects of betamethasone on thyroid autoantibody responses and outcome of radioiodine therapy were determined over a period of 1 yr in a prospective randomized study of 40 patients with Graves' disease. Twenty patients were given placebo tablets, and 20 patients were treated with betamethasone from 3 weeks before until 4 weeks after 131 I therapy. At the time of inclusion in the study, the mean serum concentrations of TSH receptor antibodies, thyroid peroxidase antibodies, and thyroglobulin antibodies (TgAb) were increased in both groups. Three weeks of treatment with betamethasone reduced the thyroid peroxidase antibody and TgAb titers as well as the serum concentrations of thyroid hormones. A decrease in the TSH receptor antibody level was not statistically significant. After radioiodine therapy, transient increases in thyroid autoantibody levels were observed. The titers of the different antibodies generally changed in parallel. In some patients a detectable level of a given antibody was found only after the radioiodine treatment, and in two cases, TgAb did not appear at all, although the two other antibodies increased temporarily. Betamethasone delayed, but did not abolish, the 131 I-induced antibody peaks. Betamethasone also caused a reduction in the total serum immunoglobulin G, a reduction which persisted throughout the study period. When the study ended, 17 patients given placebo and 9 patients given betamethasone were receiving replacement therapy due to the development of hypothyroidism. These patients at this point in time had lower antibody levels than those not requiring T4. The results of this study demonstrate that betamethasone reduces and modifies the thyroid autoantibody responses as well as the outcome of radioiodine therapy in patients with Graves' disease

  1. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide

    DEFF Research Database (Denmark)

    Dresemann, G.; Weller, M.; Ostenfeld-Rosenthal, Ann Maria

    2010-01-01

    A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor...... activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0-2 who had completed previous treatment comprising surgical resection, irradiation therapy...

  2. Is PET/CT efficient tool to evaluate the response after stereotactic radiation therapy for pancreas cancer?

    International Nuclear Information System (INIS)

    Kim, Mi Sook; Yoo, Seong Yul; Cho, Chul Koo

    2005-01-01

    In pancreas cancer, to evaluate the efficacy of PET/CT as tool to check the response after stereotactic radiation therapy and to define functional imaging role of PET/CT as alterative tool of computed tomography. From November 2003 to December 2004, among locally advanced pancreas cancer patients treated by stereotactic radiation therapy using CyberKnife(CK), 14 were evaluated by PET/CT before and after treatment. Four patients took PET/CT one month after CK, 4 patients 2 months after CK, and 6 patients 3 months after CK as the first evaluation of treatment. All of patients were also evaluated by CT or CA19-9 tumor antigen with the range of 1-2 months after CK. In addition of PET/CT to CT, lymph node metastasis were revealed as positive in 4 patients who had negative finding on CT. Furthermore, patients who showed partial or complete response on PET/CT findings that checked within 3 months after CK have significantly longer median survival time than patients who showed no response or disease progression(13 months and 9 months, respectively). Responses based on CA19-9 tumor antigen or CT, however, showed no significant difference in terms of median survival time. PET/CT can provide more information for lymph node metastasis compared to CT alone. It is very helpful for delineation of tumor extent for CK planning. And initial response on PET/CT scan could be a significant prognostic factor rather than response on CA19-9 level or CT. In the future, more study is necessary to evaluate if PET/CT could substitute CT and finally CT could be omitted during follow-up period after CK

  3. Power and Responsibility in Therapy: Integrating Feminism and Multiculturalism

    Science.gov (United States)

    Williams, Elizabeth Nutt; Barber, Jill S.

    2004-01-01

    The integration of feminist and multicultural approaches to psychotherapy, called for many times, has not yet materialized. This article reviews possible reasons this integration has not taken place and offers an approach to integration based on the guiding principles of power and responsibility, which builds on previous theories and approaches.

  4. Evolution of the health sector response to HIV in Myanmar: progress, challenges and the way forward.

    Science.gov (United States)

    Oo, Htun Nyunt; Hone, San; Fujita, Masami; Maw-Naing, Amaya; Boonto, Krittayawan; Jacobs, Marjolein; Phyu, Sabe; Bollen, Phavady; Cheung, Jacquie; Aung, Htin; Aung Sang, May Thu; Myat Soe, Aye; Pendse, Razia; Murphy, Eamonn

    2016-11-28

    Critical building blocks for the response to HIV were made until 2012 despite a series of political, social and financial challenges. A rapid increase of HIV service coverage was observed from 2012 to 2015 through collaborative efforts of government and non-governmental organisations (NGOs). Government facilities, in particular, demonstrated their capacity to expand services for antiretroviral therapy (ART), prevention of mother-to-child transmission (PMTCT) of HIV, tuberculosis and HIV co-infection and methadone-maintenance therapy (MMT). After nearly three decades into the response to HIV, Myanmar has adopted strategies to provide the right interventions to the right people in the right places to maximise impact and cost efficiency. In particular, the country is now using strategic information to classify areas into high-, medium- and low-HIV burden and risk of new infections for geographical prioritisation - as HIV remains concentrated among key population (KP) groups in specific geographical areas. Ways forward include: •Addressing structural barriers for KP to access services, and identifying and targeting KPs at higher risk;•Strengthening the network of public facilities, NGOs and general practitioners and introducing a case management approach to assist KPs and other clients with unknown HIV status, HIV-negative clients and newly diagnosed clients to access the health services across the continuum to increase the number of people testing for HIV and to reduce loss to follow-up in both prevention and treatment;•Increasing the availability of HIV testing and counselling services for KPs, clients of female sex workers (FSW), and other populations at risk, and raising the demand for timely testing including expansion of outreach and client-initiated voluntary counselling and testing (VCT) services;•Monitoring and maximising retention from HIV diagnosis to ART initiation and expanding quality HIV laboratory services, especially viral load

  5. Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

    Science.gov (United States)

    Costa, Rúbia S; Carvalho, Lucas P; Campos, Taís M; Magalhães, Andréa S; Passos, Sara T; Schriefer, Albert; Silva, Juliana A; Lago, Ednaldo; Paixão, Camilla S; Machado, Paulo; Scott, Phillip; Carvalho, Edgar M

    2018-02-14

    Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  6. Microanalysis on selected video clips with focus on communicative response in music therapy

    DEFF Research Database (Denmark)

    Ridder, Hanne Mette Ochsner

    2007-01-01

    This chapter describes a five-step procedure for video analysis where the topic of investigation is the communicative response of clients in music therapy. In this microanalysis procedure only very short video clips are used, and in order to select these clips an overview of each music therapy...... session is obtained with the help of a session-graph that is a systematic way of collecting video observations from one music therapy session and combining the data in one figure. The systematic procedures do not demand sophisticated computer equipment; only standard programmes such as Excel and a media...... player. They are based on individual music therapy work with a population who are difficult to engage in joint activities and who show little response (e.g. persons suffering from severe dementia). The video analysis tools might be relevant to other groups of clients where it is important to form a clear...

  7. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

    Directory of Open Access Journals (Sweden)

    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

  8. Prediction of electroconvulsive therapy response and remission in major depression : meta-analysis

    OpenAIRE

    Diermen, van, Linda; Ameele, van den, Seline; Kamperman, Astrid M.; Sabbe, Bernard G.C.; Vermeulen, Tom; Schrijvers, Didier; Birkenhager, Tom K.

    2018-01-01

    Abstract: Background Electroconvulsive therapy (ECT) is considered to be the most effective treatment in severe major depression. The identification of reliable predictors of ECT response could contribute to a more targeted patient selection and consequently increased ECT response rates. Aims To investigate the predictive value of age, depression severity, psychotic and melancholic features for ECT response and remission in major depression. Method A meta-analysis was conducted according to t...

  9. Nomograms Predicting Response to Therapy and Outcomes After Bladder-Preserving Trimodality Therapy for Muscle-Invasive Bladder Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Coen, John J., E-mail: jcoen@harthosp.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Paly, Jonathan J.; Niemierko, Andrzej [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Kaufman, Donald S. [Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Heney, Niall M. [Department of Urology, Massachusetts General Hospital, Boston, Massachusetts (United States); Spiegel, Daphne Y.; Efstathiou, Jason A.; Zietman, Anthony L.; Shipley, William U. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

    2013-06-01

    Purpose: Selective bladder preservation by use of trimodality therapy is an established management strategy for muscle-invasive bladder cancer. Individual disease features have been associated with response to therapy, likelihood of bladder preservation, and disease-free survival. We developed prognostic nomograms to predict the complete response rate, disease-specific survival, and likelihood of remaining free of recurrent bladder cancer or cystectomy. Methods and Materials: From 1986 to 2009, 325 patients were managed with selective bladder preservation at Massachusetts General Hospital (MGH) and had complete data adequate for nomogram development. Treatment consisted of a transurethral resection of bladder tumor followed by split-course chemoradiation. Patients with a complete response at midtreatment cystoscopic assessment completed radiation, whereas those with a lesser response underwent a prompt cystectomy. Prognostic nomograms were constructed predicting complete response (CR), disease-specific survival (DSS), and bladder-intact disease-free survival (BI-DFS). BI-DFS was defined as the absence of local invasive or regional recurrence, distant metastasis, bladder cancer-related death, or radical cystectomy. Results: The final nomograms included information on clinical T stage, presence of hydronephrosis, whether a visibly complete transurethral resection of bladder tumor was performed, age, sex, and tumor grade. The predictive accuracy of these nomograms was assessed. For complete response, the area under the receiving operating characteristic curve was 0.69. The Harrell concordance index was 0.61 for both DSS and BI-DFS. Conclusions: Our nomograms allow individualized estimates of complete response, DSS, and BI-DFS. They may assist patients and clinicians making important treatment decisions.

  10. Non-specific vaginitis: diagnostic features and response to imidazole therapy (metronidazole, ornidazole).

    Science.gov (United States)

    Meech, R J; Loutit, J

    1985-05-22

    Detailed quantitative aerobic, anaerobic, fungal and mycoplasma flora was obtained for 43 women presenting with complaints of vaginal discharge and malodour. Clinical response was associated with eradication of the abnormal anaerobic flora, despite persistence of G vaginalis in nine (26%). Topical imidazole therapy appeared to have some advantage over oral therapy. Gram stains of vaginal swabs were found to be the most useful laboratory investigation.

  11. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women

    Science.gov (United States)

    The effect of hormone therapy (HT) on the plasma concentration of remnant lipoprotein cholesterol (RLP-C) and high density lipoprotein (HDL) subpopulations and the contribution of HT-related changes in these lipoproteins to the progression of coronary heart disease (CHD) were examined in 256 postmen...

  12. Influence of macrolide maintenance therapy and bacterial colonisation on exacerbation frequency and progression of COPD (COLUMBUS: Study protocol for a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Uzun Sevim

    2012-06-01

    Full Text Available Abstract Background Chronic obstructive pulmonary disease (COPD is characterised by progressive development of airflow limitation that is poorly reversible. Because of a poor understanding of COPD pathogenesis, treatment is mostly symptomatic and new therapeutic strategies are limited. There is a direct relationship between the severity of the disease and the intensity of the inflammatory response. Besides smoking, one of the hypotheses for the persistent airway inflammation is the presence of recurrent infections. Macrolide antibiotics have bacteriostatic as well as anti-inflammatory properties in patients with cystic fibrosis and other inflammatory pulmonary diseases. There is consistent evidence that macrolide therapy reduces infectious exacerbations, decreases the requirement for additional antibiotics and improves nutritional measures. Because of these positive effects we hypothesised that maintenance macrolide therapy may also have beneficial effects in patients with COPD who have recurrent exacerbations. The effects on development of bacterial resistance to macrolides due to this long-term treatment are unknown. Until now, studies investigating macrolide therapy in COPD are limited. The objective of this study is to assess whether maintenance treatment with macrolide antibiotics in COPD patients with three or more exacerbations in the previous year decreases the exacerbation rate in the year of treatment and to establish microbial resistance due to the long-term treatment. Methods/design The study is set up as a prospective randomised double-blind placebo-controlled single-centre trial. A total of 92 patients with COPD who have had at least three exacerbations of COPD in the previous year will be included. Subjects will be randomised to receive either azithromycin 500 mg three times a week or placebo. Our primary endpoint is the reduction in the number of exacerbations of COPD in the year of treatment. Discussion We investigate whether

  13. Sleep spindles may predict response to cognitive-behavioral therapy for chronic insomnia.

    Science.gov (United States)

    Dang-Vu, Thien Thanh; Hatch, Benjamin; Salimi, Ali; Mograss, Melodee; Boucetta, Soufiane; O'Byrne, Jordan; Brandewinder, Marie; Berthomier, Christian; Gouin, Jean-Philippe

    2017-11-01

    While cognitive-behavioral therapy for insomnia constitutes the first-line treatment for chronic insomnia, only few reports have investigated how sleep architecture relates to response to this treatment. In this pilot study, we aimed to determine whether pre-treatment sleep spindle density predicts treatment response to cognitive-behavioral therapy for insomnia. Twenty-four participants with chronic primary insomnia participated in a 6-week cognitive-behavioral therapy for insomnia performed in groups of 4-6 participants. Treatment response was assessed using the Pittsburgh Sleep Quality Index and the Insomnia Severity Index measured at pre- and post-treatment, and at 3- and 12-months' follow-up assessments. Secondary outcome measures were extracted from sleep diaries over 7 days and overnight polysomnography, obtained at pre- and post-treatment. Spindle density during stage N2-N3 sleep was extracted from polysomnography at pre-treatment. Hierarchical linear modeling analysis assessed whether sleep spindle density predicted response to cognitive-behavioral therapy. After adjusting for age, sex, and education level, lower spindle density at pre-treatment predicted poorer response over the 12-month follow-up, as reflected by a smaller reduction in Pittsburgh Sleep Quality Index over time. Reduced spindle density also predicted lower improvements in sleep diary sleep efficiency and wake after sleep onset immediately after treatment. There were no significant associations between spindle density and changes in the Insomnia Severity Index or polysomnography variables over time. These preliminary results suggest that inter-individual differences in sleep spindle density in insomnia may represent an endogenous biomarker predicting responsiveness to cognitive-behavioral therapy. Insomnia with altered spindle activity might constitute an insomnia subtype characterized by a neurophysiological vulnerability to sleep disruption associated with impaired responsiveness to

  14. Cervical Intradural Disc Herniation Causing Progressive Quadriparesis After Spinal Manipulation Therapy: A Case Report and Literature Review.

    Science.gov (United States)

    Yang, Hwan-Seo; Oh, Young-Min; Eun, Jong-Pil

    2016-02-01

    Cervical intradural disc herniation (IDH) is an extremely rare condition, comprising only 0.27% of all disc herniations. Three percent of IDHs occur in the cervical, 5% in the thoracic, and over 92% in the lumbar spinal canal. There have been a total of 31 cervical IDHs reported in the literature. The pathogenesis and imaging characteristics of IDH are not fully understood. A preoperative diagnosis is key to facilitating prompt intradural exploration in patients with ambivalent findings, as well as in preventing reoperation. The purpose of reporting our case is to remind clinicians to consider the possibility of cervical IDH during spinal manipulation therapy in patient with chronic neck pain.The patient signed informed consent for publication of this case report and any accompanying image. The ethical approval of this study was waived by the ethics committee of Chonbuk National University Hospital, because this study was case report and the number of patients was manipulation for chronic neck pain over the course of a month. The day prior, he had noticed neck pain and tingling in the bilateral upper and lower extremities during the manipulation procedure. The following day, he presented with bilateral weakness of all 4 extremities, which rendered him unable to walk. Neurological examination demonstrated a positive Hoffmann sign and ankle clonus bilaterally, hypoesthesia below the C5 dermatome, 3/5 strength in the bilateral upper extremities, and 2/5 strength in the lower extremities. This motor weakness was progressive, and he further complained of voiding difficulty.Urgent magnetic resonance imaging (MRI) of the cervical spine revealed large, central disc herniations at C4-C5 and C5-C6 that caused severe spinal cord compression and surrounding edema. We performed C4-C5-C6 anterior cervical discectomy and fusion.The patient's limb weakness improved rapidly within 1 day postoperatively, and he was discharged 4 weeks later. At his 12-month follow-up, the patient had

  15. Antibody production in response to staphylococcal MS-1 phage cocktail in patients undergoing phage therapy

    Directory of Open Access Journals (Sweden)

    Maciej Żaczek

    2016-10-01

    Full Text Available In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties towards applied phages (K rate. Among 20 examined patients receiving the MS-1 phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiphage antibodies in their sera during phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiphage antibodies did not translate into unsatisfactory clinical results of phage therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiphage antibodies before and during treatment. This may imply that possible induction of antiphage antibodies is not an obstacle to the implementation of phage therapy and support our assumption that the outcome of the phage treatment does not primarily depend on the appearance of antiphage antibodies in sera of patients during therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of phage therapy in humans.

  16. Antibody Production in Response to Staphylococcal MS-1 Phage Cocktail in Patients Undergoing Phage Therapy.

    Science.gov (United States)

    Żaczek, Maciej; Łusiak-Szelachowska, Marzanna; Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Międzybrodzki, Ryszard; Owczarek, Barbara; Kopciuch, Agnieszka; Fortuna, Wojciech; Rogóż, Paweł; Górski, Andrzej

    2016-01-01

    In this study, we investigated the humoral immune response (through the release of IgG, IgA, and IgM antiphage antibodies) to a staphylococcal phage cocktail in patients undergoing experimental phage therapy at the Phage Therapy Unit, Medical Center of the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. We also evaluated whether occurring antiphage antibodies had neutralizing properties toward applied phages (K rate). Among 20 examined patients receiving the MS-1 phage cocktail orally and/or locally, the majority did not show a noticeably higher level of antiphage antibodies in their sera during phage administration. Even in those individual cases with an increased immune response, mostly by induction of IgG and IgM, the presence of antiphage antibodies did not translate into unsatisfactory clinical results of phage therapy. On the other hand, a negative outcome of the treatment occurred in some patients who showed relatively weak production of antiphage antibodies before and during treatment. This may imply that possible induction of antiphage antibodies is not an obstacle to the implementation of phage therapy and support our assumption that the outcome of the phage treatment does not primarily depend on the appearance of antiphage antibodies in sera of patients during therapy. These conclusions are in line with our previous findings. The confirmation of this thesis is of great interest as regards the efficacy of phage therapy in humans.

  17. Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

    OpenAIRE

    Chang, J. Judy; Wightman, Fiona; Bartholomeusz, Angeline; Ayres, Anna; Kent, Stephen J.; Sasadeusz, Joseph; Lewin, Sharon R.

    2005-01-01

    Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with ...

  18. Salivary biomarkers associated with gingivitis and response to therapy.

    Science.gov (United States)

    Syndergaard, Ben; Al-Sabbagh, Mohanad; Kryscio, Richard J; Xi, Jing; Ding, Xiuhua; Ebersole, Jeffrey L; Miller, Craig S

    2014-08-01

    Salivary biomarkers are potentially important for determining the presence, risk, and progression of periodontal disease. However, clinical translation of biomarker technology from lab to chairside requires studies that identify biomarkers associated with the transitional phase between health and periodontal disease (i.e., gingivitis). Eighty participants (40 with gingivitis, 40 healthy) provided saliva at baseline and 7 to 30 days later. An additional sample was collected from gingivitis participants 10 to 30 days after dental prophylaxis. Clinical parameters of gingival disease were recorded at baseline and the final visit. Salivary concentrations of interleukin (IL)-1β, IL-6, matrix metalloproteinase (MMP)-8, macrophage inflammatory protein (MIP)-1α, and prostaglandin E2 (PGE2) were measured. Clinical features of health and gingivitis were stable at both baseline visits. Participants with gingivitis demonstrated significantly higher bleeding on probing (BOP), plaque index (PI), and gingival index (GI) (P ≤0.002) and a significant drop in BOP, PI, and GI post-treatment (P ≤0.001). Concentrations of MIP-1α and PGE2 were significantly higher (2.8 times) in the gingivitis group than the healthy group (P ≤0.02). After dental prophylaxis, mean biomarker concentrations did not decrease significantly from baseline in the gingivitis group, although concentrations of IL-1β, IL-6, and MMP-8 approached healthy levels, whereas MIP-1α and PGE2 concentrations remained significantly higher than in the healthy group (P ≤0.04). Odds ratio analyses showed that PGE2 concentrations, alone and in combination with MIP-1α, readily discriminated gingivitis from health. Salivary PGE2 and MIP-1α discriminate gingivitis from health, and patients with gingivitis who return to clinical health continue to produce inflammatory mediators for weeks after dental prophylaxis.

  19. Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency.

    Science.gov (United States)

    Singh, Neeraj Kumar; Mani, Revathy; Hussaindeen, Jameel Rizwana

    To evaluate the changes in the stimulus and response Accommodative Convergence to Accommodation (AC/A) ratio following vision therapy (VT) in Convergence Insufficiency (CI). Stimulus and response AC/A ratio were measured on twenty five CI participants, pre and post 10 sessions of VT. Stimulus AC/A ratio was measured using the gradient method and response AC/A ratio was calculated using modified Thorington technique with accommodative responses measured using WAM-5500 open-field autorefractor. The gradient stimulus and response AC/A cross-link ratios were compared with thirty age matched controls. Mean age of the CI and control participants were 23.3±5.2 years and 22.7±4.2 years, respectively. The mean stimulus and response AC/A ratio for CI pre therapy was 2.2±0.72 and 6.3±2.0 PD/D that changed to 4.2±0.9 and 8.28±3.31 PD/D respectively post vision therapy and these changes were statistically significant (paired t-test; paccommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI. Copyright © 2016 Spanish General Council of Optometry. Published by Elsevier España, S.L.U. All rights reserved.

  20. Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

    Science.gov (United States)

    Liu, Chang Ching; Ma, Dong Liang; Yan, Ting-Dong; Fan, XiuBo; Poon, Zhiyong; Poon, Lai-Fong; Goh, Su-Ann; Rozen, Steve G; Hwang, William Ying Khee; Tergaonkar, Vinay; Tan, Patrick; Ghosh, Sujoy; Virshup, David M; Goh, Eyleen L K; Li, Shang

    2016-10-01

    In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed replicative senescence. However, the cellular responses of human pluripotent stem cells to telomere uncapping remain unknown. We generated telomerase knockout human embryonic stem (ES) cells through gene targeting. Telomerase inactivation in ES cells results in progressive telomere shortening. Telomere DNA damage in ES cells and neural progenitor cells induces rapid apoptosis when telomeres are uncapped, in contrast to fibroblast cells that enter a state of replicative senescence. Significantly, telomerase inactivation limits the proliferation capacity of human ES cells without affecting their pluripotency. By targeting telomerase activity, we can functionally separate the two unique properties of human pluripotent stem cells, namely unlimited self-renewal and pluripotency. We show that the potential of ES cells to form teratomas in vivo is dictated by their telomere length. By controlling telomere length of ES cells through telomerase inactivation, we can inhibit teratoma formation and potentially improve the safety of cell therapies involving terminally differentiated cells as well as specific progenitor cells that do not require sustained cellular proliferation in vivo, and thus sustained telomerase activity. Stem Cells 2016;34:2471-2484. © 2016 AlphaMed Press.

  1. Cortisol responses to mental stress and the progression of coronary artery calcification in healthy men and women.

    Directory of Open Access Journals (Sweden)

    Mark Hamer

    Full Text Available Psychosocial stress is a risk factor for coronary heart disease (CHD. The mechanisms are incompletely understood, although dysfunction of the hypothalamic pituitary adrenal (HPA axis might be involved. We examined the association between cortisol responses to laboratory-induced mental stress and the progression of coronary artery calcification (CAC.Participants were 466 healthy men and women (mean age = 62.7±5.6 yrs, without history or objective signs of CHD, drawn from the Whitehall II epidemiological cohort. At the baseline assessment salivary cortisol was measured in response to mental stressors, consisting of a 5-min Stroop task and a 5-min mirror tracing task. CAC was measured at baseline and at 3 years follow up using electron beam computed tomography. CAC progression was defined as an increase >10 Agatston units between baseline and follow up. 38.2% of the sample demonstrated CAC progression over the 3 years follow up. There was considerable variation in the cortisol stress response, with approximately 40% of the sample responding to the stress tasks with an increase in cortisol of at least 1 mmol/l. There was an association between cortisol stress reactivity (per SD and CAC progression (odds ratio = 1.27, 95% CI, 1.02-1.60 after adjustments for age, sex, pre-stress cortisol, employment grade, smoking, resting systolic BP, fibrinogen, body mass index, and use of statins. There was no association between systolic blood pressure reactivity and CAC progression (odds ratio per SD increase = 1.03, 95% CI, 0.85-1.24. Other independent predictors of CAC progression included age, male sex, smoking, resting systolic blood pressure, and fibrinogen.Results demonstrate an association between heightened cortisol reactivity to stress and CAC progression. These data support the notion that cortisol reactivity, an index of HPA function, is one of the possible mechanisms through which psychosocial stress may influence the risk of CHD.

  2. Detailed clinicopathological characterization of progressive alopecia areata patients treated with i.v. corticosteroid pulse therapy toward optimization of inclusion criteria.

    Science.gov (United States)

    Sato, Misato; Amagai, Masayuki; Ohyama, Manabu

    2014-11-01

    The management of progressive alopecia areata (AA) is often challenging. Recently, i.v. corticosteroid pulse therapy has been reported to be effective for acute and severe AA, however, inclusion criteria have not been sufficiently precise, leaving a chance that its efficacy could be further improved by optimizing therapeutic indications. In our attempts to delineate the factors that correlate with favorable outcomes, we minutely evaluated the clinicopathological findings and the prognoses of single-round steroid pulse-treated progressive AA cases with full sets of image and pathology records during the course. Almost complete hair regrowth has been achieved and maintained up to 2 years in five out of seven AA patients with varying degrees of clinical severity. Interestingly, the worst clinical presentation observed during the course correlated with the size of the area where hairs with dystrophic roots were pulled rather than the extent of visible hair loss on the first visit. Dermoscopy detected disease spread but contributed little in assessing prognoses. Dense perifollicular cell infiltration was detected in all cases treated within 4 weeks of onset and those treated later but with excellent response. Importantly, the cases with poor or incomplete hair regrowth were treated 6-8 weeks of onset and showed moderate inflammatory change with high telogen conversion rate. These findings mandate global dermoscopy and hair pull test for judging the treatment indication and suggest that early administration of high-dose corticosteroid, ideally within 4 weeks of onset, enable efficient suppression of active inflammation and maximize the effectiveness of the remedy. © 2014 Japanese Dermatological Association.

  3. COMPARISON OF EFFECTIVENESS OF A PROGRESSIVE MOBILIZATION AND MOZART MUSIC THERAPY ON NON-INVASIVE HEMODYNAMIC STATUS CHANGES IN PATIENTS WITH HEAD INJURY IN THE INTENSIVE CARE UNIT

    Directory of Open Access Journals (Sweden)

    Novi Indriani

    2018-05-01

    Full Text Available Background: The instability of hemodynamic status in patients with head injury with decreased consciousness has an effect on the increase of intracranial pressure. The recovery of hemodynamic status can be done through nursing intervention either by providing a sensory stimulus (music therapy or motor stimulus (progressive mobilization. Objective: To compare the effectiveness of progressive mobilization of level I with Mozart's music therapy on non-invasive hemodynamic status changes in patients with head injury with decreased awareness. Methods: This was a quasy-experimental study with pretest-posttest design. There were 34 samples selected using consecutive sampling, which 17 samples assigned in a group of progressive mobilization and group of music therapy. Paired t-test and Wilcoxon test were used for paired group, and Independent t-test and Mann-Whitney test for unpaired group. Results: Progressive mobilization of level I had significant effect on changes in systolic blood pressure (p = 0.0001, diastolic blood pressure (p = 0.002 and MAP (p = 0.019, and no significant effect on heart rate (p = 0.155, respiration (p = 0.895 and oxygen saturation (p = 0.248. Mozart's music therapy had a significant effect on changes in systolic blood pressure (p = 0.0001, diastolic blood pressure (p = 0.0001, respiration (p= 0.032 and oxygen saturation (p = 0.008, but no effect on MAP (p = 0.561. There was a significant difference between the two interventions in the systolic blood pressure and heart rate variables (p 0.05. Conclusion: The Mozart's music therapy is more effective on non-invasive hemodynamic status changes in patients with head injury with decreased consciousness compared with progressive mobilization of level I.

  4. Quantitative Magnetization Transfer in Monitoring Glioblastoma (GBM) Response to Therapy.

    Science.gov (United States)

    Mehrabian, Hatef; Myrehaug, Sten; Soliman, Hany; Sahgal, Arjun; Stanisz, Greg J

    2018-02-06

    Quantitative magnetization transfer (qMT) was used as a biomarker to monitor glioblastoma (GBM) response to chemo-radiation and identify the earliest time-point qMT could differentiate progressors from non-progressors. Nineteen GBM patients were recruited and MRI-scanned before (Day 0 ), two weeks (Day 14 ), and four weeks (Day 28 ) into the treatment, and one month after the end of the treatment (Day 70 ). Comprehensive qMT data was acquired, and a two-pool MT model was fit to the data. Response was determined at 3-8 months following the end of chemo-radiation. The amount of magnetization transfer ([Formula: see text]) was significantly lower in GBM compared to normal appearing white matter (p GBM are more sensitive to treatment effects compared to clinically used metrics. qMT could assess tumor aggressiveness and identify early progressors even before the treatment. Changes in qMT parameters within the first 14 days of the treatment were capable of separating early progressors from non-progressors, making qMT a promising biomarker to guide adaptive radiotherapy for GBM.

  5. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Lidia De Riccardis

    2016-12-01

    Full Text Available Glatiramer acetate (GA; Copaxone is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS. Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4+, the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4+ T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4+ T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4+ T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  6. Metabolic response to glatiramer acetate therapy in multiple sclerosis patients.

    Science.gov (United States)

    De Riccardis, Lidia; Ferramosca, Alessandra; Danieli, Antonio; Trianni, Giorgio; Zara, Vincenzo; De Robertis, Francesca; Maffia, Michele

    2016-12-01

    Glatiramer acetate (GA; Copaxone) is a random copolymer of glutamic acid, lysine, alanine, and tyrosine used for the treatment of patients with multiple sclerosis (MS). Its mechanism of action has not been already fully elucidated, but it seems that GA has an immune-modulatory effect and neuro-protective properties. Lymphocyte mitochondrial dysfunction underlines the onset of several autoimmune disorders. In MS first diagnosis patients, CD4 + , the main T cell subset involved in the pathogenesis of MS, undergo a metabolic reprogramming that consist in the up-regulation of glycolysis and in the down-regulation of oxidative phosphorylation. Currently, no works exist about CD4 + T cell metabolism in response to GA treatment. In order to provide novel insight into the potential use of GA in MS treatment, blood samples were collected from 20 healthy controls (HCs) and from 20 RR MS patients prior and every 6 months during the 12 months of GA administration. GA treated patients' CD4 + T cells were compared with those from HCs analysing their mitochondrial activity through polarographic and enzymatic methods in association with their antioxidant status, through the analysis of SOD, GPx and CAT activities. Altogether, our findings suggest that GA is able to reduce CD4 + T lymphocytes' dysfunctions by increasing mitochondrial activity and their response to oxidative stress.

  7. The Progressive Approach to EMDR Group Therapy for Complex Trauma and Dissociation: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Ana I. Gonzalez-Vazquez

    2018-02-01

    Full Text Available Eye Movement Desensitization and Reprocessing is a psychotherapeutic approach with recognized efficiency in treating post-traumatic stress disorder (PTSD, which is being used and studied in other psychiatric diagnoses partially based on adverse and traumatic life experiences. Nevertheless, there is not enough empirical evidence at the moment to support its usefulness in a diagnosis other than PTSD. It is commonly accepted that the use of EMDR in severely traumatized patients requires an extended stabilization phase. Some authors have proposed integrating both the theory of structural dissociation of the personality and the adaptive information processing model guiding EMDR therapy. One of these proposals is the Progressive Approach. Some of these EMDR procedures will be evaluated in a group therapy format, integrating them along with emotional regulation, dissociation, and trauma-oriented psychoeducational interventions. Patients presenting a history of severe traumatization, mostly early severe and interpersonal trauma, combined with additional significant traumatizing events in adulthood were included. In order to discriminate the specific effect of EMDR procedures, two types of groups were compared: TAU (treatment as usual: psychoeducational intervention only vs. TAU+EMDR (the same psychoeducational intervention plus EMDR specific procedures. In pre-post comparison, more variables presented positive changes in the group including EMDR procedures. In the TAU+EMDR group, 4 of the 5 measured variables presented significant and positive changes: general health (GHQ, general satisfaction (Schwartz, subjective well-being, and therapy session usefulness assessment. On the contrary, only 2 of the 5 variables in the TAU group showed statistically significant changes: general health (GHQ, and general satisfaction (Schwartz. Regarding post-test inter-group comparison, improvement in subjective well-being was related to belonging to the group that

  8. Aripiprazole Improves Depressive Symptoms and Immunological Response to Antiretroviral Therapy in an HIV-Infected Subject with Resistant Depression

    Directory of Open Access Journals (Sweden)

    Chiara Cecchelli

    2010-01-01

    Full Text Available Aripiprazole is the first medication approved by the FDA as an add-on treatment for MDD. The impact of aripiprazole on the response to HIV is unknown. The patient we report on was diagnosed HIV-positive in 1997 and has been treated with antiretroviral therapy since then. In 2008, we diagnosed resistant major depression, hypochondria, and panic disorder. On that occasion, blood tests showed a significantly reduced CD4 count and a positive viral load. We treated this patient with aripiprazole and citalopram. Mood, somatic symptoms, and occupational functioning progressively improved. The last blood examination showed an increase in the CD4 count and a negative viral load. On the basis of the present case study and the review of the literature concerning the effects of psychotropic agents on viral replication, we suggest that the use of aripiprazole in HIV-infected subjects warrants further research.

  9. A robust response to combination immune checkpoint inhibitor therapy in HPV-related small cell cancer: a case report.

    Science.gov (United States)

    Ho, Won Jin; Rooper, Lisa; Sagorsky, Sarah; Kang, Hyunseok

    2018-05-09

    Human papillomavirus-related small cell carcinoma of the head and neck is an extremely rare, aggressive subtype with poor outcomes. Therapeutic options are limited and are largely adopted from small cell lung cancer treatment paradigms. This report describes a 69-year old male who was diagnosed of HPV-related oropharyngeal cancer with mixed small cell and squamous cell pathology which was clinically aggressive and progressed through multimodal platinum-based therapies. Upon manifestation of worsening metastatic disease, the patient was initiated on a combination of ipilimumab and nivolumab. Within 2 months of starting immunotherapy, a robust partial response was observed. During the treatment course, the patient developed immune-related adverse effects including new diabetes mellitus, colitis, and hypothyroidism. The disease-specific survival was 26 months. Combination immunotherapy may be an attractive option for HPV-related small cell head and neck cancers resistant to other treatment modalities and thus warrants further evaluation.

  10. Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

    Science.gov (United States)

    2017-01-01

    Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs) consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs) are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review. PMID:28659978

  11. Aromatic Amino Acid Decarboxylase Deficiency Not Responding to Pyridoxine and Bromocriptine Therapy: Case Report and Review of Response to Treatment

    Directory of Open Access Journals (Sweden)

    Majid Alfadhel

    2014-01-01

    Full Text Available Aromatic L-amino acid decarboxylase (AADC deficiency (MIM #608643 is an autosomal recessive inborn error of monoamines. It is caused by a mutation in the DDC gene that leads to a deficiency in the AADC enzyme. The clinical features of this condition include a combination of dopamine, noradrenaline, and serotonin deficiencies, and a patient may present with hypotonia, oculogyric crises, sweating, hypersalivation, autonomic dysfunction, and progressive encephalopathy with severe developmental delay. We report the case of an 8-month-old boy who presented with the abovementioned symptoms and who was diagnosed with AADC deficiency based on clinical, biochemical, and molecular investigations. Treatment with bromocriptine and pyridoxine showed no improvement. These data support the findings observed among previously reported cohorts that showed poor response of this disease to current regimens. Alternative therapies are needed to ameliorate the clinical complications associated with this disorder.

  12. Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

    Directory of Open Access Journals (Sweden)

    Marie-Luce Vignais

    2017-01-01

    Full Text Available Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review.

  13. Durable complete responses off all treatment in patients with metastatic malignant melanoma after sequential immunotherapy followed by a finite course of BRAF inhibitor therapy.

    Science.gov (United States)

    Wyluda, Edward J; Cheng, Jihua; Schell, Todd D; Haley, Jeremy S; Mallon, Carol; Neves, Rogerio I; Robertson, Gavin; Sivik, Jeffrey; Mackley, Heath; Talamo, Giampaolo; Drabick, Joseph J

    2015-01-01

    We report 3 cases of durable complete response (CR) in patients with BRAF-mutated metastatic melanoma who were initially treated unsuccessfully with sequential immunotherapies (high dose interleukin 2 followed by ipilimumab with or without concurrent radiation therapy). After progression during or post immunotherapy, these patients were given BRAF inhibitor therapy and developed rapid CRs. Based on the concomitant presence of autoimmune manifestations (including vitiligo and hypophysitis), we postulated that there was a synergistic effect between the prior immune therapy and the BRAF targeting agents. Accordingly, the inhibitors were gradually weaned off beginning at 3 months and were stopped completely at 9-12 months. The three patients remain well and in CR off of all therapy at up to 15 months radiographic follow-up. The institution of the BRAF therapy was associated with development of severe rheumatoid-like arthritis in 2 patients which persisted for months after discontinuation of therapy, suggesting it was not merely a known toxicity of BRAF inhibitors (arthralgias). On immunologic analysis, these patients had high levels of non-T-regulatory, CD4 positive effector phenotype T-cells, which persisted after completion of therapy. Of note, we had previously reported a similar phenomenon in patients with metastatic melanoma who failed high dose interleukin-2 and were then placed on a finite course of temozolomide with rapid complete responses that have remained durable for many years after discontinuation of temozolomide. We postulate that a finite course of cytotoxic or targeted therapy specific for melanoma given after apparent failure of prior immunotherapy can result in complete and durable remissions that may persist long after the specific cytotoxic or targeted agents have been discontinued suggesting the existence of sequence specific synergism between immunotherapy and these agents. Here, we discuss these cases in the context of the literature on

  14. Regorafenib with a fluoropyrimidine for metastatic colorectal cancer after progression on multiple 5-FU-containing combination therapies and regorafenib monotherapy.

    Science.gov (United States)

    Marks, Eric I; Tan, Carlyn; Zhang, Jun; Zhou, Lanlan; Yang, Zhaohai; Scicchitano, Angelique; El-Deiry, Wafik S

    2015-01-01

    We present 2 patients with metastatic colorectal cancer who had progressed despite treatment with first-line FOLFOX and second-line FOLFIRI combination chemotherapy regimens. After failing these fluoropyrimidine-based regimens, both patients received additional cytotoxic and targeted therapies with eventual disease progression. These therapies included capecitabine plus dabrafenib and trametinib, regorafenib monotherapy, and regorafenib with panitumumab. After exhausting available options, both patients were offered regorafenib with either 5-fluorouracil (5-FU) or capecitabine. These therapies are individually approved for the treatment of colorectal cancer but have not yet been studied in combination. This regimen produced stable disease in both patients with acceptable toxicity. One patient continued therapy for 17 months. Although these patients previously progressed during treatment with regorafenib, capecitabine or 5-FU, the combination had some activity in both cases of refractory metastatic colorectal cancer and may be considered in the palliative setting. In bedside-to-bench cell culture experiments performed after the clinical observations, we observed sensitivity of human colorectal cancer cell lines (N = 4) to single agent regorafenib or 5-FU and evidence of synergy with the combination therapy. Synergistic effects were noted in colorectal cancer cells with KRAS mutation, BRAF mutation, and p53 mutation, as well as mismatch repair deficient cells. Regorafenib suppressed Mcl-1 and Bcl-XL in treated cancer cells that may have contributed to the anticancer efficacy including in combination with 5-FU. The safety and efficacy of regorafenib with 5-FU or capecitabine in combination should be further investigated as a therapy for patients with refractory metastatic colorectal cancer, including individuals who had progressed on regorafenib monotherapy.

  15. CSF inflammatory biomarkers responsive to treatment in progressive multiple sclerosis capture residual inflammation associated with axonal damage.

    Science.gov (United States)

    Romme Christensen, Jeppe; Komori, Mika; von Essen, Marina Rode; Ratzer, Rikke; Börnsen, Lars; Bielekova, Bibi; Sellebjerg, Finn

    2018-05-01

    Development of treatments for progressive multiple sclerosis (MS) is challenged by the lack of sensitive and treatment-responsive biomarkers of intrathecal inflammation. To validate the responsiveness of cerebrospinal fluid (CSF) inflammatory biomarkers to treatment with natalizumab and methylprednisolone in progressive MS and to examine the relationship between CSF inflammatory and tissue damage biomarkers. CSF samples from two open-label phase II trials of natalizumab and methylprednisolone in primary and secondary progressive MS. CSF concentrations of 20 inflammatory biomarkers and CSF biomarkers of axonal damage (neurofilament light chain (NFL)) and demyelination were analysed using electrochemiluminescent assay and enzyme-linked immunosorbent assay (ELISA). In all, 17 natalizumab- and 23 methylprednisolone-treated patients had paired CSF samples. CSF sCD27 displayed superior standardised response means and highly significant decreases during both natalizumab and methylprednisolone treatment; however, post-treatment levels remained above healthy donor reference levels. Correlation analyses of CSF inflammatory biomarkers and NFL before, during and after treatment demonstrated that CSF sCD27 consistently correlates with NFL. These findings validate CSF sCD27 as a responsive and sensitive biomarker of intrathecal inflammation in progressive MS, capturing residual inflammation after treatment. Importantly, CSF sCD27 correlates with NFL, consistent with residual inflammation after anti-inflammatory treatment being associated with axonal damage.

  16. Targeted Cancer Therapy: Vital Oncogenes and a New Molecular Genetic Paradigm for Cancer Initiation Progression and Treatment

    Science.gov (United States)

    Willis, Rudolph E.

    2016-01-01

    It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis. PMID:27649156

  17. Partial agonist therapy in schizophrenia: relevance to diminished criminal responsibility.

    Science.gov (United States)

    Gavaudan, Gilles; Magalon, David; Cohen, Julien; Lançon, Christophe; Léonetti, Georges; Pélissier-Alicot, Anne-Laure

    2010-11-01

    Pathological gambling (PG), classified in the DSM-IV among impulse control disorders, is defined as inappropriate, persistent gaming for money with serious personal, family, and social consequences. Offenses are frequently committed to obtain money for gambling. Pathological gambling, a planned and structured behavioral disorder, has often been described as a complication of dopamine agonist treatment in patients with Parkinson's disease. It has never been described in patients with schizophrenia receiving dopamine agonists. We present two patients with schizophrenia, previously treated with antipsychotic drugs without any suggestion of PG, who a short time after starting aripiprazole, a dopamine partial agonist, developed PG and criminal behavior, which totally resolved when aripiprazole was discontinued. Based on recent advances in research on PG and adverse drug reactions to dopamine agonists in Parkinson's disease, we postulate a link between aripiprazole and PG in both our patients with schizophrenia and raise the question of criminal responsibility. © 2010 American Academy of Forensic Sciences.

  18. Relationship between serum TSH and the responsiveness of toxic solitary autonomous thyroid nodules to radioiodine therapy

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Kirkegaard, B C

    1998-01-01

    hypothyroidism both had detectable serum TSH at the time of 131I treatment. No other clinical parameter seemed to influence the outcome. CONCLUSION: There is no clinically significant effect of circulating TSH on the response of toxic solitary autonomous thyroid nodules to 131I therapy. However, keeping...... the patients subclinically hyperthyroid when receiving 131I treatment may possibly result in a reduced frequency of hypothyroidism.......) were euthyroid, three (8%) had responded insufficiently and required further antithyroid therapy, and two (5%) had developed hypothyroidism. No significant difference in the response pattern between patients with suppressed or detectable serum TSH could be demonstrated. The two patients who developed...

  19. Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase

    Directory of Open Access Journals (Sweden)

    Vanessa Fiorini Furtado

    2015-10-01

    Full Text Available BACKGROUND: Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.METHODS: This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils ≥ 20%, platelets > 1 × 106/µL or 1 × 105/µL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin 12 months (p-value = 0.030.CONCLUSION: These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

  20. Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient

    International Nuclear Information System (INIS)

    Bernal-Estévez, David; Sánchez, Ramiro; Tejada, Rafael E.; Parra-López, Carlos

    2016-01-01

    Experimental evidence and clinical studies in breast cancer suggest that some anti-tumor therapy regimens generate stimulation of the immune system that accounts for tumor clinical responses, however, demonstration of the immunostimulatory power of these therapies on cancer patients continues to be a formidable challenge. Here we present experimental evidence from a breast cancer patient with complete clinical response after 7 years, associated with responsiveness of tumor specific T cells. T cells were obtained before and after anti-tumor therapy from peripheral blood of a 63-years old woman diagnosed with ductal breast cancer (HER2/neu+++, ER-, PR-, HLA-A*02:01) treated with surgery, followed by paclitaxel, trastuzumab (suspended due to cardiac toxicity), and radiotherapy. We obtained a leukapheresis before surgery and after 8 months of treatment. Using in vitro cell cultures stimulated with autologous monocyte-derived dendritic cells (DCs) that produce high levels of IL-12, we characterize by flow cytometry the phenotype of tumor associated antigens (TAAs) HER2/neu and NY-ESO 1 specific T cells. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and Tumor Infiltrating Lymphocytes (TILs) were performed in order to correlate both repertoires prior and after therapy. We evidence a functional recovery of T cell responsiveness to polyclonal stimuli and expansion of TAAs specific CD8+ T cells using peptide pulsed DCs, with an increase of CTLA-4 and memory effector phenotype after anti-tumor therapy. The ex vivo analysis of the TCR-Vβ repertoire of TAA specific T cells in blood and TILs showed that whereas the TCR-Vβ04-02 clonotype is highly expressed in TILs the HER2/neu specific T cells are expressed mainly in blood after therapy, suggesting that this particular TCR was selectively enriched in blood after anti-tumor therapy. Our results show the benefits of anti-tumor therapy in a breast cancer patient with clinical complete response in

  1. What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L.

    Science.gov (United States)

    Hackam, D G; Peterson, J C; Spence, J D

    2000-01-01

    High levels of plasma homocyst(e)ine (H[e]) are associated with increased vascular risk. Treatment is being contemplated, but the level at which patients should be treated is not known. We compared the response of carotid plaque to vitamin therapy in patients with H(e) above and below 14 micromol/L, a level commonly regarded as high enough to warrant treatment. Two-dimensional B-mode ultrasound measurement of carotid plaque was used to assess the response to vitamin therapy with folic acid 2.5 mg, pyridoxine 25 mg, and cyanocobalamin 250 microg daily, in 101 patients with vascular disease (51 with initial plasma levels above, and 50 below 14 micromol/L). Among patients with plasma H(e) >14 micromol/L, the rate of progression of plaque area was 0.21 +/- 0.41 cm2/year before vitamin therapy, and -0.049 +/- 0.24 cm2/year after vitamin therapy (P2 = .0001; paired t test). Among patients with levels ine and atherosclerosis and, taken with epidemiologic evidence, suggest that in patients with vascular disease, the level to treat may be <9 micromol/L.

  2. Selective progressive response of soil microbial community to wild oat roots

    Energy Technology Data Exchange (ETDEWEB)

    DeAngelis, K.M.; Brodie, E.L.; DeSantis, T.Z.; Andersen, G.L.; Lindow, S.E.; Firestone, M.K.

    2008-10-01

    Roots moving through soil enact physical and chemical changes that differentiate rhizosphere from bulk soil, and the effects of these changes on soil microorganisms have long been a topic of interest. Use of a high-density 16S rRNA microarray (PhyloChip) for bacterial and archaeal community analysis has allowed definition of the populations that respond to the root within the complex grassland soil community; this research accompanies previously reported compositional changes, including increases in chitinase and protease specific activity, cell numbers and quorum sensing signal. PhyloChip results showed a significant change in 7% of the total rhizosphere microbial community (147 of 1917 taxa); the 7% response value was confirmed by16S rRNA T-RFLP analysis. This PhyloChip-defined dynamic subset was comprised of taxa in 17 of the 44 phyla detected in all soil samples. Expected rhizosphere-competent phyla, such as Proteobacteria and Firmicutes, were well represented, as were less-well-documented rhizosphere colonizers including Actinobacteria, Verrucomicrobia and Nitrospira. Richness of Bacteroidetes and Actinobacteria decreased in soil near the root tip compared to bulk soil, but then increased in older root zones. Quantitative PCR revealed {beta}-Proteobacteria and Actinobacteria present at about 10{sup 8} copies of 16S rRNA genes g{sup -1} soil, with Nitrospira having about 10{sup 5} copies g{sup -1} soil. This report demonstrates that changes in a relatively small subset of the soil microbial community are sufficient to produce substantial changes in function in progressively more mature rhizosphere zones.

  3. How does race/ethnicity influence pharmacological response to asthma therapies?

    Science.gov (United States)

    Cazzola, Mario; Calzetta, Luigino; Matera, Maria Gabriella; Hanania, Nicola A; Rogliani, Paola

    2018-04-01

    Our understanding of whether and/or how ethnicity influences pharmacological response to asthma therapies is still very scarce. A possible explanation for the increased asthma treatment failures observed in ethnic and racial minorities receiving asthma therapies is that some of these groups may have a pharmacogenomic predisposition to either nonresponse or to adverse response with a specific class of drugs. However, the effects of ethnicity on pharmacological response to asthma therapies are also, and mainly, determined by socioeconomic and environmental factors to a varying extent, depending on the ethnic groups. Areas covered: Genetic, socioeconomic and environmental factors that can affect the pharmacotherapeutic responses to asthma medications and their link(s) to race/ethnicity have been examined and critically discussed. Expert opinion: Differences in genetic ancestry are definitely non-modifiable factors, but socioeconomic and environmental disadvantages are all factors that can be modified. It is likely that improved outcomes may be achieved when tailored and multifaceted approaches that include home, school, and clinician-based interventions are implemented. Consequently, it is critical to determine if a clinical intervention programme combined with implementation strategies that attempt to reduce inequalities can reduce asthma disparities, including the influence of ethnicity and race on pharmacological response to asthma therapies.

  4. Enhanced tumor responses through therapies combining CCNU, MISO and radiation

    International Nuclear Information System (INIS)

    Siemann, D.W.; Hill, S.A.

    1984-01-01

    Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

  5. Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

    Science.gov (United States)

    Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

    2015-12-01

    Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

  6. Efficacy of multiple anticancer therapies may depend on host immune response

    Directory of Open Access Journals (Sweden)

    Kritika Karri

    2017-06-01

    Full Text Available The host immune system is a key player in anticancer therapy response and resistance. Although the impact of host immune response in the ‘war against cancer’ has been studied and it has been the basis for immunotherapy, understanding of its role in attenuating the action of conventional anticancer therapies is an area that has not been fully explored. In spite of advances in systemic therapy, the 5-year survival rate for adenocarcinoma is still a mere 13% and the primary reason for treatment failure is believed to be due to acquired resistance to therapy. Hence, there is a need for identifying reliable biomarkers for guided treatment of lung and colon adenocarcinoma and to better predict the outcomes of specific anticancer therapies. In this work, gene expression data were analyzed using public resources and this study shows how host immune competence underscores the efficacy of various anticancer therapies. Additionally, the result provides insight on the regulation of certain biochemical pathways relating to the immune system, and suggests that smart chemotherapeutic intervention strategies could be based on a patient’s immune profile.

  7. Factors affecting responses of infants with respiratory distress syndrome to exogenous surfactant therapy.

    Science.gov (United States)

    Ho, N K

    1993-02-01

    Approximately 20% to 30% of infants with respiratory distress syndrome (RDS) do not respond to surfactant replacement therapy. Unfortunately there is no uniform definition of 'response' or 'non-response' to surfactant therapy. Response was based on improvement in a/A PO2 and/or mean airway pressure (MAP) by some and on improvement in FIO2 and/or MAP by others. Even the point of time at which evaluation of response was done is different in various reports. There is an urgent need to adopt an uniform definition. Most premature babies are surfactant deficient which is the aetiological factor of RDS. Generally good antenatal care and perinatal management are essential in avoidance of premature birth. Babies with lung hypoplasia and who are extremely premature (less than 24 weeks of gestation) do not respond well to exogenous surfactant replacement because of structural immaturity. Prompt management of asphyxiated birth and shock are necessary as there may be negative response to surfactant replacement. Foetal exposure to glucocorticoids improves responsiveness to postnatal administration of surfactant. Antenatal steroid therapy has become an important part of management of RDS with surfactant replacement. The premature lungs with high alveolar permeability tend to develop pulmonary oedema. With the presence of plasma-derived surfactant inhibitors, the response to exogenous surfactant may be affected. These inhibitors may also be released following ventilator barotrauma. The standard of neonatal intensive care such as ventilatory techniques has an important bearing on the outcome of the RDS babies.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effect of Pregnancy on Response to Antiretroviral Therapy in HIV-Infected African Women.

    Science.gov (United States)

    Kourtis, Athena P; Wiener, Jeffrey; King, Caroline C; Heffron, Renee; Mugo, Nelly R; Nanda, Kavita; Pyra, Maria; Donnell, Deborah; Celum, Connie; Lingappa, Jairam R; Baeten, Jared M

    2017-01-01

    While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy in response to antiretroviral therapy (ART). Hormonal, immune, and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART. Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention Herpes simplex virus/HIV Transmission Study, Couples Observational Study, and Partners Preexposure Prophylaxis Study) from 7 countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies per milliliter ≥6 months after ART initiation and viral suppression was defined as VL ≤400 copies per milliliter. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, World Health Organization clinical stage III/IV, and death. Linear mixed-effects models were used to assess the association between pregnancy and CD4 count and VL. All analyses were adjusted for confounders, including pre-ART CD4 count and plasma VL. A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4 count before ART initiation was 276 cells per cubic millimeter (interquartile range, 209-375); median pre-ART VL was 17,511 copies per milliliter (interquartile range, 2480-69,286). One hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to

  9. Stimuli-Responsive NO Release for On-Demand Gas-Sensitized Synergistic Cancer Therapy.

    Science.gov (United States)

    Fan, Wenpei; Yung, Bryant C; Chen, Xiaoyuan

    2018-03-08

    Featuring high biocompatibility, the emerging field of gas therapy has attracted extensive attention in the medical and scientific communities. Currently, considerable research has focused on the gasotransmitter nitric oxide (NO) owing to its unparalleled dual roles in directly killing cancer cells at high concentrations and cooperatively sensitizing cancer cells to other treatments for synergistic therapy. Of particular note, recent state-of-the-art studies have turned our attention to the chemical design of various endogenous/exogenous stimuli-responsive NO-releasing nanomedicines and their biomedical applications for on-demand NO-sensitized synergistic cancer therapy, which are discussed in this Minireview. Moreover, the potential challenges regarding NO gas therapy are also described, aiming to advance the development of NO nanomedicines as well as usher in new frontiers in this fertile research area. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. FDG and FLT-PET for Early measurement of response to 37.5 mg daily sunitinib therapy in metastatic renal cell carcinoma.

    Science.gov (United States)

    Horn, Kevin P; Yap, Jeffrey T; Agarwal, Neeraj; Morton, Kathryn A; Kadrmas, Dan J; Beardmore, Britney; Butterfield, Regan I; Boucher, Kenneth; Hoffman, John M

    2015-09-03

    Metastatic renal cell carcinoma has a poor prognosis and an intrinsic resistance to standard treatment. Sunitinib is an oral receptor tyrosine kinase inhibitor that has been used as a first-line targeted therapy in metastatic renal cell carcinoma. While computed tomography (CT) is currently the gold standard for response assessment in oncological trials, numerous studies have shown that positron emission tomography (PET) imaging can provide information predictive of tumor response to treatment earlier than the typical interval for standard of care follow-up CT imaging. In this exploratory study we sought to characterize early tumor response in patients with metastatic renal cell carcinoma treated with continuous daily 37.5 mg sunitinib therapy. Twenty patients underwent dynamic acquisition positron emission tomography (PET) imaging using (18) F-fluorodeoxyglucose (FDG) and (18) F-fluorothymidine (FLT) at baseline and early in treatment (after 1, 2, 3 or 4 weeks) with 37.5 mg continuous daily dosing of sunitinib. Semi-quantitative analyses were performed to characterize the tumor metabolic (FDG) and proliferative (FLT) responses to treatment. Proliferative responses were observed in 9/19 patients and occurred in 2 patients at one week (the earliest interval evaluated) after the initiation of therapy. A metabolic response was observed in 5/19 patients, however this was not observed until after two weeks of therapy were completed. Metabolic progression was observed in 2/19 patients and proliferative progression was observed in 1/19 patients. Baseline FDG-PET tumor maximum standardized uptake values correlated inversely with overall survival (p = 0.0036). Conversely, baseline (18) F-fluorothymidine PET imaging did not have prognostic value (p = 0.56) but showed a greater early response rate at 1-2 weeks after initiating therapy. While preliminary in nature, these results show an immediate and sustained proliferative response followed by a delayed

  11. Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

    Science.gov (United States)

    Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

    2015-04-29

    A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

  12. Case report of a KIT-mutated melanoma patient with an excellent response to apatinib and temozolomide combination therapy

    Directory of Open Access Journals (Sweden)

    Luo C

    2017-09-01

    Full Text Available Cong Luo,1 Jiayu Shen,2 Jieer Ying,1 Xianhua Fang,3 Xiaohong Wang,1 Zhixuan Fu,4 Peng Liu5 1Department of Abdominal Oncology, Zhejiang Cancer Hospital, 2The Second Clinical Medical College, Zhejiang Chinese Medical University, 3Department of Pathology, 4Department of Colorectal Surgery, 5Department of Radiotherapy, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: Malignant melanoma is one kind of malignant disease which has high rates of mortality, metastasis, and poor prognosis. The therapeutic landscape is rapidly changing with the development of novel agents in recent decades, such as anti-PD-1 agents, anti-CTLA-4 agents, and BRAF inhibitors. However, since most of these novel agents are very expensive, not all patients can afford them. Apatinib is a novel oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2 and may also be effective on Ret, c-KIT, and c-src. Temozolomide (TMZ is a second-generation alkylating agent and a cytotoxic drug for melanoma treatment. In this work, we reported a case of metastatic melanoma with an excellent response to apatinib/TMZ combination therapy with progression-free survival for more than one year. This patient showed high expression of CD117, VEGFR-3, and KIT mutation in exon 11, suggesting that apatinib may induce clinical response via inhibiting VEGFR and c-KIT. Apatinib/TMZ combination therapy could be a new option for the treatment of advanced melanoma with KIT mutation. Keywords: advanced melanoma, KIT mutation, apatinib, temozolomide, combination therapy

  13. Pitfalls in the Neuroimaging of Glioblastoma in the Era of Antiangiogenic and Immuno/Targeted Therapy - Detecting Illusive Disease, Defining Response

    Directory of Open Access Journals (Sweden)

    Raymond Yi-Kun Huang

    2015-02-01

    Full Text Available Glioblastoma, the most common malignant primary brain tumor in adults is a devastating diagnosis with an average survival of 14-16 months using the current standard of care treatment. The determination of treatment response and clinical decision making is based on the accuracy of radiographic assessment. Notwithstanding, challenges exist in the neuroimaging evaluation of patients undergoing treatment for malignant glioma.Differentiating treatment response from tumor progression is problematic and currently combines long-term follow-up using standard MRI, with clinical status and corticosteroid-dependency assessments. In the clinical trial setting, treatment with gene therapy, vaccines, immunotherapy, and targeted biologicals similarly produces MRI changes mimicking disease progression. A neuroimaging method to clearly distinguish between pseudoprogression and tumor progression has unfortunately not been found to date. With the incorporation of antiangiogenic therapies, a further pitfall in imaging interpretation is pseudoresponse. The Macdonald Criteria that correlate tumor burden with contrast enhanced imaging proved insufficient and misleading in the context of rapid blood brain barrier normalization following antiangiogenic treatment that is not accompanied by expected survival benefit. Even improved criteria, such as the RANO criteria, that incorporate non-enhancing disease, clinical status, and need for corticosteroid use, fall short of definitively distinguishing tumor progression, pseudoresponse, and pseudoprogression.This review focuses on advanced imaging techniques including perfusion MRI, diffusion MRI, MR spectroscopy, and new PET imaging tracers. The relevant image analysis algorithms and interpretation methods of these promising techniques are discussed in the context of determining response and progression during treatment of glioblastoma both in the standard of care as well as clinical trial context.

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

    Science.gov (United States)

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

    2014-04-01

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

  15. Use of molecular markers for predicting therapy response in cancer patients.

    LENUS (Irish Health Repository)

    Duffy, Michael J

    2012-02-01

    Predictive markers are factors that are associated with upfront response or resistance to a particular therapy. Predictive markers are important in oncology as tumors of the same tissue of origin vary widely in their response to most available systemic therapies. Currently recommended oncological predictive markers include both estrogen and progesterone receptors for identifying patients with breast cancers likely to benefit from hormone therapy, HER-2 for the identification of breast cancer patients likely to benefit from trastuzumab, specific K-RAS mutations for the identification of patients with advanced colorectal cancer unlikely to benefit from either cetuximab or panitumumab and specific EGFR mutations for selecting patients with advanced non-small-cell lung cancer for treatment with tyrosine kinase inhibitors such as gefitinib and erlotinib. The availability of predictive markers should increase drug efficacy and decrease toxicity, thus leading to a more personalized approach to cancer treatment.

  16. Patients with collagen vascular disease and dyspnea. The value of gallium scanning and bronchoalveolar lavage in predicting response to steroid therapy and clinical outcome

    International Nuclear Information System (INIS)

    Greene, N.B.; Solinger, A.M.; Baughman, R.P.

    1987-01-01

    Patients with collagen vascular disease with or without pulmonary symptoms were studied to determine the value of gallium scan and bronchoalveolar lavage (BAL) in predicting clinical outcome and response to steroid therapy. Thirty-six subjects, 20 with progressive dyspnea, were studied. Gallium uptake was seen in the lung in 17 of the 20 progressively dyspneic patient's and none of the 16 nonprogressive patients. The BAL fluid in the progressive patients had a higher percentage of neutrophils (13.4 percent +/- 2.88) and lymphocytes (16.1 percent +/- 2.75) than in the nonprogressive patients (neutrophils = 3.3 +/- 1.30 percent; lymphocytes = 5.6 +/- 1.57 percent. Of the 19 progressive patients who were treated with steroids or cyclophosphamide, six had only increased neutrophils in their BAL fluid and all died. The remaining 13 treated progressive patients had increased lymphocytes or a normal BAL (two patients): six had improvement in their vital capacity, six have had stable function, and one died. We found gallium scan and BAL useful in assessing progressive pulmonary fibrosis in collagen vascular disease

  17. {sup 18}F-FDG PET as novel imaging biomarker for disease progression after ablation therapy in colorectal liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Samim, M. [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands); Prevoo, W.; Wit-van der Veen, B.J. de; Stokkel, M.P.M. [Antoni van Leeuwenhoek Hospital, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Kuhlmann, K.F.; Ruers, T. [Antoni van Leeuwenhoek Hospital, Department Surgical Oncology, Amsterdam (Netherlands); Hillegersberg, R. van [University Medical Centre Utrecht, Department Surgery, Utrecht (Netherlands); Bosch, M.A.A.J. van den; Verkooijen, H.M.; Lam, M.G.E.H. [University Medical Centre Utrecht, Department Radiology and Nuclear Medicine, Utrecht (Netherlands)

    2017-07-15

    Recurrent disease following thermal ablation therapy is a frequently reported problem. Preoperative identification of patients with high risk of recurrent disease might enable individualized treatment based on patients' risk profile. The aim of the present work was to investigate the role of metabolic parameters derived from the pre-ablation {sup 18}F-FDG PET/CT as imaging biomarkers for recurrent disease in patients with colorectal liver metastases (CLM). Included in this retrospective study were all consecutive patients with CLM treated with percutaneous or open thermal ablation therapy who had a pre-treatment baseline {sup 18}F-FDG PET/CT available. Multivariable cox regression for survival analysis was performed using different models for the metabolic parameters (SUL{sub peak}, SUL{sub mean}, SUL{sub max}, partial volume corrected SUL{sub mean} (cSUL{sub mean}), and total lesion glycolysis (TLG)) corrected for tumour and procedure characteristics. The study endpoints were defined as local tumour progression free survival (LTP-FS), new intrahepatic recurrence free survival (NHR-FS) and extrahepatic recurrence free survival (EHR-FS). Clinical and imaging follow-up data was used as the reference standard. Fifty-four patients with 90 lesions were selected. Univariable cox regression analysis resulted in eight models. Multivariable analysis revealed that after adjusting for lesion size and the approach of the procedure, none of the metabolic parameters were associated with LTP-FS or EHR-FS. Percutaneous approach was significantly associated with a shorter LTP-FS. It was demonstrated that lower values of SUL{sub peak}, SUL{sub max}, SUL{sub mean}, and cSUL{sub mean} are associated with a significant better NHR-FS, independent of the lesion size and number and prior chemotherapy. We found no association between the metabolic parameters on pre-ablation {sup 18}F-FDG PET/CT and the LTP-FS. However, low values of the metabolic parameters were significantly

  18. em>In vivoem> biological response to extracorporeal shockwave therapy in human tendinopathy

    DEFF Research Database (Denmark)

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

    2015-01-01

    Extracorporeal shock wave therapy (ESWT) is a non-invasive treatment for chronic tendinopathies, however little is known about the in-vivo biological mechanisms of ESWT. Using microdialysis, we examined the real-time biological response of healthy and pathological tendons to ESWT. A single session...

  19. Regional changes over time in initial virologic response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Kirk, Ole; Gatell, Jose M

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS: Vi...... rates Udgivelsesdato: 2006/6...

  20. Computed tomography assessment of early response to neoadjuvant therapy in colon cancer

    DEFF Research Database (Denmark)

    Dam, Claus; Lund-Rasmussen, Vera; Pløen, John

    2015-01-01

    INTRODUCTION: Using multidetector computed tomography, we aimed to assess the early response of neoadjuvant drug therapy for locally advanced colon cancer. METHODS: Computed tomography with IV contrast was acquired from 67 patients before and after up to three cycles of preoperative treatment. All...

  1. Study on the effectiveness of Responsive Aggression Regulation Therapy (Re-ART)

    NARCIS (Netherlands)

    Hoogsteder, L.M.; Kuijpers, N.; Stams, G.J.J.M.; van Horn, J.E.; Hendriks, J.; Wissink, I.B.

    2014-01-01

    This article describes a pre-test/post-test quasi-experimental study of the effectiveness of Responsive Aggression Regulation Therapy (Re-ART), a Dutch intervention for 16- to 21-year-old juveniles. Re-ART aims to decrease severe aggressive behavior using a cognitive behavioral approach combined

  2. Study on the Effectiveness of Responsive Aggression Regulation Therapy (Re-ART)

    NARCIS (Netherlands)

    Hoogsteder, L.; Kuijpers, N N; Stams, G.J.J.M.; van Horn, J.; Hendriks, J.; Wissink, I.B.

    2014-01-01

    This article describes a pre-test/post-test quasi-experimental study of the effectiveness of Responsive Aggression Regulation Therapy (Re-ART), a Dutch intervention for 16- to 21-year-old juveniles. Re-ART aims to decrease severe aggressive behavior using a cognitive behavioral approach combined

  3. Childhood maltreatment and the response to cognitive behavior therapy for chronic fatigue syndrome.

    NARCIS (Netherlands)

    Heins, M.J.; Knoop, H.; Lobbestael, J.; Bleijenberg, G.

    2011-01-01

    Objective: To examine the relationship between a history of childhood maltreatment and the treatment response to cognitive behavior therapy for chronic fatigue syndrome (CFS). Methods: A cohort study in a tertiary care clinic with a referred sample of 216 adult patients meeting the Centers for

  4. Changes in stimulus and response AC/A ratio with vision therapy in Convergence Insufficiency

    Directory of Open Access Journals (Sweden)

    Neeraj Kumar Singh

    2017-07-01

    Conclusions: Stimulus and response AC/A ratio increased following VT, accompanied by clinically significant changes in vergence and accommodation parameters in subjects with convergence insufficiency. This represents the plasticity of the AC/A crosslink ratios that could be achieved with vision therapy in CI.

  5. Emotional, Motivational and Interpersonal Responsiveness of Children with Autism in Improvisational Music Therapy

    Science.gov (United States)

    Kim, Jinah; Wigram, Tony; Gold, Christian

    2009-01-01

    Through behavioural analysis, this study investigated the social-motivational aspects of musical interaction between the child and the therapist in improvisational music therapy by measuring emotional, motivational and interpersonal responsiveness in children with autism during joint engagement episodes. The randomized controlled study (n = 10)…

  6. High cortisol awakening response is associated with an impairment of the effect of bright light therapy

    DEFF Research Database (Denmark)

    Martiny, Klaus Per Juul; Lunde, Marianne Anita; Undén, M

    2009-01-01

    OBJECTIVE: We investigated the predictive validity of the cortisol awakening response (CAR) in patients with non-seasonal major depression. METHOD: Patients were treated with sertraline in combination with bright or dim light therapy for a 5-week period. Saliva cortisol levels were measured in 63...

  7. Quality of Life in Relation to Pain Response to Radiation Therapy for Painful Bone Metastases

    NARCIS (Netherlands)

    Westhoff, Paulien G.; De Graeff, Alexander; Monninkhof, Evelyn M.; Pomp, Jacqueline; Van Vulpen, Marco; Leer, Jan Willem H; Marijnen, Corrie A M; Van Der Linden, Yvette M.

    2015-01-01

    Purpose: To study quality of life (QoL) in responders and nonresponders after radiation therapy for painful bone metastases; and to identify factors predictive for a pain response. Patients and Methods: The prospectively collected data of 956 patients with breast, prostate, and lung cancer within

  8. Genetic predictors for the response to therapy in colorectal cancer cells

    NARCIS (Netherlands)

    de Bruijn, M.T.

    2011-01-01

    The general goal of this thesis is to create a better insight into the genes and signaling proteins that influence the response of colorectal cancer cells to MEK-targeted therapy and chemotherapy (5-FU and oxaliplatin). In chapter 2 of this thesis we set out to explore the mechanisms of resistance

  9. Predictors of Treatment Response to Cognitive-Behavioral Therapy for Depression in Parkinson's Disease

    Science.gov (United States)

    Dobkin, Roseanne D.; Rubino, Jade Tiu; Allen, Lesley A.; Friedman, Jill; Gara, Michael A.; Mark, Margery H.; Menza, Matthew

    2012-01-01

    Objective: The purpose of this study was to examine predictors of treatment response to cognitive-behavioral therapy (CBT) for depression in Parkinson's disease (PD). Method: The sample comprised 80 depressed ("DSM-IV" criteria) adults with PD (60% male) and their caregivers who participated in an National Institutes of Health-sponsored…

  10. The importance of myocardial contractile reserve in predicting response to cardiac resynchronization therapy

    NARCIS (Netherlands)

    Kloosterman, Mariëlle; Damman, Kevin; Van Veldhuisen, Dirk J; Rienstra, Michiel; Maass, Alexander H

    AimTo perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure. Methods and resultsWe searched MEDLINE/PubMed and Cochrane for all papers published up

  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. Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

    Science.gov (United States)

    Walzer, Stefan; Chouaid, Christos; Lister, Johanna; Gultyaev, Dmitry; Vergnenegre, Alain; de Marinis, Filippo; Meng, Jie; de Castro Carpeno, Javier; Crott, Ralph; Kleman, Martin; Ngoh, Charles

    2015-01-01

    In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line

  13. Molecularly Imprinted Polymers with Stimuli-Responsive Affinity: Progress and Perspectives

    OpenAIRE

    Wei Chen; Yue Ma; Jianmin Pan; Zihui Meng; Guoqing Pan; Börje Sellergren

    2015-01-01

    Intelligent stimuli-responsive molecularly imprinted polymers (SR-MIPs) have attracted considerable research interest in recent years due to the potential applications in drug delivery, biotechnology and separation sciences. This review comprehensively summarizes various SR-MIPs, including the design and applications of thermo-responsive MIPs, pH-responsive MIPs, photo-responsive MIPs, biomolecule-responsive MIPs and ion-responsive MIPs. Besides the development of current SR-MIPs, the advanta...

  14. Response to microneedling treatment in men with androgenetic alopecia who failed to respond to conventional therapy

    Directory of Open Access Journals (Sweden)

    Rachita Dhurat

    2015-01-01

    Full Text Available Introduction: The efficacy of conventional therapy viz. finasteride and minoxidil in androgenetic alopecia (AGA that is based on both preventing hair loss and promoting new hair growth, varies between 30% and 60%. This has led to a large number of patients unsatisfied who demand for a better cosmetic coverage over the scalp. Microneedling has recently been reported to be promising, effective and a safe treatment modality in the treatment of AGA. This augments the response of conventional therapy. Materials and Methods: Four men with AGA were on finasteride and 5% minoxidil solution since 2 to 5 years. Though there was no worsening in their respective AGA stages with the therapy, they showed no new hair growth. They were subjected to microneedling procedure over a period of 6 months along with their ongoing therapy. Patients were assessed with the use of the standardized 7-point evaluation scale and patients′ subjective hair growth assessment scale. The patients were followed up for 18 months post microneedling procedure to assess the sustainability of the response. Results: All patients showed a response of + 2 to + 3 on standardized 7-point evaluation scale. The response in the form of new hair growth started after 8-10 sessions. The patients′ satisfaction was more than 75% in three patients and more 50% in one patient, on patients′ subjective hair growth assessment scale. The obtained results were sustained post procedure during 18 months follow-up period. Conclusion : Treatment with microneedling showed an accelerated response with addition of microneedling procedure leading to significant scalp density. This is the first case series to report the boosting effect of microneedling with respect to new hair follicle stimulation in patients with androgenetic alopecia who were poor responders to conventional therapy.

  15. Measuring treatment response to systemic therapy and predicting outcome in biliary tract cancer: comparing tumor size, volume, density, and metabolism.

    Science.gov (United States)

    Sahani, Dushyant V; Hayano, Koichi; Galluzzo, Anna; Zhu, Andrew X

    2015-04-01

    The purpose of this study was to evaluate the response of biliary tract cancer treated with multidrug chemotherapy using FDG PET in comparison with morphologic and density changes. In this phase II clinical trial, 28 patients with unresectable or metastatic biliary tract cancers treated with gemcitabine and oxaliplatin combined with bevacizumab (GEMOX-B) underwent FDG PET and contrast-enhanced CT at baseline and after the second cycle of the therapy (8 weeks). A single reviewer recorded tumor maximum standardized uptake value (SUVmax) along with size, volume (3D-sphere), and density. The percentage changes of the parameters were compared with progression-free survival at 7 months. Overall survival was compared with the percentage change of SUVmax. After 8 weeks, measurable reductions (±SD) in size (7.05±4.19 to 5.52±3.28 cm, -21.70%), volume (411.38±540.08 to 212.41±293.45 cm3, -48.36%), and density (60.76±20.65 to 50.68±16.89 HU, -15.59%) were noted along with a substantial drop in SUVmax (5.95±1.95 to 3.36±1.28, -43.52%). The SUVmax change showed positive correlations with tumor size change (R2=0.39, p=0.0004) and volumetric change (R2=0.34, p=0.001). Patients who showed a larger drop in SUVmax at 8 weeks correlated with favorable progression-free survival (p=0.02). ROC analysis showed that a 45% reduction in SUVmax was the best cutoff value to detect favorable progression-free survival patients. When we used this cutoff value, Kaplan-Meier analysis showed that patients with tumors showing greater reduction in SUVmax had favorable progression-free survival and overall survival (p=0.0009, p=0.03). In biliary tract cancers treated with GEMOX-B, the reduction of SUVmax after therapy is a better predictor for survival than morphologic and density changes.

  16. Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit

    2016-06-01

    This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  17. Temporal Patterns of Fatigue Predict Pathologic Response in Patients Treated With Preoperative Chemoradiation Therapy for Rectal Cancer

    International Nuclear Information System (INIS)

    Park, Hee Chul; Janjan, Nora A.; Mendoza, Tito R.; Lin, Edward H.; Vadhan-Raj, Saroj; Hundal, Mandeep; Zhang Yiqun; Delclos, Marc E.; Crane, Christopher H.; Das, Prajnan; Wang, Xin Shelley; Cleeland, Charles S.; Krishnan, Sunil

    2009-01-01

    Purpose: To investigate whether symptom burden before and during preoperative chemoradiation therapy (CRT) for rectal cancer predicts for pathologic tumor response. Methods and Materials: Fifty-four patients with T3/T4/N+ rectal cancers were treated on a Phase II trial using preoperative capecitabine and concomitant boost radiotherapy. Symptom burden was prospectively assessed before (baseline) and weekly during CRT by patient self-reported questionnaires, the MD Anderson Symptom Inventory (MDASI), and Brief Fatigue Inventory (BFI). Survival probabilities were estimated using the Kaplan-Meier method. Symptom scores according to tumor downstaging (TDS) were compared using Student's t tests. Logistic regression was used to determine whether symptom burden levels predicted for TDS. Lowess curves were plotted for symptom burden across time. Results: Among 51 patients evaluated for pathologic response, 26 patients (51%) had TDS. Fatigue, pain, and drowsiness were the most common symptoms. All symptoms increased progressively during treatment. Patients with TDS had lower MDASI fatigue scores at baseline and at completion (Week 5) of CRT (p = 0.03 for both) and lower levels of BFI 'usual fatigue' at baseline. Conclusion: Lower levels of fatigue at baseline and completion of CRT were significant predictors of pathologic tumor response gauged by TDS, suggesting that symptom burden may be a surrogate for tumor burden. The relationship between symptom burden and circulating cytokines merits evaluation to characterize the molecular basis of this phenomenon.

  18. Failed Switching off in the MIBI-Parathyroid Scintigraphy in a Dialyzed Patient with Secondary Hyperparathyroidism Responsive to Cinacalcet Therapy

    Directory of Open Access Journals (Sweden)

    Piergiorgio Bolasco

    2010-01-01

    Full Text Available The aims of your case report is to show the predictivity of Tc99m-sestamibi (MIBI scintigraphy and doppler ultrasound imaging on secondary hyperparathyroidism (SHPT in a patient responsive to calcimimetic treatment. Moreover, it has been reported that calcimimetic has great potential in reducing the volume of the parathyroid gland. On the other hand, the MIBI scintigraphy is considered a crucial diagnostic procedure to monitor the response to therapy in terms of turnover and cellular metabolism; whereas, ultrasound to monitor the volume variation in response to treatment. It is described the case of a 73-year-old man on hemodialysis from 1995 for ESRD. Within 2 years the patient gradually developed SHPT with progressively increased iPTH up to 1,000 ρg/ml. The ultrasound, highlighted the presence of two parathyroid hyperplasia, confirmed by scintigraphy, showing focal increase uptake of sestamibi in the same anatomical areas. As a result of the patient's refusal to perform a parathyroidectomy, cinacalcet, was administered (65 mg overage daily dose. After a year of treatment, there was a striking decrease of iPTH (from 1300 to 57 ρg/ml, −95%; but, on the contrary to expectations, this positive metabolic outcome, was not followed by parathyroid changes in ultrasound and scintigraphic findings.

  19. Response Assessment in Neuro-Oncology criteria, contrast enhancement and perfusion MRI for assessing progression in glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Tensaouti, Fatima [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); Khalifa, Jonathan [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Lusque, Amelie [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Biostatistics, Toulouse (France); Plas, Benjamin [CHU Toulouse, Department of Neurosurgery, Toulouse (France); Lotterie, Jean Albert; Berry, Isabelle [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); CHU Toulouse, Department of Nuclear Medicine, Toulouse (France); Laprie, Anne [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Cohen-Jonathan Moyal, Elizabeth [Claudius Regaud Institute / Toulouse University Cancer Institute - Oncopole, Department of Radiation Oncology, Toulouse (France); Toulouse Center for Cancer Research (U1037), Inserm, Toulouse (France); Lubrano, Vincent [Universite de Toulouse, Inserm, UPS, ToNIC, Toulouse NeuroImaging Center, Toulouse (France); CHU Toulouse, Department of Neurosurgery, Toulouse (France)

    2017-10-15

    The purpose of the study was to evaluate Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma multiforme (GBM), with respect to the Macdonald criteria and changes in contrast-enhancement (CE) volume. Related variations in relative cerebral blood volume (rCBV) were investigated. Forty-three patients diagnosed between 2006 and 2010 were included. All underwent surgical resection, followed by temozolomide-based chemoradiation. MR images were retrospectively reviewed. Times to progression (TTPs) according to RANO criteria, Macdonald criteria and increased CE volume (CE-3D) were compared, and the percentage change in the 75th percentile of rCBV (rCBV75) was evaluated. After a median follow-up of 22.7 months, a total of 39 patients had progressed according to RANO criteria, 32 according to CE-3D, and 42 according to Macdonald. Median TTPs were 6.4, 9.3, and 6.6 months, respectively. Overall agreement was 79.07% between RANO and CE-3D and 93.02% between RANO and Macdonald. The mean percentage change in rCBV75 at RANO progression onset was over 73% in 87.5% of patients. In conclusion, our findings suggest that CE-3D criterion is not yet suitable to assess progression in routine clinical practice. Indeed, the accurate threshold is still not well defined. To date, in our opinion, early detection of disease progression by RANO combined with advanced MRI imaging techniques like MRI perfusion and diffusion remains the best way to assess disease progression. Further investigations that would examine the impact of treatment modifications after progression determined by different criteria on overall survival would be of great value. (orig.)

  20. Response Assessment in Neuro-Oncology criteria, contrast enhancement and perfusion MRI for assessing progression in glioblastoma

    International Nuclear Information System (INIS)

    Tensaouti, Fatima; Khalifa, Jonathan; Lusque, Amelie; Plas, Benjamin; Lotterie, Jean Albert; Berry, Isabelle; Laprie, Anne; Cohen-Jonathan Moyal, Elizabeth; Lubrano, Vincent

    2017-01-01

    The purpose of the study was to evaluate Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma multiforme (GBM), with respect to the Macdonald criteria and changes in contrast-enhancement (CE) volume. Related variations in relative cerebral blood volume (rCBV) were investigated. Forty-three patients diagnosed between 2006 and 2010 were included. All underwent surgical resection, followed by temozolomide-based chemoradiation. MR images were retrospectively reviewed. Times to progression (TTPs) according to RANO criteria, Macdonald criteria and increased CE volume (CE-3D) were compared, and the percentage change in the 75th percentile of rCBV (rCBV75) was evaluated. After a median follow-up of 22.7 months, a total of 39 patients had progressed according to RANO criteria, 32 according to CE-3D, and 42 according to Macdonald. Median TTPs were 6.4, 9.3, and 6.6 months, respectively. Overall agreement was 79.07% between RANO and CE-3D and 93.02% between RANO and Macdonald. The mean percentage change in rCBV75 at RANO progression onset was over 73% in 87.5% of patients. In conclusion, our findings suggest that CE-3D criterion is not yet suitable to assess progression in routine clinical practice. Indeed, the accurate threshold is still not well defined. To date, in our opinion, early detection of disease progression by RANO combined with advanced MRI imaging techniques like MRI perfusion and diffusion remains the best way to assess disease progression. Further investigations that would examine the impact of treatment modifications after progression determined by different criteria on overall survival would be of great value. (orig.)

  1. Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins.

    Directory of Open Access Journals (Sweden)

    Reinhard Meier

    Full Text Available Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal (PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging (DWI, dynamic contrast enhanced magnetic resonance imaging (DCE-MRI and positron emission tomography with the tracer [18F]fluorodeoxyglucose (FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 (n = 13, Avastin (n = 6 or PBS (n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset (P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset (P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy (r = -0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.

  2. Our Journal Unites Us: Global Responsibilities and Possibilities for Pediatric Physical Therapy.

    Science.gov (United States)

    Van Sant, Ann F

    2018-04-01

    This article was designed to describe personal and social responsibilities for strengthening the science of pediatric physical therapy and effective international research collaboration and communication. Common flaws in research design and analysis are reviewed with recommendations for developing research students' design and analytical skills. Our social responsibility to be informed by global knowledge is highlighted. Barriers to scientific collaboration and communication including international disparities in scientific development and language barriers are presented. Suggestions to reduce these barriers are outlined. The importance of free access to scientific literature in developing countries is reviewed. The journal should assume a leadership role in building a strong science of pediatric physical therapy through encouraging personal and social responsibility in research and serving as a model of international collaboration and communication. Treatment for children with movement disorders will be improved by stronger science, international collaboration, and communication.

  3. Neurophysiological and behavioral responses to music therapy in vegetative and minimally conscious states

    DEFF Research Database (Denmark)

    O'Kelly, Julian; James, L.; Palaniappan, R.

    2013-01-01

    for preferred music (p = 0.029) across the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05) across measures indicative of discriminatory responses to both music therapy procedures. A MCS case study highlights how more sensitive selective attention may distinguish MCS from VS. Further...... of musical stimuli on arousal, attention and emotion, irrespective of verbal or motor deficits, however, an evidence base is lacking. To address this, a neurophysiological and behavioural study was undertaken comparing EEG, heart rate variability, respiration and behavioural responses of 20 healthy subjects...... responses (p ≤ 0.05) across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses across frequency bandwidths. Whilst physiological responses were heterogeneous across...

  4. Endocrine therapy for postmenopausal women with hormone receptor-positive her2-negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement.

    Science.gov (United States)

    Pritchard, K I; Gelmon, K A; Rayson, D; Provencher, L; Webster, M; McLeod, D; Verma, S

    2013-02-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2-) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients-efect, sofea, confirm, and bolero-2-have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2- advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient's age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged.

  5. Endocrine therapy for postmenopausal women with hormone receptor–positive her2–negative advanced breast cancer after progression or recurrence on nonsteroidal aromatase inhibitor therapy: a Canadian consensus statement

    Science.gov (United States)

    Pritchard, K.I.; Gelmon, K.A.; Rayson, D.; Provencher, L.; Webster, M.; McLeod, D.; Verma, S.

    2013-01-01

    Approximately 22,700 Canadian women were expected to be diagnosed with breast cancer in 2012. Despite improvements in screening and adjuvant treatment options, a substantial number of postmenopausal women with hormone receptor positive (hr+) breast cancer will continue to develop metastatic disease during or after adjuvant endocrine therapy. Guidance on the selection of endocrine therapy for patients with hr+ disease that is negative for the human epidermal growth factor receptor 2 (her2–) and that has relapsed or progressed on earlier nonsteroidal aromatase inhibitor (nsai) therapy is of increasing clinical importance. Exemestane, fulvestrant, and tamoxifen are approved therapeutic options in this context. Four phase iii trials involving 2876 patients—efect, sofea, confirm, and bolero-2—have assessed the efficacy of various treatment options in this clinical setting. Data from those trials suggest that standard-dose fulvestrant (250 mg monthly) and exemestane are of comparable efficacy, that doubling the dose of fulvestrant from 250 mg to 500 mg monthly results in a 15% reduction in the risk of progression, and that adding everolimus to exemestane (compared with exemestane alone) results in a 57% reduction in the risk of progression, albeit with increased toxicity. Multiple treatment options are now available to women with hr+ her2– advanced breast cancer recurring or progressing on earlier nsai therapy, although current clinical trial data suggest more robust clinical efficacy with everolimus plus exemestane. Consideration should be given to the patient’s age, functional status, and comorbidities during selection of an endocrine therapy, and use of a proactive everolimus safety management strategy is encouraged. PMID:23443928

  6. Influence of model assumptions about HIV disease progression after initiating or stopping treatment on estimates of infections and deaths averted by scaling up antiretroviral therapy

    Science.gov (United States)

    Sucharitakul, Kanes; Boily, Marie-Claude; Dimitrov, Dobromir

    2018-01-01

    Background Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART. Methods A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases. Results Little absolute difference (ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expanded ART. PMID:29554136

  7. Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis.

    Science.gov (United States)

    Premkumar, Preethi; Fannon, Dominic; Sapara, Adegboyega; Peters, Emmanuelle R; Anilkumar, Anantha P; Simmons, Andrew; Kuipers, Elizabeth; Kumari, Veena

    2015-03-30

    Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region׳s role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry, emotional decision-making and CBTp responsiveness. Emotional decision-making was measured by the Iowa Gambling task (IGT). Thirty patients received CBTp+standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging. Patients׳ symptoms were assessed before and after therapy. Pre-therapy OFC GMV was measured using a region-of-interest approach, and IGT performance was measured as overall learning, attention to reward, memory for past outcomes and choice consistency. Both these measures, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC׳s function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Defibrotide for the treatment of sinusoidal obstruction syndrome: evaluation of response to therapy and patient outcomes.

    Science.gov (United States)

    Coutsouvelis, John; Avery, Sharon; Dooley, Michael; Kirkpatrick, Carl; Spencer, Andrew

    2018-03-01

    Defibrotide is an agent used to treat sinusoidal obstruction syndrome (SOS/VOD) in patients undergoing haemopoietic stem cell transplantation. The aim of this study was to evaluate the effectiveness of defibrotide used within institutional guidelines for the treatment of SOS/VOD in patients undergoing haemopoietic stem cell transplantation (HSCT). Data for 23 patients was retrospectively reviewed to evaluate the effectiveness of defibrotide and the utility of response criteria to direct therapy as specified within institution guidelines. Patients met institutional criteria for a diagnosis of SOS/VOD based on predominantly Baltimore criteria and received defibrotide. Stabilisation or improvement in symptoms and biochemical markers was required for continuation of therapy with defibrotide. Overall, 14 patients responded to therapy. Survival at day 100 post HSCT was 70%. Median serum (total) bilirubin concentrations in all evaluable patients had decreased at days 5 and 10 (p defibrotide, there was a decrease in the proportion of patients exhibiting hepatomegaly (p = 0.02), ascites (p Defibrotide to treat SOS/VOD and continued based on attainment of early response was effective management of this condition. Defibrotide should be considered in any consensus protocol providing guidance on the management of SOS/VOD, with future studies considered to assess appropriate time points for response to therapy during treatment.

  9. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 2 = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  10. Neurophysiological and behavioural responses to music therapy in vegetative and minimally conscious states

    Directory of Open Access Journals (Sweden)

    Julian eO'Kelly

    2013-12-01

    Full Text Available Assessment of awareness for those with disorders of consciousness (DOC is a challenging undertaking, due to the complex presentation of the population, where misdiagnosis rates remain high. Music therapy may be effective in the assessment and rehabilitation with this population due to effects of musical stimuli on arousal, attention and emotion, irrespective of verbal or motor deficits, however, an evidence base is lacking. To address this, a neurophysiological and behavioural study was undertaken comparing EEG, heart rate variability, respiration and behavioural responses of 20 healthy subjects with 21 individuals in vegetative or minimally conscious states (VS or MCS. Subjects were presented with live preferred music and improvised music entrained to respiration (i.e., music therapy procedures, recordings of disliked music, white noise and silence. ANOVA tests indicated a range of significant responses (p ≤ 0.05 across healthy subjects corresponding to arousal and attention in response to preferred music including concurrent increases in respiration rate with globally enhanced EEG power spectra responses across frequency bandwidths. Whilst physiological responses were heterogeneous across patients, significant post hoc EEG amplitude increases for stimuli associated with preferred music were found for frontal midline theta in 6 VS and 4 MCS subjects, and frontal alpha in 3 VS and 4 MCS subjects (p = 0.05 - 0.0001. Furthermore, behavioural data showed a significantly increased blink rate for preferred music (p = 0.029 across the VS cohort. Two VS cases are presented with concurrent changes (p ≤ 0.05 across measures indicative of discriminatory responses to both music therapy procedures. A MCS case study highlights how more sensitive selective attention may distinguish MCS from VS. Further investigation is warranted to explore the use of music therapy for prognostic indicators, and its potential to support neuroplasticity in rehabilitation

  11. MRI assessment of relapsed glioblastoma during treatment with bevacizumab: volumetric measurement of enhanced and FLAIR lesions for evaluation of response and progression--a pilot study.

    Science.gov (United States)

    Pichler, Josef; Pachinger, Corinna; Pelz, Manuela; Kleiser, Raimund

    2013-05-01

    To develop a magnetic resonance imaging (MRI) metric that is useful for therapy monitoring in patients with relapsed glioblastoma (GBM) during treatment with the antiangiogenic monoclonal antibody bevacizumab (Bev). We evaluated the feasibility of tumour volume measurement with our software tool in clinical routine and tried to establish reproducible and quantitative parameters for surveillance of patients on treatment with antiangiogenic drugs. In this retrospective institutional pilot study, 18 patients (11 men, 7 women; mean age 53.5) with recurrent GBM received bevacizumab and irinotecan every two weeks as second line therapy. Follow up scans were assessed every two to four months. Data were collected on a 1.5 T MR System (Siemens, Symphony) with the standard head coil using our standardized tumour protocol. Volumetric measurement was performed with a commercial available software stroketool in FLAIR and T1-c imaging with following procedure: Pre-processing involved cutting noise and electing a Gaussian of 3 × 3 to smooth images, selecting a ROI (region of interest) in healthy brain area of the contra lateral side with quantifying the intensity value, adding 20% to this value to define the threshold level. Only values above this threshold are left corresponding to the tumour lesion. For the volumetric measurement the detected tumour area was circuited in all slices and finally summing up all values and multiplied by slice thickness to get the whole volume. With McDonalds criteria progression was indicated in 14 out of 18 patients. In contrast, volumetric measurement showed an increase of contrast enhancement of >25%, defined as threshold for progression, in 11 patients (78%) and in 12 patients (85%) in FLAIR volume, respectively. 6 patients revealed that volumes in MRI increased earlier than the last scan, which was primarily defined as the date of progression with McDonald criteria, changing PFS after re-evaluation of the tumour volumes from 6.8 to 5.6 months

  12. Immune response to Taenia solium cysticerci after anti-parasitic therapy.

    Science.gov (United States)

    Singh, Aloukick K; Singh, Satyendra K; Singh, Amrita; Gupta, Kamlesh K; Khatoon, Jahanarah; Prasad, Amit; Rai, Ravi P; Gupta, Rakesh K; Tripathi, Mukesh; Husain, Nuzhat; Prasad, Kashi N

    2015-10-01

    Albendazole is the drug of choice for Taenia solium infection. Concomitant administration of steroid has been advocated to avoid adverse reactions to albendazole therapy in neurocysticercosis. Some T. solium cysticerci (larvae) respond to albendazole therapy while others do not and the reasons remain unexplained. We hypothesise that the immune response differs between treatment responder and non-responder cysticerci and this may determine the outcome. Twenty swine naturally infected with T. solium were purchased from the market and the infection was confirmed by magnetic resonance imaging. Swine were divided into two groups; swine in group 1 were treated with albendazole and those in group 2 were treated with albendazole plus steroid (prednisolone). All the animals underwent follow-up MRIs at 6 and 12 weeks after start of therapy and were then sacrificed. Tissues surrounding the cysticerci were collected and studied for the expression of different cytokines by reverse transcriptase PCR and ELISA. Albendazole therapy was found to be more effective in parasite killing than albendazole plus steroid (94.11% versus 70.96%, P=0.011). Albendazole therapy provoked a pro-inflammatory, Th1 (IFN-γ) and pleiotropic (IL-6) cytokine response around the dead cysticerci. Despite a heavy parasite burden in the brain, all the pigs treated with albendazole plus steroid survived. In this group of animals, a mixed pro-inflammatory Th1, Th2 (IL-4) and regulatory cytokine (IL-10) response was associated with responder cysticerci. Further, Th2 and regulatory cytokine responses were associated with non-responder cysticerci. Copyright © 2015 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  13. A case study of occupational therapy managers in NSW: Roles, responsibilities and work satisfaction.

    Science.gov (United States)

    Gamble, Jane E; Lincoln, Michelle; Adamson, Barbara

    2009-04-01

    Job satisfaction has been shown to affect levels of staff retention and productivity, but few studies have been conducted on the work of occupational therapy managers and their job satisfaction. This study explores the roles and responsibilities of occupational therapy managers who are clinician-managers or manager-administrators, and sources of their work satisfaction. A collective case study involved telephone interviews with 16 occupational therapy managers. Semistructured interview questions were based on an earlier discussion with a separate group of occupational therapy managers. Interview transcripts were analysed for emerging themes. There were no clear differences in the roles and responsibilities of the two types of managers (manager-administrators and clinician-managers); however, manager-administrators tended to be responsible for larger numbers of staff. Managers reported that taking a clinical caseload is often at their own discretion. A common challenge for managers is the balancing of priorities as a clinician and a manager. Managing people was a common source of joy and sometimes a source of frustration. Mediating between staff and senior management and the need for budget control and efficiencies was an important aspect of managers' work, as was their autonomy to make decisions. Occupational therapy managers assume responsibilities consistent with clinician managers across disciplines. The main sources of work satisfaction related to people management particularly when staff were working effectively as a team and there was respect from senior management. Further research will confirm whether there are no obvious differences between clinician-manager and manager-administrators, and whether there are clear differences in work-related frustration across sectors.

  14. Anatomic, functional and molecular imaging in lung cancer precision radiation therapy: treatment response assessment and radiation therapy personalization

    Science.gov (United States)

    Everitt, Sarah; Schimek-Jasch, Tanja; Li, X. Allen; Nestle, Ursula; Kong, Feng-Ming (Spring)

    2017-01-01

    This article reviews key imaging modalities for lung cancer patients treated with radiation therapy (RT) and considers their actual or potential contributions to critical decision-making. An international group of researchers with expertise in imaging in lung cancer patients treated with RT considered the relevant literature on modalities, including computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET). These perspectives were coordinated to summarize the current status of imaging in lung cancer and flag developments with future implications. Although there are no useful randomized trials of different imaging modalities in lung cancer, multiple prospective studies indicate that management decisions are frequently impacted by the use of complementary imaging modalities, leading both to more appropriate treatments and better outcomes. This is especially true of 18F-fluoro-deoxyglucose (FDG)-PET/CT which is widely accepted to be the standard imaging modality for staging of lung cancer patients, for selection for potentially curative RT and for treatment planning. PET is also more accurate than CT for predicting survival after RT. PET imaging during RT is also correlated with survival and makes response-adapted therapies possible. PET tracers other than FDG have potential for imaging important biological process in tumors, including hypoxia and proliferation. MRI has superior accuracy in soft tissue imaging and the MRI Linac is a rapidly developing technology with great potential for online monitoring and modification of treatment. The role of imaging in RT-treated lung cancer patients is evolving rapidly and will allow increasing personalization of therapy according to the biology of both the tumor and dose limiting normal tissues. PMID:29218270

  15. Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

    Directory of Open Access Journals (Sweden)

    Valderrama Elsa

    2007-08-01

    Full Text Available Abstract Background Idiopathic membranous nephropathy (IMN is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome. Methods A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe, histopathology, type and duration of treatment, and clinical status at final evaluation. Results 13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFRe was 127 ± 57 mL/min/m2. Three patients

  16. Molecular insights into the proliferation and progression mechanisms of the oral cancer: Strategies for the effective and personalized therapy

    Directory of Open Access Journals (Sweden)

    Masakatsu Fukuda

    2012-02-01

    Full Text Available Oral carcinogenesis is a multifactorial process involving numerous genetic events that alter normal functions of oncogenes and tumor suppressor genes. It is well established that an accumulation of genetic alterations is the basis for the progression from a normal cell to a cancer cell, referred to as multi-step carcinogenesis. This event may be increased the production of growth factors or the number of receptors on the cell surface, and/or increased transcription factors or intracellular signal messengers, further that associated with deregulated control of cell proliferation and apoptosis. Together with the loss of tumor suppressor activity, these changes lead to a cell phenotype that can increase cell proliferation, with loss of cell cohesion, and infiltration to adjacent tissue thus causing distant metastasis. Molecular medicine is responsible for defining the molecular mechanisms that underlie the onset of oral cancer. This review focuses on recent advances in our understanding of the molecular control of the innumerable pathways related to these processes. These may lead to short- or medium term improvements in the diagnosis and prognosis of oral cancerous lesions and to the development of novel therapeutic approaches to this disease.

  17. Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

    2014-10-17

    This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  19. HBV Genotype B/C and Response to Lamivudine Therapy: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Xiu-Li Chen

    2013-01-01

    Full Text Available A number of nucleoside analogues such as lamivudine (LAM, actually used for the treatment of chronic hepatitis B, can suppress HBV DNA replication, improve transaminase level and liver histology, and enhance the rate of hepatitis B e antigen (HBeAg clearance. The responses to LAM therapy involve HBeAg clearance and HBV DNA conversion of negative. However, the associations between HBV genotype B/C and response to LAM therapy remain ambiguous. The aim of this meta-analysis is to determine more precise estimations of the relationship. All the publications on the associations between HBV genotype B/C and response to LAM (HBeAg clearance and HBV DNA conversion of negative through June 2013 were collected. Relative risk (RR with 95% confidence intervals (95% CI was calculated in fixed or random model, was calculated to examine heterogeneity, and funnel plots were plotted to examine small study effects with Stata 11 software. Overall, for HBeAg clearance and genotype B/C, the RR (95% CI was 1.27 (0.94–1.71, while for HBV DNA conversion of negative and genotype B/C, the RR (95% CI was 1.07 (0.98–1.17. HBV genotype B/C shows no significance associations with response to lamivudine therapy (HBeAg clearance and HBV DNA conversion of negative.

  20. Sustained long-term immune responses after in situ gene therapy combined with radiotherapy and hormonal therapy in prostate cancer patients

    International Nuclear Information System (INIS)

    Fujita, Tetsuo; Teh, Bin S.; Timme, Terry L.; Mai, W.-Y.; Satoh, Takefumi; Kusaka, Nobuyuki; Naruishi, Koji; Fattah, Elmoataz Abdel; Aguilar-Cordova, Estuardo; Butler, E. Brian; Thompson, Timothy C.

    2006-01-01

    Purpose: To explore long-term immune responses after combined radio-gene-hormonal therapy. Methods and Materials: Thirty-three patients with prostate specific antigen 10 or higher or Gleason score of 7 or higher or clinical stage T2b to T3 were treated with gene therapy that consisted of 3 separate intraprostatic injections of AdHSV-tk on Days 0, 56, and 70. Each injection was followed by 2 weeks of valacyclovir. Intensity-modulated radiation therapy was delivered 2 days after the second AdHSV-tk injection for 7 weeks. Hormonal therapy was initiated on Day 0 and continued for 4 months or 2.3 years. Blood samples were taken before, during, and after treatment. Lymphocytes were analyzed by fluorescent antibody cell sorting (FACS). Results: Median follow-up was 26 months (range, 4-48 months). The mean percentages of DR + CD8 + T cells were increased at all timepoints up to 8 months. The mean percentages of DR + CD4 + T cells were increased later and sustained longer until 12 months. Long-term (2.3 years) use of hormonal therapy did not affect the percentage of any lymphocyte population. Conclusions: Sustained long-term (up to 8 to 12 months) systemic T-cell responses were noted after combined radio-gene-hormonal therapy for prostate cancer. Prolonged use of hormonal therapy does not suppress this response. These results suggest the potential for sustained activation of cell-mediated immune responses against cancer

  1. Baseline 18F-FDG PET image-derived parameters for therapy response prediction in oesophageal cancer

    International Nuclear Information System (INIS)

    Hatt, Mathieu; Visvikis, Dimitris; Cheze-le Rest, Catherine; Pradier, Olivier

    2011-01-01

    The objectives of this study were to investigate the predictive value of tumour measurements on 2-deoxy-2-[ 18 F]fluoro-D-glucose ( 18 F-FDG) positron emission tomography (PET) pretreatment scan regarding therapy response in oesophageal cancer and to evaluate the impact of tumour delineation strategies. Fifty patients with oesophageal cancer treated with concomitant radiochemotherapy between 2004 and 2008 were retrospectively considered and classified as complete, partial or non-responders (including stable and progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST). The classification of partial and complete responders was confirmed by biopsy. Tumours were delineated on the 18 F-FDG pretreatment scan using an adaptive threshold and the automatic fuzzy locally adaptive Bayesian (FLAB) methodologies. Several parameters were then extracted: maximum and peak standardized uptake value (SUV), tumour longitudinal length (TL) and volume (TV), SUV mean , and total lesion glycolysis (TLG = TV x SUV mean ). The correlation between each parameter and response was investigated using Kruskal-Wallis tests, and receiver-operating characteristic methodology was used to assess performance of the parameters to differentiate patients. Whereas commonly used parameters such as SUV measurements were not significant predictive factors of the response, parameters related to tumour functional spatial extent (TL, TV, TLG) allowed significant differentiation of all three groups of patients, independently of the delineation strategy, and could identify complete and non-responders with sensitivity above 75% and specificity above 85%. A systematic although not statistically significant trend was observed regarding the hierarchy of the delineation methodologies and the parameters considered, with slightly higher predictive value obtained with FLAB over adaptive thresholding, and TLG over TV and TL. TLG is a promising predictive factor of concomitant

  2. Baseline {sup 18}F-FDG PET image-derived parameters for therapy response prediction in oesophageal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, Mathieu; Visvikis, Dimitris; Cheze-le Rest, Catherine [CHU Morvan, LaTIM, INSERM U650, Brest (France); Pradier, Olivier [CHU Morvan, LaTIM, INSERM U650, Brest (France); CHU Morvan, Department of Radiotherapy, Brest (France)

    2011-09-15

    The objectives of this study were to investigate the predictive value of tumour measurements on 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) pretreatment scan regarding therapy response in oesophageal cancer and to evaluate the impact of tumour delineation strategies. Fifty patients with oesophageal cancer treated with concomitant radiochemotherapy between 2004 and 2008 were retrospectively considered and classified as complete, partial or non-responders (including stable and progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST). The classification of partial and complete responders was confirmed by biopsy. Tumours were delineated on the {sup 18}F-FDG pretreatment scan using an adaptive threshold and the automatic fuzzy locally adaptive Bayesian (FLAB) methodologies. Several parameters were then extracted: maximum and peak standardized uptake value (SUV), tumour longitudinal length (TL) and volume (TV), SUV{sub mean}, and total lesion glycolysis (TLG = TV x SUV{sub mean}). The correlation between each parameter and response was investigated using Kruskal-Wallis tests, and receiver-operating characteristic methodology was used to assess performance of the parameters to differentiate patients. Whereas commonly used parameters such as SUV measurements were not significant predictive factors of the response, parameters related to tumour functional spatial extent (TL, TV, TLG) allowed significant differentiation of all three groups of patients, independently of the delineation strategy, and could identify complete and non-responders with sensitivity above 75% and specificity above 85%. A systematic although not statistically significant trend was observed regarding the hierarchy of the delineation methodologies and the parameters considered, with slightly higher predictive value obtained with FLAB over adaptive thresholding, and TLG over TV and TL. TLG is a promising predictive factor of

  3. Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

    Science.gov (United States)

    Mathew, Aju; Davidson, Nancy E

    2015-11-01

    Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Blood responses under chronic low daily dose gamma irradiation: Pt. 1; Differential preclinical responses of irradiated male dogs in progression to either aplastic anemia or myeloproliferative disease

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Carnes, B.A.; Tolle, D.V.; Fritz, T.E. (Argonne National Lab., IL (USA))

    1989-01-01

    Male beagles chronically exposed to low daily doses of {sup 60}Co {gamma} rays show one of three hematopoietic patterns, which reflect three different distinctly responding subgroups: (1) low radioresistance with progressing aplastic anemia and shortened survival ({sup -S}-AA subgroup); (2) high radioresistance with a complex of progressing myeloproliferative disorders ({sup +}R-MPD group); or (3) high radioresistance with other nonMPD syndromes ({sup +}R-nonMPD group). Blood cell levels (granulocytes, monocytes, erythrocytes, lymphocytes, and platelets) were assessed and fitted to a flexible polynomial spline model. Results showed that relative to the overall magnitude of blood cell loss as well as to the maximum rate of suppression during the initial phase, the subgroups were generally ranked {sup -}S-AA >> {sup +}R-MPD > {sup +}R-nonMPD. Relative to the overall strength of the recovery response, the subgroups were generally ranked {sup +}R-MPD > {sup +}R-nonMPD >>> {sup -}S-AA. In terms of overall maintenance levels of circulating blood cells during the recovery phase, however, the {sup +}R-nonMPD subgroup consistently exhibited stronger responses than the {sup +}R-MPD subgroup. These results support our contention that selected subgroups of dogs have strong propensities to specific hematopathologies (i.e. aplastic anemia and myeloid leukemia) under chronic irradiation and that these pathology-prone animals exhibit a series of marked differential hematopoietic responses during early preclinical phases, which serve effectively to prognosticate subsequent pathological progression. (author).

  5. FDG PET/CT is useful for the interim evaluation of response to therapy in patients affected by haematogenous spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Nanni, Cristina; Ambrosini, Valentina; Fanti, Stefano [Azienda Ospedaliero - Universitaria di Bologna Policlinico S.Orsola Malpighi, Unit of Nuclear Medicine, Bologna (Italy); Boriani, Luca; Gasbarrini, Alessandro; Boriani, Stefano [Rizzoli Orthopaedic Institute, Oncologic and Degenerative Spine Surgery, Bologna (Italy); Salvadori, Caterina; Zamparini, Eleonora; Rorato, Giada; Tumietto, Fabio; Cristini, Francesco; Viale, Pierluigi [Azienda Ospedaliero - Universitaria di Bologna Policlinico S.Orsola Malpighi, Infectious Diseases Unit, Bologna (Italy); Scudeller, Luigia [Policlinico San Matteo Pavia Fondazione IRCCS, Pavia (Italy)

    2012-10-15

    Antibiotic therapy in patients affected by discitis is often empirical. Therefore, early evaluation of response to therapy is important. In many patients inflammatory indexes are low during all the phases of the diseases or are altered by concomitant diseases. The aim of the study was to assess the possible role of FDG PET/CT for the early evaluation of response to therapy in patients affected by infective discitis, in comparison to C-reactive protein (CRP) serum levels. Enrolled in the study were 38 patients diagnosed with haematogenous infective discitis. Of the 38 patients, 7 had tubercular infection, 1 fungal infection and 30 pyogenic discitis. Four patients were excluded because the second PET/CT scan was not performed. Thus 34 patients (18 women, mean age 64 years) were analysed. All the patients included underwent a FDG PET/CT scan and determination of CRP level at baseline and again 2 to 4 weeks after the start of therapy. The PET results in terms of SUV of the first and second scans (SUV1 and SUV2) and delta-SUVmax were compared to the inflammatory indexes and clinical status during therapy. The mean SUVmax at diagnosis was 8.6 {+-} 3.7. The mean CRP level at diagnosis was 3.8 {+-} 3.8 mg/dl. A progressive clinical response was seen in 26 patients and 8 patients showed no response. SUV1 was not correlated with the baseline CRP level (CRP1, p = 0.7) and SUV2 was not correlated with the CRP level at the time of the second scan (CRP2, p = 0.4). In responders, SUV2 and CRP2 were significantly lower than SUV1 and CRP1 (p < 0.0001 and p = 0.001, respectively). ROC curves for delta-SUVmax showed a sensitivity of 82 % and a specificity of 82 % with a cut-off of 34 %. ROC curves for SUV2 showed a sensitivity of 83 % and a specificity of 46 % with a cut-off of 6.4. ROC curves for delta-CRP showed a sensitivity of 67 % and a specificity of 89 % with a cut-off of 74 %. ROC curves for CRP2 showed a sensitivity of 65 % and a specificity of 70 % with a cut-off of 0.7 mg

  6. FDG PET/CT is useful for the interim evaluation of response to therapy in patients affected by haematogenous spondylodiscitis

    International Nuclear Information System (INIS)

    Nanni, Cristina; Ambrosini, Valentina; Fanti, Stefano; Boriani, Luca; Gasbarrini, Alessandro; Boriani, Stefano; Salvadori, Caterina; Zamparini, Eleonora; Rorato, Giada; Tumietto, Fabio; Cristini, Francesco; Viale, Pierluigi; Scudeller, Luigia

    2012-01-01

    Antibiotic therapy in patients affected by discitis is often empirical. Therefore, early evaluation of response to therapy is important. In many patients inflammatory indexes are low during all the phases of the diseases or are altered by concomitant diseases. The aim of the study was to assess the possible role of FDG PET/CT for the early evaluation of response to therapy in patients affected by infective discitis, in comparison to C-reactive protein (CRP) serum levels. Enrolled in the study were 38 patients diagnosed with haematogenous infective discitis. Of the 38 patients, 7 had tubercular infection, 1 fungal infection and 30 pyogenic discitis. Four patients were excluded because the second PET/CT scan was not performed. Thus 34 patients (18 women, mean age 64 years) were analysed. All the patients included underwent a FDG PET/CT scan and determination of CRP level at baseline and again 2 to 4 weeks after the start of therapy. The PET results in terms of SUV of the first and second scans (SUV1 and SUV2) and delta-SUVmax were compared to the inflammatory indexes and clinical status during therapy. The mean SUVmax at diagnosis was 8.6 ± 3.7. The mean CRP level at diagnosis was 3.8 ± 3.8 mg/dl. A progressive clinical response was seen in 26 patients and 8 patients showed no response. SUV1 was not correlated with the baseline CRP level (CRP1, p = 0.7) and SUV2 was not correlated with the CRP level at the time of the second scan (CRP2, p = 0.4). In responders, SUV2 and CRP2 were significantly lower than SUV1 and CRP1 (p < 0.0001 and p = 0.001, respectively). ROC curves for delta-SUVmax showed a sensitivity of 82 % and a specificity of 82 % with a cut-off of 34 %. ROC curves for SUV2 showed a sensitivity of 83 % and a specificity of 46 % with a cut-off of 6.4. ROC curves for delta-CRP showed a sensitivity of 67 % and a specificity of 89 % with a cut-off of 74 %. ROC curves for CRP2 showed a sensitivity of 65 % and a specificity of 70 % with a cut-off of 0.7 mg

  7. Effect of late-stage therapy on disease progression in AAV-mediated rescue of photoreceptor cells in the retinoschisin-deficient mouse.

    Science.gov (United States)

    Janssen, Andreas; Min, Seok H; Molday, Laurie L; Tanimoto, Naoyuki; Seeliger, Mathias W; Hauswirth, William W; Molday, Robert S; Weber, Bernhard H F

    2008-06-01

    Proof-of-concept for a successful adeno-associated virus serotype 5 (AAV5)-mediated gene therapy in X-linked juvenile retinoschisis (XLRS) has been demonstrated in an established mouse model for this condition. The initial studies concentrated on early time-points of treatment. In this study, we aimed to explore the consequences of single subretinal injections administered at various stages of more advanced disease. By electroretinogram (ERG), functional improvement in treated versus untreated eyes is found to be significant in retinoschisin-deficient mice injected at the time-points of 15 days (P15), 1 month (PM1), and 2 months (PM2) after birth. In mice treated at 7 months after birth (PM7), an age previously shown to exhibit advanced retinal disease, ERG responses reveal no beneficial effects of vector treatment. Generally, functional rescue is paralleled by sustained retinoschisin expression and significant photoreceptor survival relative to untreated eyes. Quantitative measures of photoreceptors and peanut agglutinin-labeled ribbon synapses demonstrate rescue effects even in mice injected as late as PM7. Taken together, AAV5-mediated gene replacement is beneficial in slowing disease progression in murine XLRS. In addition, we show the effectiveness of rescue efforts even if treatment is delayed until advanced signs of disease have developed. Human XLRS patients might benefit from these findings, which suggest that the effectiveness of treatment appears not to be restricted to the early stages of the disease, and that treatment may prove to be valuable even when administered at more advanced stages.

  8. Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges.

    Science.gov (United States)

    Tsapkini, Kyrana; Frangakis, Constantine; Gomez, Yessenia; Davis, Cameron; Hillis, Argye E

    Primary progressive aphasia (PPA) is a neurodegenerative disease that primarily affects language functions and often begins in the fifth or sixth decade of life. The devastating effects on work and family life call for the investigation of treatment alternatives. In this article, we present new data indicating that neuromodulatory treatment, using transcranial direct current stimulation (tDCS) combined with a spelling intervention, shows some promise for maintaining or even improving language, at least temporarily, in PPA. The main aim of the present article is to determine whether tDCS plus spelling intervention is more effective than spelling intervention alone in treating written language in PPA. We also asked whether the effects of tDCS are sustained longer than the effects of spelling intervention alone. We present data from six PPA participants who underwent anodal tDCS or sham plus spelling intervention in a within-subject crossover design. Each stimulation condition lasted 3 weeks or a total of 15 sessions with a 2-month interval in between. Participants were evaluated on treatment tasks as well as on other language and cognitive tasks at 2-week and 2-month follow-up intervals after each stimulation condition. All participants showed improvement in spelling (with sham or tDCS). There was no difference in the treated items between the two conditions. There was, however, consistent and significant improvement for untrained items only in the tDCS plus spelling intervention condition. Furthermore, the improvement lasted longer in the tDCS plus spelling intervention condition compared to sham plus spelling intervention condition. Neuromodulation with tDCS offers promise as a means of augmenting language therapy to improve written language function at least temporarily in PPA. The consistent finding of generalisation of treatment benefits to untreated items and the superior sustainability of treatment effects with tDCS justifies further investigations. However

  9. Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda.

    Science.gov (United States)

    Asiimwe, Stephen B; Fatch, Robin; Patts, Gregory; Winter, Michael; Lloyd-Travaglini, Christine; Emenyonu, Nneka; Muyindike, Winnie; Kekibiina, Allen; Blokhina, Elena; Gnatienko, Natalia; Kruptisky, Evgeny; Cheng, Debbie M; Samet, Jeffrey H; Hahn, Judith A

    2017-11-01

    In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log 10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log 10 viral load than beer/low-ethanol-content cocktail drinkers (β = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log 10 HIV viral load (β = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the

  10. Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

    Science.gov (United States)

    Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

    2017-07-01

    An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

  11. Physiological responses of preterm newborn infants submitted to classical music therapy.

    Science.gov (United States)

    da Silva, Camila Mendes; Cação, Jessica Marcelle R; Silva, Karin Cristina dos S; Marques, Cassia Fernandes; Merey, Leila Simone F

    2013-01-01

    To evaluate the physiological effects of music therapy on hospitalized preterm newborns. A noncontrolled clinical trial including 12 newborn infants with gestational age classical music therapy twice a day (morning and afternoon) for three consecutive days. The variables: heart and respiratory rates, oxygen saturation, diastolic and systolic arterial pressures, and body temperature were analyzed before and immediately after each music therapy session. There was a decrease in the heart rate after the second session of music therapy (paired t-test; p=0.002), and an increase at the end of the third session (paired t-test; p=0.005). Respiratory rate decreased during the fourth and fifth sessions (paired t-test; p=0.01 and 0.03, respectively). Regarding oxygen saturation, there was an increase after the fifth session (p=0.008). Comparison of physiological parameters among sessions, for the six studied sessions, showed only that the gain in oxygen saturation during the fifth session was significantly higher than during the sixth one (Tukey's test after variance analysis; p=0.04). Music therapy may modify short-term physiological responses of hospitalized preterm newborn infants.

  12. The host immunological response to cancer therapy: An emerging concept in tumor biology.

    Science.gov (United States)

    Voloshin, Tali; Voest, Emile E; Shaked, Yuval

    2013-07-01

    Almost any type of anti-cancer treatment including chemotherapy, radiation, surgery and targeted drugs can induce host molecular and cellular immunological effects which, in turn, can lead to tumor outgrowth and relapse despite an initial successful therapy outcome. Tumor relapse due to host immunological effects is attributed to angiogenesis, tumor cell dissemination from the primary tumors and seeding at metastatic sites. This short review will describe the types of host cells that participate in this process, the types of factors secreted from the host following therapy that can promote tumor re-growth, and the possible implications of this unique and yet only partially-known process. It is postulated that blocking these specific immunological effects in the reactive host in response to cancer therapy may aid in identifying new host-dependent targets for cancer, which in combination with conventional treatments can prolong therapy efficacy and extend survival. Additional studies investigating this specific research direction-both in preclinical models and in the clinical setting are essential in order to advance our understanding of how tumors relapse and evade therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Simplified response monitoring criteria for multiple myeloma in patients undergoing therapy with novel agents using computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Schabel, Christoph; Horger, Marius; Kum, Sara [Department of Diagnostic and Interventional Radiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany); Weisel, Katja [Department of Internal Medicine II – Hematology & Oncology, Eberhard-Karls-University Tuebingen, Otfried-Müller-Str. 5, 72076 Tuebingen (Germany); Fritz, Jan [Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 600 N Wolfe St., Baltimore, MD 21287 (United States); Ioanoviciu, Sorin D. [Department of Internal Medicine, Clinical Municipal Hospital Timisoara, Gheorghe Dima Str. 5, 300079 Timisoara (Romania); Bier, Georg, E-mail: georg.bier@med.uni-tuebingen.de [Department of Neuroradiology, Eberhard-Karls-University Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen (Germany)

    2016-12-15

    {sub med}) and response of all myeloma manifestations including osteolyses (Resp{sub total}) was performed using the corrected contingency coefficient (C{sub corr}). Results: The correlation between Resp{sub med} based on length diameter and transverse diameter and Resp{sub total} was perfect (C{sub corr} = 1.0; p < 0.0001) whereas the correlation based on density was moderate (C{sub corr} = 0.54; p < 0.0001). The evaluation of simplified response criteria with a measurement of only 2 medullary lesions yielded the best sensitivity and specificity valued for treatment-induced changes for the length diameter evaluation with 94.4%/95.7% for prediction of progressive disease and 78.6%/93.3% for prediction of therapy response. There were no significant differences between patients treated with bortezomib and lenalidomide (p > 0.05). Conclusion: Measurements of size of a minimum of two medullary lesions is sufficient for response assessment and correlates very well with the course of lytic bone lesions and that of hematologic parameters.

  14. Clinical results of intravenous and intra-arterial peptide receptor radionuclide therapy (PRRT) using Y-90 and Lu-177 DOTA-TYR3-OCTREOTATE (Y-90 DOTA-TATE) in 151 patents with metastatic progressive neuroendocrine tumors (NET)

    International Nuclear Information System (INIS)

    Baum, R.P.; Soeldner, J.; Strauss, H.-J.

    2005-01-01

    We investigated the anti-tumor efficacy and adverse effects of the somatostatin analog octreotate labelled with Y-90 or Lu-177 in patients with progressive neuroendocrine tumors and severe tumour burden. 151 patients (69 f and 82 m, age range=19-81 yrs), 307 administrations, Mean activity per cycle 3.35 GBq (max. 7000 MBq) and time between cycles 3 to 6 months. 7 pts received intra-arterial injections (8 cycles). All patients were selected based on high SST-R expression as proven by immunohistochemistry and Ga-68 DOTA-NOC receptor PET/CT or somatostatin scintigraphy. Re-staging was done using Ga-68 DOTA-NOC PET/CT, MRI, FDG-PET/CT, SST-R scintigraphy, F-18-Fluoride-PET/CT, renal scintigraphy (MAG 3), GFR measurements (DTPA) and monthly laboratory tests (haematology, liver enzymes, renal parameters, tumour markers). Results revealed 2 patients with complete remission (de novo therapy), Partial remission (PR) in 37 %, Stable disease (SD) in 52 % and disease progression (DP) in 11%. Objective tumour response (including improvement of symptoms) was seen in 85 % of the patients. A few adverse effects were also noted: Nausea and vomiting occurred in 35 % of female, and in 15 % of male patients. Anemia, leucocytopenia and thrombocytopenia (G2-3) observed in less than <15 %. None of the pts developed myelodysplastic syndrome. No hair loss was observed. We conclude that PRRT with Y-90/Lu-177 DOTA-TATE results in a high response rate with significant improvement of clinical symptoms; the treatment is tolerated with low toxicity and few adverse effects and shows promising results also in pts with progressive neuroendocrine tumours after biological treatment(interferon/sandostatin) or after chemotherapy. Renal toxicity can be reduced by prolonging the intervals between therapy cycles and reducing the maximum activity per cycle ('Bad Berka concept')

  15. Oxidative stress and antioxidant responses to progressive resistance exercise intensity in trained and untrained males

    OpenAIRE

    H Çakır-Atabek; F Özdemir; R Çolak

    2015-01-01

    The relationship between oxidative stress and some exercise components of resistance exercise (e.g. intensity, exercise volume) has not been clearly defined. Additionally, the oxidative stress markers may respond differently in various conditions. This study aims to determine the effects of progressive intensity of resistance exercise (RE) on oxidative stress and antioxidants in trained and untrained men, and also to investigate the possible threshold intensity required to evoke oxidative str...

  16. Military Readiness: Progress and Challenges in Implementing the Navy’s Optimized Fleet Response Plan

    Science.gov (United States)

    2016-05-02

    command and control under the OFRP contributes to wide swings in port workload , which in turn can have a negative effect on the private - sector industrial...for 53 percent of all private - sector aircraft carrier maintenance contracts and 70 percent of cruiser and destroyer contracts from fiscal years...their impact on the Navy; (2) the Navy’s goals and progress in implementing the OFRP; and (3) challenges faced by public and private shipyards

  17. Therapist and Patient Perceptions of Alliance and Progress in Psychological Therapy for Women Diagnosed with Gynecological Cancers

    Science.gov (United States)

    Manne, Sharon L.; Kashy, Deborah A.; Rubin, Stephen; Hernandez, Enrique; Bergman, Cynthia

    2012-01-01

    Objective: The goal was to understand both therapist and patient perspectives on alliance and session progress for women in treatment for gynecological cancer. We used a longitudinal version of the one-with-many design to partition variation in alliance and progress ratings into therapist, patient/dyad, and time-specific components. We also…

  18. Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer

    DEFF Research Database (Denmark)

    See, W; Iversen, P; Wirth, M

    2003-01-01

    To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer.......To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer....

  19. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy.

    NARCIS (Netherlands)

    Schrier, B.P.; Hollander, M.P.; Rhijn, B.W. van; Kiemeney, L.A.L.M.; Witjes, J.A.

    2004-01-01

    OBJECTIVE: To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. MATERIALS AND METHODS: From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer

  20. Image-Guided Robotic Stereotactic Body Radiation Therapy for Liver Metastases: Is There a Dose Response Relationship?

    International Nuclear Information System (INIS)

    Vautravers-Dewas, Claire; Dewas, Sylvain; Bonodeau, Francois; Adenis, Antoine; Lacornerie, Thomas; Penel, Nicolas; Lartigau, Eric; Mirabel, Xavier

    2011-01-01

    Purpose: To evaluate the outcome, tolerance, and toxicity of stereotactic body radiotherapy, using image-guided robotic radiation delivery, for the treatment of patients with unresectable liver metastases. Methods and Material: Patients were treated with real-time respiratory tracking between July 2007 and April 2009. Their records were retrospectively reviewed. Metastases from colorectal carcinoma and other primaries were not necessarily confined to liver. Toxicity was evaluated using National Cancer Institute Common Criteria for Adverse Events version 3.0. Results: Forty-two patients with 62 metastases were treated with two dose levels of 40 Gy in four Dose per Fraction (23) and 45 Gy in three Dose per Fraction (13). Median follow-up was 14.3 months (range, 3-23 months). Actuarial local control for 1 and 2 years was 90% and 86%, respectively. At last follow-up, 41 (66%) complete responses and eight (13%) partial responses were observed. Five lesions were stable. Nine lesions (13%) were locally progressed. Overall survival was 94% at 1 year and 48% at 2 years. The most common toxicity was Grade 1 or 2 nausea. One patient experienced Grade 3 epidermitis. The dose level did not significantly contribute to the outcome, toxicity, or survival. Conclusion: Image-guided robotic stereotactic body radiation therapy is feasible, safe, and effective, with encouraging local control. It provides a strong alternative for patients who cannot undergo surgery.

  1. Identification of treatment response predictors and potential molecular targets for chemo preventive and antiangiogenic therapies

    International Nuclear Information System (INIS)

    Pfeffer, U.; Albini, A.

    2009-01-01

    The aims of the project were: To evaluate the cellular responses to anti-inflammatory and anti-angiogenic natural or synthetic compounds (chemo preventives, inhibitors of cell survival and inflammation related signal transduction). To identify bio markers for treatment response through the selection of targets that are common to or specific for anti-inflammatory and anti-angiogenic activities. To analyze the regulation of the key tumor-promotion pathways Akt, HIF1α, NFκB. We focused our studies on the antiapoptotic role of the AKT survival pathway, which is involved in prostate tumor progression to an androgen-independent phenotype

  2. Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Jons, Christian; Olsen, Niels T

    2012-01-01

    A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were...... to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT....

  3. Asthma: Effect of Genotype on Response to Therapy in the Emergency Department

    Directory of Open Access Journals (Sweden)

    Henderson, Sean

    2007-08-01

    Full Text Available Objective: We examined the effect of two β2-adrenoreceptor (β2AR polymorphisms (A46G and C79G in asthmatics presenting to the Emergency Department (ED in relation to their response to standard therapy measured by change in Forced Expiratory Volume at one second (FEV1. Our hypothesis was that the polymorphisms in the β2AR gene would predict clinical response to therapy with 46G and 79C displaying decreased response to inhaled therapy. Methods: This was a pilot feasibility study of a convenience sample of patients seen in the ED for acute exacerbation of asthma. Baseline data collected included: age, gender, ethnicity, vital signs, baseline FEV1, body mass index (BMI, smoking history and medications taken prior to arrival to the ED. Patients received standard ED care and FEV1 was measured after each treatment. Blood was taken and genotyped. Results: Fifty-three patients were enrolled over a three-month period. Using mean improvement in FEV1 from baseline to the first treatment as the primary outcome of interest, we performed multivariable linear regression analyses, with the FEV1 change as the dependent variable. When modeled as an ordinal covariate representing the number of G alleles present, there was a significant positive trend for the C79G locus (p=0.035. Those who were GG homozygotes had a 0.284 L/min improvement in FEV1 (31% after their initial albuterol treatment compared to 0.123 L/min (12% in those who were CC homozygotes. This represents a 2.5 times relative difference and a 19% actual difference. Genotypes at the A46G locus were not associated with FEV1 change. Conclusion: In this pilot study of ED patients with acute asthma exacerbation, there was a significant effect of genotype on response to therapy.

  4. Uptake of combination antiretroviral therapy and HIV disease progression according to geographical origin in seroconverters in Europe, Canada, and Australia

    DEFF Research Database (Denmark)

    Jarrin, Inma; Pantazis, Nikos; Gill, M John

    2012-01-01

    We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART).......We examined differences by geographical origin (GO) in time from HIV seroconversion (SC) to AIDS, death, and initiation of antiretroviral therapy (cART)....

  5. 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.

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

    International Nuclear Information System (INIS)

    Koritzinsky, Marianne

    2015-01-01

    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

  7. CCR 20th Anniversary Commentary: Divide and Conquer-Breast Cancer Subtypes and Response to Therapy.

    Science.gov (United States)

    Pusztai, Lajos; Rouzier, Roman; Symmans, W Fraser

    2015-08-15

    The article by Rouzier and colleagues, published in the August 15, 2005, issue of Clinical Cancer Research, demonstrated that different molecular subtypes of breast cancer have different degrees of sensitivity to chemotherapy, but the extent of response to neoadjuvant therapy has a different meaning by subtype. Several molecular subtype-specific clinical trials are under way to maximize pathologic complete response rates in triple-negative breast cancer and HER2-positive cancers, and to provide adjuvant treatment options for patients with residual invasive disease. See related article by Rouzier et al., Clin Cancer Res 2005;11(16) Aug 15, 2005;5678-85. ©2015 American Association for Cancer Research.

  8. Regional changes over time in initial virological response rates to combination antiretroviral therapy across Europe

    DEFF Research Database (Denmark)

    Bannister, W; Kirk, O; Gatell, J

    2006-01-01

    BACKGROUND: Changes in virologic response to initial combination antiretroviral therapy (cART) over calendar time may indicate improvements in cART or emergence of primary resistance. Regional variations may identify differences in available antiretroviral drugs or patient management. METHODS.......026) and time (P changes were observed (south, P = 0.061; central west, P ....001; north: P = 0.070; east, P = 0.001). CONCLUSIONS: There was some evidence of regional differences in initial virologic response to cART. Improvements over time were observed, suggesting that so far, the effect of primary resistance has not been of sufficient magnitude to prevent increasing suppression...

  9. 3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

    International Nuclear Information System (INIS)

    Muruganandham, Manickam; Clerkin, Patrick P.; Smith, Brian J.; Anderson, Carryn M.; Morris, Ann; Capizzano, Aristides A.; Magnotta, Vincent; McGuire, Sarah M.; Smith, Mark C.; Bayouth, John E.; Buatti, John M.

    2014-01-01

    Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of

  10. 3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Muruganandham, Manickam; Clerkin, Patrick P. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Smith, Brian J. [Department of Biostatistics, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Anderson, Carryn M.; Morris, Ann [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Capizzano, Aristides A.; Magnotta, Vincent [Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); McGuire, Sarah M.; Smith, Mark C.; Bayouth, John E. [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States); Buatti, John M., E-mail: john-buatti@uiowa.edu [Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa (United States)

    2014-09-01

    Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of

  11. 3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

    Science.gov (United States)

    Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

    2014-09-01

    To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk

  12. Proton therapy radiation pneumonitis local dose–response in esophagus cancer patients

    International Nuclear Information System (INIS)

    Echeverria, Alfredo E.; McCurdy, Matthew; Castillo, Richard; Bernard, Vincent; Ramos, Natalia Velez; Buckley, William; Castillo, Edward; Liu, Ping; Martinez, Josue; Guerrero, Thomas

    2013-01-01

    Purpose: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. Materials/methods: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. Results: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p = 0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. Conclusions: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope

  13. Difference of protein 53 expression based on radiation therapy response in cervical cancer

    Science.gov (United States)

    Pasaribu, H. P.; Lubis, L. I.; Dina, S.; Simanjuntak, R. Y.; Siregar, H. S.; Rivany, R.

    2018-03-01

    Cervical cancer is one of most common gynecological cancer in women and the leading cause of death in developing countries. An analytic study with the case-control design was conducted to determine the difference of p53 expression based on radiation therapy response in cervical cancer. The study was performed in Obstetric and Gynecology Department and Pathology Department of Adam Malik General Hospital Medan from January to February 2017. 15 paraffin blocks of acervical cancer patient with incomplete response were obtained as study samples, and 15 paraffin blocks of acervical cancer patient with complete response were obtained as control samples, The samples were collected by consecutive sampling, andan immunohistochemical assessment of p53 expression was done to assessapoptosis count and radiation response. Data were analyzed using Kruskal-Wallis with confidence interval 83.5% and pcervical cancer.

  14. Predictive value of vrk 1 and 2 for rectal adenocarcinoma response to neoadjuvant chemoradiation therapy: a retrospective observational cohort study

    International Nuclear Information System (INIS)

    Puerto-Nevado, Laura del; Marin-Arango, Juan Pablo; Fernandez-Aceñero, Maria Jesus; Arroyo-Manzano, David; Martinez-Useros, Javier; Borrero-Palacios, Aurea; Rodriguez-Remirez, Maria; Cebrian, Arancha; Gomez del Pulgar, Teresa; Cruz-Ramos, Marlid; Carames, Cristina; Lopez-Botet, Begoña; Garcia-Foncillas, Jesús

    2016-01-01

    Neoadjuvant chemoradiotherapy (NACRT) followed by surgical resection is the standard therapy for locally advanced rectal cancer. However, tumor response following NACRT varies, ranging from pathologic complete response to disease progression. We evaluated the kinases VRK1 and VRK2, which are known to play multiple roles in cellular proliferation, cell cycle regulation, and carcinogenesis, and as such are potential predictors of tumor response and may aid in identifying patients who could benefit from NACRT. Sixty-seven pretreatment biopsies were examined for VRK1 and VRK2 expression using tissue microarrays. VRK1 and VRK2 Histoscores were combined by linear addition, resulting in a new variable designated as “composite score”, and the statistical significance of this variable was assessed by univariate and multivariate logistic regression. The Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve (AUC) analysis were carried out to evaluate calibration and discrimination, respectively. A nomogram was also developed. Univariate logistic regression showed that tumor size as well as composite score were statistically significant. Both variables remained significant in the multivariate analysis, obtaining an OR for tumor size of 0.65 (95 % CI, 0.45–0.94; p = 0.021) and composite score of 1.24 (95 % CI, 1.07–1.48; p = 0.005). Hosmer-Lemeshow test showed an adequate model calibration (p = 0.630) and good discrimination was also achieved, AUC 0.79 (95 % CI, 0.68–0.90). This study provides novel data on the role of VRK1 and VRK2 in predicting tumor response to NACRT, and we propose a model with high predictive ability which could have a substantial impact on clinical management of locally advanced rectal cancer. The online version of this article (doi:10.1186/s12885-016-2574-9) contains supplementary material, which is available to authorized users

  15. Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

    National Research Council Canada - National Science Library

    Johnson, Leigh G; Rohan, Kelly J

    2005-01-01

    ...), group cognitive-behavioral therapy (CBT), or combination therapy (CBT+LT). Atypical and typical symptoms were assessed using subscales of the Structured Interview Guide for the Hamilton Rating Scale for Depression - SAD Version (SIGH-SAD...

  16. Early response in cognitive-behavior therapy for syndromes of medically unexplained symptoms.

    Science.gov (United States)

    Kleinstäuber, Maria; Lambert, Michael J; Hiller, Wolfgang

    2017-05-25

    Early dramatic treatment response suggests a subset of patients who respond to treatment before most of it has been offered. These early responders tend to be over represented among those who are well at termination and at follow-up. Early response patterns in psychotherapy have been investigated only for a few of mental disorders so far. The main aim of the current study was to examine early response after five therapy-preparing sessions of a cognitive behavior therapy (CBT) for syndromes of medically unexplained symptoms (MUS). In the context of a randomized, waiting-list controlled trial 48 patients who suffered from ≥3 MUS over ≥6 months received 5 therapy-preparing sessions and 20 sessions of CBT for somatoform disorders. They completed self-report scales of somatic symptom severity (SOMS-7 T), depression (BDI-II), anxiety (BSI), illness anxiety and behavior (IAS) at pre-treatment, after 5 therapy-preparing sessions (FU-5P) and at therapy termination (FU-20 T). The current analyses are based on data from the treatment arm only. Repeated measure ANOVAs revealed a significant decrease of depression (d = 0.34), anxiety (d = 0.60), illness anxiety (d = 0.38) and illness behavior (d = 0.42), but no change of somatic symptom severity (d = -0.03) between pre-treatment and FU-5P. Hierarchical linear multiple regression analyses showed that symptom improvements between pre-treatment and FU-5P predict a better outcome at therapy termination for depression and illness anxiety, after controlling for pre-treatment scores. Mixed-effect ANOVAs revealed significant group*time interaction effects indicating differences in the course of symptom improvement over the therapy between patients who fulfilled a reliable change (i.e., early response) during the 5 therapy-preparing sessions and patients who did not reach an early reliable change. Demographic or clinical variables at pre-treatment were not significantly correlated with differential scores between pre

  17. Approach of combined cancer gene therapy and radiation: response of promoters to ionizing radiation

    International Nuclear Information System (INIS)

    Anstett, A.

    2005-09-01

    Gene therapy is an emerging cancer treatment modality. We are interested in developing a radiation-inducible gene therapy system to sensitize the tumor vasculature to the effects of ionizing radiation (IR) treatment. An expression system based on irradiation-inducible promoters will drive the expression of anti-tumor genes in the tumor vasculature. Solid tumors are dependent on angio genesis, a process in which new blood vessels are formed from the pre-existing vasculature. Vascular endothelial cells are un transformed and genetically stable, thus avoiding the problem of resistance to the treatments. Vascular endothelial cells may therefore represent a suitable target for this therapeutic gene therapy strategy.The identification of IR-inducible promoters native to endothelial cells was performed by gene expression profiling using cDNA micro array technology. We describe the genes modified by clinically relevant doses of IR. The extension to high doses aimed at studying the effects of total radiation delivery to the tumor. The radio-inductiveness of the genes selected for promoter study was confirmed by RT-PCR. Analysis of the activity of promoters in response to IR was also assessed in a reporter plasmid. We found that authentic promoters cloned onto a plasmid are not suitable for cancer gene therapy due to their low induction after IR. In contrast, synthetic promoters containing repeated sequence-specific binding sites for IR-activated transcription factors such as NF-κB are potential candidates for gene therapy. The activity of five tandemly repeated TGGGGACTTTCCGC elements for NF-κB binding in a luciferase reporter was increased in a dose-dependent manner. Interestingly, the response to fractionated low doses was improved in comparison to the total single dose. Thus, we put present evidence that a synthetic promoter for NF-κB specific binding may have application in the radio-therapeutic treatment of cancer. (author)

  18. Esophageal mucosal breaks in gastroesophageal reflux disease partially responsive to proton pump inhibitor therapy.

    Science.gov (United States)

    Shaheen, Nicholas J; Denison, Hans; Björck, Karin; Silberg, Debra G

    2013-04-01

    Approximately 20-30% of patients with gastroesophageal reflux disease (GERD) do not experience complete symptom resolution during proton pump inhibitor (PPI) therapy. The aim of this study was to determine the prevalence of esophageal mucosal breaks among patients who have a partial response to PPI therapy. This was an analysis of data from a phase 2b clinical trial carried out to assess the efficacy and safety of a reflux inhibitor, lesogaberan (AZD3355), as an add-on to PPI therapy in this patient population (clinicaltrials.gov reference: NCT01005251). A total of 661 patients with persistent GERD symptoms who had received a minimum of 4 weeks of PPI therapy were included in the study. The prevalence of esophageal mucosal breaks was assessed according to (i) the most recent endoscopy results from within the previous 24 months, if available ("historical" endoscopies), and (ii) the results of endoscopies performed at study baseline ("baseline" endoscopies). Baseline endoscopies were not carried out in patients who had a historical endoscopy showing an absence of esophageal mucosal breaks. Historical endoscopy results were available for 244 patients, of whom 48 (19.7%) had esophageal mucosal breaks. Baseline endoscopies were carried out in 465 patients, of whom 146 (31.4%) had esophageal mucosal breaks. Sensitivity analyses showed a prevalence of esophageal mucosal breaks of 20-30%. In both the historical and baseline endoscopies, most esophageal mucosal breaks were Los Angeles grades A or B. In patients with GERD symptoms partially responsive to PPI therapy, mild-to-moderate severity esophageal mucosal breaks are common (prevalence 20-30%), and may contribute to symptom etiology.

  19. Cerebral blood flow in hypothyroidism: Response to therapy and associated cognitive performance

    International Nuclear Information System (INIS)

    Ilgin, N.; Akdemir, U.O.; Yetkin, I.; Eroglu, A.

    2002-01-01

    Hypothyroidism is often associated with defective memory, psychomotor slowing and depression. However, the relationship between thyroid status, related cognitive state and associated cerebral circulatory and/or metabolic abnormalities have not been elucidated. Purpose: The aim of this study was to evaluate pre-and post-therapy brain perfusion patterns in 9 hypothyroid patients presenting with Hashimoto thyroiditis. Method: Patients were referred on the basis of abnormal levels of anti-thyroglobulin and anti-microsomal antibodies, hypothyroidism and symptoms of cognitive dysfunction. Cognitive performance was tested using Raven's Coloured Progressive Matrices and Bender Gestalt Test. Functional evaluation of the brain was also performed via the methods of electroencephalography (EEG) and single photon emission tomography (SPECT). An initial SPECT study was carried out after I.V. injection of Tc99m-HMPAO and semiquantitative rCBF analysis was performed by drawing irregular regions of interest (ROIs) in three slices. A total number of 12 sector regions of interest placed on the two hemispheres and regional cerebral blood flow (rCBF) was determined using cortical region/cerebellum ratios obtained in each hemisphere. A repeat SPECT study was undertaken in 5 subjects 3-6 months after the initiation of medical therapy. Results: Pre-therapy perfusion data in four patients showed that the cortical ratios were globally depressed at the levels of 0.65-0.85 where these ratios improved quickly to the near normal-above normal levels (range of rCBF improvement as % difference from baseline 25%-45%) within 3-4 months of therapy. Conclusion: These results indicate that brain activity was globally decreased in severe hypothyroidism of short duration which normalized steadily as the hypothyroid state is corrected

  20. Progressive Abduction Loading Therapy with Horizontal-Plane Viscous Resistance Targeting Weakness and Flexion Synergy to Treat Upper Limb Function in Chronic Hemiparetic Stroke: A Randomized Clinical Trial.

    Science.gov (United States)

    Ellis, Michael D; Carmona, Carolina; Drogos, Justin; Dewald, Julius P A

    2018-01-01

    Progressive abduction loading therapy has emerged as a promising exercise therapy in stroke rehabilitation to systematically target the loss of independent joint control (flexion synergy) in individuals with chronic moderate/severe upper-extremity impairment. Preclinical investigations have identified abduction loading during reaching exercise as a key therapeutic factor to improve reaching function. An augmentative approach may be to additionally target weakness by incorporating resistance training to increase constitutive joint torques of reaching with the goal of improving reaching function by "overpowering" flexion synergy. The objective was, therefore, to determine the therapeutic effects of horizontal-plane viscous resistance in combination with progressive abduction loading therapy. 32 individuals with chronic hemiparetic stroke were randomly allocated to two groups. The two groups had equivalent baseline characteristics on all demographic and outcome metrics including age (59 ± 11 years), time poststroke (10.1 ± 7.6 years), and motor impairment (Fugl-Meyer, 26.7 ± 6.5 out of 66). Both groups received therapy three times/week for 8 weeks while the experimental group included additional horizontal-plane viscous resistance. Quantitative standardized progression of the intervention was achieved using a robotic device. The primary outcomes of reaching distance and velocity under maximum abduction loading and secondary outcomes of isometric strength and a clinical battery were measured at pre-, post-, and 3 months following therapy. There was no difference between groups on any outcome measure. However, for combined groups, there was a significant increase in reaching distance (13.2%, effect size; d  = 0.56) and velocity (13.6%, effect size; d  = 0.27) at posttesting that persisted for 3 months and also a significant increase in abduction, elbow extension, and external rotation strength at posttesting that did not persist 3