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Sample records for advanced therapies cat

  1. [Report from the Committee for Advanced Therapies (CAT). Pitfalls on the way from concept to medical treatment with advanced therapy medicinal products].

    PubMed

    Reiss, M; Büttel, I C; Schneider, C K

    2011-07-01

    Advanced therapy medicinal products (ATMP) are highly innovative and complex medicines. They comprise gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products (TEP). With the European Regulation on ATMP that came into force in 2008, a consolidated regulatory framework was created, where the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA) plays a central role. This article discusses pitfalls and challenges that the CAT has experienced in its discussions of various procedures. Often ATMPs are developed by small and medium-sized enterprises (SME) which also face nonscientific challenges. The CAT wishes to meet these challenges on a scientific and regulatory level during its 2010-2015 work program.

  2. Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

    PubMed

    Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

    2015-01-01

    With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs. PMID:26374215

  3. Marketing Regulatory Oversight of Advanced Therapy Medicinal Products (ATMPs) in Europe: The EMA/CAT Perspective.

    PubMed

    Salmikangas, Paula; Schuessler-Lenz, Martina; Ruiz, Sol; Celis, Patrick; Reischl, Ilona; Menezes-Ferreira, Margarida; Flory, Egbert; Renner, Matthias; Ferry, Nicolas

    2015-01-01

    With the release of Regulation 1394/2007, a new framework for gene and cell therapy medicinal products and tissue-engineered products was established in the European Union. For all three product classes, called advanced therapy medicinal products, a centralised marketing authorisation became mandatory. The European Medicines Agency (EMA) together with its Committee for Advanced Therapies, Committee for Human Medicinal Products and the network of national agencies is responsible for scientific evaluation of the marketing authorisation applications. For a new application, data and information relating to manufacturing processes and quality control of the active substance and the final product have to be submitted for evaluation together with data from non-clinical and clinical safety and efficacy studies. Technical requirements for ATMPs are defined in the legislation, and guidance for different products is available through several EMA/CAT guidelines. Due to the diversity of ATMPs, a tailored approach for regulating these products is considered necessary. Thus, a risk-based approach has been introduced for ATMPs allowing flexibility for the regulatory requirements. Since the regulatory framework for ATMPs was established, five products have been licenced in the European Union. However, the pipeline of new ATMPs is much bigger, as seen from the significant numbers of different products discussed by the CAT in scientific advice and classification procedures. In 2013, a public consultation on the ATMP Regulation was conducted by the European Commission, and the results were published in 2014. The report proposes several improvements for the current framework and established procedures for the regulation of ATMPs.

  4. Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Products Successfully to the Market – Report from the CAT-DGTI-GSCN Workshop at the DGTI Annual Meeting 2014

    PubMed Central

    Celis, Patrick; Ferry, Nicolas; Hystad, Marit; Schüßler-Lenz, Martina; Doevendans, Pieter A.; Flory, Egbert; Beuneu, Claire; Reischl, Ilona; Salmikangas, Paula

    2015-01-01

    On September 11, 2014, a workshop entitled ‘Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Product Successfully to the Market’ was held at the 47th annual meeting of the German Society for Transfusion Medicine and Immunohematology (DGTI), co-organised by the European Medicines Agency (EMA) and the DGTI in collaboration with the German Stem Cell Network (GSCN). The workshop brought together over 160 participants from academia, hospitals, small- or medium-sized enterprise developers and regulators. At the workshop, speakers from EMA, the Committee for Advanced Therapies (CAT), industry and academia addressed the regulatory aspects of development and authorisation of advanced therapy medicinal products (ATMPs), classification of ATMPs and considerations on cell-based therapies for cardiac repair. The open forum discussion session allowed for a direct interaction between ATMP developers and the speakers from EMA and CAT. PMID:26195933

  5. Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Products Successfully to the Market - Report from the CAT-DGTI-GSCN Workshop at the DGTI Annual Meeting 2014.

    PubMed

    Celis, Patrick; Ferry, Nicolas; Hystad, Marit; Schüßler-Lenz, Martina; Doevendans, Pieter A; Flory, Egbert; Beuneu, Claire; Reischl, Ilona; Salmikangas, Paula

    2015-05-01

    On September 11, 2014, a workshop entitled 'Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Product Successfully to the Market' was held at the 47th annual meeting of the German Society for Transfusion Medicine and Immunohematology (DGTI), co-organised by the European Medicines Agency (EMA) and the DGTI in collaboration with the German Stem Cell Network (GSCN). The workshop brought together over 160 participants from academia, hospitals, small- or medium-sized enterprise developers and regulators. At the workshop, speakers from EMA, the Committee for Advanced Therapies (CAT), industry and academia addressed the regulatory aspects of development and authorisation of advanced therapy medicinal products (ATMPs), classification of ATMPs and considerations on cell-based therapies for cardiac repair. The open forum discussion session allowed for a direct interaction between ATMP developers and the speakers from EMA and CAT.

  6. Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Products Successfully to the Market - Report from the CAT-DGTI-GSCN Workshop at the DGTI Annual Meeting 2014.

    PubMed

    Celis, Patrick; Ferry, Nicolas; Hystad, Marit; Schüßler-Lenz, Martina; Doevendans, Pieter A; Flory, Egbert; Beuneu, Claire; Reischl, Ilona; Salmikangas, Paula

    2015-05-01

    On September 11, 2014, a workshop entitled 'Advanced Therapy Medicinal Products: How to Bring Cell-Based Medicinal Product Successfully to the Market' was held at the 47th annual meeting of the German Society for Transfusion Medicine and Immunohematology (DGTI), co-organised by the European Medicines Agency (EMA) and the DGTI in collaboration with the German Stem Cell Network (GSCN). The workshop brought together over 160 participants from academia, hospitals, small- or medium-sized enterprise developers and regulators. At the workshop, speakers from EMA, the Committee for Advanced Therapies (CAT), industry and academia addressed the regulatory aspects of development and authorisation of advanced therapy medicinal products (ATMPs), classification of ATMPs and considerations on cell-based therapies for cardiac repair. The open forum discussion session allowed for a direct interaction between ATMP developers and the speakers from EMA and CAT. PMID:26195933

  7. [Clinical trials with advanced therapy medicinal products].

    PubMed

    Schüssler-Lenz, M; Schneider, C K

    2010-01-01

    For advanced therapies, the same basic principles for assessment apply as for any other biotechnological medicinal product. Nevertheless, the extent of data for quality, safety, and efficacy can be highly specific. Until recently, advanced therapies were not uniformly regulated across Europe, e.g., tissue engineered products were regulated either as medicinal products or medical devices. Thus, for some products no data from clinical studies are available, e.g., for autologous chondrocyte products. The draft guideline on Good Clinical Practice for clinical trials with advanced therapies describes specific additional requirements, e.g., ensuring traceability. Most clinical studies with advanced therapies in Germany are still in early phase I or II trials with highly divergent types of products and clinical indications. The Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMEA) has been established to meet the scientific and regulatory challenges with advanced therapies.

  8. Advances in the control of Ctenocephalides felis (cat flea) on cats and dogs.

    PubMed

    Rust, Michael K

    2005-05-01

    Cat fleas are the most important ectoparasite of cats and dogs worldwide. During the past ten years, topical and oral applications of insecticides such as fipronil, imidacloprid, lufenuron and, most recently, selamectin have revolutionized cat-flea control. Recent studies show that these therapies eliminate the need to treat indoor and outdoor environments, and their use markedly reduces the severity and prevalence of flea allergic dermatitis. Surveys have yet to reveal the development of insecticide resistance to these chemical compounds. Extending the longevity of these effective host-targeted therapies should be a major goal of the veterinary community. PMID:15837612

  9. Radioactive iodine therapy in cats with hyperthyroidism

    SciTech Connect

    Turrel, J.M.; Feldman, E.C.; Hays, M.; Hornof, W.J.

    1984-03-01

    Eleven cats with hyperthyroidism were treated with radioactive iodine (/sup 131/I). Previous unsuccessful treatments for hyperthyroidism included hemithyroidectomy (2 cats) and an antithyroid drug (7 cats). Two cats had no prior treatment. Thyroid scans, using technetium 99m, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 5 cats and in both lobes in 6 cats. Serum thyroxine concentrations were high and ranged from 4.7 to 18 micrograms/dl. Radioactive iodine tracer studies were used to determine peak radioactive iodine uptake (RAIU) and effective and biological half-lives. Activity of /sup 131/I administered was calculated from peak RAIU, effective half-life, and estimated thyroid gland weight. Activity of /sup 131/I administered ranged from 1.0 to 5.9 mCi. The treatment goal was to deliver 20,000 rad to hyperactive thyroid tissue. However, retrospective calculations based on peak RAIU and effective half-life obtained during the treatment period showed that radiation doses actually ranged from 7,100 to 64,900 rad. Complete ablation of the hyperfunctioning thyroid tissue and a return to euthyroidism were seen in 7 cats. Partial responses were seen in 2 cats, and 2 cats became hypothyroid. It was concluded that /sup 131/I ablation of thyroid tumors was a reasonable alternative in the treatment of hyperthyroidism in cats. The optimal method of dosimetry remains to be determined.

  10. Cat scratch disease during infliximab therapy: a case report and literature review.

    PubMed

    Zhou, Yi; Yin, Geng; Tan, Chunyu; Liu, Yi

    2015-05-01

    Cat scratch disease may occur during etanercept therapy, but there has been no report on infliximab-associated cat scratch disease. We report a case of a 23-year-old woman who developed right inguinal lymph node enlargement following a cat scratch. The patient had received infliximab therapy for spondyloarthropathy. She was successfully managed by discontinuing infliximab and by treatment with moxifloxacin and amikacin.

  11. Cats

    MedlinePlus

    ... found on the skin of people and animals. Methicillin-resistant Staphylococcus aureus (MRSA) is the same bacterium that has become resistant to some antibiotics. Cats and other animals often can carry MRSA ...

  12. Translational research on advanced therapies.

    PubMed

    Belardelli, Filippo; Rizza, Paola; Moretti, Franca; Carella, Cintia; Galli, Maria Cristina; Migliaccio, Giovanni

    2011-01-01

    Fostering translational research of advanced therapies has become a major priority of both scientific community and national governments. Advanced therapy medicinal products (ATMP) are a new medicinal product category comprising gene therapy and cell-based medicinal products as well as tissue engineered medicinal products. ATMP development opens novel avenues for therapeutic approaches in numerous diseases, including cancer and neurodegenerative and cardiovascular diseases. However, there are important bottlenecks for their development due to the complexity of the regulatory framework, the high costs and the needs for good manufacturing practice (GMP) facilities and new end-points for clinical experimentation. Thus, a strategic cooperation between different stakeholders (academia, industry and experts in regulatory issues) is strongly needed. Recently, a great importance has been given to research infrastructures dedicated to foster translational medicine of advanced therapies. Some ongoing European initiatives in this field are presented and their potential impact is discussed.

  13. Serum thyroxine concentrations after radioactive iodine therapy in cats with hyperthyroidism

    SciTech Connect

    Meric, S.M.; Hawkins, E.C.; Washabau, R.J.; Turrel, J.M.; Feldman, E.C.

    1986-05-01

    Thirty-one cats with hyperthyroidism were given one dose of radioactive iodine (131I) IV. Serum thyroxine (T4) concentrations were measured before treatment in all cats, at 12-hour intervals after treatment in 10 cats, and at 48-hour intervals after treatment in 21 cats. Serum T4 concentrations also were measured one month after /sup 131/I therapy in 29 cats. Activity of 131I administered was 1.5 to 6.13 mCi, resulting in a dose of 20,000 rads to the thyroid. Serum T4 concentrations before /sup 131/I administration were 5.3 to 51.0 micrograms/dl, with a median T4 concentration of 11.0 micrograms/dl. Serum T4 decreased most rapidly during the first 3 to 6 days after treatment. Sixteen cats (55%) had normal serum thyroxine concentrations by day 4 after 131I administration, and 23 cats (74%) were euthyroxinemic by day 8 after treatment. One month after administration of 131I, the 29 cats evaluated were clinically improved, and 24 (83%) of the 29 cats evaluated had normal serum T4 concentrations, 3 cats (10%) remained hyperthyroxinemic, and 2 cats (7%) were hypothyroxinemic. Therefore, administration of 131I was a safe and effective method to quickly decrease serum T4 concentrations in hyperthyroid cats.

  14. Immunomicelles for advancing personalized therapy.

    PubMed

    Sawant, Rupa R; Jhaveri, Aditi M; Torchilin, Vladimir P

    2012-10-01

    Personalized medicine, which ultimately seeks to afford tailored therapeutic regimens for individual patients, is quickly emerging as a new paradigm in the diagnosis and treatment of diseases. The idea of casting aside generic treatments in favor of patient-centric therapies has become feasible owing to advances in nanotechnology and drug delivery coupled with an enhanced knowledge of genomics and an understanding of disease at the molecular level. This review highlights polymeric immunomicelles as a class of nanocarriers that have the potential to combine diagnosis, targeted drug therapy, as well as imaging and monitoring of therapeutic response, to render a personalized approach to the management of disease. Smart multi-functional immunomicelles, as the next generation of nanocarriers, are poised for facilitating personalized cancer treatment. This review provides an assessment of immunomicelles as tools for advancing personalized therapy of diseases, with cancer being the major focus. PMID:22917778

  15. Advances in radiation therapy dosimetry

    PubMed Central

    Paliwal, Bhudatt; Tewatia, Dinesh

    2009-01-01

    During the last decade, there has been an explosion of new radiation therapy planning and delivery tools. We went through a rapid transition from conventional three-dimensional (3D) conformal radiation therapy to intensity-modulated radiation therapy (IMRT) treatments, and additional new techniques for motion-adaptive radiation therapy are being introduced. These advances push the frontiers in our effort to provide better patient care; and with the addition of IMRT, temporal dimensions are major challenges for the radiotherapy patient dosimetry and delivery verification. Advanced techniques are less tolerant to poor implementation than are standard techniques. Mis-administrations are more difficult to detect and can possibly lead to poor outcomes for some patients. Instead of presenting a manual on quality assurance for radiation therapy, this manuscript provides an overview of dosimetry verification tools and a focused discussion on breath holding, respiratory gating and the applications of four-dimensional computed tomography in motion management. Some of the major challenges in the above areas are discussed. PMID:20098555

  16. Challenges with advanced therapy medicinal products and how to meet them.

    PubMed

    Schneider, Christian K; Salmikangas, Paula; Jilma, Bernd; Flamion, Bruno; Todorova, Lyubina Racheva; Paphitou, Anna; Haunerova, Ivana; Maimets, Toivo; Trouvin, Jean-Hugues; Flory, Egbert; Tsiftsoglou, Asterios; Sarkadi, Balázs; Gudmundsson, Kolbeinn; O'Donovan, Maura; Migliaccio, Giovanni; Ancāns, Jānis; Maciulaitis, Romaldas; Robert, Jean-Louis; Samuel, Anthony; Ovelgönne, Johannes H; Hystad, Marit; Fal, Andrzej Mariusz; Lima, Beatriz Silva; Moraru, Anca Stela; Turcáni, Peter; Zorec, Robert; Ruiz, Sol; Akerblom, Lennart; Narayanan, Gopalan; Kent, Alastair; Bignami, Fabrizia; Dickson, J George; Niederwieser, Dietger; Figuerola-Santos, María-Angeles; Reischl, Ilona G; Beuneu, Claire; Georgiev, Rosen; Vassiliou, Maria; Pychova, Alena; Clausen, Mette; Methuen, Taina; Lucas, Sophie; Schüssler-Lenz, Martina; Kokkas, Vasilios; Buzás, Zsuzsanna; MacAleenan, Niall; Galli, Maria Cristina; Linē, Aija; Gulbinovic, Jolanta; Berchem, Guy; Fraczek, Mariusz; Menezes-Ferreira, Margarida; Vilceanu, Nela; Hrubisko, Mikulás; Marinko, Petra; Timón, Marcos; Cheng, Wing; Crosbie, George Andrew; Meade, Nick; di Paola, Michelino Lipucci; VandenDriessche, Thierry; Ljungman, Per; D'Apote, Lucia; Oliver-Diaz, Olga; Büttel, Isabel; Celis, Patrick

    2010-03-01

    Advanced therapy medicinal products (ATMPs), which include gene therapy medicinal products, somatic cell therapy medicinal products and tissue-engineered products, are at the cutting edge of innovation and offer a major hope for various diseases for which there are limited or no therapeutic options. They have therefore been subject to considerable interest and debate. Following the European regulation on ATMPs, a consolidated regulatory framework for these innovative medicines has recently been established. Central to this framework is the Committee for Advanced Therapies (CAT) at the European Medicines Agency (EMA), comprising a multidisciplinary scientific expert committee, representing all EU member states and European Free Trade Association countries, as well as patient and medical associations. In this article, the CAT discusses some of the typical issues raised by developers of ATMPs, and highlights the opportunities for such companies and research groups to approach the EMA and the CAT as a regulatory advisor during development.

  17. Plateletworks: A screening assay for clopidogrel therapy monitoring in healthy cats

    PubMed Central

    Hamel-Jolette, Avril; Dunn, Marilyn; Bédard, Christian

    2009-01-01

    Plateletworks is a screening assay used in human medicine to monitor platelet-inhibiting drugs. As arterial thromboembolism is a common complication in cats suffering from cardiomyopathy, they are often treated with anti-platelet medication. Clopidogrel (Plavix), an anti-platelet aggregation drug, has recently been evaluated in healthy cats. The purpose of this study was to determine if the Plateletworks method can detect a decrease in platelet aggregation in cats receiving clopidogrel. Nine healthy adult cats were used for this study. Platelet aggregation was measured before and after a 3-day clopidogrel treatment (18.75 mg SID). Platelet aggregation after the clopidogrel treatment was significantly lower (P < 0.01). The Plateletworks method appears to be a promising test to monitor clopidogrel therapy in cats. PMID:19337399

  18. Recent advances in migraine therapy.

    PubMed

    Antonaci, Fabio; Ghiotto, Natascia; Wu, Shizheng; Pucci, Ennio; Costa, Alfredo

    2016-01-01

    Migraine is a common and highly disabling neurological disorder associated with a high socioeconomic burden. Effective migraine management depends on adequate patient education: to avoid unrealistic expectations, the condition must be carefully explained to the patient soon as it is diagnosed. The range of available acute treatments has increased over time. At present, abortive migraine therapy can be classed as specific (ergot derivatives and triptans) or non-specific (analgesics and non-steroidal anti-inflammatory drugs). Even though acute symptomatic therapy can be optimised, migraine continues to be a chronic and potentially progressive condition. In addition to the drugs officially approved for migraine prevention by international governmental regulatory agencies, numerous different agents are commonly used for this indication, showing various levels of evidence of efficacy and tolerability. Guidelines published in recent years, based on evidence-based medicine data on migraine prophylaxis, are a useful source of guidance, especially for primary care physicians and neurologists without specific expertise in headache medicine. Although the field of pharmacological migraine prevention has seen few advances in recent years, potential novel approaches are now being developed. This review looks at emerging pharmacological strategies for acute and preventive migraine treatment that are nearing or have already entered the clinical trial phase. Specifically, it discusses preclinical and clinical data on compounds acting on calcitonin gene-related peptide or its receptor, the serotonin 5-HT1F receptor, nitric oxide synthase, and acid-sensing ion channel blockers. PMID:27330903

  19. Advance assessment for movement of Haz Cat 3 radioactive materials.

    SciTech Connect

    Vosburg, Susan K.

    2010-04-01

    The current packaging of most HC-3 radioactive materials at SNL/NM do not meet DOT requirements for offsite shipment. SNL/NM is transporting HC-3 quantities of radioactive materials from their storage locations in the Manzano Nuclear Facilities bunkers to facilities in TA-5 to be repackaged for offsite shipment. All transportation of HC-3 rad material by SNL/NM is onsite (performed within the confines of KAFB). Transport is performed only by the Regulated Waste/Nuclear Material Disposition Department. Part of the HC3T process is to provide the CAT with the following information at least three days prior to the move: (1) RFt-Request for transfer; (2) HC3T movement report; (3) Radiological survey; and (4) Transportation Route Map.

  20. [PVB therapy for advanced testicular cancer].

    PubMed

    Nakao, M; Nakagawa, S; Toyoda, K; Nukui, M; Takada, H; Ebisui, K; Sugimoto, K; Watanabe, H; Maegawa, M; Miyakoda, K

    1989-11-01

    Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.

  1. Photodynamic therapy for the treatment of intranasal tumors in 3 dogs and 1 cat.

    PubMed

    Lucroy, Michael D; Long, Kevin R; Blaik, Margaret A; Higbee, Russell G; Ridgway, Tisha D

    2003-01-01

    Three dogs and 1 cat with intranasal tumors were treated with pyropheophorbide-a-hexyl ether-based photodynamic therapy (PDT). PDT was well tolerated by all the animals, and no adverse effects from photosensitizer injection, such as cutaneous photosensitization, were observed. Facial swelling was observed in all animals after each PDT treatment but resolved spontaneously within 72 hours after treatment. All animals had a decrease in severity of epistaxis, frequency of sneezing, and amount of nasal discharge after PDT. Clinical signs were controlled for variable time, although long-term responses were comparable with radiation therapy in 2 animals. This small case series demonstrates another application for PDT in veterinary medicine. On the basis of these findings. further studies are warranted to define the role of PDT in the management of intranasal tumors in dogs and cats.

  2. Advances in Neutron Capture Therapy

    SciTech Connect

    Soloway, A.H.; Barth, R.F.; Carpenter, D.E.

    1993-12-31

    This volume contains the proceedings of the Fifth International Symposium on Neutron Capture Therapy held September 14--17, 1992 in Columbus, Ohio. Individual papers were separately abstracted and indexed for the database.

  3. HIV gene therapy research advances.

    PubMed

    Jacobson, Jeffrey M

    2013-02-28

    In this issue of Blood, Tebas et al report antiviral effects in a clinical trial of multiple infusions of lentiviral vector–modified autologous CD4T lymphocytes in 17 HIV-infected patients aviremic on antiretroviral therapy (ART).

  4. Efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral squamous cell carcinoma.

    PubMed

    Poirier, Valérie J; Kaser-Hotz, Barbara; Vail, David M; Straw, Rodney C

    2013-01-01

    Squamous cell carcinoma (SCC) is the most common feline oral tumor. Standard radiation protocols have been reported to achieve tumor control durations of 1.5-5.5 months (45-165 days). The purpose of this study was to describe the efficacy and toxicity of an accelerated hypofractionated radiation therapy protocol in cats with oral SCC. Twenty-one cats with histologically confirmed oral SCC and T1-3N0M0 were treated with 10 once-daily fractions (Monday-Friday) of 4.8 Gy. Seventeen cats had macroscopic disease and four were microscopic after incomplete excision. Acute toxicity consisted of grade 2 mucositis in all cats and this was effectively managed using esophageal or gastric tube feeding, pain medication, and antibiotics. Late toxicity effects for cats with available follow-up data included alopecia (4 cats), leukotricia (6), tongue ulceration (1), and oronasal fistula (1). Response could be assessed in 17 cats (seven complete response and five partial response). Four cats (19%) developed metastatic disease without evidence of local progression. The median progression-free survival (PFS) was 105 days (1 year PFS of 23%), median local progression-free survival (LPFS) was 219 days (1 year LPFS of 41%), and median overall survival (OS) was 174 days (1 year OS of 29%). Only tumor stage was prognostic, with T1 having a median PFS of 590 days. Findings indicated that this accelerated hypofractionated radiation therapy protocol was well tolerated in cats with oral SCC, with manageable adverse events. Tumor response was observed in most cats and long tumor control durations were achieved in some cats.

  5. Use of PCR and culture to detect Helicobacter pylori in naturally infected cats following triple antimicrobial therapy.

    PubMed

    Perkins, S E; Yan, L L; Shen, Z; Hayward, A; Murphy, J C; Fox, J G

    1996-06-01

    Helicobacter pylori causes gastritis and peptic ulcers and is linked to gastric cancer. Domestic cats from a commercial source were found to be naturally infected with H. pylori, and studies were undertaken to eradicate H. pylori from infected cats by using triple antimicrobial therapy. Eight cats infected with H. pylori were used in the study. Six cats received a 21-day course of oral amoxicillin, metronidazole, and omeprazole, and two cats served as controls. Two weeks and 4 weeks posttreatment (p.t.), all six treated cats were negative at several sites (saliva, gastric juice, and gastric mucosa) for H. pylori by culture. However, as determined by PCR with primers specific for the 26-kDa product, the majority of cats at 2 and 4 weeks p.t. had gastric fluid samples which were positive for H. pylori and three of three cats at 2 weeks p.t. had dental plaque which was positive for H. pylori. At 6 weeks p.t., all six cats had H. pylori-negative cultures for samples from several gastric sites taken at necropsy, and only one cat had H. pylori cultured from gastric juice. PCR analysis revealed that five of six cats had H. pylori DNA amplification products from plaque, saliva, and/or gastric fluid samples. Negative bacterial cultures for cats for which there was demonstrable PCR amplification of H. pylori DNA may reflect the inability of in vitro culture techniques to isolate small numbers of H. pylori organisms, focal colonization at sites not cultured, or a failure of the antibiotics to successfully eradicate H. pylori from extragastric sites which allowed subsequent recolonization of the stomach after cessation of therapy. Alternatively, the treatment strategy may have induced in vivo viable but nonculturable coccoid forms of H. pylori. The H. pylori cat model should allow further studies to test these hypotheses as well as the efficacies of other combined therapeutic regimens. Also, because 100% of these cats were naturally infected with H.pylori, this model should

  6. Recent Advances in Combined Modality Therapy

    PubMed Central

    Nyati, Mukesh K.; Morgan, Meredith A.; Lawrence, Theodore S.

    2010-01-01

    Combined modality therapy emerged from preclinical data showing that carefully chosen drugs could enhance the sensitivity of tumor cells to radiation while having nonoverlapping toxicities. Recent advances in molecular biology involving the identification of cellular receptors, enzymes, and pathways involved in tumor growth and immortality have resulted in the development of biologically targeted drugs. This review highlights the recent clinical data in support of newer generation cytotoxic chemotherapies and systemic targeted agents in combination with radiation therapy. PMID:20413642

  7. Photodynamic Cancer Therapy - Recent Advances

    SciTech Connect

    Abrahamse, Heidi

    2011-09-22

    The basic principle of the photodynamic effect was discovered over a hundred years ago leading to the pioneering work on PDT in Europe. It was only during the 1980s, however, when 'photoradiation therapy' was investigated as a possible treatment modality for cancer. Photodynamic therapy (PDT) is a photochemotherapeutic process which requires the use of a photosensitizer (PS) that, upon entry into a cancer cell is targeted by laser irradiation to initiate a series of events that contribute to cell death. PSs are light-sensitive dyes activated by a light source at a specific wavelength and can be classified as first or second generation PSs based on its origin and synthetic pathway. The principle of PS activation lies in a photochemical reaction resulting from excitation of the PS producing singlet oxygen which in turn reacts and damages cell organelles and biomolecules required for cell function and ultimately leading to cell destruction. Several first and second generation PSs have been studied in several different cancer types in the quest to optimize treatment. PSs including haematoporphyrin derivative (HpD), aminolevulinic acid (ALA), chlorins, bacteriochlorins, phthalocyanines, naphthalocyanines, pheophorbiedes and purpurins all require selective uptake and retention by cancer cells prior to activation by a light source and subsequent cell death induction. Photodynamic diagnosis (PDD) is based on the fluorescence effect exhibited by PSs upon irradiation and is often used concurrently with PDT to detect and locate tumours. Both laser and light emitting diodes (LED) have been used for PDT depending on the location of the tumour. Internal cancers more often require the use of laser light delivery using fibre optics as delivery system while external PDT often make use of LEDs. Normal cells have a lower uptake of the PS in comparison to tumour cells, however the acute cytotoxic effect of the compound on the recovery rate of normal cells is not known. Subcellular

  8. Advances in stem cell therapy.

    PubMed

    Pérez López, Silvia; Otero Hernández, Jesús

    2012-01-01

    Since the beginning of stem cell biology, considerable effort has been focused in the translation of scientific insights into new therapies. Cell-based assays represent a new strategy for organ and tissue repair in several pathologies. Moreover, alternative treatment strategies are urgently needed due to donor organ shortage that costs many lives every year and results in lifelong immunosuppression. At the moment, only the use of hematopoietic stem cells is considered as the standard for the treatment of malignant and genetic bone marrow disorders, being all other stem cell applications highly experimental. The present chapter tries to summarize some ongoing approaches of stem cell regenerative medicine and also introduces recent findings from published studies and trials conducted in various tissues such as skeletal muscle, liver and lung.

  9. Combination Therapy for Advanced Kaposi Sarcoma

    Cancer.gov

    In this clinical trial, adult patients with any form of advanced Kaposi sarcoma will be treated with liposomal doxorubicin and bevacizumab every 3 weeks for a maximum of six treatments.  Patients who respond to this therapy or have stable disease will rec

  10. Preoperative therapy in locally advanced esophageal cancer

    PubMed Central

    Garg, Pankaj Kumar; Sharma, Jyoti; Jakhetiya, Ashish; Goel, Aakanksha; Gaur, Manish Kumar

    2016-01-01

    Esophageal cancer is an aggressive malignancy associated with dismal treatment outcomes. Presence of two distinct histopathological types distinguishes it from other gastrointestinal tract malignancies. Surgery is the cornerstone of treatment in locally advanced esophageal cancer (T2 or greater or node positive); however, a high rate of disease recurrence (systemic and loco-regional) and poor survival justifies a continued search for optimal therapy. Various combinations of multimodality treatment (preoperative/perioperative, or postoperative; radiotherapy, chemotherapy, or chemoradiotherapy) are being explored to lower disease recurrence and improve survival. Preoperative therapy followed by surgery is presently considered the standard of care in resectable locally advanced esophageal cancer as postoperative treatment may not be feasible for all the patients due to the morbidity of esophagectomy and prolonged recovery time limiting the tolerance of patient. There are wide variations in the preoperative therapy practiced across the centres depending upon the institutional practices, availability of facilities and personal experiences. There is paucity of literature to standardize the preoperative therapy. Broadly, chemoradiotherapy is the preferred neo-adjuvant modality in western countries whereas chemotherapy alone is considered optimal in the far East. The present review highlights the significant studies to assist in opting for the best evidence based preoperative therapy (radiotherapy, chemotherapy or chemoradiotherapy) for locally advanced esophageal cancer.

  11. Systemic Therapy for Advanced Soft Tissue Sarcoma.

    PubMed

    Sheng, Jennifer Y; Movva, Sujana

    2016-10-01

    Soft tissue sarcomas are rare tumors that present with distant metastasis in up to 10% of patients. Survival has improved significantly because of advancements in histologic classification and improved management approaches. Older agents such as doxorubicin, ifosfamide, gemcitabine, and paclitaxel continue to demonstrate objective response rates from 18% to 25%. Newer agents such as trabectedin, eribulin, aldoxorubicin, and olaratumab have demonstrated improvements in progression-free survival, overall survival, or toxicity profiles. Future studies on treatment of advanced soft tissue sarcoma will continue to concentrate on reducing toxicity, personalization of therapy, and targeting novel pathways. PMID:27542647

  12. Updates in Therapy for Advanced Melanoma.

    PubMed

    Singh, Bhavana P; Salama, April K S

    2016-01-15

    Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5-10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

  13. Mirror mounts designed for the Advanced Photon Source SRI-CAT

    SciTech Connect

    Shu, D.; Benson, C.; Chang, J.

    1997-09-01

    Use of a mirror for beamlines at third-generation synchrotron radiation facilities, such as the Advanced Photon Source (APS) at Argonne National laboratory, has many advantages. A mirror as a first optical component provides significant reduction in the beam peak heat flux and total power on the downstream monochromator and simplifies the bremsstrahlung shielding design for the beamline transport. It also allows one to have a system for multibeamline branching and switching. More generally, a mirror is used for beam focusing and/or low-pass filtering. Six different mirror mounts have been designed for the SRI-CAT beamlines. Four of them are designed as water-cooled mirrors for white or pink beam use, and the other two are for monochromatic beam use. Mirror mount designs, including vacuum vessel structure and precision supporting stages, are presented in this paper.

  14. CROI 2016: Advances in Antiretroviral Therapy.

    PubMed

    Taylor, Barbara S; Olender, Susan A; Tieu, Hong-Van; Wilkin, Timothy J

    2016-01-01

    The 2016 Conference on Retroviruses and Opportunistic Infections highlighted exciting advances in antiretroviral therapy, including important data on investigational antiretroviral drugs and clinical trials. Clinical trials demonstrated benefits from a long-acting injectable coformulation given as maintenance therapy, examined intravenous and subcutaneous administration of a monoclonal antibody directed at the CD4 binding site of HIV-1, and provided novel data on tenofovir alafenamide. Several studies focused on the role of HIV drug resistance, including the significance of minority variants, transmitted drug resistance, use of resistance testing, and drug class-related resistance. Novel data on the HIV care continuum in low- and middle-income settings concentrated on differentiated HIV care delivery models and outcomes. Data on progress toward reaching World Health Organization 90-90-90 targets as well as outcomes related to expedited initiation of HIV treatment and adherence strategies were presented. Results from a trial in Malawi showed reduced rates of mother-to-child transmission among HIV-infected women who initiated antiretroviral therapy prior to pregnancy, and several studies highlighted the effect of antiretroviral therapy in pediatric populations. A special session was dedicated to the findings of studies of Ebola virus disease and treatment during the outbreak in West Africa. PMID:27398863

  15. Photodynamic therapy of advanced malignant tumors

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  16. Evaluation of intranasal vaccine administration and high-dose interferon- α2b therapy for treatment of chronic upper respiratory tract infections in shelter cats.

    PubMed

    Fenimore, Audra; Carter, Kasey; Fankhauser, Jeffrey; Hawley, Jennifer R; Lappin, Michael R

    2016-08-01

    Clinical signs of upper respiratory tract infection can be hard to manage in cats, particularly those in shelters. In this study, clinical data were collected from chronically ill (3-4 weeks' duration) cats with suspected feline herpesvirus-1 (FHV-1) or feline calicivirus (FCV) infections after administration of one of two novel therapies. Group A cats were administered a commercially available formulation of human interferon-α2b at 10,000 U/kg subcutaneously for 14 days, and group B cats were administered one dose of a FHV-1 and FCV intranasal vaccine. Molecular assays for FHV-1 and FCV were performed on pharyngeal samples, and a number of cytokines were measured in the blood of some cats. A clinical score was determined daily for 14 days, with cats that developed an acceptable response by day 14 returning to the shelter for adoption. Those failing the first treatment protocol were entered into the alternate treatment group. During the first treatment period, 8/13 cats in group A (61.5%) and all 12 cats in group B (100%) had apparent responses. The seven cats positive for nucleic acids of FHV-1 or FCV responded favorably, independent of the treatment group. There were no differences in cytokine levels between cats that responded to therapy or failed therapy. Either protocol assessed here may be beneficial in alleviating chronic clinical signs of suspected feline viral upper respiratory tract disease in some cats that have failed other, more conventional, therapies. The results of this study warrant additional research involving these protocols. PMID:26269455

  17. Advances in Stem Cell Therapy for Leukemia.

    PubMed

    Tian, Hong; Qu, Qi; Liu, Liming; Wu, Depei

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD). In addition, infusion of HLA-mismatched donor granulocyte colony-stimulating factor-mobilized donor peripheral blood stem cells after chemotherapy, the so called "microtransplantation", has been shown to promote the graft-versus-leukemia effect and hasten hematopoietic recovery without amplifying GVHD. Herein, we review recent advances in stem cell therapy for leukemia with a specific focus on dual transplantation and microtransplantation.

  18. Membranous nephropathy in the cat: a clinical and pathological study.

    PubMed

    Nash, A S; Wright, N G; Spencer, A J; Thompson, H; Fisher, E W

    1979-07-28

    A series of 13 cases of feline membranous nephropathy is presented. Two groups were distinguished clinically; eight cats had the nephrotic syndrome and five others were in renal failure but not nephrotic. The definitive diagnosis was based on histological, immunofluorescence and ultrastructural examinations of renal tissue obtained at renal biopsy or necropsy. Glomerular lesions were classified according to the degree of glomerular change into three distinct groups; mild, moderately severe and advanced. A relationship was established between the mild and moderately severe groups and cats with the nephrotic syndrome, and the advanced group and cats in renal failure. Diuretic therapy was satisfactory in initial control of oedema in the nephrotic cases. Monitoring of previously nephrotic cats for up to three years indicated that the disease is progressive, although in some cases it is sufficiently slow for a cat to live a relatively normal life without continuing treatment. The prognosis for cats presented in renal failure is hopeless. PMID:552741

  19. Molecular targeted therapy for advanced gastric cancer

    PubMed Central

    2013-01-01

    Although medical treatment has been shown to improve quality of life and prolong survival, no significant progress has been made in the treatment of advanced gastric cancer (AGC) within the last two decades. Thus, the optimum standard first-line chemotherapy regimen for AGC remains debatable, and most responses to chemotherapy are partial and of short duration; the median survival is approximately 7 to 11 months, and survival at 2 years is exceptionally > 10%. Recently, remarkable progress in tumor biology has led to the development of new agents that target critical aspects of oncogenic pathways. For AGC, many molecular targeting agents have been evaluated in international randomized studies, and trastuzumab, an anti-HER-2 monoclonal antibody, has shown antitumor activity against HER-2-positive AGC. However, this benefit is limited to only ~20% of patients with AGC (patients with HER-2-positive AGC). Therefore, there remains a critical need for both the development of more effective agents and the identification of molecular predictive and prognostic markers to select those patients who will benefit most from specific chemotherapeutic regimens and targeted therapies. PMID:23525404

  20. A NOVEL SUPPORT DEVICE FOR HEAD IMMOBILIZATION DURING RADIATION THERAPY THAT IS APPLICABLE TO BOTH CATS AND DOGS.

    PubMed

    Nemoto, Yuki; Maruo, Takuya; Fukuyama, Yasuhiro; Kawarai, Shinpei; Shida, Takuo; Nakayama, Tomohiro

    2015-01-01

    Repeatable head immobilization is important for minimizing positioning error during radiation therapy for veterinary patients with head neoplasms. The purpose of this retrospective cross-sectional study was to describe a novel technique for head immobilization (Device II) and compare this technique with a previously described technique (Device I). Device II provided additional support by incorporating three teeth (vs. two teeth with Device I). Between 2011 and 2013, both devices were applied in clinically affected cats (Device I, n = 17; Device II, n = 11) and dogs (Device I, n = 85; Device II, n = 22) of various breeds and sizes. The following data were recorded for each included patient: variability in the angle of the skull (roll, yaw, and pitch), coordinates of the isocenter, and distance from the reference mark to the tumor. Devices I and II differed for skull angle variability during the treatment of dogs (roll, P = 0.0007; yaw, P = 0.0018; pitch, P = 0.0384) and for yaw of during the treatment of cats (P < 0.0001). In each case, Device II was superior to Device I. The distance from the reference mark to the center of the tumor was significantly decreased for Device II vs. Device I (dogs, P < 0.0001; cats, P = 0.0002). Device II also provided more accurate coordinates for the isocenter. Authors recommend the use of, Device II for future clinical patients. PMID:26202221

  1. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  2. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Cancer.gov

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  3. Gene Therapy for Mucopolysaccharidosis Type VI Is Effective in Cats Without Pre-Existing Immunity to AAV8

    PubMed Central

    Ferla, Rita; O'Malley, Thomas; Calcedo, Roberto; O'Donnell, Patricia; Wang, Ping; Cotugno, Gabriella; Claudiani, Pamela; Wilson, James M.; Haskins, Mark

    2013-01-01

    Abstract Liver gene transfer with adeno-associated viral (AAV) 2/8 vectors is being considered for therapy of systemic diseases like mucopolysaccharidosis type VI (MPS VI), a lysosomal storage disease due to deficiency of arylsulfatase B (ARSB). We have previously reported that liver gene transfer with AAV2/8 results in sustained yet variable expression of ARSB. We hypothesized that the variability we observed could be due to pre-existing immunity to wild-type AAV8. To test this, we compared the levels of AAV2/8-mediated transduction in MPS VI cats with and without pre-existing immunity to AAV8. In addition, since levels of lysosomal enzymes as low as 5% of normal are expected to be therapeutic, we evaluated the impact of pre-existing immunity on MPS VI phenotypic rescue. AAV2/8 administration to MPS VI cats without pre-existing neutralizing antibodies to AAV8 resulted in consistent and dose-dependent expression of ARSB, urinary glycosaminoglycan (GAG) reduction, and femur length amelioration. Conversely, animals with pre-existing immunity to AAV8 showed low levels of ARSB expression and limited phenotypic improvement. Our data support the use of AAV2/8-mediated gene transfer for MPS VI and other systemic diseases, and highlight that pre-existing immunity to AAV8 should be considered in determining subject eligibility for therapy. PMID:23194248

  4. Advanced Semiconductor Dosimetry in Radiation Therapy

    SciTech Connect

    Rosenfeld, Anatoly B.

    2011-05-05

    Modern radiation therapy is very conformal, resulting in a complexity of delivery that leads to many small radiation fields with steep dose gradients, increasing error probability. Quality assurance in delivery of such radiation fields is paramount and requires real time and high spatial resolution dosimetry. Semiconductor radiation detectors due to their small size, ability to operate in passive and active modes and easy real time multichannel readout satisfy many aspects of in vivo and in a phantom quality assurance in modern radiation therapy. Update on the recent developments and improvements in semiconductor radiation detectors and their application for quality assurance in radiation therapy, based mostly on the developments at the Centre for Medical Radiation Physics (CMRP), University of Wollongong, is presented.

  5. The advanced therapy classification procedure. Overview of experience gained so far.

    PubMed

    Voltz-Girolt, C; Celis, P; Boucaumont, M; D'Apote, L; Pinheiro, M-H; Papaluca-Amati, M

    2011-07-01

    The classification procedure, introduced by the European Regulation on advanced therapy medicinal products (ATMPs), has received a tremendous interest from companies, academic and public sponsors developing ATMPs. This procedure gives companies the opportunity to verify whether or not the product they are developing can be considered an ATMP and can therefore benefit from the new regulatory pathway introduced in the European Union for these types of medicinal products. This procedure is optional, free of charge and may take place at any stage of the development of an ATMP in advance of applying for a marketing authorisation. In case of doubt, briefing meetings organised by the European Medicines Agency Innovation Task Force may help preparing for an ATMP classification and are a starting point for the interactions between the Agency and the developers of ATMPs. This article reviews the advantages of the classification procedure for both the developers of ATMPs and the European regulatory network. Since the introduction of this procedure and up to 10 November 2010, the Committee for Advanced Therapies (CAT) has finalised 38 applications for classification.

  6. Advances in gene therapy for muscular dystrophies

    PubMed Central

    Abdul-Razak, Hayder; Malerba, Alberto; Dickson, George

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments.

  7. Advances in gene therapy for muscular dystrophies

    PubMed Central

    Abdul-Razak, Hayder; Malerba, Alberto; Dickson, George

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments. PMID:27594988

  8. Advances in gene therapy for muscular dystrophies.

    PubMed

    Abdul-Razak, Hayder; Malerba, Alberto; Dickson, George

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments. PMID:27594988

  9. Biologic therapies for advanced pancreatic cancer.

    PubMed

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

    2008-08-01

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

  10. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  11. [Gene therapy for hereditary ophthalmological diseases: Advances and future perspectives].

    PubMed

    Chacón-Camacho, Óscar Francisco; Astorga-Carballo, Aline; Zenteno, Juan Carlos

    2015-01-01

    Gene therapy is a promising new therapeutic strategy that could provide a novel and more effective way of targeting hereditary ophthalmological diseases. The eye is easily accessible, highly compartmentalized, and an immune-privileged organ that gives advantages as an ideal gene therapy target. Recently, important advances in the availability of various intraocular vector delivery routes and viral vectors that are able to efficiently transduce specific ocular cell types have been described. Gene therapy has advanced in some retinal inherited dystrophies; in this way, preliminary success is now being reported for the treatment of Leber congenital amaurosis (LCA). This review will provide an update in the field of gene therapy for the treatment of ocular inherited diseases.

  12. Recent advances in neutron capture therapy (NCT)

    SciTech Connect

    Fairchild, R.G.

    1985-01-01

    The application of the /sup 10/B(n,..cap alpha..)/sup 7/Li reaction to cancer radiotherapy (Neutron Capture therapy, or NCT) has intrigued investigators since the discovery of the neutron. This paper briefly summarizes data describing recently developed boronated compounds with evident tumor specificity and extended biological half-lives. The implication of these compounds to NCT is evaluated in terms of Therapeutic Gain (TG). The optimization of NCT using band-pass filtered beams is described, again in terms of TG, and irradiation times with these less intense beams are estimated. 24 refs., 3 figs., 3 tabs.

  13. Design and performance of a compact collimator on GM/CA-CAT at the Advanced Photon Source

    NASA Astrophysics Data System (ADS)

    Xu, S.; Fischetti, R. F.

    2007-09-01

    A new macromolecular crystallographic facility developed by The General Medicine and Cancer Institutes Collaborative Access Team (GM/CA-CAT) at the Advanced Photon Source (APS) is a part of the Biosciences Division (BIO), Argonne National Laboratory (ANL). The facility consists of three beamlines: two lines based on the first "hard" dual canted undulators and one bending magnet beamline [1]. Several compact collimator systems have been developed for the purpose of background reduction in macromolecular crystallography experiments. The apparatus consists of a tube collimator, pinhole and kinematics mount. This paper will present a series of compact collimator designs and crystallographic applications based on experimental requirements [2]. We also describe the magnet-based kinematic mounting structures [3] developed as a collimator holder.

  14. Nanomedicine in cardiovascular therapy: recent advancements.

    PubMed

    Binsalamah, Ziyad Mohammed; Paul, Arghya; Prakash, Satya; Shum-Tim, Dominique

    2012-06-01

    Cardiovascular disease (CVD) is comprised of a group of disorders affecting the heart and blood vessels of the human body and is one of the leading causes of death worldwide. Current therapy for CVD is limited to the treatment of already established disease, and it includes pharmacological and/or surgical procedures, such as percutaneous coronary intervention with stenting and coronary artery bypass grafting. However, lots of complications have been raised with these modalities of treatment, including systemic toxicity with medication, stent thrombosis with percutaneous coronary intervention and nonsurgical candidate patients for coronary artery bypass grafting. Nanomedicine has emerged as a potential strategy in dealing with these obstacles. Applications of nanotechnology in medicine are already underway and offer tremendous promise. This review explores the recent developments of nanotechnology in the field of CVD and gives an insight into its potential for diagnostics and therapeutics applications. The authors also explore the characteristics of the widely used biocompatible nanomaterials for this purpose and evaluate their opportunities and challenges for developing novel nanobiotechnological tools with high efficacy for biomedical applications, such as radiological imaging, vascular implants, gene therapy, myocardial infarction and targeted delivery systems.

  15. The transthyretin amyloidoses: advances in therapy.

    PubMed

    Dubrey, Simon; Ackermann, Elizabeth; Gillmore, Julian

    2015-08-01

    There are two forms of transthyretin (TTR) amyloidosis: non-hereditary and hereditary. The non-hereditary form (ATTRwt) is caused by native or wild-type TTR and was previously referred to as senile systemic amyloidosis. The hereditary form (ATTRm) is caused by variant TTR which results from a genetic mutation of TTR. The predominant effect of ATTRwt amyloidosis is on the heart, with patients having a greater left ventricular wall thickness at presentation than the devastating form which is light chain (AL) amyloidosis. ATTRm amyloidosis is broadly split into two categories: a type that predominantly affects the nervous system (often called familial amyloid polyneuropathy (FAP)) and one with a predilection for the heart (often called familial amyloid cardiomyopathy (FAC)). Approximately half of all TTR mutations known to express a clinical phenotype cause a cardiomyopathy. Since the introduction of orthotopic liver transplantation for ATTRm amyloidosis in 1991, several additional therapies have been developed. These therapies aim to provide a reduction or elimination of TTR from the plasma (through genetic approaches), stabilisation of the TTR molecule (to prevent deposition) and dissolution of the amyloid matrix. We describe the latest developments in these approaches to management, many of which are also applicable to wild-type amyloidosis. PMID:26048914

  16. Recent advances in systemic therapy for gastrointestinal neuroendocrine tumors.

    PubMed

    Pelley, R J; Bukowski, R M

    1999-01-01

    Neuroendocrine tumors of the gastrointestinal tract are rare tumors which can be classified as amine precursor uptake and decarboxylation tumors (APU-Domas). Although the majority of clinically apparent tumors are malignant, they are frequently slow growing. Despite this characteristic, they may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better medical therapy with chemotherapeutic agents, somatostatin analogues, and biologic therapies. This review will update the recent efforts in systemic therapies of the gastrointestinal neuroendocrine tumors.

  17. Recent advances in the optimization of cardiac resynchronization therapy.

    PubMed

    Chandraprakasam, Satish; Mentzer, Gina G

    2015-02-01

    Heart failure (HF) continues to grow and affect more than five million people in the USA. One of the leading device therapies in HF is cardiac resynchronization therapy (CRT) which has been studied for over 20 years. Recent advancements in lead placement, lead technology, patient selection, and CRT optimization by electrical maneuvers and imaging modalities have improved outcomes in morbidity, hospitalization reductions and mortalities in those who have responded CRT therapy. This review article is intended to discuss the mechanisms and benefits of CRT, clinical trials, and guidelines for CRT along with a focus on recent updates from the past 3 to 5 years and glimpse into future directions. PMID:25315038

  18. Advances in sickle cell therapies in the hydroxyurea era.

    PubMed

    Field, Joshua J; Nathan, David G

    2014-01-01

    In the hydroxyurea era, insights into mechanisms downstream of erythrocyte sickling have led to new therapeutic approaches for patients with sickle cell disease (SCD). Therapies have been developed that target vascular adhesion, inflammation and hemolysis, including innovative biologics directed against P-selectin and invariant natural killer T cells. Advances in hematopoietic stem cell transplant and gene therapy may also provide more opportunities for cures in the near future. Several clinical studies are underway to determine the safety and efficacy of these new treatments. Novel approaches to treat SCD are desperately needed, since current therapies are limited and rates of morbidity and mortality remain high. PMID:25549232

  19. Cardiac gene therapy: Recent advances and future directions.

    PubMed

    Mason, Daniel; Chen, Yu-Zhe; Krishnan, Harini Venkata; Sant, Shilpa

    2015-10-10

    Gene therapy has the potential to serve as an adaptable platform technology for treating various diseases. Cardiovascular disease is a major cause of mortality in the developed world and genetic modification is steadily becoming a more plausible method to repair and regenerate heart tissue. Recently, new gene targets to treat cardiovascular disease have been identified and developed into therapies that have shown promise in animal models. Some of these therapies have advanced to clinical testing. Despite these recent successes, several barriers must be overcome for gene therapy to become a widely used treatment of cardiovascular diseases. In this review, we evaluate specific genetic targets that can be exploited to treat cardiovascular diseases, list the important delivery barriers for the gene carriers, assess the most promising methods of delivering the genetic information, and discuss the current status of clinical trials involving gene therapies targeted to the heart.

  20. Advances in Oncolytic Virus Therapy for Glioma

    PubMed Central

    Haseley, Amy; Alvarez-Breckenridge, Christopher; Chaudhury, Abhik Ray; Kaur, Balveen

    2009-01-01

    The World Health Organization grossly classifies the various types of astrocytomas using a grade system with grade IV gliomas having the worst prognosis. Oncolytic virus therapy is a novel treatment option for GBM patients. Several patents describe various oncolytic viruses used in preclinical and clinical trials to evaluate safety and efficacy. These viruses are natural or genetically engineered from different viruses such as HSV-1, Adenovirus, Reovirus, and New Castle Disease Virus. While several anecdotal studies have indicated therapeutic advantage, recent clinical trials have revealed the safety of their usage, but demonstration of significant efficacy remains to be established. Oncolytic viruses are being redesigned with an interest in combating the tumor microenvironment in addition to defeating the cancerous cells. Several patents describe the inclusion of tumor microenvironment modulating genes within the viral backbone and in particular those which attack the tumor angiotome. The very innovative approaches being used to improve therapeutic efficacy include: design of viruses which can express cytokines to activate a systemic antitumor immune response, inclusion of angiostatic genes to combat tumor vasculature, and also enzymes capable of digesting tumor extra cellular matrix (ECM) to enhance viral spread through solid tumors. As increasingly more novel viruses are being tested and patented, the future battle against glioma looks promising. PMID:19149710

  1. Evaluation of topical therapies for the treatment of dermatophyte-infected hairs from dogs and cats.

    PubMed

    White-Weithers, N; Medleau, L

    1995-01-01

    Seven commonly used, topical antifungal products (i.e., lime sulfur, chlorhexidine, captan, povidone-iodine, sodium hypochlorite, and enilconazole solutions, and ketoconazole shampoo) were evaluated for their antifungal activity on Microsporum canis-infected hairs from dogs and cats in an in vitro study. Hairs were soaked or shampooed in each product for five minutes twice a week for four weeks. Of the seven products used in this study, lime sulfur and enilconazole solutions were superior in inhibiting fungal growth; no growth occurred on fungal cultures after two treatments with either product. Chlorhexidine and povidone iodine solutions were effective after four treatments, and sodium hypochlorite solution and ketoconazole shampoo inhibited fungal growth after eight treatments. Captan did not inhibit fungal growth during the test period.

  2. Overcoming Challenges Facing Advanced Therapies in the EU Market.

    PubMed

    Abou-El-Enein, Mohamed; Elsanhoury, Ahmed; Reinke, Petra

    2016-09-01

    While advanced therapy medicinal products offer great clinical promise, most EU-approved products have not achieved satisfactory commercial performance. Here we highlight a number of issues that prevent current products from obtaining commercial success and pitfalls that developers must overcome in future product development.

  3. Factors that Predict Who Takes Advanced Courses in Cognitive Therapy

    ERIC Educational Resources Information Center

    Pehlivanidis, Artemios

    2007-01-01

    Training in Cognitive Therapy (CT) includes theoretical and didactic components combined with clinical supervision. An introductory course in CT might satisfy training needs in psychotherapy and help in the selection of those trainees who wish to continue to an advanced training level. Predictors of success at such an introductory course have been…

  4. Retrospective study and review of ocular radiation side effects following external-beam Cobalt-60 radiation therapy in 37 dogs and 12 cats

    PubMed Central

    Pinard, Chantale L.; Mutsaers, Anthony J.; Mayer, Monique N.; Woods, J. Paul

    2012-01-01

    This retrospective study evaluated the ocular side effects of cancer-bearing dogs and cats treated with external–beam Cobalt-60 (Co-60) radiation in which one or both orbit(s) were included in the radiation field. A total of 37 dogs and 12 cats presented to the Ontario Veterinary College during the 10-year study period (1999–2009) were evaluated. The radiation protocols ranged from a maximum of 60 Gray (Gy) in 24 fractions for curative intent to a minimum of 8 Gy in 1 fraction for palliative treatment. The main ocular side effect reported in both dogs and cats was conjunctivitis (79% and 55%, respectively). Other common ocular side effects included eyelid lesions in dogs (44%), ulcerative keratitis in cats (36%), and keratoconjunctivitis sicca in both dogs and cats (44% and 27%, respectively). The high incidence of ocular side effects in both patient populations indicates a need for regular ophthalmic examinations as a component of routine follow-up for radiation therapy involving the orbit. Radiation damage to ocular tissues is also reviewed. PMID:23729828

  5. Conventional chemotherapy and emerging targeted therapy for advanced adrenocortical carcinoma.

    PubMed

    Xu, Yun-Ze; Zhu, Yu

    2013-02-01

    Adrenocortical carcinoma (ACC) is a rare but typically aggressive malignancy. Radical surgery remains the potentially curative option. However, about one third of patients initially present with distant metastases. Regarding to chemotherapy, mitotane alone or in combination with cytotoxic drugs should be the first selection. Meanwhile, a phase lll clinical trial of etoposide, doxorubicin, cisplatin plus mitotane or streptozotocin plus mitotane is currently undergoing worldwide. The study on molecular pathogenesis of ACC is progressing. A lot of targeted therapies are also enrolled in preclinical investigations and clinical trials, including small-molecule tyrosine kinase inhibitors, antiangiogenic compounds. This article introduced the conventional chemotherapy, newly developed targeted therapy for advanced ACC.

  6. Displaying Fel d1 on virus-like particles prevents reactogenicity despite greatly enhanced immunogenicity: a novel therapy for cat allergy

    PubMed Central

    Schmitz, Nicole; Dietmeier, Klaus; Bauer, Monika; Maudrich, Melanie; Utzinger, Stefan; Muntwiler, Simone; Saudan, Philippe

    2009-01-01

    Allergen-specific desensitization is the only disease-modifying therapy currently available for the treatment of allergies. These therapies require application of allergen over several years and some may induce life-threatening anaphylactic reactions. An ideal vaccine for desensitization should be highly immunogenic and should alleviate allergic symptoms upon few injections while being nonreactogenic. We describe such a vaccine for the treatment of cat allergy, consisting of the major cat allergen Fel d1 coupled to bacteriophage Qβ-derived virus-like particles (Qβ–Fel d1). Qβ–Fel d1 was highly immunogenic, and a single vaccination was sufficient to induce protection against type I allergic reactions. Allergen-specific immunoglobulin G antibodies were shown to be the critical effector molecules and alleviated symptoms by two distinct mechanisms. Although allergen-induced systemic basophil degranulation was inhibited in an FcγRIIb-dependent manner, inhibition of local mast cell degranulation in tissues occurred independently of FcγRIIb. In addition, treatment with Qβ–Fel d1 abolished IgE memory responses upon antigen recall. Despite high immunogenicity, the vaccine was essentially nonreactogenic and vaccination induced neither local nor systemic anaphylactic reactions in sensitized mice. Moreover, Qβ–Fel d1 did not induce degranulation of basophils derived from human volunteers with cat allergies. These data suggest that vaccination with Qβ–Fel d1 may be a safe and effective treatment for cat allergy. PMID:19667059

  7. [Economic perspectives of the research on advanced therapies].

    PubMed

    Pamo Larrauri, Jose María

    2014-11-03

    Since a new advanced therapy medicinal product is discovered until finally allowed its sale in the domestic market, it has to overcome a series of stages. Biomedical research is the first phase, currently its situation is encouraging to the increase in the number of clinical trials in Spain and in the rest of the world, despite the economic situation and the various difficulties that have faced the pharmaceutical laboratories. The next phase consists in obtaining the authorization of marketing of the European Medicines Agency. After authorization, will attempt to set a fair and moderate price for inclusion in the list of health provision of Social Security. A price for a drug that provides added value to health and society, a price that is generated profits for the pharmaceutical companies that hope to make up for the years of work and investment. Commitment to advanced therapy must be clear and forceful, to fund ongoing research projects and encouraging their creation with economic aid.

  8. Major Changes in Systemic Therapy for Advanced Melanoma.

    PubMed

    Thompson, John A

    2016-05-01

    Over the past 5 years, a host of new agents have radically changed the therapeutic landscape in advanced melanoma; gone are the days when the only active agents were interferon and dacarbazine. Nearly 25 years ago, few patients with stage IV melanoma reached 2-year survival; today, these survival curves have risen substantially. At the NCCN 21st Annual Conference, John A. Thompson, MD, discussed updates with longer duration of patient follow-up for immune checkpoint therapies. He also reviewed some of the newer approvals in advanced melanoma, including the combination of ipilimumab and nivolumab, high-dose ipilimumab, the oncolytic virus therapy talimogene laherparepvec, and the molecularly targeted combination of the BRAF and MEK inhibitors vemurafenib and cobimetinib. PMID:27226502

  9. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer. PMID:27619253

  10. [Advanced therapy: from European regulatory framework to national regulatory framework].

    PubMed

    Lucas-Samuel, S

    2013-05-01

    The European regulation n(o) 1394/2007/CE published on the 13th of November 2007 defined and harmonized the European regulatory framework for advanced therapy medicinal products. It creates a specialized committee located at the European Medicine Agency, in charge of the assessment of these medicinal products. The consequences of this regulation are introduced in the French regulation by the law n(o) 2011-302 published on the 22nd of March 2011. It detailed notably the possibility for public establishments (except health establishments) and nonprofit organisms to create pharmaceutical establishments. This law defined also a specific category of advanced therapy medicinal products, which fall under the "hospital exemption" framework. The rules regarding the authorizations of the establishments able to prepare these types of medicinal products and the authorization of the products are defined by the n(o) 2012-1236 decree published on the 6th of November 2012.

  11. Recent Advances and Prospects for Multimodality Therapy in Pancreatic Cancer.

    PubMed

    Chadha, Awalpreet S; Khoo, Allison; Aliru, Maureen L; Arora, Harpreet K; Gunther, Jillian R; Krishnan, Sunil

    2016-10-01

    The outcomes for treatment of pancreatic cancer have not improved dramatically in many decades. However, the recent promising results with combination chemotherapy regimens for metastatic disease increase optimism for future treatments. With greater control of overt or occult metastatic disease, there will likely be an expanding role for local treatment modalities, especially given that nearly a third of pancreatic cancer patients have locally destructive disease without distant metastatic disease at the time of death. Technical advances have allowed for the safe delivery of dose-escalated radiation therapy, which can then be combined with chemotherapy, targeted agents, immunotherapy, and nanoparticulate drug delivery techniques to produce novel and improved synergistic effects. Here we discuss recent advances and future directions for multimodality therapy in pancreatic cancer.

  12. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    PubMed

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  13. Targeted Therapies in Breast Cancer: Implications for Advanced Oncology Practice

    PubMed Central

    Bourdeanu, Laura; Luu, Thehan

    2014-01-01

    The systemic therapeutic management of breast cancer has undergone significant transformation in the past decade. Without targeted therapies, conventional treatment with cytotoxic agents has reached the limit of its potential in terms of patient survival for most types of cancer. Enhanced understanding of the pathogenesis of tumor cell growth and metastasis has led to the identification of signaling growth pathways as targets for these directed therapies. Novel therapies targeted to HER2/neu, epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), poly(ADP ribose) polymerase (PARP), mammalian target of rapamycin (mTOR), histone deacetylase (HDAC), the heat shock protein, and cyclin-dependent kinase (CDK) inhibitors have been developed and have demonstrated some efficacy in breast cancer. Recognition and management of the toxicities associated with targeted therapies is imperative. This review will describe the clinical development and utilization of targeted therapies currently in use or in clinical trials, with a focus on considerations for the oncology advanced practitioner. PMID:26110069

  14. Recent advances in gene therapy for lysosomal storage disorders

    PubMed Central

    Rastall, David PW; Amalfitano, Andrea

    2015-01-01

    Lysosomal storage disorders (LSDs) are a group of genetic diseases that result in metabolic derangements of the lysosome. Most LSDs are due to the genetic absence of a single catabolic enzyme, causing accumulation of the enzyme’s substrate within the lysosome. Over time, tissue-specific substrate accumulations result in a spectrum of symptoms and disabilities that vary by LSD. LSDs are promising targets for gene therapy because delivery of a single gene into a small percentage of the appropriate target cells may be sufficient to impact the clinical course of the disease. Recently, there have been several significant advancements in the potential for gene therapy of these disorders, including the first human trials. Future clinical trials will build upon these initial attempts, with an improved understanding of immune system responses to gene therapy, the obstacle that the blood–brain barrier poses for neuropathic LSDs, as well other biological barriers that, when overcome, may facilitate gene therapy for LSDs. In this manuscript, we will highlight the recent innovations in gene therapy for LSDs and discuss the clinical limitations that remain to be overcome, with the goal of fostering an understanding and further development of this important field. PMID:26170711

  15. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research. PMID:26925962

  16. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    NASA Astrophysics Data System (ADS)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  17. State of cat genomics.

    PubMed

    O'Brien, Stephen J; Johnson, Warren; Driscoll, Carlos; Pontius, Joan; Pecon-Slattery, Jill; Menotti-Raymond, Marilyn

    2008-06-01

    Our knowledge of cat family biology was recently expanded to include a genomics perspective with the completion of a draft whole genome sequence of an Abyssinian cat. The utility of the new genome information has been demonstrated by applications ranging from disease gene discovery and comparative genomics to species conservation. Patterns of genomic organization among cats and inbred domestic cat breeds have illuminated our view of domestication, revealing linkage disequilibrium tracks consequent of breed formation, defining chromosome exchanges that punctuated major lineages of mammals and suggesting ancestral continental migration events that led to 37 modern species of Felidae. We review these recent advances here. As the genome resources develop, the cat is poised to make a major contribution to many areas in genetics and biology.

  18. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  19. [Diarrhea in cats].

    PubMed

    Rutgers, H C

    1992-11-15

    Diarrhoea is regarded as the characteristic symptom of intestinal disturbances. However, cats with intestinal disturbances can also show other symptoms such as vomiting, increased or decreased appetite and loss of weight. Cats with diarrhoea are usually only referred to the clinic if they have a chronic problem. Acute diarrhoea reacts well to symptomatic treatment, but chronic diarrhoea requires a specific diagnosis for a directed therapy and prognosis. It is essential to examine faeces and blood when evaluating a cat with diarrhoea. In contrast to the situation for dogs, there are no good specific digestion and absorption tests available for cats to evaluate pancreatic and intestinal function. Exocrine pancreatic insufficiency rarely occurs in cats. A preliminary diagnosis of small intestine disorders can be made on the basis of the faeces staining positive for fat, an oral fat absorption test and the response to therapy. The definitive diagnosis must usually await the results of histological examination of intestinal biopsy samples. Cats with acute diarrhoea often recover spontaneously, and symptomatic treatment is only necessary for severe cases. A specific diagnosis is needed for cats with chronic diarrhoea, to enable directed treatment. Corticosteroids are used in the treatment of chronic enteritis because of their immunosuppressive and anti-inflammatory actions. Antibiotics are only indicated for specific bacterial infections (such as Salmonella and Campylobacter), bloody diarrhoea, or rampant bacterial growth. Specially formulated diets play a major role in the treatment of both acute and chronic diarrhoea.

  20. Advances in stimuli responsive nanobiomaterials for cancer therapy.

    PubMed

    Sampathkumar, Kaarunya; Arulkumar, Shylaja; Ramalingam, Murugan

    2014-03-01

    Cancer has become one of the major reasons for disease mortality with drastic increase of death rate in recent years. The reason for most of these deaths is due to the inefficacy and failure of the current methods of treatments or due to the unavailability of treatment options. Even after extensive research that has been carried out in the field, there is no gold standard in cancer therapy. With the advancement of the field of nanomedicine and materials science, many research works are being aimed at developing micro and nanocarriers for site-specific delivery of anticancer drugs. As a further advancement in the field, smart carriers, based on nanobiomaterials, which respond to various external and internal stimuli and act locally are being developed to improve the efficacy of current treatments. These smart nanobiomaterials act as carriers for not only anticancer drugs but also for gene and other biomolecules. Keeping the importance and advancement of smart carrier anticancer drug delivery system (AcDDS) in view, this review focuses on stimuli responsive nanobiomaterials that are currently being studied for cancer therapy. PMID:24730233

  1. Integrative and complementary therapies for patients with advanced cancer.

    PubMed

    Marchand, Lucille

    2014-07-01

    In integrative medicine, well-being is emphasized, and in palliative care, quality of life (QOL) is a similar concept or goal. Both can occur despite advanced cancer. Integrative medicine serves to combine the best of alternative, complementary and conventional therapies to optimize well-being and QOL, whether or not a person is at the end of their life. When integrative medicine is combined with palliative care modalities, the toolbox to provide symptom control and well-being or QOL is increased or broadened. Palliative care and integrative medicine are best provided early in the trajectory of illness such as cancer, and increase in amount as the illness progresses toward end of life. In cancer care, symptoms of the cancer, as well as symptoms produced by cancer therapies, are addressed with conventional and integrative therapies. Goals of care change as the disease progresses, and a patient's unique situation creates a different balance of integrative and conventional therapies. Integrative therapies such as music, aromatherapy, and massage might appeal to more patients than more specific, less common integrative therapies that might be more expensive, or seem more unusual such as Ayurvedic medicine and energy modalities. Each person may be drawn to different integrative modalities depending on factors such as cultural traditions, beliefs, lifestyle, internet information, advice from family and friends, books, etc. This review focuses on how integrative and complementary modalities can be included in comprehensive palliative care for patients with advanced malignancies. Nutrition and movement, often neglected in conventional treatment strategies, will also be included in the larger context of integrative and palliative modalities. Both conventional and integrative modalities in palliative care help patients live with empowerment, hope, and well-being no matter how long their lives last. A comprehensive review of all integrative and complementary therapies is

  2. Advanced therapy medicinal products: current and future perspectives

    PubMed Central

    Hanna, Eve; Rémuzat, Cécile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Background Advanced therapy medicinal products (ATMPs) are innovative therapies that encompass gene therapy, somatic cell therapy, and tissue-engineered products. These therapies are expected to bring important health benefits, but also to substantially impact the pharmaceuticals budget. Objective The aim of this study was to characterise the ATMPs in development and discuss future implications in terms of market access. Methods Clinical trials were searched in the following databases: EudraCT (EU Drug Regulating Authorities Clinical Trials), ClinicalTrials.gov, and ICTRP (International Clinical Trials Registry Platform of the World Health Organization). Trials were classified by category of ATMP as defined by European regulation EC No. 1394/2007, as well as by development phase and disease area. Results The database search identified 939 clinical trials investigating ATMPs (85% ongoing, 15% completed). The majority of trials were in the early stages (Phase I, I/II: 64.3%, Phase II, II/III: 27.9%, Phase 3: 6.9%). Per category of ATMP, we identified 53.6% of trials for somatic cell therapies, 22.8% for tissue-engineered products, 22.4% for gene therapies, and 1.2% for combined products (incorporating a medical device). Disease areas included cancer (24.8%), cardiovascular diseases (19.4%), musculoskeletal (10.5%), immune system and inflammation (11.5%), neurology (9.1%), and others. Of the trials, 47.2% enrolled fewer than 25 patients. Due to the complexity and specificity of ATMPs, new clinical trial methodologies are being considered (e.g., small sample size, non-randomised trials, single-arm trials, surrogate endpoints, integrated protocols, and adaptive designs). Evidence generation post-launch will become unavoidable to address payers’ expectations. Conclusion ATMPs represent a fast-growing field of interest. Although most of the products are in an early development phase, the combined trial phase and the potential to cure severe chronic conditions suggest

  3. [Clinical studies and accepted therapies of advanced melanoma].

    PubMed

    Liszkay, Gabriella

    2016-03-01

    The objective of the work is presentation of the available therapeutic results of the clinical trials with anti CTLA-4 and anti PD-1 treatment, which are operating on the immune checkpoints registered in advanced melanoma, and the results of T-VEC vaccination (NCT00094653, NCT00324155, KEYNOTE-001, -002, -006, CheckMate-066, -037, -067, NCT00769704). With ipilimumab therapy, long-term survival can be achieved in the case of 20% of patients, with low (10%) therapeutic response, and grade 3-4 treatment related, predominantly autoimmune adverse events occurring in 10-15% of patients. Anti-PD-1 therapy proved more effective compared to ipilimumab, resulting in 21-40% therapeutic response, with 60-74% one-year survival rate and significantly less severe and frequent side effects. Progression-free survival achieved with ipilimumab/nivolumab combination was 11.5 months with grade 3-4 side effects occurring in 55% of patients. T-VEC therapy resulted in 26.4% objective response rate without a significant survival advantage. In the possession of the new immunotherapeutic possibilities, knowledge of the results of clinical studies is essential for the optimal complex therapy of melanoma. PMID:26934345

  4. Nanoscience and Nanotechnology: From Energy Applications to Advanced Medical Therapies

    ScienceCinema

    Tijana Rajh

    2016-07-12

    Dr. Rajh will present a general talk on nanotechnology – an overview of why nanotechnology is important and how it is useful in various fields. The specific focus will be on Solar energy conversion, environmental applications and advanced medical therapies. She has broad expertise in synthesis and characterization of nanomaterials that are used in nanotechnology including novel hybrid systems connecting semiconductors to biological molecules like DNA and antibodies. This technology could lead to new gene therapy procedures, cancer treatments and other medical applications. She will also discuss technologies made possible by organizing small semiconductor particles called quantum dots, materials that exhibit a rich variety of phenomena that are size and shape dependent. Development of these new materials that harnesses the unique properties of materials at the 1-100 nanometer scale resulted in the new field of nanotechnology that currently affects many applications in technological and medical fields.

  5. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance

    PubMed Central

    Burke, Paul A.; Pun, Suzie H.; Reineke, Theresa M.

    2013-01-01

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines. PMID:24683504

  6. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance.

    PubMed

    Burke, Paul A; Pun, Suzie H; Reineke, Theresa M

    2013-10-15

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines.

  7. Advancing polymeric delivery systems amidst a nucleic acid therapy renaissance.

    PubMed

    Burke, Paul A; Pun, Suzie H; Reineke, Theresa M

    2013-10-15

    Nucleic acid therapeutics are attracting renewed interest due to recent clinical advances and product approvals. Most leading programs use chemical conjugates, or viral vectors in the case of gene therapy, while several use no delivery system at all. Polymer systems, which have been at the periphery of this renaissance, often involve greater molecular complexity than competing approaches, which must be justified by their advantages. Advanced analytical methods, along with biological tools for characterizing biotransformation and intracellular trafficking, are increasingly being applied to nucleic acid delivery systems including those based on polymers. These frontiers of investigation create the opportunity for an era where highly defined polymer compositions are optimized based on mechanistic insights in a way that has not been previously possible, offering the prospect of greater differentiation from alternatives. This will require integrated collaboration between polymer scientists and those from other disciplines. PMID:24683504

  8. Effect of Acarbose, Sitagliptin and combination therapy on blood glucose, insulin, and incretin hormone concentrations in experimentally induced postprandial hyperglycemia of healthy cats.

    PubMed

    Mori, Akihiro; Ueda, Kaori; Lee, Peter; Oda, Hitomi; Ishioka, Katsumi; Arai, Toshiro; Sako, Toshinori

    2016-06-01

    Acarbose (AC) and Sitagliptin (STGP) are oral hypoglycemic agents currently used either alone or in conjunction with human diabetic (Type 2) patients. AC has been used with diabetic cats, but not STGP thus far. Therefore, the objective of this study was to determine the potential use of AC or STGP alone and in combination for diabetic cats, by observing their effect on short-term post-prandial serum glucose, insulin, and incretin hormone (active glucagon-like peptide-1 (GLP-1) and total glucose dependent insulinotropic polypeptide (GIP)) concentrations in five healthy cats, following ingestion of a meal with maltose. All treatments tended (p<0.10; 5-7.5% reduction) to reduce postprandial glucose area under the curve (AUC), with an accompanying significant reduction (p<0.05, 35-45%) in postprandial insulin AUC as compared to no treatment. Meanwhile, a significant increase (p<0.05) in postprandial active GLP-1 AUC was observed with STGP (100% higher) and combined treatment (130% greater), as compared to either AC or no treatment. Lastly, a significant reduction (p<0.05) in postprandial total GIP AUC was observed with STGP (21% reduction) and combined treatment (7% reduction) as compared to control. Overall, AC, STGP, or combined treatment can significantly induce positive post-prandial changes to insulin and incretin hormone levels of healthy cats. Increasing active GLP-1 and reducing postprandial hyperglycemia appear to be the principal mechanisms of combined treatment. Considering the different, but complementary mechanisms of action by which AC and STGP induce lower glucose and insulin levels, combination therapy with both these agents offers great potential for treating diabetic cats in the future. PMID:27234550

  9. [Economic perspectives of the research on advanced therapies].

    PubMed

    Pamo Larrauri, Jose María

    2014-01-01

    Since a new advanced therapy medicinal product is discovered until finally allowed its sale in the domestic market, it has to overcome a series of stages. Biomedical research is the first phase, currently its situation is encouraging to the increase in the number of clinical trials in Spain and in the rest of the world, despite the economic situation and the various difficulties that have faced the pharmaceutical laboratories. The next phase consists in obtaining the authorization of marketing of the European Medicines Agency. After authorization, will attempt to set a fair and moderate price for inclusion in the list of health provision of Social Security. A price for a drug that provides added value to health and society, a price that is generated profits for the pharmaceutical companies that hope to make up for the years of work and investment. Commitment to advanced therapy must be clear and forceful, to fund ongoing research projects and encouraging their creation with economic aid. PMID:25542659

  10. Stroke: advances in medical therapy and acute stroke intervention.

    PubMed

    Barrett, Kevin M; Lal, Brajesh K; Meschia, James F

    2015-10-01

    Evidence-based therapeutic options for stroke continue to emerge based on results from well-designed clinical studies. Ischemic stroke far exceeds hemorrhagic stroke in terms of prevalence and incidence, both in the USA and worldwide. The public health effect of reducing death and disability related to ischemic stroke justifies the resources that have been invested in identifying safe and effective treatments. The emergence of novel oral anticoagulants for ischemic stroke prevention in atrial fibrillation has introduced complexity to clinical decision making for patients with this common cardiac arrhythmia. Some accepted ischemic stroke preventative strategies, such as carotid revascularization for asymptomatic carotid stenosis, require reassessment, given advances in risk factor management, antithrombotic therapy, and surgical techniques. Intra-arterial therapy, particularly with stent retrievers after intravenous tissue plasminogen activator, has recently been demonstrated to improve functional outcomes and will require investment in system-based care models to ensure that effective treatments are received by patients in a timely fashion. The purpose of this review is to describe recent advances in medical and surgical approaches to ischemic stroke prevention and acute treatment. Results from recently published clinical trials will be highlighted along with ongoing clinical trials addressing key questions in ischemic stroke management and prevention where equipoise remains.

  11. [Therapy options in the case of advanced therapy resistant Morbus Parkinson].

    PubMed

    Hakimi, R

    2010-12-01

    In Germany about 300,000 to 400,000 people are suffering from Morbus Parkinson at present. It is one of the most common neurological diseases both in Germany and in Europe as a whole. With the rising number of elderly people in our population, the number of Parkinson patients will strongly increase as well in future. About 20% of these patients are already in an advanced stage. This stage leaves its marks with motor and non-motor sequelae. With the minority of these patients oral medication is ineffective. For these relatively rare cases an indication for an L-dopa-infusion therapy (duodopa pump), an apomorphine pump therapy or a deep brain stimulation may exist. The indication for one of these 3 therapy forms is given by the neurological clinic in agreement with the patient and is only given in case of failure of oral medication. All 3 therapy options are very expensive. In case of the deep brain stimulation, close cooperation between the neurologist and the neurosurgeon as well as with the patient is necessary. Experts warn about a transplantation of stem cells because there are no clinical studies and only partial clinical improvement with severe side effects are known. The transplantation of stem cells for advanced Morbus Parkinson is not a medically necessary treatment at present.

  12. Evaluating cost benefits of combination therapies for advanced melanoma

    PubMed Central

    Jensen, Ivar S.; Zacherle, Emily; Blanchette, Christopher M.; Zhang, Jie; Yin, Wes

    2016-01-01

    Background: Although a number of monoimmunotherapies and targeted therapies are available to treat BRAF+ advanced melanoma, response rates remain relatively low in the range of 22–53% with progression-free survival (PFS) in the range of 4.8–8.8 months. Recently, combination targeted therapies have improved response rates to about 66–69%, PFS to 11.0–12.6 months and overall survival (OS) to 25.1–25.6 months. While combination immunotherapies have improved response rates of 67 compared with 19–29% with monotherapies and improved PFS of 11.7 compared with 4.4–5.8 months with monotherapies, the OS benefit is yet to be established in phase 3 trials. As healthcare costs continue to rise, US payers have a predominant interest in assessing the value of available treatments. Therefore, a cost-benefit model was developed to evaluate the value of treating BRAF+ advanced melanoma with two combination therapies: nivolumab + ipilimumab (N+I) and dabrafenib + trametinib (D+T). Scope: The model was used to estimate total costs, total costs by expenditure category, cost per month of PFS and cost per responder for the payer, and societal perspectives of treating advanced melanoma patients with the BRAF V600 mutation using combination targeted therapy (D+T) or combination immunotherapy (N+I). The model followed patients from initiation of treatment to the point of progression or death. Deterministic and probabilistic sensitivity analyses were conducted to evaluate the robustness of the results and to understand the dispersion of simulated results. Findings: Based on a hypothetical payer with one million covered lives, it was expected that fourteen metastatic melanoma patients with the BRAF V600 mutation would be treated each year. Cost-benefit with N+I and D+T was simulated from the payer perspective. The cost per month of PFS for N+I was $22,162, while that for D+T was $17,716 (−$4,446 cost difference); the cost per responder for N+I was $388,746 and that for D+T was

  13. Glucose Addiction in Cancer Therapy: Advances and Drawbacks.

    PubMed

    Granja, Sara; Pinheiro, Céline; Reis, Rui Manuel; Martinho, Olga; Baltazar, Fátima

    2015-01-01

    While normal differentiated cells primarily use mitochondrial respiration to generate the required energy for cellular processes, most cancer cells rely on glycolysis, even in sufficient oxygen conditions. This phenomenon is known as the "Warburg effect" or aerobic glycolysis and the metabolic reprogramming of cancer cells towards this altered energy metabolism is currently recognized as one of the "hallmarks of cancer". Aerobic glycolysis underlies the rapid growth of tumor cells, with high rates of glucose consumption and lactic acid production, leading to cellular acidosis. Metabolic reprogramming renders cancer cells dependent on specific metabolic enzymes or pathways that could be exploited in cancer therapy. The development of treatments that target tumor glucose metabolism is receiving renewed attention, with several drugs targeting metabolic pathways currently in clinical trials. The search for suitable targets, however, is limited by the high plasticity of the metabolic network that can induce compensatory routes. Deregulated glucose metabolism is a prominent feature associated with resistance to classical chemotherapy or oncogene-targeted therapies, strengthening the clinical potential of combining these therapies with glycolysis inhibitors. The aim of this review is to compare the advances of different therapeutic strategies targeting the glucose "addiction" of tumor cells, highlighting their potential as effective weapons against cancer. We further discuss recent evidence for the involvement of glucose metabolism as a compensatory response to the use of drugs that target different signaling pathways, where the combination with glycolysis inhibitors could prove extraordinarily useful. PMID:26504932

  14. Advance in Photosensitizers and Light Delivery for Photodynamic Therapy

    PubMed Central

    Yoon, Il; Li, Jia Zhu

    2013-01-01

    The brief history of photodynamic therapy (PDT) research has been focused on photosensitizers (PSs) and light delivery was introduced recently. The appropriate PSs were developed from the first generation PS Photofrin (QLT) to the second (chlorins or bacteriochlorins derivatives) and third (conjugated PSs on carrier) generations PSs to overcome undesired disadvantages, and to increase selective tumor accumulation and excellent targeting. For the synthesis of new chlorin PSs chlorophyll a is isolated from natural plants or algae, and converted to methyl pheophorbide a (MPa) as an important starting material for further synthesis. MPa has various active functional groups easily modified for the preparation of different kinds of PSs, such as methyl pyropheophorbide a, purpurin-18, purpurinimide, and chlorin e6 derivatives. Combination therapy, such as chemotherapy and photothermal therapy with PDT, is shortly described here. Advanced light delivery system is shown to establish successful clinical applications of PDT. Phtodynamic efficiency of the PSs with light delivery was investigated in vitro and/or in vivo. PMID:23423543

  15. [Systemic therapy and hyperthermia for locally advanced soft tissue sarcoma].

    PubMed

    Lindner, L H; Angele, M; Dürr, H R; Rauch, J; Bruns, C

    2014-05-01

    Patients with high-risk soft tissue sarcomas (FNCLCC grades 2-3, > 5 cm and deep lying) are at a high risk of local recurrence or distant metastases despite optimal surgical tumor resection. Therefore, multimodal treatment should be considered for this difficult to treat patient group. Besides surgery, radiation therapy and chemotherapy, hyperthermia has become a valid, complementary treatment option within multimodal treatment concepts. Hyperthermia in this context means the selective heating of the tumor region to temperatures of 40-43 °C for 60 min by microwave radiation in addition to simultaneous chemotherapy or radiation therapy. A randomized phase III study demonstrated that the addition of hyperthermia to neoadjuvant chemotherapy improved tumor response and was associated with a minimal risk of early disease progression as compared to chemotherapy alone. The addition of hyperthermia to a multimodal treatment regimen for high-risk soft tissue sarcoma consisting of surgery, radiation therapy and chemotherapy, either in the neoadjuvant or adjuvant setting after incomplete or marginal tumor resection, significantly improved local progression-free and disease-free survival. Based on these results and due to the generally good tolerability of hyperthermia, this treatment method in combination with chemotherapy should be considered as a standard treatment option within multimodal treatment approaches for locally advanced high-risk soft tissue sarcoma.

  16. European regulatory tools for advanced therapy medicinal products.

    PubMed

    Flory, Egbert; Reinhardt, Jens

    2013-12-01

    Increasing scientific knowledge and technical innovations in the areas of cell biology, biotechnology and medicine resulted in the development of promising therapeutic approaches for the prevention and treatment of human diseases. Advanced therapy medicinal products (ATMPs) reflect a complex and innovative class of biopharmaceuticals as these products are highly research-driven, characterised by innovative manufacturing processes and heterogeneous with regard to their origin, type and complexity. This class of ATMP integrates gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineering products and are often individualized and patient-specific products. Multiple challenges arise from the nature of ATMPs, which are often developed by micro, small and medium sized enterprises, university and academia, for whom regulatory experiences are limited and regulatory requirements are challenging. Regulatory guidance such as the reflection paper on classification of ATMPs and guidelines highlighting product-specific issues support academic research groups and pharmaceutical companies to foster the development of safe and effective ATMPs. This review provides an overview on the European regulatory aspects of ATMPs and highlights specific regulatory tools such as the ATMP classification procedure, a discussion on the hospital exemption for selected ATMPs as well as borderline issues towards transplants/transfusion products.

  17. Advances in stem cell therapy for cardiovascular disease (Review).

    PubMed

    Sun, Rongrong; Li, Xianchi; Liu, Min; Zeng, Yi; Chen, Shuang; Zhang, Peying

    2016-07-01

    Cardiovascular disease constitutes the primary cause of mortality and morbidity worldwide, and represents a group of disorders associated with the loss of cardiac function. Despite considerable advances in the understanding of the pathologic mechanisms of the disease, the majority of the currently available therapies remain at best palliative, since the problem of cardiac tissue loss has not yet been addressed. Indeed, few therapeutic approaches offer direct tissue repair and regeneration, whereas the majority of treatment options aim to limit scar formation and adverse remodeling, while improving myocardial function. Of all the existing therapeutic approaches, the problem of cardiac tissue loss is addressed uniquely by heart transplantation. Nevertheless, alternative options, particularly stem cell therapy, has emerged as a novel and promising approach. This approach involves the transplantation of healthy and functional cells to promote the renewal of damaged cells and repair injured tissue. Bone marrow precursor cells were the first cell type used in clinical studies, and subsequently, preclinical and clinical investigations have been extended to the use of various populations of stem cells. This review addresses the present state of research as regards stem cell therapy for cardiovascular disease.

  18. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies.

    PubMed

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D'Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma.

  19. Neoadjuvant therapy for locally advanced melanoma: new strategies with targeted therapies

    PubMed Central

    La Greca, Michele; Grasso, Giuseppe; Antonelli, Giovanna; Russo, Alessia Erika; Bartolotta, Salvatore; D’Angelo, Alessandro; Vitale, Felice Vito; Ferraù, Francesco

    2014-01-01

    Neoadjuvant chemotherapy has been successfully tested in several bulky solid tumors, but it has not been utilized in advanced cutaneous melanoma, primarily because effective medical treatments for this disease have been lacking. However, with the development of new immunotherapies (monoclonal antibodies specific for cytotoxic T lymphocyte-associated antigen 4 [anti-CTLA-4] and programmed death protein-1 [anti-PD1]) and small molecules interfering with intracellular pathways (anti-BRAF and mitogen-activated protein kinase kinase [anti- MEK]) the use of this approach is becoming a viable treatment strategy for locally advanced melanoma. The neoadjuvant setting provides a double opportunity for a better knowledge of these drugs: a short-term evaluation of their intrinsic activity, and a deeper analysis of their action and resistance-induction mechanisms. BRAF inhibitors seem to be ideal candidates for the neoadjuvant setting, because of their prompt, repeatedly confirmed response in V600E BRAF-mutant metastatic melanoma. In this report we summarize studies focused on the neoadjuvant use of traditional medical treatments in advanced melanoma and anecdotal cases of this approach with the use of biologic therapies. Moreover, we discuss our experience with neoadjuvant targeted therapy as a priming for radical surgery in a patient with BRAF V600E mutation-positive advanced melanoma. PMID:24971022

  20. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  1. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials

    PubMed Central

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Objective Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. Methods We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Results Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. Conclusion No failure risk rate per development phase is available for ATMPs. The discontinuation rate may

  2. Intermittent hormone therapy versus continuous hormone therapy for locally advanced prostate cancer: a meta-analysis.

    PubMed

    Dong, ZhiLong; Wang, Hanzhang; Xu, MengMeng; Li, Yang; Hou, MingLi; Wei, YanLing; Liu, Xingchen; Wang, ZhiPing; Xie, XiaoDong

    2015-01-01

    Few randomized studies have compared intermittent hormone therapy (IHT) with continuous hormone therapy (CHT) for the treatment of locally advanced prostate cancer (PCa). Here, we report the results of a meta-analysis of a randomized controlled trial, evaluating the effectiveness of IHT versus CHT for patients with locally advanced PCa. Types of intervention were IHT versus CHT. The primary endpoint of this study is overall mortality and the secondary endpoints are any progression of disease, quality of life (QOL) and adverse effects between two groups. Six randomized controlled trials totaling 2996 patients were included. Results are as follows: after hormone therapy, patients undergoing IHT demonstrated no significant difference from those undergoing CHT in terms of the overall mortality (OR = 1.0, 95% CI [0.86, 1.17]) and disease progression (OR = 1.16, 95% CI [0.86, 1.57]). Men treated with IHT also reported better QOL, fewer adverse effects and considerable economic benefit for the individual and the community. With no difference in overall mortality and incidence of progression, current clinical studies confirm that both therapeutic methods were safe and effective. However, our study also takes into account QOL. When these secondary measures are considered, IHT may be a better option over CHT as patients report a more affordable treatment with improved QOL and fewer adverse effects.

  3. [Important aspects of virus safety of advanced therapy medicinal products].

    PubMed

    Blümel, J; Stühler, A

    2010-01-01

    Virus safety of advanced therapy medicinal products is a particular challenge. These products may consist of whole cells and the manufacture of these is performed using various human or animal-derived starting materials and reagents. Therefore, extensive testing of donors and of established cell banks is required. Furthermore, the virus safety of reagents such as bovine sera, porcine trypsin, and growth factors needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced. However, it is not possible to introduce such steps for cell-based medicinal products as the activity and viability of cells will be compromised. Only in the production of small and stable non-enveloped viral gene vectors is it conceivable to implement steps to selectively inactivate or remove potential contaminating enveloped viruses.

  4. The progress of targeted therapy in advanced gastric cancer

    PubMed Central

    2013-01-01

    Although palliative chemotherapy has been shown to prolong survival and improve quality of life, the survival of advanced gastric cancer (AGC) patients remains poor. With the advent of targeted therapy, many molecular targeted agents have been evaluated in clinical studies. Trastuzumab, an anti-HER2 monoclonal antibody, has shown activity against HER2-positive AGC and becomes the first targeted agent approved in AGC. Drugs that target epidermal growth factor receptor, including monoclonal antibody and tyrosine kinase inhibitor, do not bring survival benefit to patients with AGC. Additionally, vascular endothelial growth factor inhibitors are also under investigation. Ramucirumab has shown promising result. Other targeted agents are in preclinical or early clinical development, such as mammalian target of rapamycinm inhibitors and c-MET inhibitors. PMID:24330856

  5. [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].

    PubMed

    Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva

    2014-01-01

    There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.

  6. Cat Batiks.

    ERIC Educational Resources Information Center

    Buban, Marcia H.

    1998-01-01

    Discusses an art activity where fourth-grade students created backgrounds using melted paraffin and a variety of paints for their cat batik/collage. Explains that after the students created their backgrounds, they assembled their paper cats for the collage using smaller shapes glued together and wax to add texture for fur. (CMK)

  7. [Academic cell therapy facilities are challenged by European regulation on advanced therapy medicinal products].

    PubMed

    Chabannon, Christian; Sabatier, Florence; Rial-Sebbag, Emmanuelle; Calmels, Boris; Veran, Julie; Magalon, Guy; Lemarie, Claude; Mahalatchimy, Aurélie

    2014-05-01

    Regulation (EC) n° 1394/2007 from the European Parliament and the Council describes a new category of health products termed « Advanced Therapy Medicinal Products » (ATMPs). ATMPs derive from cell engineering, tissue engineering or genetic manipulations, and can in some instances be combined with medical devices. ATMPs are distributed and administered to patients, after biotechnology or pharmaceutical companies have obtained a marketing authorization that is granted by the European Commission on the basis of the European Medicines Agency (EMA) assessment. Seven years after the publication of the regulation, few of these therapies have received a marketing authorization, and even fewer have met commercial success, suggesting that a number of medical and economic issues still need to be sorted out in order to achieve sustainability in this field. The coexistence of three sets of rules for three categories of health products that are biologically and medically related - ATMPs, ATMPs produced under the hospital exemption rule, and cell therapy products (CTPs) (a specific legal category in France) that have long been used in hematopoietic cell transplantation - constitutes a complex regulatory framework. This situation raises significant issues for historical as well as emerging operators in this moving field that are discussed thereafter.

  8. Advances in the Genetics and Therapy of Acute Lymphoblastic Leukemia.

    PubMed

    Chiaretti, Sabina; Gianfelici, Valentina; O'Brien, Susan M; Mullighan, Charles G

    2016-01-01

    Acute lymphoblastic leukemia (ALL) remains an important cause of morbidity in children and adults. In this article, we highlight advances in the genetics and therapy of three key subtypes of ALL: T-cell ALL, BCR-ABL1 (Philadelphia [Ph] chromosone-positive), and Ph-like ALL. T-ALL is an aggressive disease that accounts for about 15% and 25% of ALL among pediatric and adult cohorts, respectively, and exhibits a multistep nature of cancer initiation and progression. The integration of cytogenetics, molecular biology, and immunophenotype analyses has led to the identification of defined T-ALL subgroups, such as early T-cell precursor ALL and novel lesions with a prognostic role, for which specific inhibitors are being developed. Ph-positive ALL was historically regarded as a subtype of ALL with a poor prognosis, and allogeneic stem cell transplant was recommended for all patients who could undergo this procedure. The deep complete responses seen with combination tyrosine kinase inhibitors (TKIs) and chemotherapy in Ph-positive ALL, and the reports of long-term survival among some patients not undergoing allogeneic stem cell transplant, has raised the question of whether there is a subset of patients who could be cured without this intervention. Ph-like ALL is a subtype of B-progenitor ALL common among older children and adults and associated with a diverse range of genetic alterations that activate kinase signaling. Ph-like ALL is also associated with poor outcome, for which precision medicine trials identifying kinase alterations and testing TKI therapy are being developed. PMID:27249738

  9. Recent advances in the rational design of silica-based nanoparticles for gene therapy.

    PubMed

    Niut, Yuting; Popatt, Amirali; Yu, Meihua; Karmakar, Surajit; Gu, Wenyi; Yu, Chengzhong

    2012-10-01

    Gene therapy has attracted much attention in modern society and provides a promising approach for treating genetic disorders, diseases and cancers. Safe and effective vectors are vital tools to deliver genetic molecules to cells. This review summarizes recent advances in the rational design of silica-based nanoparticles and their applications in gene therapy. An overview of different types of genetic agents available for gene therapy is provided. The engineering of various silica nanoparticles is described, which can be used as versatile complexation tools for genetic agents and advanced gene therapy. Several challenges are raised and future research directions in the area of gene therapy using silica-based nanoparticles are proposed.

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

    PubMed Central

    Bakeer, Mostafa; Abdelgawad, Taha Taha; El-Metwaly, Raed; El-Morsi, Ahmed; El-Badrawy, Mohammad Khairy; El-Sharawy, Solafa

    2016-01-01

    Background Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. Objectives To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. Methods Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. Results In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. Conclusion BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness. PMID:27536091

  11. Advanced Biomatrix Designs for Regenerative Therapy of Periodontal Tissues

    PubMed Central

    Kim, J.H.; Park, C.H.; Perez, R.A.; Lee, H.Y.; Jang, J.H.; Lee, H.H.; Wall, I.B.; Shi, S.; Kim, H.W.

    2014-01-01

    Periodontitis is an inflammatory disease that causes loss of the tooth-supporting apparatus, including periodontal ligament, cementum, and alveolar bone. A broad range of treatment options is currently available to restore the structure and function of the periodontal tissues. A regenerative approach, among others, is now considered the most promising paradigm for this purpose, harnessing the unique properties of stem cells. How to make full use of the body’s innate regenerative capacity is thus a key issue. While stem cells and bioactive factors are essential components in the regenerative processes, matrices play pivotal roles in recapitulating stem cell functions and potentiating therapeutic actions of bioactive molecules. Moreover, the positions of appropriate bioactive matrices relative to the injury site may stimulate the innate regenerative stem cell populations, removing the need to deliver cells that have been manipulated outside of the body. In this topical review, we update views on advanced designs of biomatrices—including mimicking of the native extracellular matrix, providing mechanical stimulation, activating cell-driven matrices, and delivering bioactive factors in a controllable manner—which are ultimately useful for the regenerative therapy of periodontal tissues. PMID:25139364

  12. Technological advances in renal replacement therapy: five years and beyond.

    PubMed

    Rastogi, Anjay; Nissenson, Allen R

    2009-12-01

    The worldwide epidemic of chronic kidney disease shows no signs of abating in the near future. Current dialysis forms of renal replacement therapy (RRT), even though successful in sustaining life and improving quality of life somewhat for patients with ESRD, have many limitations that result in still unacceptably high morbidity and mortality. Transplantation is an excellent option but is limited by the scarcity of organs. An ideal form of RRT would mimic the functions of natural kidneys and be transparent to the patient, as well as affordable to society. Recent advances in technology, although generally in early stages of development, might achieve these goals. The application of nanotechnology, microfluidics, bioreactors with kidney cells, and miniaturized sorbent systems to regenerate dialysate makes clinical reality seem closer than ever before. Finally, stem cells hold much promise, both for kidney disease and as a source of tissues and organs. In summary, nephrology is at an exciting crossroad with the application of innovative and novel technologies to RRT that hold considerable promise for the near future.

  13. Pancreatitis in cats.

    PubMed

    Armstrong, P Jane; Williams, David A

    2012-08-01

    Pancreatitis was considered a rare disease in the cat until a couple of decades ago when several retrospective studies of severe acute pancreatitis were published. It was apparent that few of the diagnostic tests of value in the dog were helpful in cats. With increasing clinical suspicion, availability of abdominal ultrasonography, and introduction of pancreas-specific blood tests of increasing utility, it is now accepted that acute pancreatitis is probably almost as common in cats as it is in dogs, although the etiology(s) remain more obscure. Pancreatitis in cats often co-exists with inflammatory bowel disease, less commonly with cholangitis, and sometimes with both. Additionally, pancreatitis may trigger hepatic lipidosis, while other diseases, such as diabetes mellitus, may be complicated by pancreatitis. Therapy is similar to that used in dogs, with added emphasis on early nutritional support to prevent hepatic lipidosis. Less is known about chronic pancreatitis than the acute form, but chronic pancreatitis is more common in cats than it is in dogs and may respond positively to treatment with corticosteroids.

  14. MCNP speed advances for boron neutron capture therapy

    SciTech Connect

    Goorley, J.T.; McKinney, G.; Adams, K.; Estes, G.

    1998-04-01

    The Boron Neutron Capture Therapy (BNCT) treatment planning process of the Beth Israel Deaconess Medical Center-M.I.T team relies on MCNP to determine dose rates in the subject`s head for various beam orientations. In this time consuming computational process, four or five potential beams are investigated. Of these, one or two final beams are selected and thoroughly evaluated. Recent advances greatly decreased the time needed to do these MCNP calculations. Two modifications to the new MCNP4B source code, lattice tally and tracking enhancements, reduced the wall-clock run times of a typical one million source neutrons run to one hour twenty five minutes on a 200 MHz Pentium Pro computer running Linux and using the GNU FORTRAN compiler. Previously these jobs used a special version of MCNP4AB created by Everett Redmond, which completed in two hours two minutes. In addition to this 30% speedup, the MCNP4B version was adapted for use with Parallel Virtual Machine (PVM) on personal computers running the Linux operating system. MCNP, using PVM, can be run on multiple computers simultaneously, offering a factor of speedup roughly the same as the number of computers used. With two 200 MHz Pentium Pro machines, the run time was reduced to forty five minutes, a 1.9 factor of improvement over the single Linux computer. While the time of a single run was greatly reduced, the advantages associated with PVM derive from using computational power not already used. Four possible beams, currently requiring four separate runs, could be run faster when each is individually run on a single machine under Windows NT, rather than using Linux and PVM to run one after another with each multiprocessed across four computers. It would be advantageous, however, to use PVM to distribute the final two beam orientations over four computers.

  15. Degenerative mucinotic mural folliculitis in cats.

    PubMed

    Gross, T L; Olivry, T; Vitale, C B; Power, H T

    2001-10-01

    A novel form of mural folliculitis is described in seven cats. Clinically, all cats exhibited generalized alopecia with scaling or crusting that was more pronounced over the head, neck, and shoulders. The face and muzzle of all cats was unusually thickened. Six of seven cats were progressively lethargic but did not demonstrate any other consistent systemic abnormalities. Histologically, there was severe mixed inflammation of the wall of the follicular isthmus in all cats, accompanied by some follicular destruction in five cats. Sebaceous glands were not affected. All cats had variable, but often striking, follicular mucin deposition, as well as epidermal hyperkeratosis and crusting. The cause of the severe mural folliculitis was not identified, and all cats responded poorly to immunomodulating therapy. Follicular mucinosis may be a nonspecific finding, likely reflective of the follicular lymphocytic milieu, and does not always herald follicular lymphoma.

  16. Recent Advances in Molecular Image-Guided Cancer Radionuclide Therapy.

    PubMed

    Gao, Duo; Sun, Xianlei; Gao, Liquan; Liu, Zhaofei

    2015-01-01

    Cancer-targeted radionuclide therapy is a promising approach for the treatment of a wide variety of malignancies, especially those resistant to conventional therapies. However, to improve the use of targeted radionuclide therapy for the management of cancer patients, the in vivo behaviors, dosimetry, and efficacy of radiotherapeutic agents need to be well characterized and monitored. Molecular imaging, which is a powerful tool for the noninvasive characterization and quantification of biological processes in living subjects at the cellular and molecular levels, plays an important role in the guidance of cancer radionuclide therapy. In this review, we introduce the radiotherapeutics for cancer-targeted therapy and summarize the most recent evidence supporting the use of molecular imaging to guide cancer radionuclide therapy.

  17. Present and future evolution of advanced breast cancer therapy

    PubMed Central

    2010-01-01

    Although the introduction of novel therapies and drug combinations has improved the prognosis of metastatic breast cancer, the disease remains incurable. Increased knowledge of the biology and the molecular alterations in breast cancer has facilitated the design of targeted therapies. These agents include receptor and nonreceptor tyrosine kinase inhibitors (epidermal growth factor receptor family), intracellular signaling pathways (phosphatidylinositol-3-kinase, AKT, mammalian target of rapamycin) angiogenesis inhibitors and agents that interfere with DNA repair (poly(ADP-ribose) polymerase inhibitors). In the present review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with cytotoxic agents. PMID:21050422

  18. Technological Advancements and Error Rates in Radiation Therapy Delivery

    SciTech Connect

    Margalit, Danielle N.

    2011-11-15

    Purpose: Technological advances in radiation therapy (RT) delivery have the potential to reduce errors via increased automation and built-in quality assurance (QA) safeguards, yet may also introduce new types of errors. Intensity-modulated RT (IMRT) is an increasingly used technology that is more technically complex than three-dimensional (3D)-conformal RT and conventional RT. We determined the rate of reported errors in RT delivery among IMRT and 3D/conventional RT treatments and characterized the errors associated with the respective techniques to improve existing QA processes. Methods and Materials: All errors in external beam RT delivery were prospectively recorded via a nonpunitive error-reporting system at Brigham and Women's Hospital/Dana Farber Cancer Institute. Errors are defined as any unplanned deviation from the intended RT treatment and are reviewed during monthly departmental quality improvement meetings. We analyzed all reported errors since the routine use of IMRT in our department, from January 2004 to July 2009. Fisher's exact test was used to determine the association between treatment technique (IMRT vs. 3D/conventional) and specific error types. Effect estimates were computed using logistic regression. Results: There were 155 errors in RT delivery among 241,546 fractions (0.06%), and none were clinically significant. IMRT was commonly associated with errors in machine parameters (nine of 19 errors) and data entry and interpretation (six of 19 errors). IMRT was associated with a lower rate of reported errors compared with 3D/conventional RT (0.03% vs. 0.07%, p = 0.001) and specifically fewer accessory errors (odds ratio, 0.11; 95% confidence interval, 0.01-0.78) and setup errors (odds ratio, 0.24; 95% confidence interval, 0.08-0.79). Conclusions: The rate of errors in RT delivery is low. The types of errors differ significantly between IMRT and 3D/conventional RT, suggesting that QA processes must be uniquely adapted for each technique. There

  19. Advances in osteoporosis therapy. 2003 update of practical guidelines.

    PubMed Central

    Khan, Aliya

    2003-01-01

    OBJECTIVE: To review evidence for current therapies for postmenopausal osteoporosis and to establish practical guidelines for management of osteoporosis by family physicians. QUALITY OF EVIDENCE: MEDLINE was searched from January 1990 to January 2003. Articles retrieved were graded by level of evidence (I to III). Recommendations for diagnosis and therapy were based on evidence from randomized controlled trials and meta-analyses. MAIN MESSAGE: Osteoporosis is treatable. Early diagnosis and intervention is recommended. After excluding secondary causes of osteoporosis, physicians should advise patients to take appropriate calcium and vitamin D supplementation. Those with osteopenia at risk of fractures and those with established osteoporosis need additional therapy. CONCLUSION: Approved pharmacologic therapies include alendronate, risedronate, raloxifene, calcitonin, cyclical etidronate, and hormone replacement therapy. Family physicians can help with early diagnosis and intervention and should discuss lifestyle modification with patients. PMID:12729240

  20. Using clear aligner therapy to correct malocclusion with crowding and an open bite.

    PubMed

    Harnick, David J

    2012-01-01

    Clear aligner therapy (CAT) has been used successfully to correct minor spacing and crowding. It generally has not been indicated in more complicated malocclusions such as skeletal discrepancies and open bites; however, recent advances in technology and practitioner expertise now allow the use of CAT in these situations. This case report demonstrates the use of a CAT system (Invisalign) to correct a Class II malocclusion with crowding and an open bite tendency.

  1. Focusing, collimation and flux throughput at the IMCA-CAT bending-magnet beamline at the Advanced Photon Source.

    PubMed

    Koshelev, Irina; Huang, Rong; Graber, Timothy; Meron, Mati; Muir, J Lewis; Lavender, William; Battaile, Kevin; Mulichak, Anne M; Keefe, Lisa J

    2009-09-01

    The IMCA-CAT bending-magnet beamline was upgraded with a collimating mirror in order to achieve the energy resolution required to conduct high-quality multi- and single-wavelength anomalous diffraction (MAD/SAD) experiments without sacrificing beamline flux throughput. Following the upgrade, the bending-magnet beamline achieves a flux of 8 x 10(11) photons s(-1) at 1 A wavelength, at a beamline aperture of 1.5 mrad (horizontal) x 86 microrad (vertical), with energy resolution (limited mostly by the intrinsic resolution of the monochromator optics) deltaE/E = 1.5 x 10(-4) (at 10 kV). The beamline operates in a dynamic range of 7.5-17.5 keV and delivers to the sample focused beam of size (FWHM) 240 microm (horizontally) x 160 microm (vertically). The performance of the 17-BM beamline optics and its deviation from ideally shaped optics is evaluated in the context of the requirements imposed by the needs of protein crystallography experiments. An assessment of flux losses is given in relation to the (geometric) properties of major beamline components.

  2. Advances in Gene Therapy for Diseases of the Eye

    PubMed Central

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-01-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future. PMID:27178388

  3. Advances in Gene Therapy for Diseases of the Eye.

    PubMed

    Petit, Lolita; Khanna, Hemant; Punzo, Claudio

    2016-08-01

    Over the last few years, huge progress has been made with regard to the understanding of molecular mechanisms underlying the pathogenesis of neurodegenerative diseases of the eye. Such knowledge has led to the development of gene therapy approaches to treat these devastating disorders. Challenges regarding the efficacy and efficiency of therapeutic gene delivery have driven the development of novel therapeutic approaches, which continue to evolve the field of ocular gene therapy. In this review article, we will discuss the evolution of preclinical and clinical strategies that have improved gene therapy in the eye, showing that treatment of vision loss has a bright future.

  4. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms.

    PubMed

    Mooney, Michael A; Simon, Elias D; Little, Andrew S

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  5. Advancing Treatment of Pituitary Adenomas through Targeted Molecular Therapies: The Acromegaly and Cushing Disease Paradigms

    PubMed Central

    Mooney, Michael A.; Simon, Elias D.; Little, Andrew S.

    2016-01-01

    The current treatment of pituitary adenomas requires a balance of conservative management, surgical resection, and in select tumor types, molecular therapy. Acromegaly treatment is an evolving field where our understanding of molecular targets and drug therapies has improved treatment options for patients with excess growth hormone levels. We highlight the use of molecular therapies in this disease process and advances in this field, which may represent a paradigm shift for the future of pituitary adenoma treatment. PMID:27517036

  6. Cat scratch disease (image)

    MedlinePlus

    Cat scratch disease is an infectious illness associated with cat scratches, bites, or exposure to cat saliva, causing chronic swelling of the lymph nodes. Cat scratch disease is possibly the most common cause of chronic ...

  7. Maggot Debridement Therapy: Advancing to the Past in Wound Care.

    PubMed

    Klaus, Kelsey; Steinwedel, Cynthia

    2015-01-01

    Maggot debridement therapy (MDT) is experiencing resurgence as an effective alternative to conventional mechanical debridement in nonhealing wounds, especially those with antibiotic-resistant organisms. MDT has antibiotic, antifungal, and anti-inflammatory properties. Military use is on the rise.

  8. Advanced Interventional Therapy for Radiation-Induced Cardiovascular Disease

    PubMed Central

    2016-01-01

    This report describes the case of a 61-year-old woman who presented with dyspnea, aortic stenosis, and coronary artery disease—typical side effects of radiation therapy for Hodgkin lymphoma. A poor candidate for surgery, she underwent successful high-risk percutaneous coronary intervention and subsequent transcatheter aortic valve replacement. This report highlights some of the cardiovascular-specific sequelae of radiation therapy for cancer treatment; in addition, possible directions for future investigations are discussed. PMID:27547140

  9. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  10. The advance of poststructuralism and its influence on family therapy.

    PubMed

    Dickerson, Victoria C

    2014-09-01

    Postmodernism began to influence family therapy very early in the 1980s with articles referencing postmodern ideas, focusing on meaning and multiplicity. With the appearance of narrative therapy on the scene in the 1990s there was a shift toward poststructural thinking, which refined the movement and politicized the clinical work. Even with a bit of a backlash, whether because this was a new idea or it somehow threatened a positivistic culture, a poststructural view has continued to have effects on family therapy. This article explores the variety of influences: the expansion of narrative ideas, the innovation of Madsen's collaborative helping, and also more nuanced effects. I argue that a poststructural view has effectively changed how many family therapists think and may also be subtly influencing how they might work.

  11. Advances in biodegradable nanomaterials for photothermal therapy of cancer

    PubMed Central

    He, Chao-Feng; Wang, Shun-Hao; Yu, Ying-Jie; Shen, He-Yun; Zhao, Yan; Gao, Hui-Ling; Wang, Hai; Li, Lin-Lin; Liu, Hui-Yu

    2016-01-01

    Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochemical properties of nanomaterials, various internal and external stimuli play key roles on nanomaterials uptake, transport, and clearance. In this review, we summarized novel nanoplatforms for photothermal therapy; these nanoplatforms can elicit stimuli-triggered degradation. We focused on the recent innovative designs endowed with biodegradable photothermal agents under different stimuli, including enzyme, pH, and near-infrared (NIR) laser. PMID:27807498

  12. Recent advances of thermally responsive nanogels for cancer therapy.

    PubMed

    Wang, Yajing; Xu, Hongjiang; Ma, Lin

    2015-01-01

    Thermally responsive nanogel drug delivery systems (TRNDDS) have been widely investigated as a new strategy for active targeting tumor therapy, as these can accumulate on the tumor site and/or release the payload at the desired site by structure changes rapidly once stimulated by temperature changes. In this review, we discuss the evolution of TRNDDS and future perspectives for antitumor drug and gene delivery. With further understanding of the specificity of tumor site at the cellular and molecular level, in parallel with the development of nanomaterial design and preparation, TRNDDS show great potential for tumor targeting therapy. PMID:26478174

  13. Sex Therapy: Advances in Paradigms, Nomenclature, and Treatment

    ERIC Educational Resources Information Center

    Althof, Stanley

    2010-01-01

    Objective: The author reviews the historical paradigms that have influenced the treatment of sexual problems, changes in the diagnostic nomenclature, and recent innovations in sex therapy. Methods: The author reviews the literature and provides expert opinion. Results: The author gives a historical overview of how theoretical models of…

  14. Advances in nutritional therapy in inflammatory bowel diseases: Review

    PubMed Central

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-01

    Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn’s disease are chronic, life-long, and relapsing diseases of the gastrointestinal tract. Currently, there are no complete cure possibilities, but combined pharmacological and nutritional therapy may induce remission of the disease. Malnutrition and specific nutritional deficiencies are frequent among IBD patients, so the majority of them need nutritional treatment, which not only improves the state of nutrition of the patients but has strong anti-inflammatory activity as well. Moreover, some nutrients, from early stages of life are suspected as triggering factors in the etiopathogenesis of IBD. Both parenteral and enteral nutrition is used in IBD therapy, but their practical utility in different populations and in different countries is not clearly established, and there are sometimes conflicting theories concerning the role of nutrition in IBD. This review presents the actual data from research studies on the influence of nutrition on the etiopathogenesis of IBD and the latest findings regarding its mechanisms of action. The use of both parenteral and enteral nutrition as therapeutic methods in induction and maintenance therapy in IBD treatment is also extensively discussed. Comparison of the latest research data, scientific theories concerning the role of nutrition in IBD, and different opinions about them are also presented and discussed. Additionally, some potential future perspectives for nutritional therapy are highlighted. PMID:26811646

  15. Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy.

    PubMed

    Detappe, Alexandre; Kunjachan, Sijumon; Sancey, Lucie; Motto-Ros, Vincent; Biancur, Douglas; Drane, Pascal; Guieze, Romain; Makrigiorgos, G Mike; Tillement, Olivier; Langer, Robert; Berbeco, Ross

    2016-09-28

    Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. PMID:27423325

  16. Establishing radiation therapy advanced practice in New Zealand

    SciTech Connect

    Coleman, Karen; Jasperse, Marieke; Herst, Patries; Yielder, Jill

    2014-02-15

    Introduction: Advanced practice (AP) is of increasing interest to many radiation therapists (RTs) both nationally and internationally. In New Zealand, initial research (2005–2008) showed strong support for the development of an AP role for medical radiation technologists (MRTs). Here, we report on a nationwide survey in which RTs validated and prioritised nine AP profiles for future development. Methods: All registered RTs in New Zealand (n = 260) were invited to take part in a survey in December 2011; 73 of whom returned a complete response. Results: RTs supported the implementation of AP roles in New Zealand and the requirement of a Master's degree qualification to underpin clinical knowledge. Most RTs endorsed the criteria attributed to each of the nine proposed AP profiles. The study identified that activities may qualify as either advanced practice or standard practice depending on the department. All participants agreed that an advanced practitioner should be a leader in the field, able to initiate and facilitate future developments within as well as outside this specific role. Acceptance of the AP roles by RTs and other health professionals as well as the availability of resources for successful implementation, were concerns expressed by some RTs. Conclusion: The authors recommend (1) the development of one scope of practice titled ‘advanced practitioner’ with generic and specialist criteria for each profile as the future career pathway, (2) promotion and support for the AP pathway by the New Zealand Institute of Medical Radiation Technology and the New Zealand Medical Radiation Technologists Board.

  17. Nano polymeric carrier fabrication technologies for advanced antitumor therapy.

    PubMed

    Li, Wei; Zhao, Mengxin; Ke, Changhong; Zhang, Ge; Zhang, Li; Li, Huafei; Zhang, Fulei; Sun, Yun; Dai, Jianxin; Wang, Hao; Guo, Yajun

    2013-01-01

    Comparing with the traditional therapeutic methods, newly developed cancer therapy based on the nanoparticulates attracted extensively interest due to its unique advantages. However, there are still some drawbacks such as the unfavorable in vivo performance for nanomedicine and undesirable tumor escape from the immunotherapy. While as we know that the in vivo performance strongly depended on the nanocarrier structural properties, thus, the big gap between in vitro and in vivo can be overcome by nanocarrier's structural tailoring by fine chemical design and microstructural tuning. In addition, this fine nanocarrier's engineering can also provide practical solution to solve the problems in traditional cancer immunotherapy. In this paper, we review the latest development in nanomedicine, cancer therapy, and nanoimmunotherapy. We then give an explanation why fine nanocanrrie's engineering with special focus on the unique pathology of tumor microenvironments and properties of immunocells can obviously promote the in vivo performance and improve the therapeutic index of nanoimmunotherapy.

  18. Recent Advances in Antiviral Therapy for Chronic Hepatitis C

    PubMed Central

    Tamori, Akihiro; Enomoto, Masaru; Kawada, Norifumi

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide health problem. Chronic infection induces continuous inflammation in the liver, progression of hepatic fibrosis, eventual cirrhosis, and possible hepatocellular carcinoma. Eradication of the virus is one of the most important treatment aims. A number of promising new direct-acting antivirals (DAAs) have been developed over the past 10 years. Due to their increased efficacy, safety, and tolerability, interferon-free oral therapies with DAAs have been approved for patients with HCV, including those with cirrhosis. This review introduces the characteristics and results of recent clinical trials of several DAAs: NS3/4A protease inhibitors, NS5A inhibitors, and NS5B inhibitors. DAA treatment failure and prognosis after DAA therapy are also discussed. PMID:27022210

  19. Advances in T-cell therapy for ALL

    PubMed Central

    Grupp, Stephan A.

    2014-01-01

    CD19-directed chimeric antigen receptor T cells (CART19 or CTL019) have been used with success in pediatric and adult acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL) patients. While this therapy has caused toxicities, including cytokine release syndrome and macrophage activation syndrome, these conditions are reversible with IL-6 blockade using the monoclonal antibody tocilizumab. Furthermore, 90% of the very high-risk patients who underwent infusion with CTL019 achieved a complete response, despite the fact that they previously failed multiple therapies and/or transplant. With improved cell persistence, this immunotherapy may one day prove to be more than a bridge to transplant and may in fact be a transplant alternative. PMID:25455270

  20. Mind-body therapies: evidence and implications in advanced oncology practice.

    PubMed

    Mayden, Kelley D

    2012-11-01

    The idea that thoughts and emotions influence health outcomes is an ancient concept that was initially abandoned by Western medicine researchers. Today, researchers are showing a renewed interest in the interactions of the mind and body and the role these interactions play in disease formation and recovery. Complementary and alternative interventions, such as mind-body therapies, are increasingly being used by cancer survivors for disease prevention, immune system enhancement, and symptom control. Traditional training has not been structured to provide advanced practitioners with an in-depth knowledge of the clinical applications of mind-body therapies. The aim of this article is to acquaint the reader with common mind-body modalities (meditation/mindfulness-based stress reduction, relaxation therapy, cognitive-behavioral therapy, hypnosis, biofeedback, music therapy, art therapy, support groups, and aromatherapy) and to examine important evidence in support of or against their clinical application.

  1. Mind-Body Therapies: Evidence and Implications in Advanced Oncology Practice

    PubMed Central

    Mayden,, Kelley D.

    2012-01-01

    The idea that thoughts and emotions influence health outcomes is an ancient concept that was initially abandoned by Western medicine researchers. Today, researchers are showing a renewed interest in the interactions of the mind and body and the role these interactions play in disease formation and recovery. Complementary and alternative interventions, such as mind-body therapies, are increasingly being used by cancer survivors for disease prevention, immune system enhancement, and symptom control. Traditional training has not been structured to provide advanced practitioners with an in-depth knowledge of the clinical applications of mind-body therapies. The aim of this article is to acquaint the reader with common mind-body modalities (meditation/mindfulness-based stress reduction, relaxation therapy, cognitive-behavioral therapy, hypnosis, biofeedback, music therapy, art therapy, support groups, and aromatherapy) and to examine important evidence in support of or against their clinical application. PMID:25031967

  2. Malassezia spp. overgrowth in allergic cats.

    PubMed

    Ordeix, Laura; Galeotti, Franca; Scarampella, Fabia; Dedola, Carla; Bardagí, Mar; Romano, Erica; Fondati, Alessandra

    2007-10-01

    A series of 18 allergic cats with multifocal Malassezia spp. overgrowth is reported: atopic dermatitis was diagnosed in 16, an adverse food reaction in another and one was euthanized 2 months after diagnosis of Malassezia overgrowth. All the cats were otherwise healthy and those tested (16 out of 18) for feline leukaemia or feline immunodeficiency virus infections were all negative. At dermatological examination, multifocal alopecia, erythema, crusting and greasy adherent brownish scales were variably distributed on all cats. Cytological examination revealed Malassezia spp. overgrowth with/without bacterial infection in facial skin (n = 11), ventral neck (n = 6), abdomen (n = 6), ear canal (n = 4), chin (n = 2), ear pinnae (n = 2), interdigital (n = 1) and claw folds skin (n = 1). Moreover, in two cats Malassezia pachydermatis was isolated in fungal cultures from lesional skin. Azoles therapy alone was prescribed in seven, azoles and antibacterial therapy in eight and azoles with both antibacterial and anti-inflammatory therapy in three of the cats. After 3-4 weeks of treatment, substantial reduction of pruritus and skin lesions was observed in all 11 cats treated with a combined therapy and in five of seven treated solely with azoles. Malassezia spp. overgrowth may represent a secondary cutaneous problem in allergic cats particularly in those presented for dermatological examination displaying greasy adherent brownish scales. The favourable response to treatment with antifungal treatments alone suggests that, as in dogs, Malassezia spp. may be partly responsible for both pruritus and cutaneous lesions in allergic cats. PMID:17845619

  3. Encountering Challenges with the EU Regulation on Advance Therapy Medical Products.

    PubMed

    Mansnérus, Juli

    2015-12-01

    This article aims at analysing how well the Advanced Therapy Medical Product Regulation (EC) No. 1394/2007 (ATMP Regulation) meets the needs of small and medium-sized enterprises (SMES), academia and public tissue establishments developing advanced therapy medical products (ATMPS). Benefits and shortcomings of the ATMP Regulation are identified, and possible amendments are proposed to accelerate the translation of research into advanced therapies and to facilitate the commercialisation of ATMPS whilst ensuring safety. It was set up as a lex specialis to ensure the free movement of ATMPS within the EU in order to facilitate their access to the internal market and to foster the competitiveness of European pharmaceutical companies, while guaranteeing the highest level protection of public health. Since the adoption of the ATMP Regulation in late 2008, only 5 ATMPS have been granted marketing authorisations thus far. Hence, there is a need to analyse whether the ATMP Regulation meets its objectives. PMID:26665690

  4. Encountering Challenges with the EU Regulation on Advance Therapy Medical Products.

    PubMed

    Mansnérus, Juli

    2015-12-01

    This article aims at analysing how well the Advanced Therapy Medical Product Regulation (EC) No. 1394/2007 (ATMP Regulation) meets the needs of small and medium-sized enterprises (SMES), academia and public tissue establishments developing advanced therapy medical products (ATMPS). Benefits and shortcomings of the ATMP Regulation are identified, and possible amendments are proposed to accelerate the translation of research into advanced therapies and to facilitate the commercialisation of ATMPS whilst ensuring safety. It was set up as a lex specialis to ensure the free movement of ATMPS within the EU in order to facilitate their access to the internal market and to foster the competitiveness of European pharmaceutical companies, while guaranteeing the highest level protection of public health. Since the adoption of the ATMP Regulation in late 2008, only 5 ATMPS have been granted marketing authorisations thus far. Hence, there is a need to analyse whether the ATMP Regulation meets its objectives.

  5. Establishing radiation therapy advanced practice in New Zealand

    PubMed Central

    Coleman, Karen; Jasperse, Marieke; Herst, Patries; Yielder, Jill

    2014-01-01

    Introduction: Advanced practice (AP) is of increasing interest to many radiation therapists (RTs) both nationally and internationally. In New Zealand, initial research (2005–2008) showed strong support for the development of an AP role for medical radiation technologists (MRTs). Here, we report on a nationwide survey in which RTs validated and prioritised nine AP profiles for future development. Methods: All registered RTs in New Zealand (n = 260) were invited to take part in a survey in December 2011; 73 of whom returned a complete response. Results: RTs supported the implementation of AP roles in New Zealand and the requirement of a Master's degree qualification to underpin clinical knowledge. Most RTs endorsed the criteria attributed to each of the nine proposed AP profiles. The study identified that activities may qualify as either advanced practice or standard practice depending on the department. All participants agreed that an advanced practitioner should be a leader in the field, able to initiate and facilitate future developments within as well as outside this specific role. Acceptance of the AP roles by RTs and other health professionals as well as the availability of resources for successful implementation, were concerns expressed by some RTs. Conclusion: The authors recommend (1) the development of one scope of practice titled ‘advanced practitioner’ with generic and specialist criteria for each profile as the future career pathway, (2) promotion and support for the AP pathway by the New Zealand Institute of Medical Radiation Technology and the New Zealand Medical Radiation Technologists Board. PMID:26229634

  6. Recent advances of sonodynamic therapy in cancer treatment

    PubMed Central

    Wan, Guo-Yun; Liu, Yang; Chen, Bo-Wei; Liu, Yuan-Yuan; Wang, Yin-Song; Zhang, Ning

    2016-01-01

    Sonodynamic therapy (SDT) is an emerging approach that involves a combination of low-intensity ultrasound and specialized chemical agents known as sonosensitizers. Ultrasound can penetrate deeply into tissues and can be focused into a small region of a tumor to activate a sonosensitizer which offers the possibility of non-invasively eradicating solid tumors in a site-directed manner. In this article, we critically reviewed the currently accepted mechanisms of sonodynamic action and summarized the classification of sonosensitizers. At the same time, the breath of evidence from SDT-based studies suggests that SDT is promising for cancer treatment. PMID:27807500

  7. Recent advances in targeted therapy for Ewing sarcoma.

    PubMed

    Pishas, Kathleen I; Lessnick, Stephen L

    2016-01-01

    Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal. PMID:27635231

  8. Recent advances in targeted therapy for Ewing sarcoma

    PubMed Central

    Pishas, Kathleen I.; Lessnick, Stephen L.

    2016-01-01

    Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal. PMID:27635231

  9. Recent advances in targeted therapy for Ewing sarcoma

    PubMed Central

    Pishas, Kathleen I.; Lessnick, Stephen L.

    2016-01-01

    Ewing sarcoma is an aggressive, poorly differentiated neoplasm of solid bone that disproportionally afflicts the young. Despite intensive multi-modal therapy and valiant efforts, 70% of patients with relapsed and metastatic Ewing sarcoma will succumb to their disease. The persistent failure to improve overall survival for this subset of patients highlights the urgent need for rapid translation of novel therapeutic strategies. As Ewing sarcoma is associated with a paucity of mutations in readily targetable signal transduction pathways, targeting the key genetic aberration and master regulator of Ewing sarcoma, the EWS/ETS fusion, remains an important goal.

  10. Recent Advances of Stem Cell Therapy for Retinitis Pigmentosa

    PubMed Central

    He, Yuxi; Zhang, Yan; Liu, Xin; Ghazaryan, Emma; Li, Ying; Xie, Jianan; Su, Guanfang

    2014-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment. PMID:25141102

  11. Peptide receptor radionuclide therapy for advanced neuroendocrine tumors.

    PubMed

    Bodei, Lisa; Cremonesi, Marta; Kidd, Mark; Grana, Chiara M; Severi, Stefano; Modlin, Irvin M; Paganelli, Giovanni

    2014-08-01

    Peptide receptor radionuclide therapy (PRRT) consists of the systemic administration of a synthetic peptide, labeled with a suitable β-emitting radionuclide, able to irradiate tumors and their metastases via internalization through a specific receptor (usually somatostatin S2), over-expressed on the cell membrane. After almost 2 decades of experience, PRRT, with either (90)Y-octreotide or (177)Lu-octreotate, has established itself to be an efficient and effective therapeutic modality. As a treatment, it is relatively safe up to the known thresholds of absorbed and bio-effective isotope dosages and the renal and hematological toxicity profiles are acceptable if adequate protective measures are undertaken.

  12. Current advances in targeted therapies for metastatic gastric cancer: improving patient care.

    PubMed

    Aguiar, Pedro Nazareth; Muniz, Thiago Pimentel; Miranda, Raelson Rodrigues; Tadokoro, Hakaru; Forones, Nora Manoukian; Monteiro, Ines-de-Paula; Castelo-Branco, Pedro; Janjigian, Yelena Y; Mello, Ramon Andrade de

    2016-03-01

    In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs.

  13. Nanoparticulate drug delivery platforms for advancing bone infection therapies

    PubMed Central

    Uskoković, Vuk; Desai, Tejal A

    2015-01-01

    Introduction The ongoing surge of resistance of bacterial pathogens to antibiotic therapies and the consistently aging median member of the human race signal an impending increase in the incidence of chronic bone infection. Nanotechnological platforms for local and sustained delivery of therapeutics hold the greatest potential for providing minimally invasive and maximally regenerative therapies for this rare but persistent condition. Areas covered Shortcomings of the clinically available treatment options, including poly(methyl methacrylate) beads and calcium sulfate cements, are discussed and their transcending using calcium-phosphate/polymeric nanoparticulate composites is foreseen. Bone is a composite wherein the weakness of each component alone is compensated for by the strength of its complement and an ideal bone substitute should be fundamentally the same. Expert opinion Discrepancy between in vitro and in vivo bioactivity assessments is highlighted, alongside the inherent imperfectness of the former. Challenges entailing the cross-disciplinary nature of engineering a new generation of drug delivery vehicles are delineated and it is concluded that the future for the nanoparticulate therapeutic carriers belongs to multifunctional, synergistic and theranostic composites capable of simultaneously targeting, monitoring and treating internal organismic disturbances in a smart, feedback fashion and in direct response to the demands of the local environment. PMID:25109804

  14. Advances in endonasal low intensity laser irradiation therapy

    NASA Astrophysics Data System (ADS)

    Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

    2005-07-01

    Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

  15. Targeted Therapies for Advanced Ewing Sarcoma Family of Tumours

    PubMed Central

    Jiang, Yunyun; Ludwig, Joseph; Janku, Filip

    2015-01-01

    The prognosis of adolescent and young adult patients battling metastatic Ewing Sarcoma Family of Tumours (ESFT) remains less than 30% despite the development of systemic therapies. In the era of personalized medicine, novel molecular targets have been tested in preclinical or clinical settings in ESFT. In this review, we focus on early clinical and translational research that identified multiple molecular targets, including IGF-1R; mTOR; tyrosine kinase inhibitors; EWS-FLI1-related targets, and others. Overall, novel targeted therapies demonstrated modest efficacy; however pronounced and durable antineoplastic responses have been observed in small subsets of treated patients, for example with IGF-1R antibodies. Identifying outcome-predicting biomarkers and overcoming treatment resistance remain major challenges. Due to the rarity of ESFT, multi-institutional collaboration efforts of clinicians, basic and translational scientists are needed in order to understand biology of therapeutic response or resistance, which can lead to development of novel therapeutic methods and improved patient outcomes. PMID:25869102

  16. Reducing the Human Burden of Breast Cancer: Advanced Radiation Therapy Yields Improved Treatment Outcomes.

    PubMed

    Currey, Adam D; Bergom, Carmen; Kelly, Tracy R; Wilson, J Frank

    2015-01-01

    Radiation therapy is an important modality in the treatment of patients with breast cancer. While its efficacy in the treatment of breast cancer was known shortly after the discovery of x-rays, significant advances in radiation delivery over the past 20 years have resulted in improved patient outcomes. With the development of improved systemic therapy, optimizing local control has become increasingly important and has been shown to improve survival. Better understanding of the magnitude of treatment benefit, as well as patient and biological factors that confer an increased recurrence risk, have allowed radiation oncologists to better tailor treatment decisions to individual patients. Furthermore, significant technological advances have occurred that have reduced the acute and long-term toxicity of radiation treatment. These advances continue to reduce the human burden of breast cancer. It is important for radiation oncologists and nonradiation oncologists to understand these advances, so that patients are appropriately educated about the risks and benefits of this important treatment modality.

  17. Photodynamic therapy (PDT) in advanced inoperable bronchial carcinoma

    NASA Astrophysics Data System (ADS)

    Moghissi, Keyvan; Dixon, Kate; Stringer, Mark R.; Brown, Stanley B.

    1996-12-01

    Objective: To assess the efficacy of PDT to: Palliate symptoms, control disease and extend survival in patients with advanced inoperable cancer. Subject and Method: 55 Males and 23 females aged between 45-81 years (mean 66 years) with inoperable and advanced lung cancer with > 5O. obstructive lesions of the main, lobar or segmental bronchi. Patients had pre-treatment routine clinical radiological, functional and endoscopic assessment with proven histological diagnosis. Protocol of PDT was; Intravenous injection of 2 mg/Kg bodyweight Polyhaematoporphyrin (equivalent to Photofrin) or Photofrin followed 24-72 hours later by illumination of tumour using 630 nm light (Oxford Laser) delivered via an optical fibre with end diffuser. Treatments were carried out under general anaesthesia as a day case procedure. Patients were rebronchoscoped for debridement/retreatment 4-7 days later. Results: There was no treatment related mortality. Two patients developed mild photosensitivity reaction. All patients showed symptomatic improvement with good initial functional and radiological amelioration. Every patient responded to treatment. Seven patients had complete response and negative histology for 3-12 months. After the first treatment average Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1) improvement was 0.5 litres and 0.4 litres respectively. Twenty five percent of patients (nr 19) survived more than 2 years, 10'. (nr=8) between 1-2 years and the remaining 51 patients less than a year. Conclusion: PDT should be considered as a therapeutic modality for all stages of lung cancer and is an excellent treatment modality for palliation in advanced bronchial malignancies.

  18. Providing massage therapy for people with advanced cancer: what to expect.

    PubMed

    Smith, Marlaine C; Yamashita, Traci E; Bryant, Lucinda L; Hemphill, Linnea; Kutner, Jean S

    2009-04-01

    There is very little information in the literature to prepare massage therapists for what they might expect when they provide treatment to people with advanced cancer in hospice or palliative care. We report an analysis of a subset of data collected from a large multi-site clinical trial of the efficacy of massage therapy for people with advanced cancer. This is the first analysis of empirical data of patient presentation, massage treatment environment, and the characteristics of massage provided for this population.

  19. Advances in targeting strategies for nanoparticles in cancer imaging and therapy

    NASA Astrophysics Data System (ADS)

    YheeThese Authors Contributed The Same., Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-10-01

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  20. Advances in Induced Pluripotent Stem Cells, Genomics, Biomarkers, and Antiplatelet Therapy

    PubMed Central

    Barbato, Emanuele; Lara-Pezzi, Enrique; Stolen, Craig; Taylor, Angela; Barton, Paul J.; Bartunek, Jozef; Iaizzo, Paul; Judge, Daniel P.; Kirshenbaum, Lorrie; Blaxall, Burns C.; Terzic, Andre; Hall, Jennifer L.

    2014-01-01

    The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, pre-clinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multi-modality imaging and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context. PMID:24659088

  1. A CAT scan for cells

    SciTech Connect

    2009-01-01

    Recently, a team of scientists from Berkeley Lab, Stanford University, and the University of California, San Francisco used Berkeley Lab's National Center for X-ray Tomography to capture the changes that occur when Candida albicans is exposed to a new and promising antifungal therapy. http://newscenter.lbl.gov/feature-stories/2009/12/10/cat-scan-cells/

  2. Advancing Translational Research Through the NHLBI Gene Therapy Resource Program (GTRP)

    PubMed Central

    Benson, Janet; Cornetta, Kenneth; Diggins, Margaret; Johnston, Julie C.; Sepelak, Susan; Wang, Gensheng; Wilson, James M.; Wright, J. Fraser; Skarlatos, Sonia I.

    2013-01-01

    Abstract Translational research is a lengthy, complex, and necessary endeavor in order to bring basic science discoveries to clinical fruition. The NIH offers several programs to support translational research including an important resource established specifically for gene therapy researchers—the National Heart, Lung, and Blood Institute (NHLBI) Gene Therapy Resource Program (GTRP). This paper reviews the core components of the GTRP and describes how the GTRP provides researchers with resources that are critical to advancing investigational gene therapy products into clinical testing. PMID:23692378

  3. New advances in the mesenchymal stem cells therapy against skin flaps necrosis.

    PubMed

    Zhang, Fu-Gui; Tang, Xiu-Fa

    2014-09-26

    Mesenchymal stem cells (MSCs), multipotential cells that reside within the bone marrow, can be induced to differentiate into various cells, such as osteoblasts, adipocytes, chondrocytes, vascular endothelial progenitor cells, and other cell types. MSCs are being widely studied as potential cell therapy agents due to their angiogenic properties, which have been well established by in vitro and in vivo researches. Within this context, MSCs therapy appears to hold substantial promise, particularly in the treatment of conditions involving skin grafts, pedicle flaps, as well as free flaps described in literatures. The purpose of this review is to report the new advances and mechanisms underlying MSCs therapy against skin flaps necrosis.

  4. [Research advance on clinical blood transfusion and tumor therapy].

    PubMed

    Jiang, Xue-Bing; Zhang, Li-Ping; Wang, Yan-Ju; Ma, Cong

    2010-08-01

    Clinical blood transfusion is one of the most important supportive therapy for patients with tumor. The blood transfusion has dual effects for patients with tumor. First, blood transfusion can rectify anemia and improve oxygen saturation, accelerate oxidation and necrosis for tumor cells; the second, blood transfusion can induce immunosuppression, tumor recurrence and postoperative infection for tumor patients. Filtering white blood cells (WBC) before blood transfusion can decrease the incidence of the adverse reactions. The rational perioperative autotransfusion for patients with tumors is focus to which the world medical sciences pay close attention. In this article, the support effect of blood transfusion for treatment of tumor patients, blood transfusion and immunosuppression, blood transfusion and postoperative infection and relapse of tumor patients, depleted leukocyte blood transfusion and autologous transfusion of tumor patients are reviewed.

  5. Advanced carcinoma of the stomach treated with definitive proton therapy

    SciTech Connect

    Koyama, S.; Kawanishi, N.; Fukutomi, H.; Osuga, T.; Iijima, T.; Tsujii, H.; Kitagawa, T. )

    1990-04-01

    We report the case of a 72-yr-old man who suffered from severe chronic emphysema with poor pulmonary function, and who had advanced cancer of the stomach. Proton beam radiotherapy was applied to the lesion, since surgery was contraindicated. The total dose to the stomach lesion was 61 Gy in 7 wk. The tumor on the stomach regressed, with flattening of the round wall of the lesion. The reactive changes of the proton beam radiotherapy, based on the histopathological examination, revealed extensive tumor necrosis and sparing of vital architecture of normal tissue around the irradiated tumor tissue. Only small clusters of vital or devitalized tumor cells with less than approximately 5% of the whole tumor tissue remained after treatment. We suggest that a high dose of radiation delivered by well-defined proton field could result in an improved therapeutic outcome without undue risk of injury to normal tissue.

  6. Advances in Corticosteroid Therapy for Ocular Inflammation: Loteprednol Etabonate

    PubMed Central

    Comstock, Timothy L.; DeCory, Heleen H.

    2012-01-01

    Topical corticosteroids are effective in reducing anterior segment inflammation but are associated with adverse drug reactions (ADRs) including elevation of intraocular pressure (IOP) and cataract formation. Retrometabolic drug design has advanced the development of new corticosteroids with improved therapeutic indices. Engineered from prednisolone, loteprednol etabonate (LE) has a 17α-chloromethyl ester, in lieu of a ketone group, and a 17β-etabonate group. LE is highly lipophilic and binds with high affinity to the glucocorticoid receptor; any unbound LE is metabolized to inactive metabolites. LE has been studied in several anterior segment inflammatory conditions (giant papillary conjunctivitis, allergic conjunctivitis, anterior uveitis, and keratoconjunctivitis sicca), and in postoperative ocular inflammation and pain. Combined with tobramycin, it is effective in blepharokeratoconjunctivitis. Elevations in IOP are infrequent with LE, and the absence of a C-20 ketone precludes formation of Schiff base intermediates with lens proteins, a common first step implicated in cataract formation with ketone steroids. PMID:22536546

  7. New advances in the pathogenesis and therapy of essential thrombocythemia.

    PubMed

    Levine, Ross L; Heaney, Mark

    2008-01-01

    Essential thrombocythemia (ET) is a hematopoietic disorder that manifests clinically as thrombocytosis, and patients with ET are at increased risk for developing thrombosis, myelofibrosis, and transformation to acute myeloid leukemia. Although ET was recognized as a distinct clinical syndrome more than 6 decades ago and was classified as a myeloproliferative neoplasm (MPN) by William Dameshek in 1951, the molecular pathogenesis of ET remained unknown until 2005, when activating mutations in the JAK2 tyrosine kinase (JAK2V617F) were identified in a significant proportion of patients with ET, polycythemia vera (PV) and primary myelofibrosis (PMF). In addition, subsequent studies have identified gain-of-function mutations in the thrombopoietin receptor (MPL) in a subset of patients with JAK2V617F-negative ET, suggesting that JAK2 activation by distinct mechanisms contributes to the pathogenesis of ET. Despite these important observations, important questions remain regarding the role of JAK2/MPL mutations in ET pathogenesis, the etiology of JAK2/MPL negative ET, the factors that distinguish ET from other MPNs with the JAK2V617F mutation, and the role of JAK2-targeted therapies for the treatment of these MPNs.

  8. Nanotechnology-Based Photodynamic Therapy: Concepts, Advances, and Perspectives.

    PubMed

    Garg, Tarun; Jain, Nitin K; Rath, Goutam; Goyal, Amit Kumar

    2015-01-01

    Photodynamic therapy (PDT) is a photoactive process that uses the combination of photosensitizers (PSs) and specific wavelengths of light for the treatment of solid tumors and other diseases. PDT received increased attention after regulatory approval of several photosensitizing drugs and light applicators worldwide. With the advent of newer PSs, the role of PDT in the treatment of cancer and other diseases has been revolutionized. In addition, various targeting strategies developed for site-specific delivery of PSs will be helpful for avoiding phototoxicity to normal tissues. Receptor-mediated targeted PDT approaches using nanocarriers offer the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. At present, clinical application of PDT is well established in medicine and surgery. Successfully used in dermatology, urology, gastroenterology, and neurosurgery, PDT has also seen much progress in basic sciences and clinical photodynamics in recent years. Currently, the use of PDT is just beginning, and more research must be performed to prove its therapeutic efficacy. However, nontoxic compounds involved in PDT provide a certain hope that it will evolve to be an effective mechanism for combating chronic diseases. PMID:26559433

  9. Mustard vesicant-induced lung injury: Advances in therapy.

    PubMed

    Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-08-15

    Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant. PMID:27212445

  10. Effectiveness of the Mindfulness Art Therapy Short Version for Japanese Patients with Advanced Cancer

    ERIC Educational Resources Information Center

    Ando, Michiyo; Kira, Haruko; Hayashida, Shigeru; Ito, Sayoko

    2016-01-01

    The aim of this study was to investigate the feasibility of the Mindfulness Art Therapy Short Version for Japanese patients with advanced cancer. Patients learned mindfulness practices and then made art to express their feelings in the first session. After receiving instruction on practicing mindfulness 2 weeks later, they participated in a second…

  11. Functional inclusion bodies produced in bacteria as naturally occurring nanopills for advanced cell therapies.

    PubMed

    Vázquez, Esther; Corchero, José L; Burgueño, Joan F; Seras-Franzoso, Joaquin; Kosoy, Ana; Bosser, Ramon; Mendoza, Rosa; Martínez-Láinez, Joan Marc; Rinas, Ursula; Fernández, Ester; Ruiz-Avila, Luis; García-Fruitós, Elena; Villaverde, Antonio

    2012-04-01

    Inclusion bodies (50-500 nm in diameter) produced in recombinant bacteria can be engineered to contain functional proteins with therapeutic potential. Upon exposure, these protein particles are efficiently internalized by mammalian cells and promote recovery from diverse stresses. Being fully biocompatible, inclusion bodies are a novel platform, as tailored nanopills, for sustained drug release in advanced cell therapies.

  12. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

    PubMed

    Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

    2015-01-01

    In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

  13. Creating conditions for the success of the French industrial advanced therapy sector.

    PubMed

    Lirsac, Pierre Noel; Blin, Olivier; Magalon, Jérémy; Angot, Pierre; de Barbeyrac, Estelle; Bilbault, Pascal; Bourg, Elisabeth; Damour, Odile; Faure, Patrick; Ferry, Nicolas; Garbil, Bénédicte; Larghero, Jérôme; Nguon, Marina; Pattou, François; Thumelin, Stéphane; Yates, Frank

    2015-01-01

    Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices. The stated objective was two-fold: both to promote their industrialization and market access, while guaranteeing a high level of health protection for patients. Since publication of the regulation, few marketing authorizations have been granted in Europe, and these have not been accompanied by commercial success. However, certain recent studies show that this is a growing sector and that France remains the leading European nation in terms of clinical trials. This round table brought together a panel of representatives of French public and private protagonists from the advanced therapy sector. The discussions focused on the conditions to ensure the success of translational research and, more generally, the French advanced therapy sector. These enabled a number of obstacles to be identified, which once lifted, by means of recommendations, would facilitate the development and success of this sector. PMID:25747840

  14. [Regulation (EC) No. 1394/2007 on advanced therapy medicinal products : Incorporation into national law].

    PubMed

    Dwenger, A; Strassburger, J; Schwerdtfeger, W

    2010-01-01

    Regulation (EC) No. 1394/2007 has created a new legal framework for advanced therapy medicinal products (gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products). The Regulation is directly applicable in the Member States of the European Union and, in principle, requires no incorporation into national law. However, the amendment of Directive 2001/83/EC, which results from Regulation (EC) No. 1394/2007, has created a need for incorporation into and amendment of the German Medicinal Products Act. This is one of the objectives of the 15th amendment of the German Medicinal Products Act. In particular, the definition "advanced therapy medicinal products" and the special provisions for advanced therapy medicinal products prepared on a non-routine basis, which are based on the special provisions contained in Art. 28 No. 2 of Regulation (EC) No. 1394/2007, are to be incorporated into the German Medicinal Products Act. These special provisions will be explained in detail.

  15. Creating conditions for the success of the French industrial advanced therapy sector.

    PubMed

    Lirsac, Pierre Noel; Blin, Olivier; Magalon, Jérémy; Angot, Pierre; de Barbeyrac, Estelle; Bilbault, Pascal; Bourg, Elisabeth; Damour, Odile; Faure, Patrick; Ferry, Nicolas; Garbil, Bénédicte; Larghero, Jérôme; Nguon, Marina; Pattou, François; Thumelin, Stéphane; Yates, Frank

    2015-01-01

    Although the European Union merely followed the initiatives of the United States and Japan by introducing special regimes for orphan medicinal products, it has introduced a special status for a new category of biological medicinal products, advanced therapy medicinal products (ATMPs), adopting specific associated regulations. European Regulation (which constitutes the highest legal instrument in the hierarchy of European law texts) [EC] No. 1394/2007, published in 2007, uses this term to define somatic cell therapy medicinal products, tissue-engineered products, and gene therapy medicinal products, possibly combined with medical devices. The stated objective was two-fold: both to promote their industrialization and market access, while guaranteeing a high level of health protection for patients. Since publication of the regulation, few marketing authorizations have been granted in Europe, and these have not been accompanied by commercial success. However, certain recent studies show that this is a growing sector and that France remains the leading European nation in terms of clinical trials. This round table brought together a panel of representatives of French public and private protagonists from the advanced therapy sector. The discussions focused on the conditions to ensure the success of translational research and, more generally, the French advanced therapy sector. These enabled a number of obstacles to be identified, which once lifted, by means of recommendations, would facilitate the development and success of this sector.

  16. Experience with fast neutron therapy for locally advanced sarcomas

    SciTech Connect

    Salinas, R.; Hussey, D.H.; Fletcher, G.H.; Lindberg, R.D.; Martin, R.G.; Peters, L.J.; Sinkovics, J.G.

    1980-03-01

    Between October 1972 and April 1978, 34 patients with locally advanced sarcomas were treated with fast neutrons using the Texas A and M variable energy cyclotron. The clinical material included 29 patients with soft tissue sarcomas, 4 with chondrosarcomas, and one with an osteosarcoma. The best results were achieved for patients with soft tissue sarcomas; 69% (20/29) had local control of their tumor. Only one of 4 patients with chondrosarcomas was classified as having local tumor control, and one patient with osteosarcoma had persistent disease. With most fractionation schedules, local tumor control was superior for patients who received doses greater than 6500 rad/sub eq/ (2100 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). The incidence of major complications was notably increased when maximum radiation doses of 7500 rad/sub eq/ or greater were administered (2400 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). In patients who underwent subsequent surgery, healing was satisfactory if the maximum radiation dose was limited to 4500 to 5500 rad/sub eq/(1450 to 1775 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons).

  17. Current therapies and technological advances in aqueous aerosol drug delivery.

    PubMed

    Watts, Alan B; McConville, Jason T; Williams, Robert O

    2008-09-01

    Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.

  18. HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

    PubMed Central

    Joy, Anil A.; Rayson, Daniel; McLeod, Deanna; Brezden-Masley, Christine; Boileau, Jean-François; Gelmon, Karen A.

    2013-01-01

    Untreated human epidermal growth factor receptor-2 (HER-2)-positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER-2-directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER-2-positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER-2-directed therapy has had on disease outcomes, some patients with HER-2-positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER-2-directed therapy in patients with HER-2-positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER-2-positive ABC outcomes. PMID:24212500

  19. [Recurrence and survival rate of advanced gastric cancer after preoperative intraarterial EAP I injection therapy].

    PubMed

    Takeuchi, K; Taniguchi, H; Miyata, K; Koyama, H; Tanaka, H; Ueshima, Y; Okano, S; Oguro, A; Itoh, A; Sawai, K

    1993-08-01

    In our department, curative operations were performed for 32 patients with advanced gastric cancer from April 1989 to August 1990. Preoperative intra-arterial injection therapy with etoposide (100 mg), pirarubicin (20 mg) and cisplatin (20 mg) was given 18 patients. Recurrence and survival rate were investigated. The survival rate of patients with preoperative intra-arterial injection therapy 45 months after operation was 59.2%, while that of patients without preoperative intra-arterial injection therapy was 75.8%. There were no significant differences between these two groups. Three lymph node recurrences were seen in patients with preoperative intra-arterial injection therapy (recurrence rate, 16.7%). Four recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination 2, liver 1, local 1; recurrence rate, 28.6%). We earlier reported that preoperative intra-arterial cisplatin (40 or 60 mg) injection therapy may reduce the incidence of lymph node recurrence and liver metastasis but may not be effective to prevent postoperative peritoneal recurrence, while no peritoneal dissemination was observed in patients with preoperative intra-arterial EAP I injection therapy. Thus, it was concluded that further study of combination and dose of anti-cancer drug may improve effectiveness of preoperative intra-arterial injection therapy for gastric cancer.

  20. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel.

    PubMed

    Vedantham, Suresh; Kahn, Susan R; Goldhaber, Samuel Z; Comerota, Anthony J; Parpia, Sameer; Meleth, Sreelatha; Earp, Diane; Williams, Rick; Sista, Akhilesh K; Marston, William; Rathbun, Suman; Magnuson, Elizabeth A; Razavi, Mahmood K; Jaff, Michael R; Kearon, Clive

    2016-08-01

    Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS.

  1. Endovascular therapy for advanced post-thrombotic syndrome: Proceedings from a multidisciplinary consensus panel

    PubMed Central

    Vedantham, Suresh; Kahn, Susan R; Goldhaber, Samuel Z; Comerota, Anthony J; Parpia, Sameer; Meleth, Sreelatha; Earp, Diane; Williams, Rick; Sista, Akhilesh K; Marston, William; Rathbun, Suman; Magnuson, Elizabeth A; Razavi, Mahmood K; Jaff, Michael R; Kearon, Clive

    2016-01-01

    Patients with advanced post-thrombotic syndrome (PTS) and chronic iliac vein obstruction suffer major physical limitations and impairment of health-related quality of life. Currently there is a lack of evidence-based treatment options for these patients. Early studies suggest that imaging-guided, catheter-based endovascular therapy can eliminate iliac vein obstruction and saphenous venous valvular reflux, resulting in reduced PTS severity; however, these observations have not been rigorously validated. A multidisciplinary expert panel meeting was convened to plan a multicenter randomized controlled clinical trial to evaluate endovascular therapy for the treatment of advanced PTS. This article summarizes the findings of the panel, and is expected to assist in developing a National Institutes of Health-sponsored clinical trial and other studies to improve the care of patients with advanced PTS. PMID:27247235

  2. CELL THERAPY FOR INTERVERTEBRAL DISC REPAIR: ADVANCING CELL THERAPY FROM BENCH TO CLINICS

    PubMed Central

    Benneker, L.M.; Andersson, G.; Iatridis, J.C.; Sakai, D.; Härtl, R.; Ito, K.; Grad, S.

    2016-01-01

    Intervertebral disc (IVD) degeneration is a major cause of pain and disability; yet therapeutic options are limited and treatment often remains unsatisfactory. In recent years, research activities have intensified in tissue engineering and regenerative medicine, and pre-clinical studies have demonstrated encourageing results. Nonetheless, the translation of new biological therapies into clinical practice faces substantial barriers. During the symposium “Where Science meets Clinics”, sponsored by the AO Foundation and held in Davos, Switzerland, from September 5–7, 2013, hurdles for translation were outlined, and ways to overcome them were discussed. With respect to cell therapy for IVD repair, it is obvious that regenerative treatment is indicated at early stages of disc degeneration, before structural changes have occurred. It is envisaged that in the near future, screening techniques and non-invasive imageing methods will be available to detect early degenerative changes. The promises of cell therapy include a sustained effect on matrix synthesis, inflammation control, and prevention of angio- and neurogenesis. Discogenic pain, originating from “black discs” or annular injury, prevention of adjacent segment disease, and prevention of post-discectomy syndrome were identified as prospective indications for cell therapy. Before such therapy can safely and effectively be introduced into clinics, the identification of the patient population and proper standardisation of diagnostic parameters and outcome measurements are indispensable. Furthermore, open questions regarding the optimal cell type and delivery method need to be resolved in outline order to overcome the safety concerns implied with certain procedures. Finally, appropriate large animal models and well-designed clinical studies will be required, particularly addressing safety aspects. PMID:24802611

  3. Treatment of advanced head and neck cancer: multiple daily dose fractionated radiation therapy and sequential multimodal treatment approach.

    PubMed

    Nissenbaum, M; Browde, S; Bezwoda, W R; de Moor, N G; Derman, D P

    1984-01-01

    Fifty-eight patients with advanced head and neck cancer were entered into a randomised trial comparing chemotherapy (DDP + bleomycin) alone, multiple daily fractionated radiation therapy, and multimodality therapy consisting of chemotherapy plus multiple fractionated radiation therapy. Multimodal therapy gave a significantly higher response rate (69%) than either single-treatment modality. The use of a multiple daily dose fractionation allowed radiation therapy to be completed over 10 treatment days, and the addition of chemotherapy to the radiation treatment did not significantly increase toxicity. Patients receiving multimodal therapy also survived significantly longer (median 50 weeks) than those receiving single-modality therapy (median 24 weeks).

  4. Cat and Dog Bites

    MedlinePlus

    MENU Return to Web version Cat and Dog Bites Cat and Dog Bites How should I take care of a bite from a cat or a dog? Whether from a family pet or a neighborhood stray, cat and dog bites are common. Here are some ...

  5. Dawn of advanced molecular medicine: nanotechnological advancements in cancer imaging and therapy.

    PubMed

    Kaittanis, Charalambos; Shaffer, Travis M; Thorek, Daniel L J; Grimm, Jan

    2014-01-01

    Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy. PMID:25271430

  6. Dawn of Advanced Molecular Medicine: Nanotechnological Advancements in Cancer Imaging and Therapy

    PubMed Central

    Kaittanis, Charalambos; Shaffer, Travis M.; Thorek, Daniel L. J.; Grimm, Jan

    2014-01-01

    Nanotechnology plays an increasingly important role not only in our everyday life (with all its benefits and dangers) but also in medicine. Nanoparticles are to date the most intriguing option to deliver high concentrations of agents specifically and directly to cancer cells; therefore, a wide variety of these nanomaterials has been developed and explored. These span the range from simple nanoagents to sophisticated smart devices for drug delivery or imaging. Nanomaterials usually provide a large surface area, allowing for decoration with a large amount of moieties on the surface for either additional functionalities or targeting. Besides using particles solely for imaging purposes, they can also carry as a payload a therapeutic agent. If both are combined within the same particle, a theranostic agent is created. The sophistication of highly developed nanotechnology targeting approaches provides a promising means for many clinical implementations and can provide improved applications for otherwise suboptimal formulations. In this review we will explore nanotechnology both for imaging and therapy to provide a general overview of the field and its impact on cancer imaging and therapy. PMID:25271430

  7. Cell therapy, advanced materials, and new approaches to acute kidney injury.

    PubMed

    Yevzlin, Alexander S; Humes, H David

    2009-12-01

    Acute renal failure (ARF) is a common clinical syndrome characterized by an abrupt deterioration in kidney function, resulting in abnormalities in volume-regulatory, metabolic-regulatory, excretory, and endocrine functions. Despite decades of improvements in the provision of intensive care, and specifically in the provision of renal replacement therapy, the morbidity and mortality associated with acute kidney injury (AKI) remain extremely high. This article highlights novel cell therapies, advanced materials, and approaches to AKI with the aim of illuminating a potential path for future basic, translational, and clinical research using these novel modalities.

  8. [Immunomodulator Intensification of Etioropic Therapy in Patients with Advanced Pulmonary Tuberculosis].

    PubMed

    Kolomiets, V M; Abramov, A V; Rachina, N V; Rubleva, N V

    2015-01-01

    The study was aimed at possible increase of the therapy efficacy in patients with advanced tuberculosis by including immunomodulators to the treatment schemes. The data concerning 6034 patients with advanced tuberculosis, mainly fibrocavernous tuberculosis of the lungs, were analysed. Four groups of the patients were randomized. In group 1 the management of the patients included etiotropic therapy and some treatment and rehabilitation measures with the use of Cycloferon. The group 2 patients in addition to the etiotropic therapy and some treatment and rehabilitation measures were given Omega-3. In group 3 the management included the etiotropic therapy and some treatment and rehabilitation measures. In group 4 the etioropic therapy was used alone. The analysis showed that 3419 patients had primary pulmonary tuberculosis, 340 patients had relapsing tuberculosis and 2275 patients had long-term process. The etiotropic therapy efficacy was estimated after an intensive phase of not more than 3 months. In the cases with Mycobacterium tuberculosis drug resistance and some other unfavourable factors it was estimated after a 5-month intensive phase. The results confirmed that inclusion of immunomodulators to the treatment schemes allowed to increase the therapy efficacy and the patients' adherence to the treatment, as well as to shorten the period of the bacteria carriage. Thus, the use of Cycloferon in the schemes of the treatment of the patients with fibrocavernous pulmonary tuberculosis allowed to shorten the period of the pathogen carriage (as well as the drug resistant forms) in 94.1 ± 3.33% of the patients in spite of concomitant diseases. The effect of Cycloferon in such cases was likely due to both its direct immunoprotective action and the improvement of the general state of the patients and their higher adherence to the treatment.

  9. Therapy of metastatic pancreatic neuroendocrine tumors (pNETs): recent insights and advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato

    2013-01-01

    Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. PMID:22886480

  10. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  11. But does it do any good? Measuring the impact of music therapy on people with advanced dementia: (Innovative practice).

    PubMed

    Gold, Karen

    2014-03-01

    This article describes the impact of music therapy upon a group of nine people with advanced dementia in a hospital setting. It demonstrates how the impact of music therapy was measured using the case notes completed by nursing and care staff and how these notes suggested that music therapy had a positive effect on the mood and behaviour on eight of the nine people receiving music therapy.

  12. But does it do any good? Measuring the impact of music therapy on people with advanced dementia: (Innovative practice).

    PubMed

    Gold, Karen

    2014-03-01

    This article describes the impact of music therapy upon a group of nine people with advanced dementia in a hospital setting. It demonstrates how the impact of music therapy was measured using the case notes completed by nursing and care staff and how these notes suggested that music therapy had a positive effect on the mood and behaviour on eight of the nine people receiving music therapy. PMID:24339096

  13. A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement.

    PubMed

    Roderique, Joseph D; Josef, Christopher S; Feldman, Michael J; Spiess, Bruce D

    2015-08-01

    The first descriptions of carbon monoxide (CO) and its toxic nature appeared in the literature over 100 years ago in separate publications by Drs. Douglas and Haldane. Both men ascribed the deleterious effects of this newly discovered gas to its strong interaction with hemoglobin. Since then the adverse sequelae of CO poisoning has been almost universally attributed to hypoxic injury secondary to CO occupation of oxygen binding sites on hemoglobin. Despite a mounting body of literature suggesting other mechanisms of injury, this pathophysiology and its associated oxygen centric therapies persists. This review attempts to elucidate the remarkably complex nature of CO as a gasotransmitter. While CO's affinity for hemoglobin remains undisputed, new research suggests that its role in nitric oxide release, reactive oxygen species formation, and its direct action on ion channels is much more significant. In the course of understanding the multifaceted character of this simple molecule it becomes apparent that current oxygen based therapies meant to displace CO from hemoglobin may be insufficient and possibly harmful. Approaching CO as a complex gasotransmitter will help guide understanding of the complex and poorly understood sequelae and illuminate potentials for new treatment modalities.

  14. Endoscopic therapy for early gastric cancer: Standard techniques and recent advances in ESD

    PubMed Central

    Kume, Keiichiro

    2014-01-01

    The technique of endoscopic submucosal dissection (ESD) is now a well-known endoscopic therapy for early gastric cancer. ESD was introduced to resect large specimens of early gastric cancer in a single piece. ESD can provide precision of histologic diagnosis and can also reduce the recurrence rate. However, the drawback of ESD is its technical difficulty, and, consequently, it is associated with a high rate of complications, the need for advanced endoscopic techniques, and a lengthy procedure time. Various advances in the devices and techniques used for ESD have contributed to overcoming these drawbacks. PMID:24914364

  15. Advances in Cell and Gene-based Therapies for Cystic Fibrosis Lung Disease

    PubMed Central

    Oakland, Mayumi; Sinn, Patrick L; McCray Jr, Paul B

    2012-01-01

    Cystic fibrosis (CF) is a disease characterized by airway infection, inflammation, remodeling, and obstruction that gradually destroy the lungs. Direct delivery of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to airway epithelia may offer advantages, as the tissue is accessible for topical delivery of vectors. Yet, physical and host immune barriers in the lung present challenges for successful gene transfer to the respiratory tract. Advances in gene transfer approaches, tissue engineering, and novel animal models are generating excitement within the CF research field. This review discusses current challenges and advancements in viral and nonviral vectors, cell-based therapies, and CF animal models. PMID:22371844

  16. [Triple therapy in cirrhotic patients and those with advanced fibrosis: relevant aspects in clinical practice].

    PubMed

    Albillos, Agustín; Luis Calleja, José; Molina, Esther; Planas, Ramon; Romero-Gómez, Manuel; Turnes, Juan; Hernández-Guerra, Manuel

    2014-07-01

    The first-line option in the treatment of patients with advanced fibrosis and cirrhosis due to genotype 1 hepatitis C virus is currently triple therapy with boceprevir/telaprevir and pegylated interferon-ribavirin. However, certain limitations could constitute a barrier to starting treatment or achieving sustained viral response in these patients. These limitations include the patient's or physician's perception of treatment effectiveness in routine clinical practice-which can weight against the decision to start treatment-, the advanced stage of the disease with portal hypertension and comorbidity, treatment interruption due to poor adherence, and adverse effects, mainly anemia. In addition, it is now possible to identify patients who could benefit from a shorter therapeutic regimen with a similar cure rate. This review discusses these issues and their possible effect on the use of triple therapy. PMID:25907434

  17. Trimodality Therapy for an Advanced Thymic Carcinoma With Both Aorta and Vena Cava Invasion.

    PubMed

    Momozane, Tohru; Inoue, Masayoshi; Shintani, Yasushi; Funaki, Soichiro; Kawamura, Tomohiro; Minami, Masato; Shirakawa, Yukitoshi; Kuratani, Toru; Sawa, Yoshiki; Okumura, Meinoshin

    2016-08-01

    A case of locally advanced thymic carcinoma that was successfully resected with the great vessels after chemoradiation therapy is reported. A 57-year-old man with Masaoka stage III thymic carcinoma received two cycles of cisplatin/docetaxel and 60 Gy irradiation. The response was stable disease with 19% size reduction, and a radical resection with the ascending aorta and superior vena cava with the patient under circulatory arrest with the use of cardiopulmonary bypass was performed. The postoperative course was uneventful, and the patient has been free of disease for 28 months. Trimodality therapy with use of a cardiovascular surgical procedure might be a valuable option in locally advanced thymic carcinoma. PMID:27449450

  18. Selective androgen receptor modulators as improved androgen therapy for advanced breast cancer.

    PubMed

    Coss, Christopher C; Jones, Amanda; Dalton, James T

    2014-11-01

    Androgens were at one time a therapeutic mainstay in the treatment of advanced breast cancer. Despite comparable efficacy, SERMs and aromatase inhibitors eventually became the therapies of choice due to in part to preferred side-effect profiles. Molecular characterization of breast tumors has revealed an abundance of androgen receptor expression but the choice of an appropriate androgen receptor ligand (agonist or antagonist) has been confounded by multiple conflicting reports concerning the role of the receptor in the disease. Modern clinical efforts have almost exclusively utilized antagonists. However, the recent clinical development of selective androgen receptor modulators with greatly improved side-effect profiles has renewed interest in androgen agonist therapy for advanced breast cancer.

  19. Recent Advances in Upconversion Nanoparticles-Based Multifunctional Nanocomposites for Combined Cancer Therapy.

    PubMed

    Tian, Gan; Zhang, Xiao; Gu, Zhanjun; Zhao, Yuliang

    2015-12-16

    Lanthanide-doped upconversion nanoparticles (UCNPs) have the ability to generate ultraviolet or visible emissions under continuous-wave near-infrared (NIR) excitation. Utilizing this special luminescence property, UCNPs are approved as a new generation of contrast agents in optical imaging with deep tissue-penetration ability and high signal-to-noise ratio. The integration of UCNPs with other functional moieties can endow them with highly enriched functionalities for imaging-guided cancer therapy, which makes composites based on UCNPs emerge as a new class of theranostic agents in biomedicine. Here, recent progress in combined cancer therapy using functional nanocomposites based on UCNPs is reviewed. Combined therapy referring to the co-delivery of two or more therapeutic agents or a combination of different treatments is becoming more popular in clinical treatment of cancer because it generates synergistic anti-cancer effects, reduces individual drug-related toxicity and suppresses multi-drug resistance through different mechanisms of action. Here, the recent advances of combined therapy contributed by UCNPs-based nanocomposites on two main branches are reviewed: i) photodynamic therapy and ii) chemotherapy, which are the two most widely adopted therapies of UCNPs-based composites. The future prospects and challenges in this emerging field will be also discussed.

  20. Manual ventilation therapy and aggressive potassium supplementation in the management of respiratory failure secondary to severe hypokalaemia in a cat with exocrine pancreatic insufficiency.

    PubMed

    Daste, Thomas; Dossin, Olivier; Reynolds, Brice S; Aumann, Marcel

    2014-04-01

    A domestic shorthair cat was referred for progressive muscle weakness and dyspnoea. The cat had a 2-month history of severe weight loss, small intestinal diarrhoea, polyphagia and polyuria/polydipsia. Biochemical analysis and venous blood gas evaluation revealed severe hypokalaemia [1.7 mmol/l; reference interval (RI): 3.5-5.1 mmol/l] and hypoventilation (partial pressure of carbon dioxide = 68 mmHg; RI: 34-38 mmHg). Aggressive potassium supplementation was initiated. The cat was manually ventilated until serum potassium increased to 3 mmol/l. A diagnosis of exocrine pancreatic insufficiency (EPI) was made based on clinical signs and serum feline trypsin-like immunoreactivity (0.1 μg/l; RI: 12-82 μg/l). Medical management of the EPI resulted in clinical recovery.

  1. Effect of Mandibular Advancement Device Therapy on the Signs and Symptoms of Temporomandibular Disorders

    PubMed Central

    Raunio, Antti; Sipilä, Kirsi; Raustia, Aune

    2012-01-01

    ABSTRACT Objectives Mandibular advancement device therapy is effectively used in the treatment of obstructive sleep apnea, but also several side effects in the masticatory system have been reported. The aim of this study was to evaluate the subjective symptoms and clinical signs of temporomandibular disorders connected to mandibular advancement device therapy. Material and Methods The material consisted of 15 patients (9 men and 6 women, mean age 51.1 years, range 21 to 70 years) diagnosed with obstructive sleep apnea (OSA). Subjective symptoms and clinical temporomandibular disorders (TMD) signs were recorded at the beginning of the treatment (baseline) and at 1-month, 3-month, 6-month and 24-month follow-ups. The degree of TMD was assessed using the anamnestic (Ai) and the clinical dysfunction index (Di) of Helkimo. For assessing the effect of TMD the patients were divided in discontinuing and continuing groups. Results According to Ai and Di, the severity of TMD remained unchanged during the follow-up in most of the patients. Temporomandibular joint (TMJ) crepitation was found more frequently in discontinuing patients at all follow-ups. The difference was statistically significant (P < 0.05) at the six-month follow-up. Masticatory muscle pain during palpation was a frequent clinical sign at the baseline and during the follow-up period but the difference between discontinuing and continuing patients was not significant. Conclusions It seems that signs and symptoms of temporomandibular disorders do not necessarily increase during long-term mandibular advancement device therapy. However, it seems that patients with clinically assessed temporomandibular joint crepitation may discontinue their mandibular advancement device therapy due to temporomandibular disorders. PMID:24422023

  2. Developing treatment and control conditions in a clinical trial of massage therapy for advanced cancer.

    PubMed

    Smith, Marlaine; Kutner, Jean; Hemphill, Linnea; Yamashita, Traci; Felton, Susanne

    2007-01-01

    The purpose of this article is to describe the challenges faced by a research team in developing treatment and control conditions in a study of the efficacy of massage therapy for advanced cancer. Five design considerations were addressed related to developing a massage therapy protocol: (1) dosage, that is, the number, spacing and length of treatments; (2) type of massage therapy; (3) degree to which the protocol for the treatment is standardized; (4) qualifications of the persons providing the treatment; and (5) conditions under which the treatment is provided. Five criteria for structuring the control condition of the study are elaborated: (1) equivalency of contact; (2) similarity of form; (3) minimum adverse or negative effects; (4) expectancy of therapeutic benefit; and (5) minimum therapeutic benefit.

  3. Stem cell therapies for amyotrophic lateral sclerosis: Recent advances and prospects for the future

    PubMed Central

    Lunn, J. Simon; Sakowski, Stacey A.; Feldman, Eva L.

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell-based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long-term safety are required, these studies represent an important first step towards the development of effective cellular therapies for the treatment of ALS. PMID:24448926

  4. Concise review: Stem cell therapies for amyotrophic lateral sclerosis: recent advances and prospects for the future.

    PubMed

    Lunn, J Simon; Sakowski, Stacey A; Feldman, Eva L

    2014-05-01

    Amyotrophic lateral sclerosis (ALS) is a lethal disease involving the loss of motor neurons. Although the mechanisms responsible for motor neuron degeneration in ALS remain elusive, the development of stem cell-based therapies for the treatment of ALS has gained widespread support. Here, we review the types of stem cells being considered for therapeutic applications in ALS, and emphasize recent preclinical advances that provide supportive rationale for clinical translation. We also discuss early trials from around the world translating cellular therapies to ALS patients, and offer important considerations for future clinical trial design. Although clinical translation is still in its infancy, and additional insight into the mechanisms underlying therapeutic efficacy and the establishment of long-term safety are required, these studies represent an important first step toward the development of effective cellular therapies for the treatment of ALS.

  5. Pemetrexed Maintenance Therapy Following Bevacizumab-Containing First-Line Chemotherapy in Advanced Malignant Pleural Mesothelioma

    PubMed Central

    Jing, Xu-Quan; Zhou, Lei; Sun, Xin-Dong; Yu, Jin-Ming; Meng, Xue

    2016-01-01

    Abstract Malignant pleural mesothelioma (MPM) is a lethal disease with poor prognosis. The combination of cisplatin and pemetrexed has been confirmed as the standard of care for nonoperable MPM. Data have shown that the adoption of pemetrexed maintenance therapy (PMT) following first-line treatment appears extremely promising. We describe a 57-year-old man diagnosed as advanced MPM. We treated this patient with PMT after first-line cisplatin-based bevacizumab-containing chemotherapy and residual tumor disappeared after 6 course of PMT. A perfect response and a long progression-free survival (PFS) were reached with tumor mass disappearing and 14 months duration of PFS. This case suggests that adding bevacizumab to standard first-line chemotherapy is feasible and that PMT could be promising and useful for treating advanced MPM. We further entail a review of the literature on the first-line treatment, continuation maintenance therapy, switch maintenance therapy, and second-line treatment of patients with advanced MPM. PMID:27057918

  6. Management of advanced bladder cancer in the era of targeted therapies.

    PubMed

    Soave, A; Engel, O; Von Amsberg, G; Becker, A; Dahlem, R; Shariat, S F; Fisch, M; Rink, M

    2015-06-01

    Systemic chemotherapy is the standard treatment of advanced and metastatic urothelial carcinoma of the bladder (UCB). Unfortunately, systemic chemotherapy is ineffective in a significant number of patients, while side effects occur frequently. Detailed molecular-genetic investigations revealed a broad heterogeneity of underlying genomic mutations in UCB and led to the detection of cancer-specific therapeutic targets. These findings may allow a more tailored and individualized patient-based therapy, focusing on specific genomic variations, which may cause chemo-resistance in patients progressing or relapsing after standard chemotherapy. Targeted therapies hold the potential to be more effective in inhibiting cancer cell growth and progression, as well as to cause fewer side effects. While targeted therapies have been successfully established in the treatment of various malignancies including renal cell carcinoma, the clinical impact of these modern treatment strategies still remains unsettled for UCB. In this review, we comprehensively summarize the most current and relevant findings on targeted therapy in advanced and metastatic UCB, elucidating chances and limitations and discussing future perspectives.

  7. Molecular targeted therapies in advanced or metastatic chordoma patients: facts and hypotheses.

    PubMed

    Lebellec, Loïc; Aubert, Sébastien; Zaïri, Fahed; Ryckewaert, Thomas; Chauffert, Bruno; Penel, Nicolas

    2015-07-01

    Chordomas, derived from undifferentiated notochordal remnants, represent less than 4% of bone primary tumors. Despite surgery followed by radiotherapy, local and metastatic relapses are frequent. In case of locally advanced or metastatic chordomas, medical treatment is frequently discussed. While chemotherapy is ineffective, it would appear that some molecular targeted therapies, in particular imatinib, could slow down the tumor growth in case-reports, retrospective series, and phase I or II trials. Nineteen publications, between January 1990 and September 2014, have been found describing the activity of these targeted therapies. A systematic analysis of these publications shows that the best objective response with targeted therapies was stabilization in 52 to 69% of chordomas. Given the indolent course of advanced chordoma and because of the absence of randomized trial, the level of evidence to treat chordomas with molecular therapy is low (level III), whatever the drug. Furthermore, we could not draw firm conclusion on the activity of imatinib. Other putative targets have also been described. Therefore, further clinical trials are expected, especially with these targets. Nevertheless, it seems essential, in those future studies, to consider the naturally slow course of the disease.

  8. Selecting deep brain stimulation or infusion therapies in advanced Parkinson's disease: an evidence-based review.

    PubMed

    Volkmann, Jens; Albanese, Alberto; Antonini, Angelo; Chaudhuri, K Ray; Clarke, Carl E; de Bie, Rob M A; Deuschl, Günther; Eggert, Karla; Houeto, Jean-Luc; Kulisevsky, Jaime; Nyholm, Dag; Odin, Per; Østergaard, Karen; Poewe, Werner; Pollak, Pierre; Rabey, Jose Martin; Rascol, Olivier; Ruzicka, Evzen; Samuel, Michael; Speelman, Hans; Sydow, Olof; Valldeoriola, Francesc; van der Linden, Chris; Oertel, Wolfgang

    2013-11-01

    Motor complications in Parkinson's disease (PD) result from the short half-life and irregular plasma fluctuations of oral levodopa. When strategies of providing more continuous dopaminergic stimulation by adjusting oral medication fail, patients may be candidates for one of three device-aided therapies: deep brain stimulation (DBS), continuous subcutaneous apomorphine infusion, or continuous duodenal/jejunal levodopa/carbidopa pump infusion (DLI). These therapies differ in their invasiveness, side-effect profile, and the need for nursing care. So far, very few comparative studies have evaluated the efficacy of the three device-aided therapies for specific motor problems in advanced PD. As a result, neurologists currently lack guidance as to which therapy could be most appropriate for a particular PD patient. A group of experts knowledgeable in all three therapies reviewed the currently available literature for each treatment and identified variables of clinical relevance for choosing one of the three options such as type of motor problems, age, and cognitive and psychiatric status. For each scenario, pragmatic and (if available) evidence-based recommendations are provided as to which patients could be candidates for either DBS, DLI, or subcutaneous apomorphine. PMID:23287972

  9. Concurrent cisplatin, 5-FU, paclitaxel, and radiation therapy in patients with locally advanced esophageal cancer

    SciTech Connect

    Roof, Kevin S. . E-mail: kroof@sero.net; Coen, John; Lynch, Thomas J.; Wright, Cameron; Fidias, Panos; Willett, Christopher G.; Choi, Noah C.

    2006-07-15

    Purpose: Phase I-II data regarding neoadjuvant cisplatin, 5-fluorouracil (5-FU), paclitaxel, and radiation (PFT-R) from our institution demonstrated encouraging pathologic complete response (pCR) rates. This article updates our experience with PFT-R, and compares these results to our experience with cisplatin, 5-FU, and radiation therapy (PF-R) in locally advanced esophageal cancer. Patients and Methods: We searched the Massachusetts General Hospital cancer registry for esophageal cancer patients treated with radiation therapy and chemotherapy between 1994-2002. Records of patients treated with curative, neoadjuvant therapy were examined for chemotherapeutic regimen. Outcomes of patients treated with PF-R or PFT-R were assessed for response to therapy, toxicity, and survival. Results: A total of 177 patients were treated with neoadjuvant therapy with curative intent; 164 (93%) received PF-R (n = 81) or PFT-R (n = 83). Median overall survival was 24 months. After a median follow-up of 54 months for surviving patients, 3-year overall survival was 40% with no significant difference between PF-R (39%) and PFT-R (42%). Conclusions: Our findings failed to demonstrate an improvement in pCR or survival with PFT-R vs. PF-R. These results do not support this regimen of concurrent neoadjuvant PFT-R in esophageal cancer, and suggest that further investigations into alternative regimens and novel agents are warranted.

  10. Age Disparity in Palliative Radiation Therapy Among Patients With Advanced Cancer

    SciTech Connect

    Wong, Jonathan; Xu, Beibei; Yeung, Heidi N.; Roeland, Eric J.; Martinez, Maria Elena; Le, Quynh-Thu; Mell, Loren K.; Murphy, James D.

    2014-09-01

    Purpose/Objective: Palliative radiation therapy represents an important treatment option among patients with advanced cancer, although research shows decreased use among older patients. This study evaluated age-related patterns of palliative radiation use among an elderly Medicare population. Methods and Materials: We identified 63,221 patients with metastatic lung, breast, prostate, or colorectal cancer diagnosed between 2000 and 2007 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. Receipt of palliative radiation therapy was extracted from Medicare claims. Multivariate Poisson regression analysis determined residual age-related disparity in the receipt of palliative radiation therapy after controlling for confounding covariates including age-related differences in patient and demographic covariates, length of life, and patient preferences for aggressive cancer therapy. Results: The use of radiation decreased steadily with increasing patient age. Forty-two percent of patients aged 66 to 69 received palliative radiation therapy. Rates of palliative radiation decreased to 38%, 32%, 24%, and 14% among patients aged 70 to 74, 75 to 79, 80 to 84, and over 85, respectively. Multivariate analysis found that confounding covariates attenuated these findings, although the decreased relative rate of palliative radiation therapy among the elderly remained clinically and statistically significant. On multivariate analysis, compared to patients 66 to 69 years old, those aged 70 to 74, 75 to 79, 80 to 84, and over 85 had a 7%, 15%, 25%, and 44% decreased rate of receiving palliative radiation, respectively (all P<.0001). Conclusions: Age disparity with palliative radiation therapy exists among older cancer patients. Further research should strive to identify barriers to palliative radiation among the elderly, and extra effort should be made to give older patients the opportunity to receive this quality of life-enhancing treatment at the end

  11. Cat-Scratch Disease

    MedlinePlus

    ... Patients Infants and Young Children Publications & Materials Announcements Cat-Scratch Disease Recommend on Facebook Tweet Share Compartir ( ... play and learn how to attack prey. How cats and people become infected Kitten playing with a ...

  12. Cat Scratch Disease

    MedlinePlus

    Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry the infection ... symptoms of CSD, call your doctor. Centers for Disease Control and Prevention

  13. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

    PubMed Central

    Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

    2016-01-01

    Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

  14. Advance Care Planning and HIV Infection in the Era of Antiretroviral Therapy: A Review.

    PubMed

    Sangarlangkarn, Aroonsiri; Merlin, Jessica S; Tucker, Rodney O; Kelley, Amy S

    In the era of antiretroviral therapy, HIV infection has become a chronic illness with associated multimorbidity, and practitioners are faced with an emerging population of HIV-infected patients with evolving needs for advance care planning (ACP), defined as communication between individuals and their proxies to plan for future health care decisions. This article provides a review of original research studies on ACP in HIV-infected adults in the era of antiretroviral therapy (1996-present) from PubMed, EMBASE, and PsycINFO. Eleven studies conducted between 1996 and 2015 met the selection criteria, with study sizes ranging from 9 to 2864 participants. Most studies consisted of white men in outpatient settings and had poorly defined definitions of ACP. Prevalence of ACP was variable (36%-54% had end-of-life communication, 8%-47% had advance directives). Lack of ACP was most commonly associated with low income, followed by lower severity of illness, low education level, black or Hispanic race, female sex, younger age, injection drug use, and social isolation. Practitioners reported limited time or energy and inadequate preparation or training as barriers to ACP. Existing literature on ACP in the era of antiretroviral therapy is limited, but shows that ACP prevalence in HIV-infected individuals is variable depending on socioeconomic factors, severity of illness, and practitioner resources and training. More research is needed to increase ACP among HIV-infected individuals. PMID:27398771

  15. Nitroreductase gene-directed enzyme prodrug therapy: insights and advances toward clinical utility.

    PubMed

    Williams, Elsie M; Little, Rory F; Mowday, Alexandra M; Rich, Michelle H; Chan-Hyams, Jasmine V E; Copp, Janine N; Smaill, Jeff B; Patterson, Adam V; Ackerley, David F

    2015-10-15

    This review examines the vast catalytic and therapeutic potential offered by type I (i.e. oxygen-insensitive) nitroreductase enzymes in partnership with nitroaromatic prodrugs, with particular focus on gene-directed enzyme prodrug therapy (GDEPT; a form of cancer gene therapy). Important first indications of this potential were demonstrated over 20 years ago, for the enzyme-prodrug pairing of Escherichia coli NfsB and CB1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. However, it has become apparent that both the enzyme and the prodrug in this prototypical pairing have limitations that have impeded their clinical progression. Recently, substantial advances have been made in the biodiscovery and engineering of superior nitroreductase variants, in particular development of elegant high-throughput screening capabilities to enable optimization of desirable activities via directed evolution. These advances in enzymology have been paralleled by advances in medicinal chemistry, leading to the development of second- and third-generation nitroaromatic prodrugs that offer substantial advantages over CB1954 for nitroreductase GDEPT, including greater dose-potency and enhanced ability of the activated metabolite(s) to exhibit a local bystander effect. In addition to forging substantial progress towards future clinical trials, this research is supporting other fields, most notably the development and improvement of targeted cellular ablation capabilities in small animal models, such as zebrafish, to enable cell-specific physiology or regeneration studies.

  16. Mesenchymal Stem Cells in Chronic Wounds: The Spectrum from Basic to Advanced Therapy

    PubMed Central

    Otero-Viñas, Marta; Falanga, Vincent

    2016-01-01

    Significance: Almost 7 million Americans have chronic cutaneous wounds and billions of dollars are spent on their treatment. The number of patients with nonhealing wounds keeps increasing worldwide due to an ever-aging population, increasing number of obese and diabetic patients, and cardiovascular disease. Recent Advances: Advanced treatments for difficult wounds are needed. Therapy with mesenchymal stem cells (MSCs) is attractive due to their differentiating potential, their immunomodulating properties, and their paracrine effects. Critical Issues: New technologies (including growth factors and skin substitutes) are now widely used for stimulating wound healing. However, in spite of these advances, the percentage of complete wound closure in most clinical situations is around 50–60%. Moreover, there is a high rate of wound recurrence. Future Directions: Recently, it has been demonstrated that MSCs speed up wound healing by decreasing inflammation, by promoting angiogenesis, and by decreasing scarring. However, there are some potential limitations to successful MSC therapy. These limitations include the need to improve cell delivery methods, cell viability, heterogeneity in MSC preparations, and suboptimal wound bed preparation. Further large, controlled clinical trials are needed to establish the safety of MSCs before widespread clinical application. PMID:27076993

  17. Getting a CAT Scan

    MedlinePlus

    ... Here's Help White House Lunch Recipes Getting a CAT Scan (Video) KidsHealth > For Kids > Getting a CAT Scan (Video) A A A en español Obtención de una tomografía computada (video) CAT stands for "computerized axial tomography." Translated, that means ...

  18. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population. PMID:23159421

  19. Accelerated fractionation radiation therapy for advanced squamous cell carcinoma of the head and neck

    SciTech Connect

    Giri, P.G.; Gemer, L.S. )

    1991-09-01

    The authors treated 14 patients who had advanced head and neck cancer with an accelerated fractionation schedule of irradiation consisting of two fractions given 6 hours apart. In the morning a volume of 1.7 Gy was given to an area that encompassed the entire tumor, enlarged lymph nodes, and all areas at risk for microscopic disease. Six hours later, 1.1 Gy was given to an area that included only the tumor and any enlarged lymph nodes, with a 2-cm margin. The treatment was well tolerated; of the 13 patients who completed therapy, six did not require a break in therapy, and seven patients did. The median rest period was 2 days. There was no grade 4 toxicity. Grade 3 toxicity included skin changes (one case), mucositis (two), dysphagia (two), weight loss (three), and a decrease in the hemoglobin level (one case). The response rate in the 13 who completed therapy was 13/13 (100%); 11 of the 13 (83%) had a complete response. Only one of the 11 who achieved a complete response had failure at the primary site. At a median follow-up of 24 months, the absolute survival was 7/13 (54%) and the corrected survival was 7/10 (70%). This technique permits radiation therapy to be given on an accelerated schedule without a planned break in treatment. The overall response rate and survival at 2 years was excellent.

  20. Response and Tolerance to Oral Vasodilator Uptitration after Intravenous Vasodilator Therapy in Advanced Decompensated Heart Failure

    PubMed Central

    Verbrugge, Frederik H.; Dupont, Matthias; Finucan, Michael; Gabi, Alaa; Hawwa, Nael; Mullens, Wilfried; Taylor, David O.; Young, James B.; Starling, Randall C.; Wilson Tang, W.H.

    2015-01-01

    Aims To assess the hemodynamic response and tolerance to aggressive oral hydralazine/isosorbide dinitrate (HYD/ISDN) uptitration after intravenous vasodilator therapy in advanced decompensated heart failure (ADHF). Methods and Results Medical records of 147 consecutive ADHF patients who underwent placement of a pulmonary artery catheter and received intravenous vasodilator therapy were reviewed. Intravenous sodium nitroprusside and sodium nitroglycerin as first-line agent for those with preserved blood pressures were utilized in 143 and 32 patients, respectively. Sixty-one percent of patients were converted to oral HYD/ISDN combination therapy through a standardized conversion protocol. These patients had a significantly higher admission mean pulmonary arterial wedge pressure compared to patients not converted (28 ± 7 versus 25 ± 8 mmHg, respectively; P-value=0.024). Beneficial hemodynamic response to decongestive therapy, defined as low cardiac filling pressures and cardiac index ≥2.20 L/min/m² without emergent hypotension, was achieved in 32% and 29% of patients who did or did not receive oral HYD/ISDN, respectively (P-value=0.762). HYD/ISDN dosing was progressively and consistently decreased up to the moment of hospital discharge and during outpatient follow-up primarily due to incident hypotension. Conclusion The use of a standardized hemodynamically-guided uptitration protocol for conversion from intravenous to oral vasodilators may warrant subsequent dose reductions upon stabilization. PMID:26213182

  1. Predicting compliance for mandible advancement splint therapy in 96 obstructive sleep apnea patients.

    PubMed

    Ingman, Tuula; Arte, Sirpa; Bachour, Adel; Bäck, Leif; Mäkitie, Antti

    2013-12-01

    The treatment of choice in obstructive sleep apnea (OSA) is continuous positive airway pressure (CPAP). Mandible advancement splint (MAS) offers an option for patients with mild or moderate OSA, who refuse or are unable to tolerate CPAP. The aim of the study was to find predictive factors in OSA for MAS therapy. The study group comprised 96 consecutive OSA patients who were sent for MAS therapy during 2008. Data were collected on the patients' general and dental condition, diagnosis, and treatment for OSA. Panoramic and cephalometric radiographs were analysed. The treatment compliance rate and problems with the use of the MAS were recorded. This rate was 57% and the significant affecting factors were protrusion of the mandible with MAS during the adaptation to the appliance as well as shorter maxillary and mandible lengths. The compliance of the MAS therapy was best in patients with short maxilla and mandible, which should be taken into consideration when planning MAS therapy for OSA patients. Finally, a sleep study should be part of the follow-up in this patient population.

  2. Beyond HER2: recent advances and future directions in targeted therapies in esophagogastric cancers

    PubMed Central

    2016-01-01

    Esophagogastric cancers (EGCa) are a leading cause of cancer related mortality worldwide. It has been recognized that they represent heterogenous diseases based on histology and anatomy. However, it is also increasingly evident that these are diverse malignancies based on genetic alterations, and this is increasingly making these diseases amenable to targeted therapies. While epidermal growth factor receptor (EGFR) and mTOR inhibitors have failed to prove effective in the treatment of advanced EGCa, vascular endothelial growth factor (VEGF) inihibitor have now been demonstrated to improve survival, at least in the 2nd line setting of adenocarcinomas. Other promising approaches are being investigated, including targeted therapies such as MET and FGFR inhibitors, as well as immunotherapy and agents that may affect synthetic lethality. PMID:27747090

  3. The steady progress of targeted therapies, promising advances for lung cancer

    PubMed Central

    Bombardelli, Lorenzo; Berns, Anton

    2016-01-01

    Lung cancer remains one of the most complex and challenging cancers, being responsible for almost a third of all cancer deaths. This grim picture seems however to be changing, for at least a subset of lung cancers. The number of patients who can benefit from targeted therapies is steadily increasing thanks to the progress made in identifying actionable driver lesions in lung tumours. The success of the latest generation of EGFR and ALK inhibitors in the clinic not only illustrates the value of targeted therapies, but also shows how almost inevitably drug resistance develops. Therefore, more sophisticated approaches are needed to achieve long-term remissions. Although there are still significant barriers to be overcome, technological advances in early detection of relevant mutations and the opportunity to test new drugs in predictive preclinical models justify the hope that we will overcome these obstacles. PMID:27350784

  4. Recent advances in diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract.

    PubMed

    Pelley, R J; Bukowski, R M

    1997-01-01

    Neuroendocrine tumors of the gastrointestinal tract are rare tumors that can be classified as APU-Domas (amine precursor uptake and decarboxylation). They can be subdivided into the carcinoid tumors of the gastrointestinal submucosa and the islet cell endocrine tumors of the pancreas. Although the majority of tumors that become clinically apparent are malignant, they are frequently slow growing. Despite this, neuroendocrine tumors may generate disabling hormonal syndromes requiring aggressive treatment to achieve palliation. Recent advances in understanding the pathophysiology of these tumors has led to better radiographic imaging and more accurate localization techniques. Medical therapies with somatostatin analogues, omeprazole, and locoregional tumor ablation have made a positive impact on curative and palliative therapy. This review updates the recent efforts made in the radiographic imaging and therapeutics of the gastrointestinal neuroendocrine tumors.

  5. Advances in induced pluripotent stem cells, genomics, biomarkers, and antiplatelet therapy highlights of the year in JCTR 2013.

    PubMed

    Barbato, Emanuele; Lara-Pezzi, Enrique; Stolen, Craig; Taylor, Angela; Barton, Paul J; Bartunek, Jozef; Iaizzo, Paul; Judge, Daniel P; Kirshenbaum, Lorrie; Blaxall, Burns C; Terzic, Andre; Hall, Jennifer L

    2014-07-01

    The Journal provides the clinician and scientist with the latest advances in discovery research, emerging technologies, preclinical research design and testing, and clinical trials. We highlight advances in areas of induced pluripotent stem cells, genomics, biomarkers, multimodality imaging, and antiplatelet biology and therapy. The top publications are critically discussed and presented along with anatomical reviews and FDA insight to provide context.

  6. Opportunities for Regenerative Rehabilitation and Advanced Technologies in Physical Therapy: Perspective From Academia.

    PubMed

    Norland, Ryan; Muchnick, Matthew; Harmon, Zachary; Chin, Tiffany; Kakar, Rumit Singh

    2016-04-01

    As rehabilitation specialists, physical therapists must continue to stay current with advances in technologies to provide appropriate rehabilitation protocols, improve patient outcomes, and be the preferred clinician of choice. To accomplish this vision, the physical therapy profession must begin to develop a culture of lifelong learning at the early stages of education and clinical training in order to embrace cutting-edge advancements such as stem cell therapies, tissue engineering, and robotics, to name a few. The purposes of this article are: (1) to provide a current perspective on faculty and graduate student awareness of regenerative rehabilitation concepts and (2) to advocate for increased integration of these emerging technologies within the doctor of physical therapy (DPT) curriculum. An online survey was designed to gauge awareness of principles in regenerative rehabilitation and to determine whether the topic was included and assessed in doctoral curricula. The survey yielded 1,006 responses from 82 DPT programs nationwide and indicated a disconnect in familiarity with the term "regenerative rehabilitation" and awareness of the inclusion of this material in the curriculum. To resolve this disconnect, the framework of the curriculum can be used to integrate new material via guest lecturers, interdisciplinary partnerships, and research opportunities. Successfully mentoring a generation of clinicians and rehabilitation scientists who incorporate new medical knowledge and technology into their own clinical and research practice depends greatly on sharing the responsibility among graduate students, professors, the American Physical Therapy Association (APTA), and DPT programs. Creating an interdisciplinary culture and integrating regenerative medicine and rehabilitation concepts into the curriculum will cultivate individuals who will be advocates for interprofessional behaviors and will ensure that the profession meets the goals stated in APTA Vision 2020.

  7. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU.

    PubMed

    Pellegrini, Graziella; Lambiase, Alessandro; Macaluso, Claudio; Pocobelli, Augusto; Deng, Sophie; Cavallini, Gian Maria; Esteki, Roza; Rama, Paolo

    2016-06-01

    In 1997, the human corneal epithelium was reconstructed in vitro and transplanted on patients. Later, it became a routine treatment, before regulations considered advanced therapy medicinal products and drugs on the same lines. Manufacturing, before and after good manufacturing practice setting, was established in different facilities and the clinical application in several hospitals. Advanced therapy medicinal products, including stem cells, are unique products with different challenges than other drugs: some uncertainties, in addition to benefit, cannot be avoided. This review will focus on all recent developments in the stem cell-based corneal therapy. PMID:27091398

  8. From discovery to approval of an advanced therapy medicinal product-containing stem cells, in the EU.

    PubMed

    Pellegrini, Graziella; Lambiase, Alessandro; Macaluso, Claudio; Pocobelli, Augusto; Deng, Sophie; Cavallini, Gian Maria; Esteki, Roza; Rama, Paolo

    2016-06-01

    In 1997, the human corneal epithelium was reconstructed in vitro and transplanted on patients. Later, it became a routine treatment, before regulations considered advanced therapy medicinal products and drugs on the same lines. Manufacturing, before and after good manufacturing practice setting, was established in different facilities and the clinical application in several hospitals. Advanced therapy medicinal products, including stem cells, are unique products with different challenges than other drugs: some uncertainties, in addition to benefit, cannot be avoided. This review will focus on all recent developments in the stem cell-based corneal therapy.

  9. Cartilage tissue engineering: recent advances and perspectives from gene regulation/therapy.

    PubMed

    Li, Kuei-Chang; Hu, Yu-Chen

    2015-05-01

    Diseases in articular cartilages affect millions of people. Despite the relatively simple biochemical and cellular composition of articular cartilages, the self-repair ability of cartilage is limited. Successful cartilage tissue engineering requires intricately coordinated interactions between matrerials, cells, biological factors, and phycial/mechanical factors, and still faces a multitude of challenges. This article presents an overview of the cartilage biology, current treatments, recent advances in the materials, biological factors, and cells used in cartilage tissue engineering/regeneration, with strong emphasis on the perspectives of gene regulation (e.g., microRNA) and gene therapy.

  10. Access to advanced therapy medicinal products in the EU: where do we stand?

    PubMed

    Mahalatchimy, A

    2011-05-01

    The European Union has a public health strategy and will generally ensure in all its policies and activities a "high level of human health protection". The new Regulation (EC) n 1394/2007 on advanced therapy medicinal products (ATMP), stems from this global policy and aims to harmonise access to the ATMP market. A real will for the harmonisation is clearly expressed in legal texts and enforced in the implementable procedures and requirements. However, several barriers remain. On the one hand, the scope of the ATMP Regulation is limited. On the other hand, Member States benefit from a wide margin of action.

  11. Participation of patients in the development of advanced therapy medicinal products.

    PubMed

    Bignami, F; Kent, A J; Lipucci di Paola, M; Meade, N

    2011-07-01

    An increasing number of advanced therapy medicinal products (ATMPs) are under development and in clinical trials. Patients are central to this progress. In research, patients have funded, catalysed, coordinated and led projects. In regulation, patient groups have contributed to the creation of the political momentum for regulation of ATMPs, contributed to the debate and now participate in the regulatory process. Once licensed, patients will have a role in the pharmacovigilance, health technology assessment and reimbursement arrangements for these products. Patient groups contribute valuably as equal stakeholders at every step of the development of an ATMP.

  12. Targeted therapy for advanced gastric cancer: A review of current status and future prospects

    PubMed Central

    Kanat, Ozkan; O’Neil, Bert; Shahda, Safi

    2015-01-01

    In the West in particular, the vast majority of gastric cancer (GC) patients present with advanced-stage disease. Although combination chemotherapy is still the most important component of treatment for these patients, it confers a modest survival advantage. Recently, increased knowledge of the key molecular signaling pathways involved in gastric carcinogenesis has led to the discovery of specific molecular-targeted therapeutic agents. Some of these agents such as trastuzumab and ramucirumab have changed the treatment paradigm for this disease. In this paper, we will summarize the current clinical status of targeted drug therapy in the management of GC. PMID:26690491

  13. Advances in methodology and current prospects for primary drug therapies for Alzheimer's disease.

    PubMed

    Knopman, D S

    2000-01-01

    There has been gratifying progress in the development of drugs for Alzheimer's disease (AD). Even though the current generation of medications, the cholinesterase inhibitors (CEIs), has produced only modest benefits, our concept of an "effective" therapy has matured considerably over this time. A less visible but equally important advance has been a quantum leap in expertise in clinical trial methodology. This chapter reviews the methodological underpinnings of clinical trials in AD: patient selection issues, key design issues, and an overview of currently available agents and the prospects for drugs of the future.

  14. Eight-drug/radiation therapy program (MOPP/ABDV/RT) for advanced Hodgkin's disease

    SciTech Connect

    Straus, D.J.; Myers, J.; Passe, S.

    1980-07-15

    Eighty-four evaluable patients with advanced Hodgkin's disease (Stages IIB, IIIA age > 35 or mixed cellularity or lymphocyte depletion histology, IIIB, IVA, and IVB) were treated with alternating monthly MOPP and Adriamycin, bleomycin, dacarbazine, and vinblastine (ABDV). Radiation therapy (RT), 2000 rads in two weeks, was given to areas of initial bulky disease in untreated patients. Complete remission (CR) rates were 80% for previously untreated, 65% for prior RT or minimal chemotherapy treated, and 50% for heavily pretreated patients. Among 49 previously untreated patients there were no primary treatment failures. The estimated two-year relapse rate for the CR group was 9%. The therapeutic effectiveness of this program may have been due to either or both of the following elements: (1) two non-cross-resistant drug combinations; (2) low dose adjuvant RT to initial sites of bulky disease. These early results are among the best reported for the treatment of advanced Hodgkin's disease.

  15. New molecular targeted therapies for advanced non-small-cell lung cancer

    PubMed Central

    Méndez, Míriam; Custodio, Ana; Provencio, Mariano

    2011-01-01

    Non-small-cell lung cancer (NSCLC) is a uniformly fatal disease and most patients will present with advanced stage. Treatment outcomes remain unsatisfactory, with low long-term survival rates. Standard treatment, such as palliative chemotherapy and radiotherapy, offers a median survival not exceeding 1 year. Hence, considerable efforts have started to be made in order to identify new biological agents which may safely and effectively be administered to advanced NSCLC patients. Two cancer cell pathways in particular have been exploited, the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. However, novel targeted therapies that interfere with other dysregulated pathways in lung cancer are already in the clinic. This review outlines the most promising research approaches to the treatment of NSCLC, discussed according to the specific molecular pathway targeted. PMID:22263060

  16. Genitourinary tumours in the targeted therapies era: new advances in clinical practice and future perspectives.

    PubMed

    Messina, Carlo; Buzzatti, Giulia; Dellepiane, Chiara; Cavo, Alessia; Tolomeo, Francesco; Cattrini, Carlo; Boccardo, Francesco

    2016-11-01

    Genitourinary cancers represent a heterogeneous group of malignancies arising from genitourinary tract, and are responsible for almost 359 000 newly diagnosed cases and 58 420 related deaths in USA. Continuous advances in cancer genetics and genomics have contributed towards changing the management paradigms of these neoplasms. Neoangiogenesis, through the activation of the tyrosine-kinase receptors signalling pathways, represents the key mediator event in promoting tumour proliferation, differentiation, invasiveness and motility. In the last decade, several treatments have been developed with the specific aim of targeting different cell pathways that have been recognized to drive tumour progression. The following review attempts to provide a comprehensive overview of the literature, focusing on new advances in targeted therapies for genitourinary tumours. Furthermore, the promising results of the latest clinical trials and future perspectives will be discussed.

  17. Exceptional Response to Systemic Therapy in Advanced Metastatic Gastric Cancer: A Case Report

    PubMed Central

    Hartley, Marion; Manning, Maria A; Carroll, John E; Xiu, Joanne; Smaglo, Brandon G; Mikhail, Sameh; Salem, Mohamed E

    2016-01-01

    Gastroesophageal adenocarcinomas represent one of the top five most common types of cancer worldwide. Despite significant advancement, it is still not known which first-line chemotherapy option is best matched to an individual patient. The vast advances in molecular biology have led to the discovery of many potential predictive biomarkers, such as HER-2 neu, thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and topoisomerase-1 (TOPO1). These markers could allow us to select treatment based on an individual’s tumor profile, resulting in an improvement of outcome. Our report highlights two patients with metastatic gastric cancer that achieved an exceptional response with traditional therapy and provides insights into the future perspectives of molecular profile-directed chemotherapy. PMID:26918225

  18. Nutritional rehabilitation in patients with advanced head and neck cancer receiving radiation therapy.

    PubMed

    Daly, J M; Hearne, B; Dunaj, J; LePorte, B; Vikram, B; Strong, E; Green, M; Muggio, F; Groshen, S; DeCosse, J J

    1984-10-01

    maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.

  19. Pulmonary thromboembolism in cats.

    PubMed

    Schermerhorn, Thomas; Pembleton-Corbett, Julie R; Kornreich, Bruce

    2004-01-01

    Pulmonary thromboembolism (PTE) is rarely diagnosed in cats, and the clinical features of the disease are not well known. PTE was diagnosed at postmortem examination in 17 cats, a prevalence of 0.06% over a 24-year period. The age of affected cats ranged from 10 months to 18 years, although young (<4 years) and old (>10 years) cats were more commonly affected than were middle-aged cats. Males and females were equally affected. The majority of cats with PTE (n = 16) had concurrent disease, which was often severe. The most common diseases identified in association with PTE were neoplasia, anemia of unidentified cause, and pancreatitis. Cats with glomerulonephritis, encephalitis, pneumonia, heart disease, and hepatic lipidosis were also represented in this study. Most cats with PTE demonstrated dyspnea and respiratory distress before death or euthanasia, but PTE was not recognized ante mortem in any cat studied. In conclusion, PTE can affect cats of any age and is associated with a variety of systemic and inflammatory disorders. It is recommended that the same clinical criteria used to increase the suspicion of PTE in dogs should also be applied to cats. PMID:15320593

  20. Idiopathic epilepsy in dogs and cats.

    PubMed

    Thomas, William B

    2010-01-01

    Idiopathic epilepsy is the most common brain disease in dogs and also occurs in cats. Optimal management entails an accurate diagnosis and appropriate drug therapy. In dogs, either phenobarbital or bromide is appropriate as initial therapy. Phenobarbital is the drug of choice for cats. Several other drugs including zonisamide and levetiracetam have the advantage of fewer side effects and are being increasingly used in veterinary medicine. Treatment is successful in most cases, allowing the pet and client to enjoy a good quality of life.

  1. Pilot study of local hyperthermia, radiation therapy, etanidazole, and cisplatin for advanced superficial tumours.

    PubMed

    Bornstein, B A; Herman, T S; Hansen, J L; Buswell, L; Zouranjian, P S; Fraser, S M; Teicher, B A; Svensson, G K; Coleman, C N

    1995-01-01

    Five patients (six hyperthermia sites) with advanced superficial tumours were treated with combined etanidazole, cisplatin, local hyperthermia, and radiation therapy as part of a Phase I pilot study. Treatment was given once weekly and consisted of etanidazole 3 gm/m2 IV bolus, cisplatin 50 mg/m2 IV bolus, hyperthermia for 60 min with a target temperature of 43 degrees C, and radiation therapy 500 cGy/fraction (median total dose 3000 cGy) for a total of six weeks. Blood levels of etanidazole were taken during treatment at week 1 and week 4. Etanidazole drug exposure was calculated using the trapezoidal rule and expressed as the area under the curve (AUC) of plasma concentration x time. Five of six treatment sites had received prior irradiation. Prior chemotherapy had been given in three patients and tamoxifen therapy given in the other two patients. The median follow-up time is 34 months; 3/5 patients have died of disease. The most significant toxicity was grade I or II nausea and vomiting associated with 19/32 treatments (59%) and a second degree burn in 2/6 fields. None of the five patients experienced peripheral neuropathy, skin ulceration, or needed surgical repair. In addition, there was mild renal toxicity; pharmacokinetic analysis showed a 28-75% increase in the week 1 to week 4 AUC in three patients, all of whom had a decrease in creatinine clearance over the same time of 15-47%. This pilot study suggests this combined modality therapy can be delivered without major complications and that renal function, determined by creatinine clearance, affects clearance of etanidazole and alters the AUC. Therefore, monitoring renal function is important in patients receiving etanidazole in addition to other nephrotoxic agents such as cisplatin. The impact of etanidazole on the therapeutic index of hyperthermia, radiation therapy and cisplatin may be worth of study, especially since a positive interaction between these modalities is found in laboratory models. PMID

  2. Advances in targeted and immunobased therapies for colorectal cancer in the genomic era

    PubMed Central

    Seow, Heng Fong; Yip, Wai Kien; Fifis, Theodora

    2016-01-01

    Targeted therapies require information on specific defective signaling pathways or mutations. Advances in genomic technologies and cell biology have led to identification of new therapeutic targets associated with signal-transduction pathways. Survival times of patients with colorectal cancer (CRC) can be extended with combinations of conventional cytotoxic agents and targeted therapies. Targeting EGFR- and VEGFR-signaling systems has been the major focus for treatment of metastatic CRC. However, there are still limitations in their clinical application, and new and better drug combinations are needed. This review provides information on EGFR and VEGF inhibitors, new therapeutic agents in the pipeline targeting EGFR and VEGFR pathways, and those targeting other signal-transduction pathways, such as MET, IGF1R, MEK, PI3K, Wnt, Notch, Hedgehog, and death-receptor signaling pathways for treatment of metastatic CRC. Additionally, multitargeted approaches in combination therapies targeting negative-feedback loops, compensatory networks, and cross talk between pathways are highlighted. Then, immunobased strategies to enhance antitumor immunity using specific monoclonal antibodies, such as the immune-checkpoint inhibitors anti-CTLA4 and anti-PD1, as well as the challenges that need to be overcome for increased efficacy of targeted therapies, including drug resistance, predictive markers of response, tumor subtypes, and cancer stem cells, are covered. The review concludes with a brief insight into the applications of next-generation sequencing, expression profiling for tumor subtyping, and the exciting progress made in in silico predictive analysis in the development of a prescription strategy for cancer therapy. PMID:27099521

  3. Notoedres cati in cats and its management.

    PubMed

    Sivajothi, S; Sudhakara Reddy, B; Rayulu, V C; Sreedevi, C

    2015-06-01

    Notoedres cati was observed in two domestic cats. Cats exhibited crust formation, hyperkeratosis, alopecia and intense pruritus. Distribution of lesions observed at the ear margins, face, and legs. Owners also had intense pruritus over the hands, small erythematic crusted papules on the wrists and both the legs. Laboratory examination of skin scrapings from the cat revealed the presence of ova, adult mites of N. cati. The infected cats were treated with weekly twice oral administration of ivermectin at 200 μg/kg body weight, oral administration of 2 ml of multi-vitamin and mineral syrup daily. Improvement was noticed by complete clinical recovery along with absence of mites in skin scrapings, after completion of four doses of oral ivermectin along with supportive therapy.

  4. WE-D-BRD-01: Innovation in Radiation Therapy Delivery: Advanced Digital Linac Features

    SciTech Connect

    Xing, L; Wong, J; Li, R

    2014-06-15

    Last few years has witnessed significant advances in linac technology and therapeutic dose delivery method. Digital linacs equipped with high dose rate FFF beams have been clinically implemented in a number of hospitals. Gated VMAT is becoming increasingly popular in treating tumors affected by respiratory motion. This session is devoted to update the audience with these technical advances and to present our experience in clinically implementing the new linacs and dose delivery methods. Topics to be covered include, technical features of new generation of linacs from different vendors, dosimetric characteristics and clinical need for FFF-beam based IMRT and VMAT, respiration-gated VMAT, the concept and implementation of station parameter optimized radiation therapy (SPORT), beam level imaging and onboard image guidance tools. Emphasis will be on providing fundamental understanding of the new treatment delivery and image guidance strategies, control systems, and the associated dosimetric characteristics. Commissioning and acceptance experience on these new treatment delivery technologies will be reported. Clinical experience and challenges encountered during the process of implementation of the new treatment techniques and future applications of the systems will also be highlighted. Learning Objectives: Present background knowledge of emerging digital linacs and summarize their key geometric and dosimetric features. SPORT as an emerging radiation therapy modality specifically designed to take advantage of digital linacs. Discuss issues related to the acceptance and commissioning of the digital linacs and FFF beams. Describe clinical utility of the new generation of digital linacs and their future applications.

  5. The use of music therapy to address the suffering in advanced cancer pain.

    PubMed

    Magill, L

    2001-01-01

    Pain associated with advanced cancer is multifaceted and complex, and is influenced by physiological, psychological, social, and spiritual phenomena. Suffering may be identified in patients when pain is associated with impending loss, increased dependency, and an altered understanding of one's existential purpose. Comprehensive pain management aims to address problematic symptoms in order to improve comfort, peace of mind, and quality of life. Music therapy is a treatment modality of great diversity that can offer a range of benefits to patients with advanced cancer pain and symptoms of suffering. Music therapists perform comprehensive assessments that include reviews of social, cultural, and medical history; current medical status; and the ways in which emotions are affecting the pain. A variety of music therapy techniques may be used, including vocal techniques, listening, and instrumental techniques. These techniques provide opportunities for exploration of the feelings and issues compounding the pain experience. Case examples are presented to demonstrate the "lifting", "transporting", and "bringing of peace" qualities of music that offer patients moments of release, reflection, and renewal. PMID:11816757

  6. Recent Advances in the Diagnosis and Management of Cirrhosis-Associated Cardiomyopathy in Liver Transplant Candidates: Advanced Echo Imaging, Cardiac Biomarkers, and Advanced Heart Failure Therapies

    PubMed Central

    Farr, Maryjane; Schulze, Paul Christian

    2014-01-01

    Patients with end-stage liver disease in need of liver transplantation increasingly are older with a greater burden of cardiac disease and other co-morbidities, which may increase perioperative risk and adversely affect long-term prognosis. Cirrhosis of any etiology manifests hemodynamically as a state of low systemic vascular resistance, with high peripheral, but low central blood volume, leading to a state of neurohormonal activation and high cardiac output, which may adversely affect cardiac reserve under extreme perioperative stress, aptly termed cirrhosis-associated or cirrhotic cardiomyopathy. Evidence of asymptomatic cirrhotic cardiomyopathy may be found in subtle electrocardiographic and echocardiographic changes, but may progress to severe heart failure under the demands of bleeding and transfusions, vasopressors, rebounding peripheral vascular resistance, withdrawal of cardioprotective beta-blockers and mineralocorticoid antagonists, exacerbated by sepsis or systemic inflammatory response syndrome. This review will add to the current body of literature on cirrhotic cardiomyopathy by focusing on the role of advanced echocardiographic imaging techniques, cardiac biomarkers, and advanced heart failure therapies available to manage patients with cirrhotic cardiomyopathy while waiting for liver transplant and during the perioperative period. PMID:25657603

  7. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  8. Planned preoperative radiation therapy for advanced laryngeal carcinoma. [/sup 60/Co

    SciTech Connect

    Kazem, I.; van den Broek, P.; Huygen, P.L.M.

    1982-09-01

    One hundred ten patients with predominantly advanced laryngeal carcinoma were treated in the period 1969-1978 with planned preoperative radiation therapy followed by surgery. Site distribution was: 63 supraglottic, 26 glottic, 15 transglottic and 6 subglottic. There were 4 Stage II patients, 66 Stage III and 40 Stage IV. Preoperative radiation therapy consisted of Telecobalt irradiation to a total dose of 25 Gy given to a target volume encompassing the larynx and regional neck nodes, given in 5 equal daily fractions of 5 Gy in 5 consecutive days. Surgery was performed 2 days later. Total laryngectomy was performed on 48 patients, total laryngectomy with neck dissection on 55 patients, supraglottic laryngectomy on 5 and supraglottic laryngectomy with neck dissection on 2 patients. Crude actuarial 5 and 10 year survival probability for the whole group is 71 and 61%, respectively. The corrected 5 and 10 year survival is 75%. For patients with T/sub 3/-T/sub 4/-N/sub 0/ tumors 5 and 10 year survival probability is: crude 65 and 58%, and corrected 70% respectively. For T/sub 3/-T/sub 4/-N/sub +/ crude: 75 and 60% and corrected: 78%. Of 110 patients, one died postoperative, three died of intercurrent disease, five died as a result of second malignancy, and 23 died of their larynx carcinoma: 12/23 because of locoregional failure, and 11/23 because of distant metastasis. We concluded that short intensive preoperative radiation therapy and surgery offer a high cure rate in the treatment of advanced resectable laryngeal carcinoma. The merits of this technique are outlined in the text.

  9. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  10. Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

    SciTech Connect

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-10-01

    Purpose: To evaluate the feasibility of delivering experimental radiation therapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials: After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by x-ray CT. With this technique we delineated the pancreas and both orthotopic xenografts and genetically engineered disease. Computed tomographic imaging was validated by comparison with magnetic resonance imaging. Therapeutic radiation was delivered via a 1-cm diameter field. Selective x-ray radiation therapy of the noninvasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360° arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic x-ray radiation therapy to orthotopic tumors. Results: Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times after treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions: This advance permits evaluation of radiation planning and dosing parameters. Accurate noninvasive longitudinal imaging and monitoring of tumor progression and therapeutic response in preclinical models is now possible and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

  11. Toxoplasmosis in two cats with inflammatory intestinal disease.

    PubMed

    Peterson, J L; Willard, M D; Lees, G E; Lappin, M R; Dieringer, T; Floyd, E

    1991-08-15

    Lymphocytic-plasmacytic enteritis, a chronic inflammatory intestinal disease, was diagnosed in 2 cats. In 1 cat, recurrence of clinical signs after initiating treatment was attributed to relapse of the inflammatory intestinal disease, but was found to be attributable to relapsing toxoplasmosis secondary to immunosuppressive drug therapy. Treatment with clindamycin resolved the recurrent toxoplasmosis. In the second cat, clinical signs of toxoplasmosis did not develop, but serologic testing yielded evidence of active toxoplasmosis. Treatment with clindamycin caused the titers to decrease. Relapsing toxoplasmosis may be responsible for apparent resistance to treatment in cats for inflammatory intestinal disease being treated with immunosuppressive drugs.

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

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren 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{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 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.

  13. Cat-scratch Disease.

    PubMed

    Klotz, Stephen A; Ianas, Voichita; Elliott, Sean P

    2011-01-15

    Cat-scratch disease is a common infection that usually presents as tender lymphadenopathy. It should be included in the differential diagnosis of fever of unknown origin and any lymphadenopathy syndrome. Asymptomatic, bacteremic cats with Bartonella henselae in their saliva serve as vectors by biting and clawing the skin. Cat fleas are responsible for horizontal transmission of the disease from cat to cat, and on occasion, arthropod vectors (fleas or ticks) may transmit the disease to humans. Cat-scratch disease is commonly diagnosed in children, but adults can present with it as well. The causative microorganism, B. henselae, is difficult to culture. Diagnosis is most often arrived at by obtaining a history of exposure to cats and a serologic test with high titers (greater than 1:256) of immunoglobulin G antibody to B. henselae. Most cases of cat-scratch disease are self-limited and do not require antibiotic treatment. If an antibiotic is chosen, azithromycin has been shown in one small study to speed recovery. Infrequently, cat-scratch disease may present in a more disseminated form with hepatosplenomegaly or meningoencephalitis, or with bacillary angiomatosis in patients with AIDS.

  14. GMP facilities for manufacturing of advanced therapy medicinal products for clinical trials: an overview for clinical researchers.

    PubMed

    Alici, Evren; Blomberg, Pontus

    2010-12-01

    To be able to produce advanced therapy medicinal products, compliance with regulatory standards while maintaining flexibility is mandatory. For this purpose, careful planning is vital in the design or upgrade of a facility. Similarly, extensive foresight is elemental to anticipate upcoming needs and requirements. Failing this may lead to the facility's in-ability to meet the demands. In this chapter we aimed to outline the current issues with regards to the European Union Directives (EUD) and the proposal for Advanced Therapies, which are of importance to cellular and gene therapy facilities in Europe. This chapter is an attempt to elucidate what the minimum requirements for GMP facilities for cell and gene therapy products are and what is considered necessary to comply with the regulations in Europe.

  15. The committee for advanced therapies' of the European Medicines Agency reflection paper on management of clinical risks deriving from insertional mutagenesis.

    PubMed

    Aiuti, Alessandro; Cossu, Giulio; de Felipe, Pablo; Galli, Maria Cristina; Narayanan, Gopalan; Renner, Matthias; Stahlbom, Axel; Schneider, Christian K; Voltz-Girolt, Caroline

    2013-06-01

    In the European Union, the Committee for Advanced Therapies of the European Medicines Agency takes the lead in the scientific assessment for marketing authorization applications for advanced therapy medicinal products, which include gene therapy medicinal products, somatic cell therapy medicinal products, and tissue-engineered products. The Committee for Advanced Therapies also takes the lead in defining the scientific framework for the quality, nonclinical and clinical development of such products. This reflection paper represents the Committee's current thinking on management of clinical risks deriving from insertional mutagenesis. A multidisciplinary approach to insertional mutagenesis is provided. This reflection paper has been adopted by the committee in its April 2013 meeting.

  16. Advances in regenerative therapies for spinal cord injury: a biomaterials approach

    PubMed Central

    Tsintou, Magdalini; Dalamagkas, Kyriakos; Seifalian, Alexander Marcus

    2015-01-01

    Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mechanism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing research interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaffold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerative/neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction. PMID:26109946

  17. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided. PMID:26807609

  18. Advances in Neurotrophic Factor and Cell-Based Therapies for Parkinson's Disease: A Mini-Review.

    PubMed

    Staudt, Michael D; Di Sebastiano, Andrea R; Xu, Hu; Jog, Mandar; Schmid, Susanne; Foster, Paula; Hebb, Matthew O

    2016-01-01

    Parkinson's disease (PD) affects an estimated 7-10 million people worldwide and remains without definitive or disease-modifying treatment. There have been many recent developments in cell-based therapy (CBT) to replace lost circuitry and provide chronic biological sources of therapeutic agents to the PD-affected brain. Early neural transplantation studies underscored the challenges of immune compatibility, graft integration and the need for renewable, autologous graft sources. Neurotrophic factors (NTFs) offer a potential class of cytoprotective pharmacotherapeutics that may complement dopamine (DA) replacement and CBT strategies in PD. Chronic NTF delivery may be an integral goal of CBT, with grafts consisting of autologous drug-producing (e.g., DA, NTF) cells that are capable of integration and function in the host brain. In this mini-review, we outline the past experience and recent advances in NTF technology and CBT as promising and integrated approaches for the treatment of PD. PMID:26330171

  19. White paper on how to go forward with cell-based advanced therapies in Europe.

    PubMed

    Erben, Reinhold G; Silva-Lima, Beatriz; Reischl, Ilona; Steinhoff, Gustav; Tiedemann, Gudrun; Dalemans, Wilfried; Vos, Alexander; Janssen, Rob T A; Le Blanc, Katarina; van Osch, Gerjo J V M; Luyten, Frank P

    2014-10-01

    The current White paper summarizes the discussions and exchange of experiences during the first European Interdisciplinary Summit on Cell-Based ATMPs held in Vienna, Austria, May 02-03, 2013. The meeting was supported by the Research Networking Programme REMEDIC (regenerative medicine) funded by the European Science Foundation and by the British Medical Research Council. To improve the competitiveness of Europe in the field of cell-based Advanced Medicinal Therapy Products (ATMPs), the following key issues were identified during the meeting: removal of national hurdles in the European Union, harmonization of national and subnational differences in Hospital Exemption rules, improved treatment algorithms for reimbursement, better knowledge on the mode of action, predictive preclinical efficacy and safety testing, need for innovative systems for preclinical testing, appropriate product characterization, manufacturing with cost of goods in mind, and appropriate design of clinical trials.

  20. The Role of Interventional Radiology in the Management of Deep Venous Thrombosis: Advanced Therapy

    SciTech Connect

    O'Sullivan, Gerard J.

    2011-06-15

    Deep vein thrombosis (DVT) is often managed with a health care pathway that funnels patients to anticoagulation therapy alone. This 'usual treatment' is designed to stop propagation and embolisation of venous thrombus but not remove it. Surgical thrombectomy was once the only option in severe cases in which limbs were threatened, but thrombus removal is no longer restricted to emergency cases. Interventional radiologists are now using advanced endovascular techniques to achieve thrombus removal in a minimally invasive manner in a very short treatment time, thereby quickly restoring patency, relieving acute symptoms, and potentially limiting the subsequent development of postthrombotic syndrome when followed with anticoagulation and compression regimens. This article provides an overview of the interventions available for treating DVT. One of the newer 'single-session' techniques is isolated pharmacomechanical thrombolysis, which is described here in detail with supporting cases.

  1. The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

    PubMed

    Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

    2016-02-01

    Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided.

  2. Evaluation of advanced cooling therapy's esophageal cooling device for core temperature control.

    PubMed

    Naiman, Melissa; Shanley, Patrick; Garrett, Frank; Kulstad, Erik

    2016-05-01

    Managing core temperature is critical to patient outcomes in a wide range of clinical scenarios. Previous devices designed to perform temperature management required a trade-off between invasiveness and temperature modulation efficiency. The Esophageal Cooling Device, made by Advanced Cooling Therapy (Chicago, IL), was developed to optimize warming and cooling efficiency through an easy and low risk procedure that leverages heat transfer through convection and conduction. Clinical data from cardiac arrest, fever, and critical burn patients indicate that the Esophageal Cooling Device performs very well both in terms of temperature modulation (cooling rates of approximately 1.3°C/hour, warming of up to 0.5°C/hour) and maintaining temperature stability (variation around goal temperature ± 0.3°C). Physicians have reported that device performance is comparable to the performance of intravascular temperature management techniques and superior to the performance of surface devices, while avoiding the downsides associated with both. PMID:27043177

  3. An Advanced Pharmacy Practice Experience in a Student-Staffed Medication Therapy Management Call Center

    PubMed Central

    Hall, Anna M.; Roane, Teresa E.; Mistry, Reena

    2012-01-01

    Objective. To describe the implementation of an advanced pharmacy practice experience (APPE) in medication therapy management (MTM) designed to contribute to student pharmacists’ confidence and abilities in providing MTM. Design. Sixty-four student pharmacists provided MTM services during an APPE in a communication and care center. Assessment. Students conducted 1,495 comprehensive medication reviews (CMRs) identifying 6,056 medication-related problems. Ninety-eight percent of the students who completed a survey instrument (52 of 53) following the APPE expressed that they had the necessary knowledge and skills to provide MTM services. Most respondents felt that pharmacist participation in providing Medicare MTM could move the profession of pharmacy forward and that pharmacists will have some role in deciding the specific provisions of the Medicare MTM program (92% and 91%, respectively). Conclusion. Students completing the MTM APPE received patient-centered experiences that supplemented their confidence, knowledge, and skill in providing MTM services in the future. PMID:22919086

  4. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  5. Tuberculosis--advances in development of new drugs, treatment regimens, host-directed therapies, and biomarkers.

    PubMed

    Wallis, Robert S; Maeurer, Markus; Mwaba, Peter; Chakaya, Jeremiah; Rustomjee, Roxana; Migliori, Giovanni Battista; Marais, Ben; Schito, Marco; Churchyard, Gavin; Swaminathan, Soumya; Hoelscher, Michael; Zumla, Alimuddin

    2016-04-01

    Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to

  6. Advanced Pancreatic Cancer: Flourishing Novel Approaches in the Era of Biological Therapy

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-09-01

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

  8. Advanced malignant solitary fibrous tumor in pelvis responding to radiation therapy.

    PubMed

    Kawamura, Shinobu; Nakamura, Takafumi; Oya, Takeshi; Ishizawa, Shin; Sakai, Yuta; Tanaka, Tomonori; Saito, Shigeru; Fukuoka, Junya

    2007-04-01

    Solitary fibrous tumor (SFT) is a rare spindle cell neoplasm that is benign in most cases. Although SFT was first recognized to arise only in the pleura, recent reports indicate that SFT can involve a wide range of anatomical sites. To date, 17 cases of pelvic SFT have been reported. Herein is reported a case of a 74-year-old woman with a giant malignant SFT in the pelvis. Along with massive invasion to adjacent organs and multiple lung metastases detected on radiography, biopsy from the tumor through the vaginal wall showed malignant looking spindle-cell neoplasm with increased cellularity, areas of necrosis, and high mitotic activity (5/10 high-power fields). Immunohistochemically, the tumor cells were diffusely and strongly positive for CD34, CD99, and bcl-2. Based on pathological features and clinical presentation, diagnosis of malignant SFT was made. The patient received systemic and the intra-arterial chemotherapy followed by whole pelvic radiation therapy (50 Gy). Initial chemotherapies failed to control the tumor. Afterwards, improvement was observed radiologically and pathologically in the 12 months' follow up after the radiation therapy. This is the first report related to therapeutic remarks on advanced malignant SFT.

  9. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

    PubMed Central

    Chen, Zhi-Yi; Wang, Yi-Xiang; Lin, Yan; Zhang, Jin-Shan; Yang, Feng; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy. PMID:24689058

  10. Invited review: Stem cells and muscle diseases: advances in cell therapy strategies.

    PubMed

    Negroni, Elisa; Gidaro, Teresa; Bigot, Anne; Butler-Browne, Gillian S; Mouly, Vincent; Trollet, Capucine

    2015-04-01

    Despite considerable progress to increase our understanding of muscle genetics, pathophysiology, molecular and cellular partners involved in muscular dystrophies and muscle ageing, there is still a crucial need for effective treatments to counteract muscle degeneration and muscle wasting in such conditions. This review focuses on cell-based therapy for muscle diseases. We give an overview of the different parameters that have to be taken into account in such a therapeutic strategy, including the influence of muscle ageing, cell proliferation and migration capacities, as well as the translation of preclinical results in rodent into human clinical approaches. We describe recent advances in different types of human myogenic stem cells, with a particular emphasis on myoblasts but also on other candidate cells described so far [CD133+ cells, aldehyde dehydrogenase-positive cells (ALDH+), muscle-derived stem cells (MuStem), embryonic stem cells (ES) and induced pluripotent stem cells (iPS)]. Finally, we provide an update of ongoing clinical trials using cell therapy strategies.

  11. Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib.

    PubMed

    Germano, D; Tinessa, V; Barletta, E; Cannella, L; Daniele, B

    2013-11-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Worldwide progressive population aging demands consensus development for decision making when treating elderly patients. Age itself might not be a critical determinant for the selection of a therapeutic option. In the past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and the involvement of a number of pathways, including angiogenesis, aberrant signal transduction, and dysregulated cell cycle control, have been demonstrated, leading to evaluation of the activity and toxicity of some of the new molecularly targeted agents. Sorafenib was demonstrated to significantly increase the survival of patients with advanced HCC in two prospective, randomized, placebo-controlled trials. Subsequently, a number of retrospective or prospective studies have indicated that the effectiveness of sorafenib therapy in the treatment of HCC is similar in elderly and non-elderly patients. The aim of this review is to describe the impact of age on the effects of sorafenib-targeted therapy in patients with HCC, and the next treatment options with new targeted agents (everolimus, tivantinib, linifanib, etc.). PMID:24097332

  12. Advances in image-guided radiation therapy-the role of PET-CT

    SciTech Connect

    Heron, Dwight E. . E-mail: heronD2@upmc.edu; Smith, Ryan P.; Andrade, Regiane S.

    2006-04-01

    In the era of image-guided radiation therapy (IGRT), the greatest challenge remains target delineation, as the opportunity to maximize cures while simultaneously decreasing radiation dose to the surrounding normal tissues is to be realized. Over the last 2 decades, technological advances in radiographic imaging, biochemistry, and molecular biology have played an increasing role in radiation treatment planning, delivery, and evaluation of response. Previously, fluoroscopy formed the basis of radiation treatment planning. Beginning in the late 1980s, computed tomography (CT) has become the basis for modern radiation treatment planning and delivery, coincident with the rise of 3-dimensional conformal radiation therapy (3DCRT). Additionally, multi-modality anatomic imaging registration was the solution pursued to augment delineation of tumors and surrounding structures on CT-based treatment planning. Although these imaging modalities provide the customary anatomic details necessary for radiation treatment planning, they have limitations, including difficulty with identification of small tumor deposits, tumor extension, and distinction from scar tissues. To overcome these limitations, PET and, more recently, PET-CT have been innovative regarding the extent of disease appraisal, target delineation in the treatment planning, and assessment of therapy response. We review the role of functional imaging in IGRT as it reassures transformations on the field of radiation oncology. As we move toward the era of IGRT, the use of multi-modality imaging fusion, and the introduction of more sensitive and specific PET-CT tracers may further assist target definition. Furthermore, the potential to predict early outcome or even detect early recurrence of tumor, may allow for the tailoring of intervention in cancer patients. The convergence of a biological target volume, and perhaps multi-tracer tumor, molecular, and genetic profile tumors will probably be vital in cancer treatment

  13. Energy Therapies in Advanced Practice Oncology: An Evidence-Informed Practice Approach

    PubMed Central

    Potter, Pamela J.

    2013-01-01

    Advanced practitioners in oncology want patients to receive state-of-the-art care and support for their healing process. Evidence-informed practice (EIP), an approach to evaluating evidence for clinical practice, considers the varieties of evidence in the context of patient preference and condition as well as practitioner knowledge and experience. This article offers an EIP approach to energy therapies, namely, Therapeutic Touch (TT), Healing Touch (HT), and Reiki, as supportive interventions in cancer care; a description of the author’s professional experience with TT, HT, and Reiki in practice and research; an overview of the three energy healing modalities; a review of nine clinical studies related to oncology; and recommendations for EIP. These studies demonstrate a response to previous research design critiques. Findings indicate a positive benefit for oncology patients in the realms of pain, quality of life, fatigue, health function, and mood. Directionality of healing in immune response and cell line studies affirms the usual explanation that these therapies bring harmony and balance to the system in the direction of health. Foremost, the research literature demonstrates the safety of these therapies. In order to consider the varieties of evidence for TT, HT, and Reiki, EIP requires a qualitative examination of patient experiences with these modalities, exploration of where these modalities have been integrated into cancer care and how the practice works in the oncology setting, and discovery of the impact of implementation on provider practice and self-care. Next steps toward EIP require fleshing out the experience of these modalities by patients and health-care providers in the oncology care setting. PMID:25031994

  14. Energy therapies in advanced practice oncology: an evidence-informed practice approach.

    PubMed

    Potter, Pamela J

    2013-05-01

    Advanced practitioners in oncology want patients to receive state-of-the-art care and support for their healing process. Evidence-informed practice (EIP), an approach to evaluating evidence for clinical practice, considers the varieties of evidence in the context of patient preference and condition as well as practitioner knowledge and experience. This article offers an EIP approach to energy therapies, namely, Therapeutic Touch (TT), Healing Touch (HT), and Reiki, as supportive interventions in cancer care; a description of the author's professional experience with TT, HT, and Reiki in practice and research; an overview of the three energy healing modalities; a review of nine clinical studies related to oncology; and recommendations for EIP. These studies demonstrate a response to previous research design critiques. Findings indicate a positive benefit for oncology patients in the realms of pain, quality of life, fatigue, health function, and mood. Directionality of healing in immune response and cell line studies affirms the usual explanation that these therapies bring harmony and balance to the system in the direction of health. Foremost, the research literature demonstrates the safety of these therapies. In order to consider the varieties of evidence for TT, HT, and Reiki, EIP requires a qualitative examination of patient experiences with these modalities, exploration of where these modalities have been integrated into cancer care and how the practice works in the oncology setting, and discovery of the impact of implementation on provider practice and self-care. Next steps toward EIP require fleshing out the experience of these modalities by patients and health-care providers in the oncology care setting. PMID:25031994

  15. Cell and Gene Therapy for the Beta-Thalassemias: Advances and Prospects.

    PubMed

    Mansilla-Soto, Jorge; Riviere, Isabelle; Boulad, Farid; Sadelain, Michel

    2016-04-01

    The beta-thalassemias are inherited anemias caused by mutations that severely reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a related beta-globin gene disorder, they are ideal candidates for performing a genetic correction in patient hematopoietic stem cells (HSCs). The most advanced approach utilizes complex lentiviral vectors encoding the human β-globin gene, as first reported by May et al. in 2000. Considerable progress toward the clinical implementation of this approach has been made in the past five years, based on effective CD34+ cell mobilization and improved lentiviral vector manufacturing. Four trials have been initiated in the United States and Europe. Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them developed a durable clonal expansion, which regressed after several years without transformation. Although globin lentiviral vectors have so far proven to be safe, this occurrence suggests that powerful insulators with robust enhancer-blocking activity will further enhance this approach. The combined discovery of Bcl11a-mediated γ-globin gene silencing and advances in gene editing are the foundations for another gene therapy approach, which aims to reactivate fetal hemoglobin (HbF) production. Its clinical translation will hinge on the safety and efficiency of gene targeting in true HSCs and the induction of sufficient levels of HbF to achieve transfusion independence. Altogether, the progress achieved over the past 15 years bodes well for finding a genetic cure for severe globin disorders in the next decade.

  16. Recent advances in managing chronic HCV infection: focus on therapy in patients with severe liver disease

    PubMed Central

    Maan, Raoel; van der Meer, Adriaan J.

    2016-01-01

    Chronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcome and reduced mortality rates. In the past few years, treatment has improved considerably by the implementation of direct-acting antivirals (DAAs). From 2014 onwards, sofosbuvir, simeprevir, daclatasvir, ledipasvir, paritaprevir, ombitasvir, and dasabuvir have been approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA). Regimens with various combinations of these new drugs, without the use of interferon (IFN), proved to be very effective and well tolerated, even among patients with advanced liver disease. Moreover, treatment duration could be shortened to 12 weeks in the majority of patients. The high costs of these DAAs, however, limit the availability of IFN-free therapy worldwide. Even in wealthy countries, it is deemed necessary to prioritize DAA treatment in order to limit the immediate impact on the health budget. As patients with advanced liver disease are in most need of HCV clearance, many countries decided to treat those patients first. In the current review, we focus on the currently available IFN-free treatment options for patients with cirrhosis. We discuss the virological efficacy as well as the clinical relevance of these regimens among this specific patient population. PMID:27006761

  17. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  18. Photodynamic Therapy (PDT) with Chemotherapy for Advanced Lung Cancer with Airway Stenosis.

    PubMed

    Kimura, Masakazu; Miyajima, Kuniharu; Kojika, Masakazu; Kono, Takafumi; Kato, Harubumi

    2015-10-23

    Intractable advanced lung cancer can be treated palliatively with photodynamic therapy (PDT) combined with chemotherapy to remove central and peripheral (lobar or segmental bronchi) bronchial stenosis and obstruction. We present data for 12 (eight men, four women) consecutive patients with 13 advanced non-small cell lung carcinomas in whom curative operations were contraindicated, who underwent PDT combined with chemotherapy for local control of the intraluminal lesions. The mean age was 73.3 years (range, 58-80 years), and the stages of cancer were IIA-IV. The median stenosis rates before treatment, one week post-treatment, and one month post-treatment were 60% (range, 30%-100%), 15% (range, 15%-99%), and 15% (range 15%-60%), respectively. The mean and median survival times were 9.3 and 5.9 months, respectively. The overall 1-year survival rate was 30.0%. No PDT-related morbidity or mortality occurred. In this single-institution study, all patients experienced improved symptoms and quality of life at one week after treatment; furthermore, an objective response was evidenced by the substantial increase in the openings of the bronchial lumen and prevention of obstructive pneumonia. Therefore, PDT with chemotherapy was useful and safe for the treatment of bronchial obstruction.

  19. Preoperative Kidney Tumor Embolization as Procedure for Therapy of Advanced Kidney Cancer

    PubMed Central

    Jaganjac, Suad; Schefe, L.; Avdagić, Edin; Spahović, Hajrudin; Hiros, Mustafa

    2014-01-01

    ABSTRACT Introduction: Preoperative kidney tumor embolization is standard procedure for therapy in advanced kidney cancer. Preoperative embolization has a goal to reduce intraoperative bleeding and also to shorten the time of surgery. Materials and methods: We retrospectively observed 50 patients between 2000-2011, in which the preoperative embolization was performed. Mean age of patients was 64 years. All patients with preoperative embolization were compared with the group of 51 patients from Urology Sarajevo, who underwent nephrectomy without preoperative embolization. Results: Symptoms that are dominating among patients were haematuria and pain. Analysis of mean size of tumors based on CT evaluation showed statistically significance in between the biggest size of tumors in group from Hamburg (9.11±3cm) and the smallest size of tumors in Sarajevo group (4.94±1.6cm) p=0.0001. Reason for this is difference in selection of patients for treatment in Hamburg from Sarajevo. Conclusion Kidney as functional finishing organ is extremely suitable for transcatheter therapeutic procedures. The gold standard in the treatment of advanced and metastatic tumor is the nephrectomy. As preparation for nephrectomy in metastatic cancer total capillary embolization is performed. After embolization, surgery is shorter, procedure can be done 24-48 hours after embolization or delayed nephrectomy done 2-3 weeks after the intervention. PMID:25568577

  20. Development of advanced therapies in Italy: Management models and sustainability in six Italian cell factories.

    PubMed

    Gaipa, Giuseppe; Introna, Martino; Golay, Josee; Nolli, Maria Luisa; Vallanti, Giuliana; Parati, Eugenio; Giordano, Rosaria; Romagnoli, Luca; Melazzini, Mario; Biondi, Andrea; Biagi, Ettore

    2016-04-01

    On November 10, 2014, the representatives of all six certified Good Manufacturing Practices (GMP) cell factories operating in the Lombardy Region of Italy convened a 1-day workshop in Milan titled "Management Models for the Development And Sustainability of Cell Factories: Public-Private Partnership?" The speakers and panelists addressed not only the many scientific, technological and cultural challenges faced by Lombardy Cell Factories, but also the potential impact of advanced therapy medicinal products (ATMPs) on public health and the role played by translational research in this process. Future perspectives for research and development (R&D) and manufacturing processes in the field of regenerative medicine were discussed as well. This report summarizes the most important issues raised by the workshop participants with particular emphasis on strengths and limitations of the R&D and manufacturing processes for innovative therapeutics in Lombardy and what can be improved in this context while maintaining GMP standards. The participants highlighted several strategies to translate patient-specific advanced therapeutics into scaled manufacturing products for clinical application. These included (i) the development of a synergistic interaction between public and private institutions, (ii) better integration with Italian regulatory agencies and (iii) the creation of a network among Lombardy cell factories and other Italian and European institutions.

  1. Development of advanced therapies in Italy: Management models and sustainability in six Italian cell factories.

    PubMed

    Gaipa, Giuseppe; Introna, Martino; Golay, Josee; Nolli, Maria Luisa; Vallanti, Giuliana; Parati, Eugenio; Giordano, Rosaria; Romagnoli, Luca; Melazzini, Mario; Biondi, Andrea; Biagi, Ettore

    2016-04-01

    On November 10, 2014, the representatives of all six certified Good Manufacturing Practices (GMP) cell factories operating in the Lombardy Region of Italy convened a 1-day workshop in Milan titled "Management Models for the Development And Sustainability of Cell Factories: Public-Private Partnership?" The speakers and panelists addressed not only the many scientific, technological and cultural challenges faced by Lombardy Cell Factories, but also the potential impact of advanced therapy medicinal products (ATMPs) on public health and the role played by translational research in this process. Future perspectives for research and development (R&D) and manufacturing processes in the field of regenerative medicine were discussed as well. This report summarizes the most important issues raised by the workshop participants with particular emphasis on strengths and limitations of the R&D and manufacturing processes for innovative therapeutics in Lombardy and what can be improved in this context while maintaining GMP standards. The participants highlighted several strategies to translate patient-specific advanced therapeutics into scaled manufacturing products for clinical application. These included (i) the development of a synergistic interaction between public and private institutions, (ii) better integration with Italian regulatory agencies and (iii) the creation of a network among Lombardy cell factories and other Italian and European institutions. PMID:26971677

  2. Advanced onset of puberty after metformin therapy in swine with thrifty genotype.

    PubMed

    Astiz, S; Gonzalez-Bulnes, A; Astiz, I; Barbero, A; Perez-Solana, M L; Garcia-Real, I

    2014-09-01

    The prevention and treatment of obesity in children is based on adequate nutrition and exercise plus antihyperglycaemic drugs. Currently, the incidence of childhood obesity is aggravated in ethnicities with thrifty genotype, but there is no available information on the effects of metformin therapy. The relative effects of lifestyle and metformin on patterns of growth, fattening, metabolic status and attainment of puberty were assessed in females of an obese swine model (Iberian gilts), allocated to three experimental groups (group A, obesogenic diet and scarce exercise; group DE, adequate diet and opportunity for exercise; and group DEM, adequate diet and opportunity for exercise plus metformin). Group A evidenced high weight, corpulence and adiposity, high plasma triglycerides and impairments of glucose regulation predisposing to insulin resistance. These features were favourably modulated by adequate lifestyle (group DE), and these effects were strengthened by metformin treatment (group DEM), which induced an improvement in body development by favouring muscle deposition. However, contrary to expectations, metformin advanced the onset of puberty. Metformin treatments would have positive effects on growth patterns, adiposity and metabolic features of young females from ethnicities with thrifty genotype or developing leptin resistance, but a negative effect by advancing the attainment of puberty. This study provides a warning regarding the use of metformin, without further studies, in girls from these ethnicities.

  3. Hyperadrenocorticism in a cat.

    PubMed

    Zerbe, C A; Nachreiner, R F; Dunstan, R W; Dalley, J B

    1987-03-01

    A diabetic cat with hyperadrenocorticism had polydipsia, polyuria, ventral abdominal alopecia, thin dry skin, and a pendulous abdomen. Results of laboratory testing indicated persistent resting hypercortisolemia, hyperresponsiveness of the adrenal glands (increased cortisol concentration) to ACTH gel, and no suppression of cortisol concentrations after administration of dexamethasone at 0.01 or 1.0 mg/kg of body weight. Necropsy revealed a pituitary gland tumor, bilateral adrenal hyperplasia, hepatic neoplasia, and demodicosis. Adrenal gland function was concurrently assessed in 2 cats with diabetes mellitus. One cat had resting hypercortisolemia, and both had hyperresponsiveness to ACTH gel (increased cortisol concentration) at one hour. After administration of dexamethasone (0.01 and 1.0 mg/kg), the diabetic cats appeared to have normal suppression of cortisol concentrations. The effects of mitotane were investigated in 4 clinically normal cats. Adrenocortical suppression of cortisol production occurred in 2 of 4 cats after dosages of 25, 37, and 50 mg/kg. Three cats remained clinically normal throughout the study. One cat experienced vomiting, diarrhea, and anorexia.

  4. That Fat Cat

    ERIC Educational Resources Information Center

    Lambert, Phyllis Gilchrist

    2012-01-01

    This activity began with a picture book, Nurit Karlin's "Fat Cat On a Mat" (HarperCollins; 1998). The author and her students started their project with a 5-inch circular template for the head of their cats. They reviewed shapes as they drew the head and then added the ears and nose, which were triangles. Details to the face were added when…

  5. Obesity in show cats.

    PubMed

    Corbee, R J

    2014-12-01

    Obesity is an important disease with a high prevalence in cats. Because obesity is related to several other diseases, it is important to identify the population at risk. Several risk factors for obesity have been described in the literature. A higher incidence of obesity in certain cat breeds has been suggested. The aim of this study was to determine whether obesity occurs more often in certain breeds. The second aim was to relate the increased prevalence of obesity in certain breeds to the official standards of that breed. To this end, 268 cats of 22 different breeds investigated by determining their body condition score (BCS) on a nine-point scale by inspection and palpation, at two different cat shows. Overall, 45.5% of the show cats had a BCS > 5, and 4.5% of the show cats had a BCS > 7. There were significant differences between breeds, which could be related to the breed standards. Most overweight and obese cats were in the neutered group. It warrants firm discussions with breeders and cat show judges to come to different interpretations of the standards in order to prevent overweight conditions in certain breeds from being the standard of beauty. Neutering predisposes for obesity and requires early nutritional intervention to prevent obese conditions. PMID:24612018

  6. Diseases Transmitted by Cats.

    PubMed

    Goldstein, Ellie J C; Abrahamian, Fredrick M

    2015-10-01

    Humans and cats have shared a close relationship since ancient times. Millions of cats are kept as household pets, and 34% of households have cats. There are numerous diseases that may be transmitted from cats to humans. General modes of transmission, with some overlapping features, can occur through inhalation (e.g., bordetellosis); vector-borne spread (e.g., ehrlichiosis); fecal-oral route (e.g., campylobacteriosis); bite, scratch, or puncture (e.g., rabies); soil-borne spread (e.g., histoplasmosis); and direct contact (e.g., scabies). It is also likely that the domestic cat can potentially act as a reservoir for many other zoonoses that are not yet recognized. The microbiology of cat bite wound infections in humans is often polymicrobial with a broad mixture of aerobic (e.g., Pasteurella, Streptococcus, Staphylococcus) and anaerobic (e.g., Fusobacterium, Porphyromonas, Bacteroides) microorganisms. Bacteria recovered from infected cat bite wounds are most often reflective of the oral flora of the cat, which can also be influenced by the microbiome of their ingested prey and other foods. Bacteria may also originate from the victim's own skin or the physical environment at the time of injury. PMID:26542039

  7. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

    SciTech Connect

    Kumar, Rachit; Wild, Aaron T.; Ziegler, Mark A.; Hooker, Ted K.; Dah, Samson D.; Tran, Phuoc T.; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M.; Tryggestad, Erik; Ford, Eric; Herman, Joseph M.

    2013-10-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D{sub max} of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D{sub mean}, D{sub max}, D{sub 1cc}, D{sub 4%}, and V{sub 20} {sub Gy} compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V{sub 95%} (p = 0.01) and D{sub mean} (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at

  8. Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: a dosimetric analysis.

    PubMed

    Kumar, Rachit; Wild, Aaron T; Ziegler, Mark A; Hooker, Ted K; Dah, Samson D; Tran, Phuoc T; Kang, Jun; Smith, Koren; Zeng, Jing; Pawlik, Timothy M; Tryggestad, Erik; Ford, Eric; Herman, Joseph M

    2013-01-01

    Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non-duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax of<30Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal Dmean, Dmax, D1cc, D4%, and V20Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V95% (p = 0.01) and Dmean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised target coverage

  9. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  10. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    PubMed

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity.

  11. Comparative study of aural microflora in healthy cats, allergic cats and cats with systemic disease.

    PubMed

    Pressanti, Charline; Drouet, Clémence; Cadiergues, Marie-Christine

    2014-12-01

    Twenty healthy cats (group 1) with clinically normal ears, 15 cats with systemic disease (group 2) and 15 allergic cats (group 3) were included in a prospective study. The experimental unit was the ear. A clinical score was established for each ear canal after otoscopic examination. Microbial population was assessed on cytological examination of smears performed with the cotton-tipped applicator smear technique. Fungal population was significantly more prominent in allergic cats (P <0.001) and in diseased cats compared with healthy cats (P <0.02). Bacterial population was significantly higher in allergic cats than in healthy cats (P <0.001) and cats suffering from systemic disease (P <0.001). Bacterial overgrowth was also higher in cats with systemic disease than healthy cats. In cats from group 2, only fungal overgrowth was associated with otitis severity. In group 3, only bacterial overgrowth was associated with otitis severity. PMID:24509255

  12. The Regulatory Pathway for Advanced Cell Therapy and Gene Therapy Products in Brazil: A Road to Be Built.

    PubMed

    de Freitas, Daniel Roberto Coradi

    2015-01-01

    The regulation of cell therapy and gene therapy products is a major challenge for the Brazilian state. From a legal point of view, the legislative apparatus, including constitutional, prohibits the marketing and patent of human substances. From the point of view of the organization of the state bureaucracy, the responsibilities for the regulation of research and application of these technologies in humans may involve up to four different institutions. The National Agency for Health Surveillance (ANVISA) has been the protagonist in structuring the regulation of cell therapy and gene therapy in Brazil, and steps have been taken to ensure quality of these products. However, obstacles such as the commercialization of these therapies and the need to determine whether these products will be regulated following the assumptions adopted in Brazil for drugs and biological products or for human blood and tissues still remain. PMID:26374221

  13. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  14. New advances in the pathophysiology of intestinal ion transport and barrier function in diarrhea and the impact on therapy.

    PubMed

    Hoque, Kazi Mirajul; Chakraborty, Subhra; Sheikh, Irshad Ali; Woodward, Owen M

    2012-06-01

    Diarrhea remains a continuous threat to human health worldwide. Scaling up the best practices for diarrhea prevention requires improved therapies. Diarrhea results from dysregulation of normal intestinal ion transport functions. Host-microbe contact is a key determinant of this response. Underlying mechanisms in the disease state are regulated by intracellular signals that modulate the activity of individual transport proteins responsible for ion transport and barrier function. Similarly, virulence factors of pathogens and their complex interaction with the host has shed light on the mechanism of enteric infection. Great advances in our understanding of the pathophysiologic mechanisms of epithelial transport, and host-microbe interaction have been made in recent years. Application of these new advances may represent strategies to decrease pathogen attachment, enhance intestinal cation absorption, decrease anion secretion and repair barrier function. This review highlights the new advances and better understanding in the pathophysiology of diarrheal diseases and their impact on therapy.

  15. Aortic Counterpulsation Therapy in Patients with Advanced Heart Failure: Analysis of the TBRIDGE Registry

    PubMed Central

    Bezerra, Cristiano Guedes; Adam, Eduardo Leal; Baptista, Mariana Lins; Ciambelli, Giuliano Serafino; Bernoche, Liliane Kopel, Claudia; Lopes, Leonardo Nicolau Geisler Daud; Macatrão-Costa, Milena Frota; Falcão, Breno de Alencar Araripe; Lage, Silvia Gelas

    2016-01-01

    Background The use of aortic counterpulsation therapy in advanced heart failure is controversial. Objectives To evaluate the hemodynamic and metabolic effects of intra-aortic balloon pump (IABP) and its impact on 30-day mortality in patients with heart failure. Methods Historical prospective, unicentric study to evaluate all patients treated with IABP betwen August/2008 and July/2013, included in an institutional registry named TBRIDGE (The Brazilian Registry of Intra-aortic balloon pump in Decompensated heart failure - Global Evaluation). We analyzed changes in oxygen central venous saturation (ScvO2), arterial lactate, and use of vasoactive drugs at 48 hours after IABP insertion. The 30-day mortality was estimated by the Kaplan-Meier method and diferences in subgroups were evaluated by the Log-rank test. Results A total of 223 patients (mean age 49 ± 14 years) were included. Mean left ventricle ejection fraction was 24 ± 10%, and 30% of patients had Chagas disease. Compared with pre-IABP insertion, we observed an increase in ScvO2 (50.5% vs. 65.5%, p < 0.001) and use of nitroprusside (33.6% vs. 47.5%, p < 0.001), and a decrease in lactate levels (31.4 vs. 16.7 mg/dL, p < 0.001) and use of vasopressors (36.3% vs. 25.6%, p = 0.003) after IABP insertion. Thirty-day survival was 69%, with lower mortality in Chagas disease patients compared without the disease (p = 0.008). Conclusion After 48 hours of use, IABP promoted changes in the use of vasoactive drugs, improved tissue perfusion. Chagas etiology was associated with lower 30-day mortality. Aortic counterpulsation therapy is an effective method of circulatory support for patients waiting for heart transplantation. PMID:26690691

  16. Advances in 4D Treatment Planning for Scanned Particle Beam Therapy — Report of Dedicated Workshops

    PubMed Central

    Bert, Christoph; Graeff, Christian; Riboldi, Marco; Nill, Simeon; Baroni, Guido; Knopf, Antje-Christin

    2014-01-01

    We report on recent progress in the field of mobile tumor treatment with scanned particle beams, as discussed in the latest editions of the 4D treatment planning workshop. The workshop series started in 2009, with about 20 people from 4 research institutes involved, all actively working on particle therapy delivery and development. The first workshop resulted in a summary of recommendations for the treatment of mobile targets, along with a list of requirements to apply these guidelines clinically. The increased interest in the treatment of mobile tumors led to a continuously growing number of attendees: the 2012 edition counted more than 60 participants from 20 institutions and commercial vendors. The focus of research discussions among workshop participants progressively moved from 4D treatment planning to complete 4D treatments, aiming at effective and safe treatment delivery. Current research perspectives on 4D treatments include all critical aspects of time resolved delivery, such as in-room imaging, motion detection, beam application, and quality assurance techniques. This was motivated by the start of first clinical treatments of hepato cellular tumors with a scanned particle beam, relying on gating or abdominal compression for motion mitigation. Up to date research activities emphasize significant efforts in investigating advanced motion mitigation techniques, with a specific interest in the development of dedicated tools for experimental validation. Potential improvements will be made possible in the near future through 4D optimized treatment plans that require upgrades of the currently established therapy control systems for time resolved delivery. But since also these novel optimization techniques rely on the validity of the 4DCT, research focusing on alternative 4D imaging technique, such as MRI based 4DCT generation will continue. PMID:24354749

  17. Recent advances in treating multiple sclerosis: efficacy, risks and place in therapy.

    PubMed

    Jeffery, Douglas R

    2013-01-01

    The development of new pharmacologic agents for the treatment of multiple sclerosis (MS) and advances in testing for exposure to the JC virus have led to changes in the treatment of MS. In addition several new agents are in late stage development for MS and their entry onto the market will provide additional treatment options. In 2012 and in early 2013, it is likely that both terifunomide and BG-12 will be approved by the United States Food and Drug Administration (FDA) for the treatment of relapsing forms of MS. The therapeutic environment has already changed and is likely to change rapidly over the next several years. Fingolimod was the first oral agent approved for the treatment of MS and this agent is now widely used in patients intolerant of injections and the side effects associated with the older platform therapies. In many settings it is also used a first-line agent. Owing to the risk of progressive multifocal leukoencephalopathy, natalizumab had previously been reserved for patients with active disease who were intolerant of first-line agents or patients who were worsening despite standard therapy. With the availability of JC virus antibody testing, natalizumab is now being used as a first-line agent in patients negative for JC virus antibodies. Teriflunomide and BG-12 will become available in the next year. Both agents have suitable efficacy and a favorable safety and tolerability profile. There are advantages and disadvantages associated with all of the oral agents. In this article we summarize the clinical trial results regarding the efficacy and safety of the oral agents and discuss the changes that are already taking place in the therapeutic landscape for MS. PMID:23342246

  18. Reverse-contrast imaging and targeted radiation therapy of advanced pancreatic cancer models

    PubMed Central

    Thorek, Daniel L.J.; Kramer, Robin M.; Chen, Qing; Jeong, Jeho; Lupu, Mihaela E.; Lee, Alycia M.; Moynahan, Mary E.; Lowery, Maeve; Ulmert, H. David; Zanzonico, Pat; Deasy, Joseph O.; Humm, John L.; Russell, James

    2015-01-01

    Purpose To evaluate the feasibility of delivering experimental radiotherapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by X-ray CT. With this technique we delineated the pancreas, and both orthotopic xenografts and genetically engineered disease. CT imaging was validated by comparison with magnetic resonance (MR) imaging. Therapeutic radiation was delivered via a 1 cm diameter field. Selective X-ray radiation therapy (XRT) of the non-invasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360-degree arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic XRT to orthotopic tumors. Results Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times post-treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions This advance permits evaluation of radiation planning and dosing parameters. Accurate non-invasive longitudinal imaging and monitoring of tumor progression and therapeutic response in pre-clinical models is now possible, and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response. PMID:26238952

  19. KRAS Testing for Anti-EGFR Therapy in Advanced Colorectal Cancer

    PubMed Central

    2010-01-01

    specimens. It is believed that KRAS status is not affected by treatments, therefore, for patients for whom surgical tissue is available for KRAS testing, additional biopsies prior to treatment with these targeted agents is not necessary. For patients that have not undergone surgery or for whom surgical tissue is not available, a biopsy of either the primary or metastatic site is required to determine their KRAS status. This is possible as status at the metastatic and primary tumour sites is considered to be similar. Research Question To determine if there is predictive value of KRAS testing in guiding treatment decisions with anti-EGFR targeted therapies in advanced colorectal cancer patients refractory to chemotherapy. Research Methods Literature Search The Medical Advisory Secretariat followed its standard procedures and on May 18, 2010, searched the following electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment database. The subject headings and keywords searched included colorectal cancer, cetuximab, panitumumab, and KRAS testing. The search was further restricted to English-language articles published between January 1, 2009 and May 18, 2010 resulting in 1335 articles for review. Excluded were case reports, comments, editorials, nonsystematic reviews, and letters. Studies published from January 1, 2005 to December 31, 2008 were identified in a health technology assessment conducted by the Agency for Healthcare Research and Quality (AHRQ), published in 2010. In total, 14 observational studies were identified for inclusion in this EBA: 4 for cetuximab monotherapy, 7 for the cetuximab-irinotecan combination therapy, and 3 to be included in the review for panitumumab monotherapy Inclusion Criteria English-language articles, and English or French-language HTAs

  20. Metaphyseal osteopathy in a British Shorthair cat.

    PubMed

    Adagra, Carl; Spielman, Derek; Adagra, Angela; Foster, Darren J

    2015-04-01

    Metaphyseal osteopathy, otherwise known as hypertrophic osteodystrophy, is a disease that causes pyrexia and lethargy accompanied by pain in the thoracic and pelvic limbs of rapidly growing large-breed dogs. While metaphyseal osteopathy has been descibed in association with slipped capital femoral epiphysis in cats, it has not previously been reported as a cause of limb pain and pyrexia in this species. A 7-month-old British Shorthair cat presented with a 1 month history of pyrexia, lethargy and pain in all limbs. Investigation included radiographs of the limbs and chest, abdominal ultrasound, serum biochemical analysis, haematology, bone biopsy, joint fluid aspiration and cytology. Findings were consistent with a diagnosis of metaphyseal osteopathy. The cat's clinical signs resolved following the administration of prednisolone. Symptoms recurred 1 month after the cessation of prednisolone therapy, but resolved when administration was resumed.

  1. Cell and Gene Therapy for the Beta-Thalassemias: Advances and Prospects.

    PubMed

    Mansilla-Soto, Jorge; Riviere, Isabelle; Boulad, Farid; Sadelain, Michel

    2016-04-01

    The beta-thalassemias are inherited anemias caused by mutations that severely reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a related beta-globin gene disorder, they are ideal candidates for performing a genetic correction in patient hematopoietic stem cells (HSCs). The most advanced approach utilizes complex lentiviral vectors encoding the human β-globin gene, as first reported by May et al. in 2000. Considerable progress toward the clinical implementation of this approach has been made in the past five years, based on effective CD34+ cell mobilization and improved lentiviral vector manufacturing. Four trials have been initiated in the United States and Europe. Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them developed a durable clonal expansion, which regressed after several years without transformation. Although globin lentiviral vectors have so far proven to be safe, this occurrence suggests that powerful insulators with robust enhancer-blocking activity will further enhance this approach. The combined discovery of Bcl11a-mediated γ-globin gene silencing and advances in gene editing are the foundations for another gene therapy approach, which aims to reactivate fetal hemoglobin (HbF) production. Its clinical translation will hinge on the safety and efficiency of gene targeting in true HSCs and the induction of sufficient levels of HbF to achieve transfusion independence. Altogether, the progress achieved over the past 15 years bodes well for finding a genetic cure for severe globin disorders in the next decade. PMID:27021486

  2. Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer.

    PubMed

    Nakao, Toshihiro; Iwata, Takashi; Hotchi, Masanori; Yoshikawa, Kozo; Higashijima, Jun; Nishi, Masaaki; Takasu, Chie; Eto, Shohei; Teraoku, Hiroki; Shimada, Mitsuo

    2015-10-01

    Preoperative chemoradiotherapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer. However, no specific biomarker has been identified to predict a response to preoperative CRT. The aim of the present study was to assess the gene expression patterns of patients with advanced rectal cancer to predict their responses to preoperative CRT. Fifty-nine rectal cancer patients were subjected to preoperative CRT. Patients were randomly assigned to receive CRT with tegafur/gimeracil/oteracil (S-1 group, n=30) or tegafur-uracil (UFT group, n=29). Gene expression changes were studied with cDNA and miRNA microarray. The association between gene expression and response to CRT was evaluated. cDNA microarray showed that 184 genes were significantly differentially expressed between the responders and the non‑responders in the S-1 group. Comparatively, 193 genes were significantly differentially expressed in the responders in the UFT group. TBX18 upregulation was common to both groups whereas BTNL8, LOC375010, ADH1B, HRASLS2, LOC284232, GCNT3 and ALDH1A2 were significantly differentially lower in both groups when compared with the non-responders. Using miRNA microarray, we found that 7 and 16 genes were significantly differentially expressed between the responders and non-responders in the S-1 and UFT groups, respectively. miR-223 was significantly higher in the responders in the S-1 group and tended to be higher in the responders in the UFT group. The present study identified several genes likely to be useful for establishing individualized therapies for patients with rectal cancer.

  3. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy.

    PubMed

    Pérez-Herrero, Edgar; Fernández-Medarde, Alberto

    2015-06-01

    mainly deliver chemotherapeutic agents to molecular targets overexpressed on the surface of tumor cells. In particular, we offer a detailed description of different cytotoxic drug carriers, such as liposomes, carbon nanotubes, dendrimers, polymeric micelles, polymeric conjugates and polymeric nanoparticles, in passive and active targeted cancer therapy, by enhancing the permeability and retention or by the functionalization of the surface of the carriers, respectively, emphasizing those that have received FDA approval or are part of the most important clinical studies up to date. These drug carriers not only transport the chemotherapeutic agents to tumors, avoiding normal tissues and reducing toxicity in the rest of the body, but also protect cytotoxic drugs from degradation, increase the half-life, payload and solubility of cytotoxic agents and reduce renal clearance. Despite the many advantages of all the anticancer drug carriers analyzed, only a few of them have reached the FDA approval, in particular, two polymer-protein conjugates, five liposomal formulations and one polymeric nanoparticle are available in the market, in contrast to the sixteen FDA approval of monoclonal antibodies. However, there are numerous clinical trials in progress of polymer-protein and polymer-drug conjugates, liposomal formulations, including immunoliposomes, polymeric micelles and polymeric nanoparticles. Regarding carbon nanotubes or dendrimers, there are no FDA approvals or clinical trials in process up to date due to their unresolved toxicity. Moreover, we analyze in detail the more promising and advanced preclinical studies of the particular case of polymeric nanoparticles as carriers of different cytotoxic agents to active and passive tumor targeting published in the last 5 years, since they have a huge potential in cancer therapy, being one of the most widely studied nano-platforms in this field in the last years. The interest that these formulations have recently achieved is

  4. Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson's disease (PD SURG trial): a randomised, open-label trial

    PubMed Central

    Williams, Adrian; Gill, Steven; Varma, Thelekat; Jenkinson, Crispin; Quinn, Niall; Mitchell, Rosalind; Scott, Richard; Ives, Natalie; Rick, Caroline; Daniels, Jane; Patel, Smitaa; Wheatley, Keith

    2010-01-01

    Summary Background Surgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. Methods The PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with Current Controlled Trials, number ISRCTN34111222. Findings 366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences

  5. Pancreatitis and triaditis in cats: causes and treatment.

    PubMed

    Simpson, K W

    2015-01-01

    Pancreatitis in cats is frequently accompanied by concurrent disease in other organ systems. Co-morbidities include hepatic lipidosis, inflammatory liver disease, bile duct obstruction, diabetes mellitus, inflammatory bowel disease, vitamin deficiency (B12/cobalamin, folate or K), intestinal lymphoma, nephritis, pulmonary thromboembolism and pleural and peritoneal effusions. "Triaditis" is the term used to describe concurrent inflammation of the pancreas, liver and small intestines. Triaditis has been reported in 50 to 56% of cats diagnosed with pancreatitis and 32 to 50% of those with cholangitis/inflammatory liver disease. A definitive diagnosis of triaditis is based on the histopathological evaluation of each organ. However, the specific conditions of each organ that constitute a diagnosis of triaditis remains to be defined. While the aetiopathogenesis of pancreatitis and its relationship to inflammation in other organ systems is unclear, preliminary studies point to a heterogeneous group of conditions with differential involvement of host inflammatory and immune responses and enteric bacteria. Comprehensive, prospective studies that simultaneously evaluate the presence of predefined clinical, clinicopathological and histopathological abnormalities, coupled with high-resolution evaluation of pancreaticobiliary morphology, immunological profiling and screening for bacterial colonisation are required to advance diagnosis and therapy.

  6. Mandibular advancement oral appliance therapy for obstructive sleep apnoea: effect on awake calibre of the velopharynx

    PubMed Central

    Ryan, C; Love, L; Peat, D; Fleetham, J; Lowe, A

    1999-01-01

    BACKGROUND—The mechanisms of action of oral appliance therapy in obstructive sleep apnoea are poorly understood. Videoendoscopy of the upper airway was used during wakefulness to examine whether the changes in pharyngeal dimensions produced by a mandibular advancement oral appliance are related to the improvement in the severity of obstructive sleep apnoea.
METHODS—Fifteen patients with mild to moderate obstructive sleep apnoea (median (range) apnoea index (AI) 4(0-38)/h, apnoea-hypopnoea index (AHI) 28(9-45)/h) underwent overnight polysomnography and imaging of the upper airway before and after insertion of the oral appliance. Images were obtained in the hypopharynx, oropharynx, and velopharynx at end tidal expiration during quiet nasal breathing in the supine position. The cross sectional area and diameters of the upper airway were measured using image processing software with an intraluminal catheter as a linear calibration.
RESULTS—AI decreased to a median (range) value of 0 (0-6)/h (p<0.01) and AHI to 8 (1-28)/h (p<0.001) following insertion of the oral appliance. The median (95% confidence interval) cross sectional area of the upper airway increased by 18% (3 to 35) (p<0.02) in the hypopharynx and by 25% (11 to 69) (p<0.005) in the velopharynx, but not significantly in the oropharynx. Although in general the shape of the pharynx did not change following insertion of the oral appliance, the lateral diameter of the velopharynx increased to a greater extent than the anteroposterior diameter. Following insertion of the oral appliance the reduction in AHI was related to the increase in cross sectional area of the velopharynx (p= 0.01).
CONCLUSIONS—A mandibular advancement oral appliance increases the cross sectional area of the upper airway during wakefulness, particularly in the velopharynx. Assuming this effect on upper airway calibre is not eliminated by sleep, mandibular advancement oral appliances may reduce the severity of obstructive sleep

  7. Cat-scratch disease

    MedlinePlus

    ... Sometimes, an infected lymph node may form a tunnel ( fistula ) through the skin and drain (leak fluid). ... disease: Wash your hands thoroughly with soap and water after playing with your cat. Especially wash any ...

  8. Indium-111-antimyosin scintigraphy after doxorubicin therapy in patients with advanced breast cancer

    SciTech Connect

    Estorch, M.; Carrio, I.; Berna, L.; Martinez-Duncker, C.; Alonso, C.; Germa, J.R.; Ojeda, B. )

    1990-12-01

    Indium-111-antimyosin ({sup 111}In-antimyosin) scans were performed in 20 women with advanced breast cancer after 10 cycles of chemotherapy consisting of cyclophosphamide, 5-fluorouracil and doxorubicin (total cumulative dose of doxorubicin of 500 mg/m2). Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). Antimyosin uptake in the myocardium was observed in 17/20 (85%) patients, and HLR after chemotherapy was 1.86 +/- 0.25. Left ventricular ejection fraction (EF) was determined before and after chemotherapy. Patients with decreased EF (8/20, 40%) presented with more intense antimyosin uptake (HLR of 2.11 +/- 0.10 versus 1.70 +/- 0.16 (p = 0.01)). HLR values correlated with EF values after chemotherapy (r = -0.47, p less than 0.05). Positive antimyosin studies after chemotherapy including doxorubicin, indicate the presence of myocardial damage in these patients. Antimyosin studies are a sensitive method to detect myocyte damage in patients after doxorubicin therapy.

  9. Side effects of bone-targeted therapies in advanced breast cancer.

    PubMed

    Domschke, Christoph; Schuetz, Florian

    2014-10-01

    In up to 75% of cases, advanced breast cancer patients eventually develop bone metastases with often debilitating skeletal-related events (SREs). Osteoclast inhibitors are commonly used as therapeutic mainstay with clinical studies showing superiority of denosumab over bisphosphonates (e.g., zoledronate) for the prevention of SREs. The present review discusses the adverse event profile of these agents, and addresses the prevention and management of untoward side effects. Adverse events associated with osteoclast inhibitors comprise osteonecrosis of the jaw and hypocalcemia. Hypocalcemia is more common with denosumab, particularly in severe renal dysfunction. During therapy, the appropriate prevention of these adverse events includes close attention to dental health, avoidance of invasive dental procedures, supplementation with calcium and vitamin D unless patients are hypercalcemic, and regular monitoring of relevant serum values. Relating to the risk of nephrotoxicity, bisphosphonates but not denosumab have been incriminated. Therefore, serum creatinine levels should be checked prior to each dose of zoledronate, and in severe renal dysfunction (creatinine clearance < 30 ml/min) zoledronate is contraindicated anyway. Acute-phase reactions are particularly linked to bisphosphonates. Consequently, if these adverse events predominate, switching to denosumab is recommended. PMID:25759613

  10. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  11. [Problems in microbial safety of advanced therapy medicinal products. Squaring the circle].

    PubMed

    Montag-Lessing, T; Störmer, M; Schurig, U; Brachert, J; Bubenzer, M; Sicker, U; Beshir, R; Spreitzer, I; Löschner, B; Bache, C; Becker, B; Schneider, C K

    2010-01-01

    Today, sterility of parenteral drugs is practically guaranteed. Well-defined procedures in the pharmaceutical industry enable effective protection against contamination by bacteria and fungi. In contrast, problems regarding microbial safety of advanced therapy medicinal products (ATMPs), especially of cell therapeutics, are at best only partially solved. The latter should be understood as a challenge for manufacturers, regulators, and physicians. Many of the manufacturing principles mentioned above are not applicable in production of cell therapeutics. Sterility of source materials cannot be guaranteed and the hitherto known procedures for sterilization are, as a rule, not feasible. Thus, the sterility of the final product cannot be guaranteed. Considering the extremely short shelf life of many cell therapeutics, sometimes only a few hours, the results from established methods for sterility testing are often available too late. Furthermore, the sterility of a test sample does not indicate sterility of the whole product. In most cases, conventional methods for pyrogen testing are not applicable for ATMPs. This paper demonstrates relevant limitations regarding microbial safety and pyrogenicity. Possibilities to overcome these problems are discussed and some novel solutions are proposed.

  12. [Scientific advice by the national and European approval authorities concerning advanced therapy medicinal products].

    PubMed

    Jost, Nils; Schüssler-Lenz, Martina; Ziegele, Bettina; Reinhardt, Jens

    2015-11-01

    The aim of scientific advice is to support pharmaceutical developers in regulatory and scientific questions, thus facilitating the development of safe and efficacious new medicinal products. Recent years have shown that the development of advanced therapy medicinal products (ATMPs) in particular needs a high degree of regulatory support. On one hand, this is related to the complexity and heterogeneity of this group of medicinal products and on the other hand due to the fact that mainly academic research institutions and small- and medium-sized enterprises (SMEs) are developing ATMPs. These often have limited regulatory experience and resources. In 2009 the Paul-Ehrlich-Institut (PEI) initiated the Innovation Office as a contact point for applicants developing ATMPs. The mandate of the Innovation Office is to provide support on regulatory questions and to coordinate national scientific advice meetings concerning ATMPs for every phase in drug development and especially with view to the preparation of clinical trial applications. On the European level, the Scientific Advice Working Party (SAWP) of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicinal Agency (EMA) offers scientific advice. This article describes the concepts of national and EMA scientific advice concerning ATMPs and summarizes the experience of the last six years.

  13. A Positive Prospective Trial of Antibiotic Therapy in Advanced Stage, Non-Bulky Indolent Lymphoma

    PubMed Central

    Portlock, Carol S; Hamlin, Paul A; Gerecitano, John F; Noy, Ariela; Palomba, Maria Lia; Walkley, Janelle; Corcoran, Stacie; Migliacci, Jocelyn; Schoder, Heiko; Papanicolaou, Genovefa; Markowitz, Arnold J

    2016-01-01

    Background We have prospectively studied a three month course of clarithromycin (substituted by Prevpac®, lansoprazole/ amoxicillin/ clarithromycin, in the first two wks when stool H pylori+) for non-bulky, advanced stage indolent lymphoma. These patients are often candidates for expectant monitoring and it is during this period that a window of opportunity may exist to identify and treat associated infections. Methods All previously untreated patients with a new diagnosis of indolent lymphoma (FL and non-FL) meeting GELF criteria were treated with 12 weeks of clarithromycin. There were 32 evaluable patients, 4 of whom had stool H pylori. Results At one month post-antibiotic therapy, we have observed lymphoma responses in 7 of 32 patients (21.9%). Two additional patients had objective response during followup (28.1% overall response). The median treatment free survival for antibiotic responders is 69.9 months and for non-responders, 30.6 months (p = 0.019). Conclusion Three response patterns have been noted, perhaps suggestive of an immune-mediated response -- prompt PET negative; flair with delayed PET negative response; and gradual continuous improvement. This prospective study appears promising, may be a step toward developing a lymphoma prevention strategy by reducing “antigen drive,” and deserves further clinical/biological study. http://clinicaltrials.gov/show/NCT00461084 PMID:26798624

  14. [Scientific advice by the national and European approval authorities concerning advanced therapy medicinal products].

    PubMed

    Jost, Nils; Schüssler-Lenz, Martina; Ziegele, Bettina; Reinhardt, Jens

    2015-11-01

    The aim of scientific advice is to support pharmaceutical developers in regulatory and scientific questions, thus facilitating the development of safe and efficacious new medicinal products. Recent years have shown that the development of advanced therapy medicinal products (ATMPs) in particular needs a high degree of regulatory support. On one hand, this is related to the complexity and heterogeneity of this group of medicinal products and on the other hand due to the fact that mainly academic research institutions and small- and medium-sized enterprises (SMEs) are developing ATMPs. These often have limited regulatory experience and resources. In 2009 the Paul-Ehrlich-Institut (PEI) initiated the Innovation Office as a contact point for applicants developing ATMPs. The mandate of the Innovation Office is to provide support on regulatory questions and to coordinate national scientific advice meetings concerning ATMPs for every phase in drug development and especially with view to the preparation of clinical trial applications. On the European level, the Scientific Advice Working Party (SAWP) of the Committee for Medicinal Products for Human Use (CHMP) of the European Medicinal Agency (EMA) offers scientific advice. This article describes the concepts of national and EMA scientific advice concerning ATMPs and summarizes the experience of the last six years. PMID:26369763

  15. Understanding public perceptions of risk regarding outdoor pet cats to inform conservation action.

    PubMed

    Gramza, Ashley; Teel, Tara; VandeWoude, Susan; Crooks, Kevin

    2016-04-01

    Free-ranging domestic cats (Felis catus) incur and impose risks on ecosystems and represent a complex issue of critical importance to biodiversity conservation and cat and human health globally. Prior social science research on this topic is limited and has emphasized feral cats even though owned cats often comprise a large proportion of the outdoor cat population, particularly in urban areas. To address this gap, we examined public risk perceptions and attitudes toward outdoor pet cats across varying levels of urbanization, including along the wildland-urban interface, in Colorado (U.S.A.), through a mail survey of 1397 residents. Residents did not view all types of risks uniformly. They viewed risks of cat predation on wildlife and carnivore predation on cats as more likely than disease-related risks. Additionally, risk perceptions were related to attitudes, prior experiences with cats and cat-wildlife interactions, and cat-owner behavior. Our findings suggest that changes in risk perceptions may result in behavior change. Therefore, knowledge of cat-related risk perceptions and attitudes could be used to develop communication programs aimed at promoting risk-aversive behaviors among cat owners and cat-management strategies that are acceptable to the public and that directly advance the conservation of native species.

  16. Understanding public perceptions of risk regarding outdoor pet cats to inform conservation action.

    PubMed

    Gramza, Ashley; Teel, Tara; VandeWoude, Susan; Crooks, Kevin

    2016-04-01

    Free-ranging domestic cats (Felis catus) incur and impose risks on ecosystems and represent a complex issue of critical importance to biodiversity conservation and cat and human health globally. Prior social science research on this topic is limited and has emphasized feral cats even though owned cats often comprise a large proportion of the outdoor cat population, particularly in urban areas. To address this gap, we examined public risk perceptions and attitudes toward outdoor pet cats across varying levels of urbanization, including along the wildland-urban interface, in Colorado (U.S.A.), through a mail survey of 1397 residents. Residents did not view all types of risks uniformly. They viewed risks of cat predation on wildlife and carnivore predation on cats as more likely than disease-related risks. Additionally, risk perceptions were related to attitudes, prior experiences with cats and cat-wildlife interactions, and cat-owner behavior. Our findings suggest that changes in risk perceptions may result in behavior change. Therefore, knowledge of cat-related risk perceptions and attitudes could be used to develop communication programs aimed at promoting risk-aversive behaviors among cat owners and cat-management strategies that are acceptable to the public and that directly advance the conservation of native species. PMID:26379227

  17. Cognitive activation theory of stress (CATS).

    PubMed

    Ursin, Holger; Eriksen, Hege R

    2010-05-01

    The cognitive activation theory of stress (CATS) is based on a long series of experiments on animals and on humans, in the laboratory, and in real life situations. From the common sense coping concept formulated by Seymour Levine; coping is when my "tommy" does not hurt, we have advanced to a systematic theory for what is behind the relaxed and happy coping rat (and cat). We also cover the translational leap to humans, starting with the now classic parachutist study. The bridge is based on formal and symbolic definitions, a theoretical short cut that Levine actually never really accepted. The essential pathophysiological concept is the potential pathological effects of sustained activation, which may occur in the absence of coping (positive response outcome expectancy). We review the current status of CATS in Behavioural Medicine by discussing its potential explanatory power in epidemiology, prevention and treatment of "subjective health complaints".

  18. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  19. Anti-PD-1/PD-L1 antibody therapy for pretreated advanced nonsmall-cell lung cancer

    PubMed Central

    Zhou, Guo-Wu; Xiong, Ye; Chen, Si; Xia, Fan; Li, Qiang; Hu, Jia

    2016-01-01

    Abstract Background: Anti-PD-1/PD-L1 antibody therapy is a promising clinical treatment for nonsmall-cell lung cancer (NSCLC). However, whether anti-PD-1/PD-L1 antibody therapy can provide added benefits for heavily pretreated patients with advanced NSCLC and whether the efficacy of anti-PD-1/PD-L1 antibody therapy relates to the tumor PD-L1 expression level remain controversial. Thus, this meta-analysis evaluated the efficacy and safety of anti-PD-1/PD-L1 antibody therapy for pretreated patients with advanced NSCLC. Methods: Randomized clinical trials were retrieved by searching the PubMed, EMBASE, ASCO meeting abstract, clinicaltrial.gov, and Cochrane library databases. The pooled hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios for the overall response rate and adverse events (AEs) were calculated by STATA software. Results: Three randomized clinical trials involving 1141 pretreated patients with advanced NSCLC were included. These trials all compared the efficacy and safety of anti-PD-1/PD-L1 antibodies (nivolumab and MPDL3280A) with docetaxel. The results suggested that, for all patients, anti-PD-1/PD-L1 therapy could acquire a greater overall response (odds ratio = 1.50, 95% CI: 1.08–2.07, P = 0.015, P for heterogeneity [Ph] = 0.620) and longer OS (HR = 0.71, 95% CI: 0.61–0.81, P < 0.001, Ph = 0.361) than docetaxel, but not PFS (HR = 0.83, 95% CI: 0.65–1.06, P = 0.134; Ph = 0.031). Subgroup analyses according to the tumor PD-L1 expression level showed that anti-PD-1/PD-L1 therapy could significantly improve both OS and PFS in patients with high expressions of PD-L1, but not in those with low expressions. Generally, the rates of grade 3 or 4 AEs of anti-PD-1/PD-L1 therapy were significantly lower than that of docetaxel. However, the risks of pneumonitis and hypothyroidism were significantly higher. Conclusion: Anti-PD-1/PD-L1 antibody therapy may significantly improve

  20. Steady advance of stem cell therapies: report from the 2011 World Stem Cell Summit, Pasadena, California, October 3-5.

    PubMed

    Swan, Melanie

    2011-12-01

    Stem cell research and related therapies (including regenerative medicine and cellular therapies) could have a significant near-term impact on worldwide public health and aging. One reason is the industry's strong linkage between policy, science, industry, and patient advocacy, as was clear in the attendance and programming at the 7(th) annual World Stem Cell Summit held in Pasadena, California, October 3-5, 2011. A special conference session sponsored by the SENS Foundation discussed how stem cell therapies are being used to extend healthy life span. Stem cells are useful not only in cell-replacement therapies, but also in disease modeling, drug discovery, and drug toxicity screening. Stem cell therapies are currently being applied to over 50 diseases, including heart, lung, neurodegenerative, and eye disease, cancer, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Dozens of companies are developing therapeutic solutions that are in different stages of clinical use and clinical trials. Some high-profile therapies include Dendreon's Provenge for prostate cancer, Geron's first-ever embryonic stem cell trials for spinal cord injury, Fibrocell's laViv cellular therapy for wrinkles, and well-established commercial skin substitutes (Organogenesis' Apligraf and Advanced BioHealing's Dermagraft). Stem cell policy issues under consideration include medical tourism, standards for large-scale stem cell manufacturing, and lingering ethical debates over the use of embryonic stem cells. Contemporary stem cell science advances include a focus on techniques for the direct reprogramming of cells from one lineage to another without returning to pluripotency as an intermediary step, improved means of generating and characterizing induced pluripotent cells, and progress in approaches to neurodegenerative disease.

  1. State of the art: diagnostic tools and innovative therapies for treatment of advanced thymoma and thymic carcinoma.

    PubMed

    Ried, Michael; Marx, Alexander; Götz, Andrea; Hamer, Okka; Schalke, Berthold; Hofmann, Hans-Stefan

    2016-06-01

    In this review article, state-of-the-art diagnostic tools and innovative treatments of thymoma and thymic carcinoma (TC) are described with special respect to advanced tumour stages. Complete surgical resection (R0) remains the standard therapeutic approach for almost all a priori resectable mediastinal tumours as defined by preoperative standard computed tomography (CT). If lymphoma or germ-cell tumours are differential diagnostic considerations, biopsy may be indicated. Resection status is the most important prognostic factor in thymoma and TC, followed by tumour stage. Advanced (Masaoka-Koga stage III and IVa) tumours require interdisciplinary therapy decisions based on distinctive findings of preoperative CT scan and ancillary investigations [magnetic resonance imaging (MRI)] to select cases for primary surgery or neoadjuvant strategies with optional secondary resection. In neoadjuvant settings, octreotide scans and histological evaluation of pretherapeutic needle biopsies may help to choose between somatostatin agonist/prednisolone regimens and neoadjuvant chemotherapy as first-line treatment. Finally, a multimodality treatment regime is recommended for advanced and unresectable thymic tumours. In conclusion, advanced stage thymoma and TC should preferably be treated in experienced centres in order to provide all modern diagnostic tools (imaging, histology) and innovative therapy techniques. Systemic and local (hyperthermic intrathoracic chemotherapy) medical treatments together with extended surgical resections have increased the therapeutic options in patients with advanced or recurrent thymoma and TC.

  2. Predictors for resectability and survival in locally advanced pancreatic cancer after gemcitabine-based neoadjuvant therapy

    PubMed Central

    2014-01-01

    Background To evaluate the predictors for resectability and survival of patients with locally advanced pancreatic cancer (LAPC) treated with gemcitabine-based neoadjuvant therapy (GBNAT). Methods Between May 2003 and Dec 2009, 41 tissue-proved LAPC were treated with GBNAT. The location of pancreatic cancer in the head, body and tail was 17, 18 and 6 patients respectively. The treatment response was evaluated by RECIST criteria. Surgical exploration was based on the response and the clear plan between tumor and celiac artery/superior mesentery artery. Kaplan–Meier analysis and Cox Model were used to calculate the resectability and survival rates. Results Finally, 25 patients received chemotherapy (CT) and 16 patients received concurrent chemoradiation therapy (CRT). The response rate was 51% (21 patients), 2 CR (1 in CT and 1 in CRT) and 19 PR (10 in CT and 9 in CRT). 20 patients (48.8%) were assessed as surgically resectable, in which 17 (41.5%) underwent successful resection with a 17.6% positive-margin rate and 3 failed explorations were pancreatic head cancer for dense adhesion. Two pancreatic neck cancer turned fibrosis only. Patients with surgical intervention had significant actuarial overall survival. Tumor location and post-GBNAT CA199 < 152 were predictors for resectability. Post-GBNAT CA-199 < 152 and post-GBNAT CA-125 < 32.8 were predictors for longer disease progression-free survival. Pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, and post-op CEA < 6 were predictors for longer overall survival. Conclusion Tumor location and post-GBNAT CA199 < 152 are predictors for resectability while pre-GBNAT CA-199 < 294, post-GBNAT CA-125 < 32.8, post-GBNAT CA-199 < 152 and post-op CEA < 6 are survival predictors in LAPC patients with GBNAT. PMID:25258022

  3. Advances in three-dimensional conformal radiation therapy physics with intensity modulation.

    PubMed

    Webb, S

    2000-09-01

    Intensity-modulated radiation therapy, a specific form of conformal radiation therapy, is currently attracting a lot of attention, and there are high expectations for this class of treatment techniques. Several new technologies are in development, but physicists are still working to improve the physical basis of radiation therapy.

  4. Advancing Multicultural and Diversity Competence in Art Therapy: American Art Therapy Association Multicultural Committee 1990-2015

    ERIC Educational Resources Information Center

    Potash, Jordan S.; Doby-Copeland, Cheryl; Stepney, Stella A.; Washington, Brittney N.; Vance, Lindsey D.; Short, Gwendolyn M.; Boston, Charlotte G.; Ballbé ter Maat, Mercedes

    2015-01-01

    For 25 years the Multicultural Committee of the American Art Therapy Association has provided education, networking, and mentoring activities for all art therapists, as well as support for art therapists of color. The formation of the committee demonstrates increasing cultural competence within the profession, and its continuation promises future…

  5. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  6. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer.

  7. Systemic therapy in the management of metastatic or advanced salivary gland cancers

    PubMed Central

    2012-01-01

    Salivary gland cancers are very rare tumors. They are characterized by a histologic heterogeneity and a poor outcome. According to this rarity, few prospective data are available to date. No standard recommendations could be held for the use of systemic therapy in these tumors. Several case reports and small studies have investigated the contribution of different agents of chemotherapy. With the extension of molecular biology approach in oncology several signaling pathways have been discovered in different cancers including salivary gland cancers; thus a number of targeted therapies have been investigated. This paper reviewed exhaustively the studies investigating the role of systemic therapies (chemotherapy, targeted therapy, hormone therapy) in salivary gland cancers. PMID:22558945

  8. Pharmacists’ perceptions of advancing public health priorities through medication therapy management

    PubMed Central

    2016-01-01

    Background: Public health priorities can be addressed by pharmacists through channels such as medication therapy management (MTM) to optimize patient and population outcomes. However, no studies have specifically assessed pharmacists’ perceptions of addressing public health priorities through MTM. Objective: The objective of this study was to assess pharmacists’ opinions regarding the feasibility and appropriateness of addressing seven areas of public health priority through MTM services to impact public health in direct patient care settings. Methods: An anonymous 37-question electronic survey was conducted to evaluate Ohio pharmacists’ opinions of advancing seven public health priorities identified from Healthy People 2020 (family planning, preconception care, smoking cessation, immunizations, nutrition/biometric wellness assessments, point-of-care testing, fall prevention) through MTM activities; to identify potential barriers; and to collect demographic information. The cross-sectional survey was sent to a random sample of 500 pharmacists registered with the Ohio State Board of Pharmacy. Results: Seventy-six pharmacists responded to the survey, resulting in a 16% response rate. On average, it took respondents 5-10 minutes to complete the survey. The majority of respondents thought that each of the seven public health priorities were “important” or “very important” to patient health; the most commonly identified areas included smoking cessation, immunizations, and fall prevention (97.5%). When asked to indicate which of the seven areas they thought they could potentially have a role to provide services through MTM, on average pharmacists picked 4 of the priority areas. Only 6.6% indicated there was no role for pharmacists to provide MTM services for any of the listed categories. Staffing, time, and reimbursement represented the most commonly perceived barriers for pharmacists in providing MTM services. Fifty-seven percent indicated an interest in

  9. A Randomized Controlled Trial of the embrace Advanced Scar Therapy Device to Reduce Incisional Scar Formation

    PubMed Central

    Longaker, Michael T.; Rohrich, Rod J.; Greenberg, Lauren; Furnas, Heather; Wald, Robert; Bansal, Vivek; Seify, Hisham; Tran, Anthony; Weston, Jane; Korman, Joshua M.; Chan, Rodney; Kaufman, David; Dev, Vipul R.; Mele, Joseph A.; Januszyk, Michael; Cowley, Christy; McLaughlin, Peggy; Beasley, Bill; Gurtner, Geoffrey C.; Longaker, Michael T.; Gurtner, Geoffrey C.

    2015-01-01

    Background Scarring represents a significant biomedical burden in clinical medicine. Mechanomodulation has been linked to scarring through inflammation, but until now a systematic approach to attenuate mechanical force and reduce scarring has not been possible. Methods The authors conducted a 12-month, prospective, open-label, randomized, multicenter clinical trial to evaluate abdominoplasty scar appearance following postoperative treatment with the embrace Advanced Scar Therapy device to reduce mechanical forces on healing surgical incisions. Incisions from 65 healthy adult subjects were randomized to receive embrace treatment on one half of an abdominoplasty incision and control treatment (surgeon's optimal care methods) on the other half. The primary endpoint for this study was the difference between assessments of scar appearance for the treated and control sides using the visual analogue scale scar score. Results Final 12-month study photographs were obtained from 36 subjects who completed at least 5 weeks of dressing application. The mean visual analogue scale score for embrace-treated scars (2.90) was significantly improved compared with control-treated scars (3.29) at 12 months (difference, 0.39; 95 percent confidence interval, 0.14 to 0.66; p = 0.027). Both subjects and investigators found that embrace-treated scars demonstrated significant improvements in overall appearance at 12 months using the Patient and Observer Scar Assessment Scale evaluation (p = 0.02 and p < 0.001, respectively). No serious adverse events were reported. Conclusions These results demonstrate that the embrace device significantly reduces scarring following abdominoplasty surgery. To the authors’ knowledge, this represents the first level I evidence for postoperative scar reduction. PMID:24804638

  10. Long-term results of intraoperative electron beam radiation therapy for nonmetastatic locally advanced pancreatic cancer

    PubMed Central

    Chen, Yingtai; Che, Xu; Zhang, Jianwei; Huang, Huang; Zhao, Dongbing; Tian, Yantao; Li, Yexiong; Feng, Qinfu; Zhang, Zhihui; Jiang, Qinglong; Zhang, Shuisheng; Tang, Xiaolong; Huang, Xianghui; Chu, Yunmian; Zhang, Jianghu; Sun, Yuemin; Zhang, Yawei; Wang, Chengfeng

    2016-01-01

    Abstract To assess prognostic benefits of intraoperative electron beam radiation therapy (IOERT) in patients with nonmetastatic locally advanced pancreatic cancer (LAPC) and evaluate optimal adjuvant treatment after IOERT. A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Two hundred forty-seven consecutive patients with nonmetastatic LAPC who underwent IOERT between January 2008 and May 2015 were identified and included in the study. Overall survival (OS) was calculated from the day of IOERT. Prognostic factors were examined using Cox proportional hazards models. The 1-, 2-, and 3-year actuarial survival rates were 40%, 14%, and 7.2%, respectively, with a median OS of 9.0 months. On multivariate analysis, an IOERT applicator diameter < 6 cm (hazards ratio [HR], 0.67; 95% confidence interval [CI], 0.47–0.97), no intraoperative interstitial sustained-release 5-fluorouracil chemotherapy (HR, 0.46; 95% CI, 0.32–0.66), and receipt of postoperative chemoradiotherapy followed by chemotherapy (HR, 0.11; 95% CI, 0.04–0.25) were significantly associated with improved OS. Pain relief after IOERT was achieved in 111 of the 117 patients, with complete remission in 74 and partial remission in 37. Postoperative complications rate and mortality were 14.0% and 0.4%, respectively. Nonmetastatic LAPC patients with smaller size tumors could achieve positive long-term survival outcomes with a treatment strategy incorporating IOERT and postoperative adjuvant treatment. Chemoradiotherapy followed by chemotherapy might be a recommended adjuvant treatment strategy for well-selected cases. Intraoperative interstitial sustained-release 5-fluorouracil chemotherapy should not be recommended for patients with nonmetastatic LAPC. PMID:27661028

  11. Cats protecting birds revisited.

    PubMed

    Fan, Meng; Kuang, Yang; Feng, Zhilan

    2005-09-01

    In this paper, we revisit the dynamical interaction among prey (bird), mesopredator (rat), and superpredator (cat) discussed in [Courchamp, F., Langlais, M., Sugihara, G., 1999. Cats protecting birds: modelling the mesopredator release effect. Journal of Animal Ecology 68, 282-292]. First, we develop a prey-mesopredator-superpredator (i.e., bird-rat-cat, briefly, BRC) model, where the predator's functional responses are derived based on the classical Holling's time budget arguments. Our BRC model overcomes several model construction problems in Courchamp et al. (1999), and admits richer, reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rat or the cat when the bird is endangered. We establish the existence of two types of mesopredator release phenomena: severe mesopredator release, where once superpredators are suppressed, a burst of mesopredators follows which leads their shared prey to extinction; and mild mesopredator release, where the mesopredator release could assert more negative impact on the endemic prey but does not lead the endemic prey to extinction. A sharp sufficient criterion is established for the occurrence of severe mesopredator release. We also show that, in a prey-mesopredator-superpredator trophic food web, eradication of introduced superpredators such as feral domestic cats in the BRC model, is not always the best solution to protect endemic insular prey. The presence of a superpredator may have a beneficial effect in such systems. PMID:15998496

  12. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    PubMed

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia. PMID:27151773

  13. The Feline Mystique: Dispelling the Myth of the Independent Cat.

    ERIC Educational Resources Information Center

    Soltow, Willow

    1984-01-01

    Describes learning activities about cats for primary and intermediate grades. Primary grade activity subjects include cat behavior, needs, breeds, storybook cats, and celestial cats. Intermediate grade activity subjects include cat history, care, language, literary cats, and cats in art. (BC)

  14. Multimodal Therapy including Yttrium-90 Radioembolization as a Bridging Therapy to Liver Transplantation for a Huge and Locally Advanced Intrahepatic Cholangiocarcinoma.

    PubMed

    Rayar, Michel; Levi Sandri, Giovanni Battista; Houssel-Debry, Pauline; Camus, Christophe; Sulpice, Laurent; Boudjema, Karim

    2016-09-01

    Treatment of intrahepatic cholangiocarcinoma remains a major challenge. For an unresectable lesion without extrahepatic spread, liver transplantation could be a potential solution but it is still associated with poor oncologic results owing to the absence of effective neoadjuvant treatment. We report the case of a young man with locally advanced intrahepatic cholangiocarcinoma presenting with multiple intrahepatic metastases and vascular structure involvement. The lesion was significantly downstaged by a multimodal therapy including intra-arterial Yttrium-90 radioembolization, systemic chemotherapy and external radiotherapy, allowing liver transplantation. Three years after the procedure, oncologic outcome is excellent with no sign of recurrence. Multimodal therapy including Yttrium-90 radioembolization could be relevant as neoadjuvant treatment before liver transplantation for unresectable intrahepatic cholangiocarcinoma. PMID:27689207

  15. [Chronic inflammatory bowel diseases in cats].

    PubMed

    Ghermai, A K

    1989-01-01

    The aetiology of chronic idiopathic intestinal inflammation is unknown. It is characterized by a diffuse infiltration with inflammatory cells into the intestinal mucosa and sometimes submucosa. Cats with chronic intermittent vomiting and diarrhoea, later on accompanied by anorexia and weight loss, are presented. Definitive diagnosis can be obtained by intestinal biopsy only. An immune pathogenesis is suspected, which is supported by the fact, that chronic inflammatory bowel disease responds to steroid therapy.

  16. A retrospective study of daylily toxicosis in cats.

    PubMed

    Hadley, R M; Richardson, J A; Gwaltney-Brant, S M

    2003-02-01

    The Easter, Japanese, stargazer and tiger lilies (Lilium sp) are nephrotoxic to cats. This study examined risks posed to cats by the common daylily (Hemerocallis sp: H. dumortierei, H. fulvi, H. graminea, H. seiboldii) following ingestion. Records describing ingestion of Hemerocallis sp between January 1998 and June 2002 were reviewed for signalment, quantity ingested, clinical signs (onset, severity, duration), treatments administered, and outcome. Twenty-two cases of confirmed exposure resulting in toxicosis were evaluated. Cats that ingest daylilies are at risk for gastrointestinal distress and acute renal failure. Successful treatment can be accomplished with early decontamination and aggressive fluid therapy. PMID:12583697

  17. NCCN Task Force Report: Optimizing Treatment of Advanced Renal Cell Carcinoma With Molecular Targeted Therapy

    PubMed Central

    Hudes, Gary R.; Carducci, Michael A.; Choueiri, Toni K.; Esper, Peg; Jonasch, Eric; Kumar, Rashmi; Margolin, Kim A.; Michaelson, M. Dror; Motzer, Robert J.; Pili, Roberto; Roethke, Susan; Srinivas, Sandy

    2015-01-01

    The outcome of patients with metastatic renal cell carcinoma has been substantially improved with administration of the currently available molecularly targeted therapies. However, proper selection of therapy and management of toxicities remain challenging. NCCN convened a multidisciplinary task force panel to address the clinical issues associated with these therapies in attempt to help practicing oncologists optimize patient outcomes. This report summarizes the background data presented at the task force meeting and the ensuing discussion. PMID:21335444

  18. [Declawing in cats?].

    PubMed

    de Jonge, I

    1983-02-15

    Those forms of behaviour in which cats use their claws are reviewed. Forms of undesirable use of the claws and possible solutions to this problem are discussed. An inquiry among veterinary practitioners showed that nearly fifty per cent of these practitioners refused to declaw cats on principle. Approximately seventy-five per cent of the veterinarians taking part in the inquiry advocated that the Royal Netherlands Veterinary Association should state its position with regard to declawing. It is concluded by the present author that declawing is unacceptable for ethical and ethological reasons. PMID:6836550

  19. Current technological advances in magnetic resonance with critical impact for clinical diagnosis and therapy.

    PubMed

    Runge, Val M

    2013-12-01

    The last 5 years of technological advances with major impact on clinical magnetic resonance (MR) are discussed, with greater emphasis on those that are most recent. These developments have already had a critical positive effect on clinical diagnosis and therapy and presage continued rapid improvements for the next 5 years. This review begins with a discussion of 2 topics that encompass the breadth of MR, in terms of anatomic applications, contrast media, and MR angiography. Subsequently, innovations are discussed by anatomic category, picking the areas with the greatest development, starting with the brain, moving forward to the liver and kidney, and concluding with the musculoskeletal system, breast, and prostate. Two final topics are then considered, which will likely, with time, become independent major fields in their own right, interventional MR and MR positron emission tomography (PET).The next decade will bring a new generation of MR contrast media, with research focused on substantial improvements (>100-fold) in relaxivity (contrast effect), thus providing greater efficacy, safety, and tissue targeting. Magnetic resonance angiography will see major advances because of the use of compressed sensing, in terms of spatial and temporal resolution, with movement away from nondynamic imaging. The breadth of available techniques and tissue contrast has greatly expanded in brain imaging, benefiting both from the introduction of new basic categories of imaging techniques, such as readout-segmented echo planar imaging and 3D fast spin echo imaging with variable flip angles, and from new refinements specific to anatomic areas, such as double inversion recovery and MP2RAGE. Liver imaging has benefited from the development of techniques to easily and rapidly assess lipid, and will see, overall, a marked improvement in the next 5 years from new techniques on the verge of clinical introduction, such as controlled aliasing in parallel imaging results in higher acceleration

  20. Community-based treatment of advanced HIV disease: introducing DOT-HAART (directly observed therapy with highly active antiretroviral therapy).

    PubMed Central

    Farmer, P.; Léandre, F.; Mukherjee, J.; Gupta, R.; Tarter, L.; Kim, J. Y.

    2001-01-01

    In 2000, acquired immunodeficiency syndrome (AIDS) overtook tuberculosis (TB) as the world's leading infectious cause of adult deaths. In affluent countries, however, AIDS mortality has dropped sharply, largely because of the use of highly active antiretroviral therapy (HAART). Antiretroviral agents are not yet considered essential medications by international public health experts and are not widely used in the poor countries where human immunodeficiency virus (HIV) takes its greatest toll. Arguments against the use of HAART have mainly been based on the high cost of medications and the lack of the infrastructure necessary for using them wisely. We re- examine these arguments in the setting of rising AIDS mortality in developing countries and falling drug prices, and describe a small community-based treatment programme based on lessons gained in TB control. With the collaboration of Haitian community health workers experienced in the delivery of home-based and directly observed treatment for TB, an AIDS-prevention project was expanded to deliver HAART to a subset of HIV patients deemed most likely to benefit. The inclusion criteria and preliminary results are presented. We conclude that directly observed therapy (DOT) with HAART, "DOT-HAART", can be delivered effectively in poor settings if there is an uninterrupted supply of high-quality drugs. PMID:11799447

  1. Vibrational Schroedinger Cats

    NASA Technical Reports Server (NTRS)

    Kis, Z.; Janszky, J.; Vinogradov, An. V.; Kobayashi, T.

    1996-01-01

    The optical Schroedinger cat states are simple realizations of quantum states having nonclassical features. It is shown that vibrational analogues of such states can be realized in an experiment of double pulse excitation of vibrionic transitions. To track the evolution of the vibrational wave packet we derive a non-unitary time evolution operator so that calculations are made in a quasi Heisenberg picture.

  2. CAT altitude avoidance system

    NASA Technical Reports Server (NTRS)

    Gary, B. L. (Inventor)

    1982-01-01

    A method and apparatus are provided for indicating the altitude of the tropopause or of an inversion layer wherein clear air turbulence (CAT) may occur, and the likely severity of any such CAT, includes directing a passive microwave radiometer on the aircraft at different angles with respect to the horizon. The microwave radiation measured at a frequency of about 55 GHz represents the temperature of the air at an ""average'' range of about 3 kilometers, so that the sine of the angle of the radiometer times 3 kilometers equals the approximate altitude of the air whose temperature is measured. A plot of altitude (with respect to the aircraft) versus temperature of the air at that altitude, can indicate when an inversion layer is present and can indicate the altitude of the tropopause or of such an inversion layer. The plot can also indicate the severity of any CAT in an inversion layer. If CAT has been detected in the general area, then the aircraft can be flown at an altitude to avoid the tropopause or inversion layer.

  3. The molecular cat.

    PubMed

    Pedio, Maddalena; Chergui, Majed

    2009-02-23

    A manifestation of electronic entanglement in core-level spectroscopic measurements of diatomic molecules, reported recently by Schöffler and co-workers, is discussed. The results are reminiscent of Schrödinger's famous Gedanken experiment with the cat (see picture).

  4. Membranous nephropathy in sibling cats.

    PubMed

    Nash, A S; Wright, N G

    1983-08-20

    Membranous nephropathy was diagnosed in two sibling cats from the same household. Both cases presented with the nephrotic syndrome but 33 months elapsed before the second cat became ill, by which time the first cat had been in full clinical remission for over a year. PMID:6623883

  5. Cat Scratch Disease (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Cat Scratch Disease KidsHealth > For Parents > Cat Scratch Disease Print A A A Text Size ... Doctor en español Enfermedad por arañazo de gato Cat scratch disease is a bacterial infection that a ...

  6. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

    PubMed Central

    Li, Kaichun; Li, Jin

    2016-01-01

    Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

  7. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  8. Therapeutic targeting of the phosphatidylinositol 3-kinase signaling pathway: novel targeted therapies and advances in the treatment of colorectal cancer

    PubMed Central

    Yu, Ming

    2012-01-01

    Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the USA, and more effective treatment of CRC is therefore needed. Advances in our understanding of the molecular pathogenesis of this malignancy have led to the development of novel molecule-targeted therapies. Among the most recent classes of targeted therapies being developed are inhibitors targeting the phosphatidylinositol 3-kinase (PI3K) signaling pathway. As one of the most frequently deregulated pathways in several human cancers, including CRC, aberrant PI3K signaling plays an important role in the growth, survival, motility and metabolism of cancer cells. Targeting this pathway therefore has considerable potential to lead to novel and more effective treatments for CRC. Preclinical and early clinical studies have revealed the potential efficacy of drugs that target PI3K signaling for the treatment of CRC. However, a major challenge that remains is to study these agents in phase III clinical trials to see whether these early successes translate into better patient outcomes. In this review we focus on providing an up-to-date assessment of our current understanding of PI3K signaling biology and its deregulation in the molecular pathogenesis of CRC. Advances in available agents and challenges in targeting the PI3K signaling pathway in CRC treatment will be discussed and placed in the context of the currently available therapies for CRC. PMID:22973417

  9. [Advanced radiation therapy project for cancer treatment--from Hokkaido to the world, the world access to Hokkaido].

    PubMed

    Shimizu, Shinichi; Tsuchiya, Kazuhiko; Takao, Seishin; Shirato, Hiroki

    2014-05-01

    Cancer is the most major cause of death in Japan recently. In this symposium, we explained advanced treatment technology for cancer treatment, now used and that will be used in near future at the Hokkaido University Hospital. Intensity Moderated Radiation Therapy (IMRT) and Proton Beam Therapy (PBT) are considered to be the most promising and advanced technologies for cancer treatment. Various kinds of radiation treatment equipment and methods have been developed and constructed at the Hokkaido University. One of the most worlds wide famous one is the real time tumor tracking radiotherapy system. The FIRST (Funding for World-Leading Innovative R&D on Science and Technology) Program has been supporting us to produce cutting-edge technology. We hope that this symposium would help the audience to understand the latest technology for cancer treatment especially in the field of radiation therapy and also we wish the audience would recognize the importance of the research aspect that have been performed at Hokkaido University and its Hospital.

  10. [Recurrence and survival rate of advanced gastric cancer after preoperative EAP-II intra-arterial infusion therapy].

    PubMed

    Masuyama, M; Taniguchi, H; Takeuchi, K; Miyata, K; Koyama, H; Tanaka, H; Higashida, T; Koishi, Y; Mugitani, T; Yamaguchi, T

    1994-09-01

    Ninety-eight patients with advanced gastric cancers underwent gastrectomy from Jan. 1989 to Dec. 1991. For these patients, preoperative intra-arterial injection therapy using EAP-II (etoposide 100 mg, epirubicin 20 mg, carboplatin 100 mg) was given to 24 patients. In this report, the recurrence and survival rate of these patients were investigated. After curative resection, the survival rate of patients with EAP-II 36 months after operation was 76.9%, while that of patients without EAP-II was 78.6%. There were no significant differences between these two groups. Two peritoneal carcinomatoses and two liver metastases were seen in patients with EAP-II (recurrence rate, 30.7%). Eight recurrences were observed in patients without preoperative injection therapy (peritoneal dissemination, 4; local recurrence, 3; lymph node recurrence, 1). Previously, we reported that drugs were remarkably accumulated in gastric cancer tissue and regional lymph nodes after EAP-II intra-arterial injection therapy. This high accumulation might cause no local or lymph node recurrence was seen in patient with EAP-II. Thus, it was concluded that preoperative EAP-II intra-arterial injection may prevent local and lymph node recurrences, and that further study of the combination and dose of anti-cancer drug needed to improve the postoperative survival rate in advanced gastric cancer patients.

  11. Volumetric tumor growth in advanced NSCLC patients with EGFR mutations during EGFR-TKI therapy: Developing criteria to continue therapy beyond RECIST progression

    PubMed Central

    Nishino, Mizuki; Dahlberg, Suzanne E.; Cardarella, Stephanie; Jackman, David M.; Rabin, Michael S.; Ramaiya, Nikhil H.; Hatabu, Hiroto; Jänne, Pasi A.; Johnson, Bruce E.

    2013-01-01

    Purpose Define volumetric tumor growth rate in advanced NSCLC patients with sensitizing EGFR mutations initially treated with EGFR-TKI therapy beyond progression. Methods The study included 58 advanced NSCLC patients with sensitizing EGFR mutations treated with first-line gefitinib or erlotinib, who had baseline CT showing measurable lung lesion and at least two follow-up CTs while on TKI and experienced volumetric tumor growth. Tumor volume (mm3) of the dominant lung lesion was measured on baseline and follow-up CT scans during therapy. A total of 405 volume measurements were analyzed in a linear mixed effects model, fitting time as a random effect, to define the growth rate of the logarithm of tumor volume (logeV). Results A linear mixed effects model was fitted to predict growth of logeV, adjusting for time in months from baseline. LogeV was estimated as a function of time in months, in patients whose tumors have started growing after nadir: logeV=0.12*time+7.68 In this formula, the regression coefficient for time, 0.12/month, represents the growth rate of logeV (SE: 0.015; p<0.001). When adjusted for baseline volume, logeV0, the growth rate was also 0.12/month (SE: 0.015; p<0.001; logeV =0.12*months+0.72 logeV0+0.61). Conclusion Tumor volume models defined volumetric tumor growth after the nadir in EGFR-mutant advanced NSCLC patients receiving TKI, providing a reference value for the tumor growth rate in patients progressing after the nadir on TKI. The results can be further studied in additional cohorts to develop practical criteria which help to identify patients who are slowly progressing and can safely remain on EGFR-TKIs. PMID:23922022

  12. Efficacy of Skin-Directed Therapy for Cutaneous Metastases From Advanced Cancer: A Meta-Analysis

    PubMed Central

    Spratt, Daniel E.; Gordon Spratt, Elizabeth A.; Wu, Shenhong; DeRosa, Antonio; Lee, Nancy Y.; Lacouture, Mario E.; Barker, Christopher A.

    2014-01-01

    Purpose To perform the first meta-analysis of the efficacy of skin-directed therapies for cutaneous metastases. Methods MEDLINE, EMBASE, The Cochrane Library, and ClinicalTrials.gov databases were searched for reports of prospective clinical studies published between 1960 and 2013 that assessed the response of skin-directed therapy for cutaneous metastases (47 of 2,955 unique studies were selected). Primary end points of the study were complete and objective response rates. Secondary analyses were preplanned and included subgroup analyses by skin-directed therapy, histology, and recurrence rates. Meta-analyses were performed with random-effect modeling, and extent of heterogeneity between studies was determined with the Cochran Q and I2 tests. Results After applying exclusion criteria, 47 prospective studies of 4,313 cutaneous metastases were assessed. Five skin-directed therapies were identified: electrochemotherapy, photodynamic therapy, radiotherapy, intralesional therapy, and topical therapy. Among all cutaneous metastases, complete response rate was 35.5% (95% CI, 27.6% to 44.3%) and objective response rate was 60.2% (95% CI, 50.6% to 69.0%). Overall recurrence rate was estimated to be 9.2% (95% CI, 3.7% to 21.2%). Melanoma and breast carcinoma comprised 96.8% of all cutaneous metastases studied and had similar objective response rates (54.5% [95% CI, 48.3% to 60.7%] and 54.0% [95% CI, 48.3% to 59.7%], respectively). Grade ≥ 3 toxicity was reported in less than 6% of patients. Conclusion Response to skin-directed therapy for cutaneous metastases is high but heterogeneous across treatment modalities, with low rates of recurrence post-treatment. Treatment was generally well tolerated and conferred improvements in quality of life. Standardization of response criteria for cutaneous metastases and treatment algorithms to optimally use the available skin-directed therapies are needed. PMID:25154827

  13. [Advances in Bevacizumab Therapy for Non-small Cell Lung Cancer 
with Brain Metastases].

    PubMed

    Qu, Liyan; Geng, Rui; Song, Xia

    2016-08-20

    Brain metastases are frequently encountered in patients with non-small cell lung cancer (NSCLC) and are a significant cause of morbidity and mortality. Antiangiogenesis therapy plays a major role in the management of brain metastases in lung cancer. Bevacizumab have become the novel method for the treatment of lung cancer with brain metastases beyond the whole brain radiation therapy, stereotactic radiosurgery and chemotherapy. Recently, more and more studies and trials laid emphasis on the bevacizumab for NSCLC with brain metastases treatment. The key point is the efficacy and safety. In this review, bevacizumab therapy of NSCLC with brain metastases were summarized. PMID:27561800

  14. [Advances in the research of effects of music therapy on pain and anxiety in burn patients].

    PubMed

    Jinyi, Li; Yungui, Wang

    2015-06-01

    Pain and anxiety engender major psychic problems during all phases of treatment for burn patients. Analgesic alone does not allay these problems satisfactorily in these patients. Music therapy, as an important complementary and alternative therapy, has been widely used in multiple medical fields. However, its positive effect on alleviation of pain and anxiety in burn patients is undefined. The objective of this review is to summarize the feasibility, application fields, methods, and the effectiveness of music therapy in allaying pain and anxiety of burn patients during the whole course of treatment.

  15. [Advances in the research of effects of music therapy on pain and anxiety in burn patients].

    PubMed

    Jinyi, Li; Yungui, Wang

    2015-06-01

    Pain and anxiety engender major psychic problems during all phases of treatment for burn patients. Analgesic alone does not allay these problems satisfactorily in these patients. Music therapy, as an important complementary and alternative therapy, has been widely used in multiple medical fields. However, its positive effect on alleviation of pain and anxiety in burn patients is undefined. The objective of this review is to summarize the feasibility, application fields, methods, and the effectiveness of music therapy in allaying pain and anxiety of burn patients during the whole course of treatment. PMID:26564564

  16. Advances in boron neutron capture therapy (BNCT) at kyoto university - From reactor-based BNCT to accelerator-based BNCT

    NASA Astrophysics Data System (ADS)

    Sakurai, Yoshinori; Tanaka, Hiroki; Takata, Takushi; Fujimoto, Nozomi; Suzuki, Minoru; Masunaga, Shinichiro; Kinashi, Yuko; Kondo, Natsuko; Narabayashi, Masaru; Nakagawa, Yosuke; Watanabe, Tsubasa; Ono, Koji; Maruhashi, Akira

    2015-07-01

    At the Kyoto University Research Reactor Institute (KURRI), a clinical study of boron neutron capture therapy (BNCT) using a neutron irradiation facility installed at the research nuclear reactor has been regularly performed since February 1990. As of November 2014, 510 clinical irradiations were carried out using the reactor-based system. The world's first accelerator-based neutron irradiation system for BNCT clinical irradiation was completed at this institute in early 2009, and the clinical trial using this system was started in 2012. A shift of BCNT from special particle therapy to a general one is now in progress. To promote and support this shift, improvements to the irradiation system, as well as its preparation, and improvements in the physical engineering and the medical physics processes, such as dosimetry systems and quality assurance programs, must be considered. The recent advances in BNCT at KURRI are reported here with a focus on physical engineering and medical physics topics.

  17. EDITORIAL Complexity of advanced radiation therapy necessitates multidisciplinary inquiry into dose reconstruction and risk assessment Complexity of advanced radiation therapy necessitates multidisciplinary inquiry into dose reconstruction and risk assessment

    NASA Astrophysics Data System (ADS)

    Newhauser, Wayne

    2010-07-01

    The availability of low-cost, high-performance computing is rapidly transforming the landscape of cancer research. Computational techniques are playing an increasingly important role and have become the third major method of scientific inquiry, supplementing traditional methods of observation and theory. This evolution began in the 1940s when high-performance computing techniques were developed for military applications, including radiation transport calculations. These same basic methods are still widely utilized in a broad spectrum of computational problems in medicine, including radiation cancer therapy (Rogers 2006, Spezi 2010) and radiologic diagnostic imaging (Doi 2006, Kalender 2006). Supercomputing is also now being used to study the genetics and genomics of cancer (Geurts van Kessel 2010), with application to gene sequencing (Mardis 2008), genome-wide association studies (Pearson and Manolio 2008), biomolecular dynamics (Sanbonmatsu and Tung 2007) and systems biology (Wolkenhauer et al 2010). The extensive and growing body of literature is evidence of a remarkable expansion of activity and enormous boost to cancer research from the application of high-performance computing. Early successes were facilitated by inexpensive computing resources and advances in modeling algorithms. Many contemporary models require extensive approximations and phenomenological approaches. In fact, many critical problems remain computationally intractable; the underlying physical and biological processes are simply too complex to model with contemporary theory and computing capacity. In the future, a vast stream of new insights will flow from studies that use increasingly exact models and first-principles approaches. Hence, in the war on cancer the present status of computational research could be summarized as the beginning of the beginning. For these reasons, there is a vital need for scientists and clinicians to periodically discuss progress and future plans regarding

  18. Cat scratch disease in an immunosuppressed patient with systemic lupus erythematosus.

    PubMed

    Vargas-Hitos, J A; Sabio, J M; Navarrete-Navarrete, N; Arenas-Miras, M del M; Zamora-Pasadas, M; Jiménez-Alonso, J

    2016-03-01

    Cat scratch disease is an infectious disorder transmitted by cats that typically affects children and young adults. Immunosuppression is a well-known risk factor for the development of severe and atypical forms of the disease; hence it is under-diagnosed in patients with compromised immunity. We are reporting the first case of cat scratch disease, which presented as fever and fatigue, in a patient with systemic lupus erythematosus while receiving immunosuppressant therapy after a kidney transplant.

  19. Genetic testing in domestic cats.

    PubMed

    Lyons, Leslie A

    2012-12-01

    Varieties of genetic tests are currently available for the domestic cat that support veterinary health care, breed management, species identification, and forensic investigations. Approximately thirty-five genes contain over fifty mutations that cause feline health problems or alterations in the cat's appearance. Specific genes, such as sweet and drug receptors, have been knocked-out of Felidae during evolution and can be used along with mtDNA markers for species identification. Both STR and SNP panels differentiate cat race, breed, and individual identity, as well as gender-specific markers to determine sex of an individual. Cat genetic tests are common offerings for commercial laboratories, allowing both the veterinary clinician and the private owner to obtain DNA test results. This article will review the genetic tests for the domestic cat, and their various applications in different fields of science. Highlighted are genetic tests specific to the individual cat, which are a part of the cat's genome.

  20. NRF2 Mutation Confers Malignant Potential and Resistance to Chemoradiation Therapy in Advanced Esophageal Squamous Cancer1

    PubMed Central

    Shibata, Tatsuhiro; Kokubu, Akiko; Saito, Shigeru; Narisawa-Saito, Mako; Sasaki, Hiroki; Aoyagi, Kazuhiko; Yoshimatsu, Yuki; Tachimori, Yuji; Kushima, Ryoji; Kiyono, Tohru; Yamamoto, Masayuki

    2011-01-01

    Esophageal squamous cancer (ESC) is one of the most aggressive tumors of the gastrointestinal tract. A combination of chemotherapy and radiation therapy (CRT) has improved the clinical outcome, but the molecular background determining the effectiveness of therapy remains unknown. NRF2 is a master transcriptional regulator of stress adaptation, and gain of-function mutation of NRF2 in cancer confers resistance to stressors including anticancer therapy. Direct resequencing analysis revealed that Nrf2 gain-of-function mutation occurred recurrently (18/82, 22%) in advanced ESC tumors and ESC cell lines (3/10). The presence of Nrf2 mutation was associated with tumor recurrence and poor prognosis. Short hairpin RNA-mediated down-regulation of NRF2 in ESC cells that harbor only mutated Nrf2 allele revealed that themutant NRF2 conferred increased cell proliferation, attachment-independent survival, and resistance to 5-fluorouracil and γ-irradiation. Based on the Nrf2 mutation status, gene expression signatures associated with NRF2 mutation were extracted from ESC cell lines, and their potential utility for monitoring and prognosis was examined in a cohort of 33 pre-CRT cases of ESC. The molecular signatures of NRF2 mutation were significantly predictive and prognostic for CRT response. In conclusion, recurrent NRF2 mutation confers malignant potential and resistance to therapy in advanced ESC, resulting in a poorer outcome. Molecular signatures of NRF2 mutation can be applied as predictive markers of response to CRT, and efficient inhibition of aberrant NRF2 activation could be a promising approach in combination with CRT. PMID:21969819

  1. Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer

    PubMed Central

    Houston, S J; Plunkett, T A; Barnes, D M; Smith, P; Rubens, R D; Miles, D W

    1999-01-01

    The present study investigated the interaction between c-erbB2 overexpression and the response to first-line endocrine therapy in patients with advanced breast cancer. The primary tumours of 241 patients who were treated at first relapse with endocrine therapy were assessed for overexpression of c-erbB2 by immunohistochemistry. c-erbB2 was overexpressed in 76 (32%) of primary breast cancers and did not correlate with any other prognostic factor. The overall response to treatment and time to progression were significantly lower in patients with c-erbB2-positive tumours compared to those that were c-erbB2-negative (38% vs 56%, P = 0.02; and 4.1 months vs 8.7 months, P < 0.001, respectively). In multivariate analysis, c-erbB2 status was the most significant predictive factor for a short time to progression (P = 0.0009). In patients with ER-positive primary tumours treated at relapse with tamoxifen (n = 170), overexpression of c-erbB2 was associated with a significantly shorter time to progression (5.5 months vs 11.2 months, P < 0.001). In conclusion, overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. In patients with ER-positive primary tumours, the overexpression of c-erbB2 defines a subgroup less likely to respond to endocrine therapy. © 1999 Cancer Research Campaign PMID:10098763

  2. The Modern Role of Radiation Therapy in Treating Advanced-Stage Retinoblastoma: Long-Term Outcomes and Racial Differences

    SciTech Connect

    Orman, Amber; Koru-Sengul, Tulay; Miao, Feng; Markoe, Arnold; Panoff, Joseph E.

    2014-12-01

    Purpose/Objective(s): To evaluate the effects of various patient characteristics and radiation therapy treatment variables on outcomes in advanced-stage retinoblastoma. Methods and Materials: This was a retrospective review of 41 eyes of 30 patients treated with external beam radiation therapy between June 1, 1992, and March 31, 2012, with a median follow-up time of 133 months (11 years). Outcome measures included overall survival, progression-free survival, local control, eye preservation rate, and toxicity. Results: Over 90% of the eyes were stage V. Definitive external beam radiation therapy (EBRT) was delivered in 43.9% of eyes, adjuvant EBRT in 22% of eyes, and second-line/salvage EBRT in 34.1% of eyes. A relative lens sparing (RLS) technique was used in 68.3% of eyes and modified lens sparing (MLS) in 24.4% of eyes. Three eyes were treated with other techniques. Doses ≥45 Gy were used in 68.3% of eyes. Chemotherapy was a component of treatment in 53.7% of eyes. The 10-year overall survival was 87.7%, progression-free survival was 80.5%, and local control was 87.8%. White patients had significantly better overall survival than did African-American patients in univariate analysis (hazard ratio 0.09; 95% confidence interval 0.01-0.84; P=.035). Toxicity was seen in 68.3% of eyes, including 24.3% with isolated acute dermatitis. Conclusions: External beam radiation therapy continues to be an effective treatment modality for advanced retinoblastoma, achieving excellent long-term local control and survival with low rates of treatment-related toxicity and secondary malignancy.

  3. Regulation of nanomedicines in the EU: distilling lessons from the pediatric and the advanced therapy medicinal products approaches.

    PubMed

    Chowdhury, Nupur

    2010-01-01

    As the market for nanomedicines in the EU is growing, the development of regulatory guidance in this area assumes priority. Currently, the nanomedicine market is poised at a critical stage wherein clear regulatory guidance is imperative in providing for clarity and legal certainty to manufacturers of nanomedicine. The regulation of the pharmaceutical sector in the EU has witnessed several developments and innovations guided by the philosophy of single market and balancing the principle of ensuring high public health protection and safety of medicines. Both the pediatric and the advanced therapies medicinal products (ATMP) regimes offer important regulatory guidance that could be adopted for the regulation of nanomedicines in the EU.

  4. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    PubMed

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.

  5. Advanced gastric cancer (GC) and cancer of the gastro-oesophageal junction (GEJ): focus on targeted therapies.

    PubMed

    Cappetta, Alessandro; Lonardi, Sara; Pastorelli, Davide; Bergamo, Francesca; Lombardi, Giuseppe; Zagonel, Vittorina

    2012-01-01

    Despite recent improvements in surgical techniques and chemotherapy treatments, locally advanced/metastatic gastroesophageal junction (GEJ) and gastric cancer (GC) are still associated with poor clinical outcome. However, increased understanding of molecular mechanisms underlying carcinogenesis and its implementation in the treatment of breast, colon, lung, and other cancers in recent years have spurred focus on the development and incorporation of targeted agents in current therapeutic options for this difficult-to-treat disease. Such agents have the ability to target a variety of cancer relevant targets, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) and its receptor. In this review, we describe the current status of targeted therapies in the treatment of advanced GC and GEJ cancer, focusing on pre-clinical and clinical data available on monoclonal antibodies and tyrosine kinase inhibitors acting in these pathways, including completed and ongoing phase III studies.

  6. AIR: Advances in Respiration - Music therapy in the treatment of chronic pulmonary disease.

    PubMed

    Canga, Bernardo; Azoulay, Ronit; Raskin, Jonathan; Loewy, Joanne

    2015-12-01

    The aim of this randomized control study is to examine the effect of a multimodal psycho-music therapy intervention on respiratory symptoms, psychological well-being and quality of life of patients with Chronic Obstructive Pulmonary Disease and other lung diseases as adjunct to Pulmonary Rehabilitation with a design of music therapy plus PR compared to Pulmonary Rehabilitation alone. Music therapy group treatment including music visualization, wind playing and singing was provided weekly. This was compared with standard care treatment. Adults ages 48 to 88 (mean 70.1) with moderate to severe GOLD stage II-IV lung disease as well as other diseases processes that lead to chronic airflow limitations were included (n = 98). Participants in both conditions were followed from baseline enrollment to six weeks post control/treatment. Outcome measures included the Beck Depression Inventory Scale 2nd edition-Fast Screen (BDI-FS), Chronic Respiratory Questionnaire Self-Reported (CRQ-SR), and Dyspnea Visual Analog Scale (VAS). Results showed improvement in symptoms of depression (LS mean -0.2) in the music therapy group with statistical divergence between groups (p = 0.007). The CRQ-SR demonstrated improvement in dyspnea (p = 0.01 LS mean 0.5) and mastery (p = 0.06 LS mean 0.5) in the music therapy group and fatigue (p = 0.01 LS mean 0.3). VAS demonstrated highly significant effect in the music therapy group between weeks 5 and 6 (p < 0.001). The findings of this study suggest that music therapy combined with standard PR may prove to be an effective modality in the management of pulmonary disease.

  7. Associations of ATM Polymorphisms With Survival in Advanced Esophageal Squamous Cell Carcinoma Patients Receiving Radiation Therapy

    SciTech Connect

    Du, Zhongli; Zhang, Wencheng; Zhou, Yuling; Yu, Dianke; Chen, Xiabin; Chang, Jiang; Qiao, Yan; Zhang, Meng; Huang, Ying; Wu, Chen; Xiao, Zefen; Tan, Wen; and others

    2015-09-01

    Purpose: To investigate whether single nucleotide polymorphisms (SNPs) in the ataxia telangiectasia mutated (ATM) gene are associated with survival in patients with esophageal squamous cell carcinoma (ESCC) receiving radiation therapy or chemoradiation therapy or surgery only. Methods and Materials: Four tagSNPs of ATM were genotyped in 412 individuals with clinical stage III or IV ESCC receiving radiation therapy or chemoradiation therapy, and in 388 individuals with stage I, II, or III ESCC treated with surgery only. Overall survival time of ESCC among different genotypes was estimated by Kaplan-Meier plot, and the significance was examined by log-rank test. The hazard ratios (HRs) and 95% confidence intervals (CIs) for death from ESCC among different genotypes were computed by a Cox proportional regression model. Results: We found 2 SNPs, rs664143 and rs664677, associated with survival time of ESCC patients receiving radiation therapy. Individuals with the rs664143A allele had poorer median survival time compared with the rs664143G allele (14.0 vs 20.0 months), with the HR for death being 1.45 (95% CI 1.12-1.89). Individuals with the rs664677C allele also had worse median survival time than those with the rs664677T allele (14.0 vs 23.5 months), with the HR of 1.57 (95% CI 1.18-2.08). Stratified analysis showed that these associations were present in both stage III and IV cancer and different radiation therapy techniques. Significant associations were also found between the SNPs and locosregional progression or progression-free survival. No association between these SNPs and survival time was detected in ESCC patients treated with surgery only. Conclusion: These results suggest that the ATM polymorphisms might serve as independent biomarkers for predicting prognosis in ESCC patients receiving radiation therapy.

  8. Streptococcus canis arthritis in a cat breeding colony.

    PubMed

    Iglauer, F; Kunstýr, I; Mörstedt, R; Farouq, H; Wullenweber, M; Damsch, S

    1991-01-01

    This is the first description of a pathologic condition--arthritis in cats affecting mainly one joint, i.e. monarthritis--caused by Streptococcus canis (S. canis), of the Lancefield serologic group G. Six cases were recorded in a closed cat breeding colony during a 6 month period in 1988, and one additional case in 1990. Therapy with penicillin and streptomycin led to full recovery in four of six cases. The bacterium had been detected from different purulent processes sporadically--including one case of purulent arthritis in 1982--as a nosocomial infection since 1980, the year the breeding colony was established. A possible genetic predisposition (high inbreeding) may have contributed to the accumulation of the six cases in 1988. Although S. canis was isolated in mouse, rat, rabbit and dog, cat and man seem to be more frequently affected. There are some similarities between S. canis-arthritis in cat and man.

  9. Cat scratch disease.

    PubMed

    Bozhkov, V; Madjov, R; Plachkov, I; Arnaudov, P; Chernopolsky, P; Krasnaliev, I

    2014-01-01

    Approximately 24,000 people are infected with cat scratch disease (CSD) every year. CSD is caused by the bacteria Bartonella henselae, a gram-negative bacteria most often transmitted to humans through a bite or scratch from an infected cat or kitten. Although CSD is often a benign and self-limiting condition, it can affect any major organ system in the body, manifesting in different ways and sometimes leading to lifelong sequelae. It is a disease that is often overlooked in primary care because of the wide range of symptom presentation and relative rarity of serious complications. It is important for health care providers to recognize patients at risk for CSD, know what laboratory testing and treatments are available, and be aware of complications that may arise from this disease in the future.

  10. Crystallized Schroedinger cat states

    SciTech Connect

    Castanos, O.; Lopez-Pena, R.; Man`ko, V.I.

    1995-11-01

    Crystallized Schroedinger cat states (male and female) are introduced on the base of extension of group construction for the even and odd coherent states of the electromagnetic field oscillator. The Wigner and Q functions are calculated and some are plotted for C{sub 2}, C{sub 3}, C{sub 4}, C{sub 5}, C{sub 3v} Schroedinger cat states. Quadrature means and dispersions for these states are calculated and squeezing and correlation phenomena are studied. Photon distribution functions for these states are given explicitly and are plotted for several examples. A strong oscillatory behavior of the photon distribution function for some field amplitudes is found in the new type of states.

  11. Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head

    PubMed Central

    Ma, Yue Wen; Jiang, Dong Lei; Zhang, Dai; Wang, Xiao Bei; Yu, Xiao Tong

    2016-01-01

    ABSTRACT This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients. PMID:27003206

  12. Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head.

    PubMed

    Ma, Yue Wen; Jiang, Dong Lei; Zhang, Dai; Wang, Xiao Bei; Yu, Xiao Tong

    2016-09-01

    This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients. PMID:27003206

  13. Rethinking end-points for bone-targeted therapy in advanced cancer.

    PubMed

    Gómez García, Susana; Clemons, Mark; Amir, Eitan

    2016-08-01

    The principal objective for any medical therapy is to improve either the duration of life and/or its quality. Metastases in bone can lead to clinically defined events termed skeletal-related events (SREs) which are a quantifiable measure of skeletal morbidity. Avoidance and/or delay of SREs have become the principal objective in trials exploring the efficacy of bone-targeted therapy in patients with skeletal metastases. Despite reductions in the frequency or rate of SRE occurrence, trials of bone-targeted therapy have failed to show any effect on either progression-free or overall survival when compared with placebo or other bone-targeting agents. Similarly, trials of bone-targeted therapy have not shown consistent effects on quality of life. The validity of SRE-based primary outcome measures in cancer clinical trials is therefore, questionable. More novel end-point selection for trials of bone-targeted therapy seems warranted. Composite measures comprising occurrence of symptomatic skeletal events and patient reported outcomes may be an effective solution and warrants further investigation. PMID:27299662

  14. Radial Extracorporeal Shock Wave Therapy in a Person With Advanced Osteonecrosis of the Femoral Head.

    PubMed

    Ma, Yue Wen; Jiang, Dong Lei; Zhang, Dai; Wang, Xiao Bei; Yu, Xiao Tong

    2016-09-01

    This case report describes the first patient with avascular necrosis of the femoral head of Association Research Circulation Osseous stage IV, treated with radial extracorporeal shock wave therapy. By contrast, previous studies demonstrated the efficacy of a single treatment of focused extracorporeal shock wave therapy in improving pain and Harris Hip Scale in patients with avascular necrosis of the femoral head of Association Research Circulation Osseous stage I to III. The affected hip was treated with 6000 impulses of radial extracorporeal shock wave therapy at 10 Hz and an intensity ranging from 2.5 to 4.0 bar at 7-day intervals for 24 mos. The Harris Hip Scale values were 33, 43, 56, 77, 81, 88, and 92 at baseline and 1, 3, 6, 12, 18, and 24 mos, respectively. The radiographs showed that the subluxation of the right hip was slightly aggravated. Joint effusion was reduced, bone marrow edema disappeared, the density became more uniform, and the gluteal muscles were more developed based on magnetic resonance imaging. Increased tracer uptake was evident along the joint margin and superolateral aspect of the head both before and after radial extracorporeal shock wave therapy. This case report demonstrates the feasibility of long-term radial extracorporeal shock wave therapy in Association Research Circulation Osseous stage IV patients.

  15. Dose Escalation for Locally Advanced Lung Cancer Using Adaptive Radiation Therapy With Simultaneous Integrated Volume-Adapted Boost

    SciTech Connect

    Weiss, Elisabeth; Fatyga, Mirek; Wu, Yan; Dogan, Nesrin; Balik, Salim; Sleeman, William; Hugo, Geoffrey

    2013-07-01

    Purpose: To test the feasibility of a planned phase 1 study of image-guided adaptive radiation therapy in locally advanced lung cancer. Methods and Materials: Weekly 4-dimensional fan beam computed tomographs (4D FBCT) of 10 lung cancer patients undergoing concurrent chemoradiation therapy were used to simulate adaptive radiation therapy: After an initial intensity modulated radiation therapy plan (0-30 Gy/2 Gy), adaptive replanning was performed on week 2 (30-50 Gy/2 Gy) and week 4 scans (50-66 Gy/2 Gy) to adjust for volume and shape changes of primary tumors and lymph nodes. Week 2 and 4 clinical target volumes (CTV) were deformably warped from the initial planning scan to adjust for anatomical changes. On the week 4 scan, a simultaneous integrated volume-adapted boost was created to the shrunken primary tumor with dose increases in 5 0.4-Gy steps from 66 Gy to 82 Gy in 2 scenarios: plan A, lung isotoxicity; plan B, normal tissue tolerance. Cumulative dose was assessed by deformably mapping and accumulating biologically equivalent dose normalized to 2 Gy-fractions (EQD2). Results: The 82-Gy level was achieved in 1 in 10 patients in scenario A, resulting in a 13.4-Gy EQD2 increase and a 22.1% increase in tumor control probability (TCP) compared to the 66-Gy plan. In scenario B, 2 patients reached the 82-Gy level with a 13.9 Gy EQD2 and 23.4% TCP increase. Conclusions: The tested image-guided adaptive radiation therapy strategy enabled relevant increases in EQD2 and TCP. Normal tissue was often dose limiting, indicating a need to modify the present study design before clinical implementation.

  16. Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma

    PubMed Central

    Shaikh, Atik Badshah; Li, Fangfei; Li, Min; He, Bing; He, Xiaojuan; Chen, Guofen; Guo, Baosheng; Li, Defang; Jiang, Feng; Dang, Lei; Zheng, Shaowei; Liang, Chao; Liu, Jin; Lu, Cheng; Liu, Biao; Lu, Jun; Wang, Luyao; Lu, Aiping; Zhang, Ge

    2016-01-01

    Osteosarcoma (OS) is a bone cancer mostly occurring in pediatric population. Current treatment regime of surgery and intensive chemotherapy could cure about 60%–75% patients with primary osteosarcoma, however only 15% to 30% can be cured when pulmonary metastasis or relapse has taken place. Hence, novel precise OS-targeting therapies are being developed with the hope of addressing this issue. This review summarizes the current development of molecular mechanisms and targets for osteosarcoma. Therapies that target these mechanisms with updated information on clinical trials are also reviewed. Meanwhile, we further discuss novel therapeutic targets and OS-targeting drug delivery systems. In conclusion, a full insight in OS pathogenesis and OS-targeting strategies would help us explore novel targeted therapies for metastatic osteosarcoma. PMID:27058531

  17. Bone marrow derived stem cells in regenerative medicine as advanced therapy medicinal products.

    PubMed

    Astori, Giuseppe; Soncin, Sabrina; Lo Cicero, Viviana; Siclari, Francesco; Sürder, Daniel; Turchetto, Lucia; Soldati, Gianni; Moccetti, Tiziano

    2010-05-15

    Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cell-based therapies. Clinical trial results, have revealed both safety and efficacy of the cell reinfusion procedure in many cardiovascular diseases. Many of these early clinical trials were performed in a period before the entry into force of the US and European regulation on cell-based therapies. As a result, conflicting data have been generated on the effectiveness of those therapies in certain conditions as acute myocardial infarction. As more academic medical centers and private companies move toward exploiting the full potential of cell-based medicinal products, needs arise for the development of the infrastructure necessary to support these investigations. This review describes the regulatory environment surrounding the production of cell based medicinal products and give practical aspects for cell isolation, characterization, production following Good Manufacturing Practice, focusing on the activities associated with the investigational new drug development.

  18. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    PubMed

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  19. Neoadjuvant therapy and surgical resection for locally advanced non-small cell lung cancer.

    PubMed

    Meko, J; Rusch, V W

    2000-10-01

    During the past 15 years, treatment of stage IIIA (N2) non-small cell lung cancer has evolved considerably because of improvements in patients selection, staging, and combined modality therapy. Results of several clinical trials suggest that induction chemotherapy or chemoradiation and surgical resection is superior to surgery alone. However, the optimal induction regimen has not been defined. An intergroup trial is also underway to determine whether chemoradiation and surgical resection leads to better survival than chemotherapy and radiation alone. Future studies will assess ways to combine radiation and novel chemotherapeutic agents, and will identify molecular abnormalities that predict response to induction therapy.

  20. Automated, Miniaturized and Integrated Quality Control-on-Chip (QC-on-a-Chip) for Advanced Cell Therapy Applications

    NASA Astrophysics Data System (ADS)

    Wartmann, David; Rothbauer, Mario; Kuten, Olga; Barresi, Caterina; Visus, Carmen; Felzmann, Thomas; Ertl, Peter

    2015-09-01

    The combination of microfabrication-based technologies with cell biology has laid the foundation for the development of advanced in vitro diagnostic systems capable of evaluating cell cultures under defined, reproducible and standardizable measurement conditions. In the present review we describe recent lab-on-a-chip developments for cell analysis and how these methodologies could improve standard quality control in the field of manufacturing cell-based vaccines for clinical purposes. We highlight in particular the regulatory requirements for advanced cell therapy applications using as an example dendritic cell-based cancer vaccines to describe the tangible advantages of microfluidic devices that overcome most of the challenges associated with automation, miniaturization and integration of cell-based assays. As its main advantage lab-on-a-chip technology allows for precise regulation of culturing conditions, while simultaneously monitoring cell relevant parameters using embedded sensory systems. State-of-the-art lab-on-a-chip platforms for in vitro assessment of cell cultures and their potential future applications for cell therapies and cancer immunotherapy are discussed in the present review.

  1. Advances in Computational Radiation Biophysics for Cancer Therapy: Simulating Nano-Scale Damage by Low-Energy Electrons

    NASA Astrophysics Data System (ADS)

    Kuncic, Zdenka

    Computational radiation biophysics is a rapidly growing area that is contributing, alongside new hardware technologies, to ongoing developments in cancer imaging and therapy. Recent advances in theoretical and computational modeling have enabled the simulation of discrete, event-by-event interactions of very low energy (≪ 100 eV) electrons with water in its liquid thermodynamic phase. This represents a significant advance in our ability to investigate the initial stages of radiation induced biological damage at the molecular level. Such studies are important for the development of novel cancer treatment strategies, an example of which is given by microbeam radiation therapy (MRT). Here, new results are shown demonstrating that when excitations and ionizations are resolved down to nano-scales, their distribution extends well outside the primary microbeam path, into regions that are not directly irradiated. This suggests that radiation dose alone is insufficient to fully quantify biological damage. These results also suggest that the radiation cross-fire may be an important clue to understanding the different observed responses of healthy cells and tumor cells to MRT.

  2. Advances in Computational Radiation Biophysics for Cancer Therapy: Simulating Nano-Scale Damage by Low-Energy Electrons

    NASA Astrophysics Data System (ADS)

    Kuncic, Zdenka

    2015-10-01

    Computational radiation biophysics is a rapidly growing area that is contributing, alongside new hardware technologies, to ongoing developments in cancer imaging and therapy. Recent advances in theoretical and computational modeling have enabled the simulation of discrete, event-by-event interactions of very low energy (≪ 100 eV) electrons with water in its liquid thermodynamic phase. This represents a significant advance in our ability to investigate the initial stages of radiation induced biological damage at the molecular level. Such studies are important for the development of novel cancer treatment strategies, an example of which is given by microbeam radiation therapy (MRT). Here, new results are shown demonstrating that when excitations and ionizations are resolved down to nano-scales, their distribution extends well outside the primary microbeam path, into regions that are not directly irradiated. This suggests that radiation dose alone is insufficient to fully quantify biological damage. These results also suggest that the radiation cross-fire may be an important clue to understanding the different observed responses of healthy cells and tumor cells to MRT.

  3. 1993 CAT workshop on beamline optical designs

    SciTech Connect

    Not Available

    1993-11-01

    An Advanced Photon Source (APS) Collaborative Access Team (CAT) Workshop on Beamline Optical Designs was held at Argonne National Laboratory on July 26--27, 1993. The goal of this workshop was to bring together experts from various synchrotron sources to provide status reports on crystal, reflecting, and polarizing optics as a baseline for discussions of issues facing optical designers for CAT beamlines at the APS. Speakers from the European Synchrotron Radiation Facility (ESRF), the University of Chicago, the National Synchrotron Light Source, and the University of Manchester (England) described single- and double-crystal monochromators, mirrors, glass capillaries, and polarizing optics. Following these presentations, the 90 participants divided into three working groups: Crystal Optics Design, Reflecting Optics, and Optics for Polarization Studies. This volume contains copies of the presentation materials from all speakers, summaries of the three working groups, and a ``catalog`` of various monochromator designs.

  4. [A case of advanced esophageal cancer with liver metastases: efficacy of combination therapy of docetaxel/cisplatin/5-FU].

    PubMed

    Ehara, Kazuhisa; Tsutsumi, Kenji; Kinoshita, Yoshihiro; Ueno, Masaki; Mine, Shinji; Udagawa, Harushi

    2008-08-01

    The combination chemotherapy with docetaxel/CDDP/5-FU(DCF)for head and neck squamous carcinoma(SCC) has been widely accepted. It seems quite natural that DCF therapy is expected to be equally effective against esophageal SCC because of their histological similarity. In this report, we present a case of unresectable advanced esophageal SCC with multiple liver metastases which showed remarkable regression by DCF therapy, with relatively slight adverse effects. The patient was a 46-year-old female, who underwent upper gastrointestinal fiber-optic endoscopy for dysphasia and was diagnosed to have upper middle thoracic esophageal SCC. Abdominal CT scan showed multiple liver metastases with para-aortic lymph node involvement. The clinical stage diagnosis was T3N4M1, Stage IVB, obviously non-resectable far-advanced esophageal SCC. Systemic chemotherapy with DCF was started as the initial treatment. The chemotherapy regimen was as follows. 5-FU 500 mg/m(2) was administered as continuous intravenous infusion through day 1 to 5, while docetaxl 60 mg/m(2) and cisplatin 50 mg/m(2) were given intravenously on day 2. Each course was followed by a 23-day drug-free period, and the entire course was repeated every 28 days. Ten cycles of this DCF chemotherapy were carried out. After 4 cycles, primary lesion was judged as complete response(CR)by endoscopy. After 8 cycles, the liver metastases were judged as CR and para-aortic lymph nodes showed a partial response(PR)by CT scan. After 10 cycles, all we could detect was a small local recurrence of the primary tumor, which was then treated with chemoradiotherapy at the outpatient clinic. Until this writing, we added 2 more cycles of DCF therapy for the recurrent para-aortic and inguinal lymph node metastasis. Three years have passed from her first visit, and the patient is still in a stable disease state. The adverse effects were grade 3 at most in both hematological and non-hematological toxicity. We conclude that DCF therapy is

  5. Safety and Benefit of Discontinuing Statin Therapy in the Setting of Advanced, Life-Limiting Illness

    PubMed Central

    Kutner, Jean S.; Blatchford, Patrick J.; Taylor, Don H.; Ritchie, Christine S.; Bull, Janet H.; Fairclough, Diane L.; Hanson, Laura C.; LeBlanc, Thomas W.; Samsa, Greg P.; Wolf, Steven; Aziz, Noreen M.; Currow, David C.; Ferrell, Betty; Wagner-Johnston, Nina; Zafar, S. Yousuf; Cleary, James F.; Dev, Sandesh; Goode, Patricia S.; Kamal, Arif H.; Kassner, Cordt; Kvale, Elizabeth A.; McCallum, Janelle G.; Ogunseitan, Adeboye B.; Pantilat, Steven Z.; Portenoy, Russell K.; Prince-Paul, Maryjo; Sloan, Jeff A.; Swetz, Keith M.; Von Gunten, Charles F.; Abernethy, Amy P.

    2015-01-01

    IMPORTANCE For patients with limited prognosis, some medication risks may outweigh the benefits, particularly when benefits take years to accrue; statins are one example. Data are lacking regarding the risks and benefits of discontinuing statin therapy for patients with limited life expectancy. OBJECTIVE To evaluate the safety, clinical, and cost impact of discontinuing statin medications for patients in the palliative care setting. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, parallel-group, unblinded, pragmatic clinical trial. Eligibility included adults with an estimated life expectancy of between 1 month and 1 year, statin therapy for 3 months or more for primary or secondary prevention of cardiovascular disease, recent deterioration in functional status, and no recent active cardiovascular disease. Participants were randomized to either discontinue or continue statin therapy and were monitored monthly for up to 1 year. The study was conducted from June 3, 2011, to May 2, 2013. All analyses were performed using an intent-to-treat approach. INTERVENTIONS Statin therapy was withdrawn from eligible patients who were randomized to the discontinuation group. Patients in the continuation group continued to receive statins. MAIN OUTCOMES AND MEASURES Outcomes included death within 60 days (primary outcome), survival, cardiovascular events, performance status, quality of life (QOL), symptoms, number of nonstatin medications, and cost savings. RESULTS A total of 381 patients were enrolled; 189 of these were randomized to discontinue statins, and 192 were randomized to continue therapy. Mean (SD) age was 74.1 (11.6) years, 22.0% of the participants were cognitively impaired, and 48.8% had cancer. The proportion of participants in the discontinuation vs continuation groups who died within 60 days was not significantly different (23.8% vs 20.3%; 90% CI, −3.5% to 10.5%; P = .36) and did not meet the noninferiority end point. Total QOL was better for the group

  6. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation.

    PubMed

    Rincon, Melvin Y; VandenDriessche, Thierry; Chuah, Marinee K

    2015-10-01

    Gene therapy is a promising modality for the treatment of inherited and acquired cardiovascular diseases. The identification of the molecular pathways involved in the pathophysiology of heart failure and other associated cardiac diseases led to encouraging preclinical gene therapy studies in small and large animal models. However, the initial clinical results yielded only modest or no improvement in clinical endpoints. The presence of neutralizing antibodies and cellular immune responses directed against the viral vector and/or the gene-modified cells, the insufficient gene expression levels, and the limited gene transduction efficiencies accounted for the overall limited clinical improvements. Nevertheless, further improvements of the gene delivery technology and a better understanding of the underlying biology fostered renewed interest in gene therapy for heart failure. In particular, improved vectors based on emerging cardiotropic serotypes of the adeno-associated viral vector (AAV) are particularly well suited to coax expression of therapeutic genes in the heart. This led to new clinical trials based on the delivery of the sarcoplasmic reticulum Ca(2+)-ATPase protein (SERCA2a). Though the first clinical results were encouraging, a recent Phase IIb trial did not confirm the beneficial clinical outcomes that were initially reported. New approaches based on S100A1 and adenylate cyclase 6 are also being considered for clinical applications. Emerging paradigms based on the use of miRNA regulation or CRISPR/Cas9-based genome engineering open new therapeutic perspectives for treating cardiovascular diseases by gene therapy. Nevertheless, the continuous improvement of cardiac gene delivery is needed to allow the use of safer and more effective vector doses, ultimately bringing gene therapy for heart failure one step closer to reality.

  7. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

    PubMed

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2015-09-22

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients.

  8. [The certification of advanced therapy medicinal products. A quality label for product development in small and medium-sized enterprises].

    PubMed

    Berger, A; Schüle, S; Flory, E

    2011-07-01

    Advanced therapy medicinal products (ATMPs) are gene therapy, cell therapy, and tissue engineered products. To gain access to the market within the European Union, ATMPs must be authorized by the European Commission (EC). Especially for small and medium-sized enterprises (SMEs), the European centralized procedure of marketing authorization that is conducted by the European Medicines Agency (EMA) constitutes a major challenge, because SMEs often have little experience with regulatory procedures and many have limited financial possibilities. To tackle these challenges, a certification procedure exclusively for SMEs and their ATMP development was introduced by the EC. Independently from a marketing authorization application, development and/or production processes can be certified. An issued certificate demonstrates that the respective process meets the current regulatory and scientific requirements of the EMA, representing a valuable milestone for putative investors and licensees. This article highlights the background, the detailed procedure, the minimum requirements, as well as the costs of certification, while giving further noteworthy guidance for interested parties.

  9. Advanced Therapy Medicinal Products and Exemptions to the Regulation 1394/2007: How Confident Can We be? An Exploratory Analysis.

    PubMed

    Van Wilder, Philippe

    2012-01-01

    The market authorization procedure for medicinal products for human use is relying on their demonstrated efficacy, safety, and pharmaceutical quality. This applies to all medicinal products whether of chemical or biological origin. Since October 2009, the first advanced therapy medicinal product (ATMP) has been authorized through the centralized procedure. ATMPs are gene therapy medicinal products, somatic cell therapy medicinal products or tissue-engineered products. An appropriate ATMP - Regulation is dealing with ATMP requirements. Two exemptions are foreseen to the ATMP Regulation: (a) Products, which were legally on the Community market when the Regulation became applicable, should comply to the Regulation by December 30, 2012. (b) The hospital exemption rule for non-routine products for an individual patient. In this work we explored whether the actual application of the Regulation on ATMPs is in line with the aim of the Regulation in terms of guaranteeing the highest level of health protection for patients. Based on the analysis of the relative efficacy of the only EC authorized ATMP and its exempted alternatives, there is evidence against this Regulation 1394/2007 assumption.

  10. Comparative effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in advanced gastric cancer: A meta-analysis of randomized controlled trials

    PubMed Central

    Zhu, Yanjie; Huang, Jiale; Liu, Yanna; Zhao, Liying; Li, Zhijia; Liu, Hao; Wang, Qi-long; Qi, Xiaolong

    2016-01-01

    Background & Aims Platinum-based drugs are the most significant chemotherapy for advanced gastric cancer. The study aims to compare the efficacy and safety of oxaliplatin-based therapy versus cisplatin-based therapy in patients with advanced gastric cancer. Materials and Methods An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness and safety between oxaliplatin-based and cisplatin-based therapy in patients with advanced gastric cancer were eligible. The primary endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). The second endpoint was the adverse events. Results Five phase II or III RCTs involving a total of 2,046 patients were identified. The results showed that there were no significant difference in ORR (OR = 1.17, 95% CI = 0.98–1.40, p = 0.08, I2 = 0%), PFS (HR = 0.92, 95% CI = 0.84–1.01, p = 0.09, I2 = 0%) and OS (HR = 0.91, 95% CI = 0.82–1.01, p = 0.07, I2 = 0%) between oxaliplatin-based therapy and cisplatin-based therapy. In addition, oxaliplatin-based therapy had lower risk of neutropenia, anemia, nausea, alopecia, thromboembolism, stomatitis and creatinine increased at all grades, and neutropenia, anemia, leukopenia and alopecia at 3–4 grades than cisplatin-based therapy. However, oxaliplatin-based therapy was associated with increased risk of neurosensory toxicity and thrombocytopenia. Conclusions Our meta-analysis showed that there were no significant difference in ORR, PFS and OS between oxaliplatin-based therapy and cisplatin-based therapy. The oxaliplatin-based therapy could generally decrease the risk of adverse effects except neurosensory toxicity and thrombocytopenia. PMID:27166187

  11. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

    PubMed Central

    Kaseb, Ahmed O; Morris, Jeffrey S; Iwasaki, Michiko; Al-Shamsi, Humaid O; Raghav, Kanwal Pratap Singh; Girard, Lauren; Cheung, Sheree; Nguyen, Van; Elsayes, Khaled M; Xiao, Lianchun; Abdel-Wahab, Reham; Shalaby, Ahmed S; Hassan, Manal; Hassabo, Hesham M; Wolff, Robert A; Yao, James C

    2016-01-01

    Trial registry Clinicaltrials.gov #NCT01180959. Background Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC) have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib). Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined). The 16-week progression-free survival rate was 43% (95% CI: 28%–59%), median time to progression was 3.9 months (95% CI: 2.0–8.3 months), and median overall survival duration was 9.9 months (95% CI: 8.3–15.5 months). Grade 3–4 adverse events included fatigue (13%), acne (11%), diarrhea (9%), anemia (7%), and upper gastrointestinal hemorrhage (7%). Conclusion Bevacizumab plus erlotinib was tolerable and showed a signal of survival benefit in the second-line setting for patients with advanced HCC. Because standard-of-care options are lacking in this setting, further studies to identify predictors of response to this regimen are warranted. PMID:26929648

  12. HPV Genotypes Predict Survival Benefits From Concurrent Chemotherapy and Radiation Therapy in Advanced Squamous Cell Carcinoma of the Cervix

    SciTech Connect

    Wang, Chun-Chieh; Lai, Chyong-Huey; Huang, Yi-Ting; Chao, Angel; Chou, Hung-Hsueh; Hong, Ji-Hong

    2012-11-15

    Purpose: To study the prognostic value of human papillomavirus (HPV) genotypes in patients with advanced cervical cancer treated with radiation therapy (RT) alone or concurrent chemoradiation therapy (CCRT). Methods and Materials: Between August 1993 and May 2000, 327 patients with advanced squamous cell carcinoma of the cervix (International Federation of Gynecology and Obstetrics stage III/IVA or stage IIB with positive lymph nodes) were eligible for this study. HPV genotypes were determined using the Easychip Registered-Sign HPV genechip. Outcomes were analyzed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Results: We detected 22 HPV genotypes in 323 (98.8%) patients. The leading 4 types were HPV16, 58, 18, and 33. The 5-year overall and disease-specific survival estimates for the entire cohort were 41.9% and 51.4%, respectively. CCRT improved the 5-year disease-specific survival by an absolute 9.8%, but this was not statistically significant (P=.089). There was a significant improvement in disease-specific survival in the CCRT group for HPV18-positive (60.9% vs 30.4%, P=.019) and HPV58-positive (69.3% vs 48.9%, P=.026) patients compared with the RT alone group. In contrast, the differences in survival with CCRT compared with RT alone in the HPV16-positive and HPV-33 positive subgroups were not statistically significant (P=.86 and P=.53, respectively). An improved disease-specific survival was observed for CCRT treated patients infected with both HPV16 and HPV18, but these differenced also were not statistically significant. Conclusions: The HPV genotype may be a useful predictive factor for the effect of CCRT in patients with advanced squamous cell carcinoma of the cervix. Verifying these results in prospective trials could have an impact on tailoring future treatment based on HPV genotype.

  13. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance

    PubMed Central

    Jotte, Robert M; Spigel, David R

    2015-01-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  14. Advances in molecular-based personalized non-small-cell lung cancer therapy: targeting epidermal growth factor receptor and mechanisms of resistance.

    PubMed

    Jotte, Robert M; Spigel, David R

    2015-11-01

    Molecularly targeted therapies, directed against the features of a given tumor, have allowed for a personalized approach to the treatment of advanced non-small-cell lung cancer (NSCLC). The reversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib had undergone turbulent clinical development until it was discovered that these agents have preferential activity in patients with NSCLC harboring activating EGFR mutations. Since then, a number of phase 3 clinical trials have collectively shown that EGFR-TKI monotherapy is more effective than combination chemotherapy as first-line therapy for EGFR mutation-positive advanced NSCLC. The next generation of EGFR-directed agents for EGFR mutation-positive advanced NSCLC is irreversible TKIs against EGFR and other ErbB family members, including afatinib, which was recently approved, and dacomitinib, which is currently being tested in phase 3 trials. As research efforts continue to explore the various proposed mechanisms of acquired resistance to EGFR-TKI therapy, agents that target signaling pathways downstream of EGFR are being studied in combination with EGFR TKIs in molecularly selected advanced NSCLC. Overall, the results of numerous ongoing phase 3 trials involving the EGFR TKIs will be instrumental in determining whether further gains in personalized therapy for advanced NSCLC are attainable with newer agents and combinations. This article reviews key clinical trial data for personalized NSCLC therapy with agents that target the EGFR and related pathways, specifically based on molecular characteristics of individual tumors, and mechanisms of resistance. PMID:26310719

  15. Hypereosinophilic syndrome in two cats.

    PubMed

    Takeuchi, Yoshinori; Matsuura, Shinobu; Fujino, Yasuhito; Nakajima, Mayumi; Takahashi, Masashi; Nakashima, Ko; Sakai, Yusuke; Uetsuka, Koji; Ohno, Koichi; Nakayama, Hiroyuki; Tsujimoto, Hajime

    2008-10-01

    Two cats showing chronic vomiting, diarrhea and weight loss were found to have leukocytosis with marked eosinophilia. Both cats were diagnosed with hypereosinophilic syndrome by the findings of increased eosinophils and their precursors in the bone marrow, eosinophilic infiltration into multiple organs, and exclusion of other causes for eosinophilia. Although cytoreductive chemotherapy with hydroxycarbamide and prednisolone was performed, these two cats died 48 days and 91 days after the initial presentation. PMID:18981665

  16. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results.

    PubMed

    Bowen, J D; Kraft, G H; Wundes, A; Guan, Q; Maravilla, K R; Gooley, T A; McSweeney, P A; Pavletic, S Z; Openshaw, H; Storb, R; Wener, M; McLaughlin, B A; Henstorf, G R; Nash, R A

    2012-07-01

    The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). TBI, CY and antithymocyte globulin were followed by transplantation of autologous, CD34-selected PBSCs. Neurological examinations, brain magnetic resonance imaging and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean Expanded Disability Status Scale (EDSS)=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ≥1.0 EDSS point was 0.52 (95% confidence interval, 0.30-0.75). Five patients had an EDSS at baseline of ≤6.0; four of them had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable for as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS.

  17. Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results

    PubMed Central

    Bowen, James D.; Kraft, George H.; Wundes, Annette; Guan, QingYan; Maravilla, Kenneth R.; Gooley, Theodore A.; McSweeney, Peter A.; Pavletic, Steven Z.; Openshaw, Harry; Storb, Rainer; Wener, Mark; McLaughlin, Bernadette A.; Henstorf, Gretchen R.; Nash, Richard A.

    2011-01-01

    The purpose of the study was to determine the long-term safety and effectiveness of high-dose immunosuppressive therapy (HDIT) followed by autologous hematopoietic cell transplantation (AHCT) in advanced multiple sclerosis (MS). Total body irradiation, cyclophosphamide, and antithymocyte globulin were followed by transplantation of autologous, CD34-selected peripheral blood stem cells (PBSC). Neurological examinations, brain MRIs and cerebrospinal fluid (CSF) for oligoclonal bands (OCB) were serially evaluated. Patients (n=26, mean EDSS=7.0, 17 secondary progressive, 8 primary progressive, 1 relapsing/remitting) were followed for a median of 48 months after HDIT followed by AHCT. The 72-month probability of worsening ≥ 1.0 EDSS point was 0.52 (95% CI, 0.30 to 0.75). Five patients had an EDSS at baseline of ≤ 6.0; four of these had not failed treatment at last study visit. OCB in CSF persisted with minor changes in the banding pattern. Four new or enhancing lesions were seen on MRI, all within 13 months of treatment. In this population with high baseline EDSS, a significant proportion of patients with advanced MS remained stable as long as 7 years after transplant. Non-inflammatory events may have contributed to neurological worsening after treatment. HDIT/AHCT may be more effective in patients with less advanced relapsing/remitting MS. PMID:22056644

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

    PubMed

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

    2011-06-01

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

  19. Role for Occupational Therapy in Community Mental Health: Using Policy to Advance Scholarship of Practice.

    PubMed

    Mahaffey, Lisa; Burson, Kathrine A; Januszewski, Celeste; Pitts, Deborah B; Preissner, Katharine

    2015-01-01

    Occupational therapists must be aware of professional and policy trends. More importantly, occupational therapists must be involved in efforts to influence policy both for the profession and for the people they serve (Bonder, 1987). Using the state of Illinois as an example, this article reviews the policies and initiatives that impact service decisions for persons with psychiatric disabilities as well as the rationale for including occupational therapy in community mental health service provision. Despite challenges in building a workforce of occupational therapists in the mental health system, this article makes the argument that the current climate of emerging policy and litigation combined with the supporting evidence provides the impetus to strengthen mental health as a primary area of practice. Implications for scholarship of practice related to occupational therapy services in community mental health programs for individuals with psychiatric disability are discussed. PMID:26115330

  20. Novel Systemic Therapies in Advanced Liposarcoma: A Review of Recent Clinical Trial Results

    PubMed Central

    Tseng, William W.; Somaiah, Neeta; Lazar, Alexander J.; Lev, Dina C.; Pollock, Raphael E.

    2013-01-01

    Liposarcoma is one of the most common adult soft tissue sarcomas an consists of three histologic subtypes (well and dedifferentiated, myxoid/round cell, and pleomorphic). Surgery is the mainstay of treatment for localized disease; however for unresectable or metastatic disease, effective treatment options are currently limited. In the past decade, a better understanding of the distinct genetic and molecular aberrations for each of the three histologic subtypes has led to the development of several novel systemic therapies. Data from phase I and early phase II clinical trials have been reported. Despite challenges with conducting clinical trials in liposarcoma, preliminary results for several of these novel, biology-driven therapies are encouraging. PMID:24216990

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

    PubMed Central

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

    2011-01-01

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

  2. Advances in 4D radiation therapy for managing respiration: part I - 4D imaging.

    PubMed

    Hugo, Geoffrey D; Rosu, Mihaela

    2012-12-01

    Techniques for managing respiration during imaging and planning of radiation therapy are reviewed, concentrating on free-breathing (4D) approaches. First, we focus on detailing the historical development and basic operational principles of currently-available "first generation" 4D imaging modalities: 4D computed tomography, 4D cone beam computed tomography, 4D magnetic resonance imaging, and 4D positron emission tomography. Features and limitations of these first generation systems are described, including necessity of breathing surrogates for 4D image reconstruction, assumptions made in acquisition and reconstruction about the breathing pattern, and commonly-observed artifacts. Both established and developmental methods to deal with these limitations are detailed. Finally, strategies to construct 4D targets and images and, alternatively, to compress 4D information into static targets and images for radiation therapy planning are described.

  3. [Potential of hematopoietic stem cells as the basis for generation of advanced therapy medicinal products].

    PubMed

    Bönig, H; Heiden, M; Schüttrumpf, J; Müller, M M; Seifried, E

    2011-07-01

    Individualized, (stem) cell-based therapies of congenital and acquired illnesses are among the most exciting medical challenges of the twenty-first century. Before the full potential of such therapies can be achieved, many basic scientific and biotechnological questions remain to be answered. What is the ideal source for the generation of such cellular drugs is one of those issues. In many respects, hematopoietic stem cells fulfill the requirements for stem cells as starting material for novel cellular therapeutics, including the simple access to large amounts of stem cells, the availability of good phenotypic markers for their prospective isolation, and an extensive body of knowledge about the in vitro manipulation of these cells. This manuscript discusses the general and specific usability of hematopoietic stem cells as starting material for novel cellular therapeutics and presents some examples of hematological and nonhematological therapeutic approaches which are based on hematopoietic stem cells.

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

    PubMed

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

    2011-06-01

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

  5. Advances in 4D Radiation Therapy for Managing Respiration: Part I – 4D Imaging

    PubMed Central

    Hugo, Geoffrey D.; Rosu, Mihaela

    2014-01-01

    Techniques for managing respiration during imaging and planning of radiation therapy are reviewed, concentrating on free-breathing (4D) approaches. First, we focus on detailing the historical development and basic operational principles of currently-available “first generation” 4D imaging modalities: 4D computed tomography, 4D cone beam computed tomography, 4D magnetic resonance imaging, and 4D positron emission tomography. Features and limitations of these first generation systems are described, including necessity of breathing surrogates for 4D image reconstruction, assumptions made in acquisition and reconstruction about the breathing pattern, and commonly-observed artifacts. Both established and developmental methods to deal with these limitations are detailed. Finally, strategies to construct 4D targets and images and, alternatively, to compress 4D information into static targets and images for radiation therapy planning are described. PMID:22784929

  6. [Research advances of K-ras mutation in the prognosis and targeted therapy of gastric cancer].

    PubMed

    Huang, Y; Wei, J; Liu, B R

    2016-02-01

    K-ras mutations have been described in 30% of human cancers with significantly different mutation frequencies. High K-ras mutation frequency is found in many cancers such as pancreas and lung cancers, whereas, gastric cancer has a relatively low K-ras mutation frequency. In recent years, numerous researches have focused on the K-ras mutation in gastric cancer. This review summarizes the K-ras mutation frequency in gastric cancer, the relationship of K-ras mutation with clinicopathologic features and prognosis of gastric cancer patients, targeted therapy for K-ras mutated gastric cancer, some small-molecular inhibitors of K-ras, and development of targeted therapy drugs for K-ras signaling pathway in gastric cancer.

  7. Planned preoperative radiation therapy vs. definitive radiotherapy for advanced laryngeal carcinoma

    SciTech Connect

    Kazem, I.; van den Broek, P.

    1984-10-01

    In the period 1970-1980 inclusive, 191 patients with T3T4 laryngeal carcinoma (glottic: 63 and supraglottic: 128) received either definitive radiation therapy (RT) (60-65 Gy in 6-7 weeks) or planned preoperative radiation therapy (25 Gy in 5 equal daily fractions of 5 Gy) followed by laryngectomy with or without neck dissection (RT + S). Selection for RT vs. RT + S was based on medical operability and/or patient's refusal to undergo surgery. All patients are evaluable with minimum of 2 years observation. Crude 5 and 10-year survival probability for 32 patients with glottic localization who received RT is 55% and 38% vs. 65% and 65% respectively for 31 treated with RT + S. For 52 patients with supraglottic site who received RT, the 5 and 10-year survival is 44% and 44% vs. 82% and 60% for 76 patients treated with RT + S.

  8. Role for Occupational Therapy in Community Mental Health: Using Policy to Advance Scholarship of Practice.

    PubMed

    Mahaffey, Lisa; Burson, Kathrine A; Januszewski, Celeste; Pitts, Deborah B; Preissner, Katharine

    2015-01-01

    Occupational therapists must be aware of professional and policy trends. More importantly, occupational therapists must be involved in efforts to influence policy both for the profession and for the people they serve (Bonder, 1987). Using the state of Illinois as an example, this article reviews the policies and initiatives that impact service decisions for persons with psychiatric disabilities as well as the rationale for including occupational therapy in community mental health service provision. Despite challenges in building a workforce of occupational therapists in the mental health system, this article makes the argument that the current climate of emerging policy and litigation combined with the supporting evidence provides the impetus to strengthen mental health as a primary area of practice. Implications for scholarship of practice related to occupational therapy services in community mental health programs for individuals with psychiatric disability are discussed.

  9. The p53-mediated cytotoxicity of photodynamic therapy of cancer: Recent advances

    SciTech Connect

    Zawacka-Pankau, Joanna Krachulec, Justyna Grulkowski, Ireneusz Bielawski, Krzysztof P. Selivanova, Galina

    2008-11-01

    Photodynamic therapy (PDT) is a promising modality for the treatment of both pre-malignant and malignant lesions. The mechanism of action converges mainly on the generation of reactive oxygen species which damage cancer cells directly as well as indirectly acting on tumor vasculature. The exact mechanism of PDT action is not fully understood, which is a formidable barrier to its successful clinical application. Elucidation of the mechanisms of cancer cell elimination by PDT might help in establishing highly specific, non-genotoxic anti-cancer treatment of tomorrow. One of the candidate PDT targets is the well-known tumor suppressor p53 protein recognized as the guardian of the genome. Together with its family members, p73 and p63 proteins, p53 is involved in apoptosis induction upon stress stimuli. The wild-type and mutant p53-targeting chemotherapeutics are currently extensively investigated as a promising strategy for highly specific anti-cancer therapy. In photodynamic therapy porphyrinogenic sensitizers are the most widely used compounds due to their potent biophysical and biochemical properties. Recent data suggest that the p53 tumor suppressor protein might play a significant role in porphyrin-PDT-mediated cell death by direct interaction with the drug which leads to its accumulation and induction of p53-dependent cell death both in the dark and upon irradiation. In this review we describe the available evidence on the role of p53 in PDT.

  10. Advances in targeted therapies and new promising targets in esophageal cancer

    PubMed Central

    Belkhiri, Abbes; El-Rifai, Wael

    2015-01-01

    Esophageal cancer, comprising squamous carcinoma and adenocarcinoma, is a leading cause of cancer-related death in the world. Notably, the incidence of esophageal adenocarcinoma has increased at an alarming rate in the Western world. Unfortunately, the standard first-line chemo-radiotherapeutic approaches are toxic and of limited efficacy in the treatment of a significant number of cancer patients. The molecular analysis of cancer cells has uncovered key genetic and epigenetic alterations underlying the development and progression of tumors. These discoveries have paved the way for the emergence of targeted therapy approaches. This review will highlight recent progress in the development of targeted therapies in esophageal cancer. This will include a review of drugs targeting receptor tyrosine kinases and other kinases in esophageal cancer. Additional studies will be required to develop a rational integration of these targeted agents with respect to histologic types of esophageal cancer and the optimal selection of cancer patients who would most likely benefit from targeted therapy. Identification of AURKA and AXL as key molecular players in esophageal tumorigenesis and drug resistance strongly justifies the evaluation of the available drugs against these targets in clinical trials. PMID:25593196

  11. [Examination of the safety of docetaxel/cyclophosphamide combination therapy for advanced recurrent breast cancer].

    PubMed

    Yoneyama, Kimiyasu; Koshida, Yoshitomo; Toriumi, Fumiki; Murayama, Takaya; Toeda, Hiroyuki; Imazu, Yoshihiro; Motegi, Katsuhiko; Akamatsu, Hidetoshi; Ohyama, Renpei

    2006-10-01

    In the treatment of recurrent breast cancer in patients previously treated with anthracycline drugs, taxane drugs are generally used. This time, we retrospectively studied the safety of docetaxel/cyclophosphamide combination therapy (hereinafter referred to as TC therapy). Ten patients (mean age: 52.8 years old) were included in the study. Metastatic/recurrent sites included 3 skin, 2 each of contralateral breast, lung and bone, and 1 each of liver, carcinomatous pleurisy and supraclavicular lymph node. Seven patients had a history of anthracycline treatment. The patients received TC at doses of 60 mg/m(2) and 500 mg/m(2), respectively, every 3 weeks. With regard to adverse events, non-hematotoxic events included alopecia in all the patients, generalized malaise in 5, and abnormal nail in 1. Hematotoxic events were grades 2 and 3 decreased neutrophil count in 5 patients. One patient had grade 4 pyrexia associated with oral candida. The patient was admitted and treated with fluid replacement and granulocyte colony-stimulating factor (G-CSF). There were no other patients in whom the treatment was prolonged or dosage was reduced due to adverse reactions. TC therapy is considered to be a beneficial treatment method in terms of safety since it can be instituted on an outpatient basis. PMID:17033252

  12. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    PubMed Central

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2016-01-01

    Purpose To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n = 28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01–3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%–30.3%). The median contralateral lung V5 was 0.34% (range, 0%–5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0–65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03–3.50 Gy (RBE)]. Conclusions Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  13. Early Toxicity in Patients Treated With Postoperative Proton Therapy for Locally Advanced Breast Cancer

    SciTech Connect

    Cuaron, John J.; Chon, Brian; Tsai, Henry; Goenka, Anuj; DeBlois, David; Ho, Alice; Powell, Simon; Hug, Eugen; Cahlon, Oren

    2015-06-01

    Purpose: To report dosimetry and early toxicity data in breast cancer patients treated with postoperative proton radiation therapy. Methods and Materials: From March 2013 to April 2014, 30 patients with nonmetastatic breast cancer and no history of prior radiation were treated with proton therapy at a single proton center. Patient characteristics and dosimetry were obtained through chart review. Patients were seen weekly while on treatment, at 1 month after radiation therapy completion, and at 3- to 6-month intervals thereafter. Toxicity was scored using Common Terminology Criteria for Adverse Events version 4.0. Frequencies of toxicities were tabulated. Results: Median dose delivered was 50.4 Gy (relative biological equivalent [RBE]) in 5 weeks. Target volumes included the breast/chest wall and regional lymph nodes including the internal mammary lymph nodes (in 93%). No patients required a treatment break. Among patients with >3 months of follow-up (n=28), grade 2 dermatitis occurred in 20 patients (71.4%), with 8 (28.6%) experiencing moist desquamation. Grade 2 esophagitis occurred in 8 patients (28.6%). Grade 3 reconstructive complications occurred in 1 patient. The median planning target volume V95 was 96.43% (range, 79.39%-99.60%). The median mean heart dose was 0.88 Gy (RBE) [range, 0.01-3.20 Gy (RBE)] for all patients, and 1.00 Gy (RBE) among patients with left-sided tumors. The median V20 of the ipsilateral lung was 16.50% (range, 6.1%-30.3%). The median contralateral lung V5 was 0.34% (range, 0%-5.30%). The median maximal point dose to the esophagus was 45.65 Gy (RBE) [range, 0-65.4 Gy (RBE)]. The median contralateral breast mean dose was 0.29 Gy (RBE) [range, 0.03-3.50 Gy (RBE)]. Conclusions: Postoperative proton therapy is well tolerated, with acceptable rates of skin toxicity. Proton therapy favorably spares normal tissue without compromising target coverage. Further follow-up is necessary to assess for clinical outcomes and cardiopulmonary

  14. Dermal mass aspirate from a Persian cat.

    PubMed

    Zimmerman, Kurt; Feldman, Bernard; Robertson, John; Herring, Erin S; Manning, Thomas

    2003-01-01

    A 1-year-old spayed female Persian cat with alopecia and weight loss had numerous variably ulcerated dermal nodules. Cytologic examination of an aspirate of one of the nodules revealed pyogranulomatous inflammation along with septate hyphae and basophilic round bodies, 0.5-1.0 microm in diameter, surrounded by a thin clear halo (arthrospores). The cytologic diagnosis was dermatophytic pseudomycetoma. Histologically, there were dermal granulomas containing poorly staining, septate hyphae with bulbous spores embedded within abundant amorphous eosinophilic material (Splendore-Hoeppli reaction), and the histologic diagnosis was pseudomycetoma-associated chronic multifocal severe granulomatous dermatitis with lymphocytic perifolliculitis and furunculosis. Microsporum canis was cultured from the lesion. Pseudomycetomas are distinguished from fungal mycetomas, or eumycotic mycetomas, by the findings of multiple lesions, lack of a history of skin trauma, an association with dermatophytes, most commonly Microsporum canis, and, histologically, lack of true cement material and a more abundant Splendore-Hoeppli reaction in pseudomycetomas. Additionally, pseudomycetomas differ from dermatophytosis, in which lesions are restricted to epidermal structures. Persian cats have a high incidence of pseudomycetoma formation, suggesting a heritable predisposition. The prognosis is fair with systemic antifungal therapy. When examining cytologic specimens from Persian cats with single or multiple dermal nodules, especially if pyogranulomatous inflammation is present, a diagnosis of pseudomycetoma should be suspected and is warranted if arthrospores and refractile septate hyphae are present.

  15. Optimal tumor shrinkage predicts long-term outcome in advanced nonsmall cell lung cancer (NSCLC) treated with target therapy

    PubMed Central

    He, Xiaobo; Zhang, Yang; Ma, Yuxiang; Zhou, Ting; Zhang, Jianwei; Hong, Shaodong; Sheng, Jin; Zhang, Zhonghan; Yang, Yunpeng; Huang, Yan; Zhang, Li; Zhao, Hongyun

    2016-01-01

    Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are used as standard therapies for advanced nonsmall cell lung cancer (NSCLC) patients with EGFR mutation positive. Because these targeted therapies could cause tumor necrosis and shrinkage, the purpose of the study is to search for a value of optimal tumor shrinkage as an appropriate indicator of outcome for advanced NSCLC. A total of 88 NSCLC enrollees of 3 clinical trials (IRESSA registration clinical trial, TRUST study and ZD6474 study), who received Gefitinib (250 mg, QD), Erlotinib (150 mg, QD), and ZD6474 (100 mg, QD), respectively, during December 2003 and October 2007, were retrospectively analyzed. The response evaluation criteria in solid tumors (RECIST) were used to identify responders, who had complete response (CR) or partial responses (PR) and nonresponders who had stable disease (SD) or progressive disease (PD). Receiver operating characteristics (ROC) analysis was used to find the optimal tumor shrinkage as an indicator for tumor therapeutic outcome. Univariate and multivariate Cox regression analyses were performed to compare the progression-free survival (PFS) and overall survival (OS) between responders and nonresponders stratified based on radiologic criteria. Among the 88 NSCLC patients, 26 were responders and 62 were nonresponders based on RECIST 1.0. ROC indicated that 8.32% tumor diameter shrinkage in the sum of the longest tumor diameter (SLD) was the cutoff point of tumor shrinkage outcomes, resulting in 46 responders (≤8.32%) and 42 nonresponders (≥8.32%). Univariate and multivariate Cox regression analyses indicated that (1) the responders (≤8.32%) and nonresponders (≥ −8.32%) were significantly different in median PFS (13.40 vs 1.17 months, P < 0.001) and OS (19.80 vs 7.90 months, P < 0.001) and (2) –8.32% in SLD could be used as the optimal threshold for PFS (hazard ratio [HR], 8.11, 95% CI, 3.75 to 17.51, P < 0.001) and OS

  16. Fiber-optic technologies for advanced thermo-therapy applied ex vivo to liver tumors

    NASA Astrophysics Data System (ADS)

    Tosi, D.; Perrone, G.; Vallan, A.; Braglia, A.; Liu, Y.; Macchi, E. G.; Braschi, G.; Gallati, M.; Cigada, A.; Poeggel, S.; Duraibabu, D. B.; Leen, G.; Lewis, E.

    2015-07-01

    Thermal ablation, using radiofrequency, microwave, and laser sources, is a common treatment for hepatic tumors. Sensors allow monitoring, at the point of treatment, the evolution of thermal ablation procedures. We present optical fiber sensors that allow advanced capabilities for recording the biophysical phenomena occurring in the tissue in real time. Distributed or quasi-distributed thermal sensors allow recording temperature with spatial resolution ranging from 0.1 mm to 5 mm. In addition, a thermally insensitive pressure sensor allows recording pressure rise, supporting advanced treatment of encapsulated tumors. Our investigation is focused on two case studies: (1) radiofrequency ablation of hepatic tissue, performed on a phantom with a stem-shaped applicator; (2) laser ablation of a liver phantom, performed with a fiber laser. The main measurement results are discussed, comparing the technologies used for the investigation, and drawing the potential for using optical fiber sensors for "smart"-ablation.

  17. Adverse events in 50 cats with allergic dermatitis receiving ciclosporin.

    PubMed

    Heinrich, Nicole A; McKeever, Patrick J; Eisenschenk, Melissa C

    2011-12-01

    Ciclosporin is an immunosuppressive drug that has been used to treat allergies and other immune-mediated diseases in cats, dogs and humans. Information about the adverse effects of ciclosporin in cats has been limited to smaller studies and case reports. Adverse effects in dogs are mainly gastrointestinal in nature, but humans can also experience hypertension and altered renal function. The aim of this retrospective case series study was to document the occurrence and clinical appearance of adverse events in cats receiving ciclosporin to treat allergic skin disease. The medical records of 50 cats with allergic dermatitis treated with oral ciclosporin (1.9-7.3 mg/kg/day) were reviewed. Adverse events occurred in 66% (33 cats). Adverse events likely to be associated with ciclosporin included the following: vomiting or diarrhoea within 1-8 weeks of receiving ciclosporin (24%), weight loss (16%), anorexia and subsequent hepatic lipidosis (2%) and gingival hyperplasia (2%). Other adverse events less likely to be associated with ciclosporin therapy included the following: weight gain (14%), dental tartar and gingivitis (10%), otitis (4%), chronic diarrhoea (4%), inflammatory bowel disease with indolent gastrointestinal lymphoma (2%), urinary tract infection (2%), cataract (2%), elevated liver enzymes (2%), hyperthyroidism and renal failure (2%) and transient inappropriate urination (2%). Some cats experienced multiple adverse events. Case-control studies are needed to prove cause and effect of ciclosporin with regard to these adverse events. PMID:21545660

  18. Hedgehog- and mTOR-targeted therapies for advanced basal cell carcinomas.

    PubMed

    Piérard-Franchimont, Claudine; Hermanns-Lê, Trinh; Paquet, Philippe; Herfs, Michael; Delvenne, Philippe; Piérard, Gérald E

    2015-11-01

    Basal cell carcinomas (BCCs) are the most frequent human cancer. Over 90% of all BCCs have a mutation in PTCH1 or smoothened, two conducting proteins of the Hedgehog pathway. They rarely progress deeply and metastasize; however, if they do, these advanced basal cell carcinoma become amenable to treatment by inhibiting the Hedgehog and the P13K-mTOR pathways. Such innovative drugs include vismodegib, cyclopamine, itraconazole, everolimus and a few other agents that are in early clinical development. PMID:26437034

  19. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  20. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  1. The advancement of human pluripotent stem cell-derived therapies into the clinic.

    PubMed

    Thies, R Scott; Murry, Charles E

    2015-09-15

    Human pluripotent stem cells (hPSCs) offer many potential applications for drug screening and 'disease in a dish' assay capabilities. However, a more ambitious goal is to develop cell therapeutics using hPSCs to generate and replace somatic cells that are lost as a result of disease or injury. This Spotlight article will describe the state of progress of some of the hPSC-derived therapeutics that offer the most promise for clinical use. Lessons from developmental biology have been instrumental in identifying signaling molecules that can guide these differentiation processes in vitro, and will be described in the context of these cell therapy programs.

  2. Evaluation of canned therapeutic diets for the management of cats with naturally occurring chronic diarrhea.

    PubMed

    Laflamme, Dorothy P; Xu, Hui; Cupp, Carolyn J; Kerr, Wendell W; Ramadan, Ziad; Long, Grace M

    2012-10-01

    Dietary therapy plays an important role in the management of most gastrointestinal disorders. This study was designed to test the efficacy of a new therapeutic diet for cats with diarrhea, compared to the top selling brand. Sixteen adult cats with chronic diarrhea were grouped and assigned to diet X (Hill's Prescription Diet i/d Feline) or diet Y (Purina Veterinary Diets EN Gastroenteric Feline Formula). Following baseline evaluations, cats were fed their assigned test diet for 4 weeks. Fecal scores (FS; 7=very watery; 1=extremely dry and firm) were recorded daily during the last week on each diet. Each cat was then switched to the alternate test diet and the procedure was repeated. Fifteen cats completed the study. Both therapeutic diets resulted in a significant improvement in average FS and diet Y also resulted in significantly better results compared with diet X. Average FS improved at least one unit in 40% of the cats while fed diet X and in 67% of the cats while fed diet Y, resulting in normal stools (average FS≤3) in 13.3% of cats fed diet X and 46.7% of cats fed diet Y. This study confirms the value of dietary change in the management of chronic diarrhea in cats. PMID:22577048

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

    PubMed

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

    2012-08-01

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

  4. A Phase II Trial of Cetuximab, Gemcitabine, 5-Fluorouracil, and Radiation Therapy in Locally Advanced Nonmetastatic Pancreatic Adenocarcinoma

    PubMed Central

    Piperdi, Bilal; Bathini, Venu; Walsh, William V.; Yunus, Shakeeb; Tseng, Jennifer F.; Whalen, Giles F.; Wassef, Wahid Y.; Kadish, Sidney P.; FitzGerald, Thomas J.; Mikule, Christine; Wang, Yuxia; Grossman, Steven R.

    2013-01-01

    ABSTRACT BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. A minority of patients present with localized disease and surgical resection still offers patients the only hope for long-term survival. Locally advanced pancreatic cancer is defined as surgically unresectable, but has no evidence of distant metastases. The purpose of this study is to evaluate the efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along with radiation therapy in locally advanced non-resectable, pancreatic adenocarcinoma, using progression free survival as the primary end point. METHODS: This was a prospective, single arm, open label pilot phase II study to evaluate the anti-tumor activity of gemcitabine (200 mg/m2 per week) and cetuximab (250 mg/m2 per week after an initial 400 mg/m2 loading dose) with continuous infusion 5-FU (800 mg/m2 over 96 hours) and daily concurrent external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in patients with non-metastatic, locally advanced pancreatic adenocarcinoma. Following neoadjuvant treatment, subjects were re-evaluated for response and surgical candidacy with restaging scans. After resection, or also if not resected; subjects received further therapy with four 28-day cycles (cycles 2-5) of weekly gemcitabine (1000 mg/m2) and cetuximab (250 mg/m2) on days 1, 8, and 15. RESULTS: Between 2006 and 2011, twenty-six patients were screened and eleven of them were enrolled in the study. Most common reasons for screen failures were having resectable disease, metastatic disease or co-morbidity. Ten patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One patient stopped the study prematurely due to grade III diarrhea. All except this one patient received planned radiation therapy. The response evaluation after cycle 1 showed one Partial Response, eight Stable Disease and two Progressive Disease. Four patients subsequently underwent surgical

  5. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy

    PubMed Central

    Schimke, Magdalena M.; Marozin, Sabrina; Lepperdinger, Günter

    2015-01-01

    Multipotential mesenchymal stromal cells (MSC) are present as a rare subpopulation within any type of stroma in the body of higher animals. Prominently, MSC have been recognized to reside in perivascular locations, supposedly maintaining blood vessel integrity. During tissue damage and injury, MSC/pericytes become activated, evade from their perivascular niche and are thus assumed to support wound healing and tissue regeneration. In vitro MSC exhibit demonstrated capabilities to differentiate into a wide variety of tissue cell types. Hence, many MSC-based therapeutic approaches have been performed to address bone, cartilage, or heart regeneration. Furthermore, prominent studies showed efficacy of ex vivo expanded MSC to countervail graft-vs.-host-disease. Therefore, additional fields of application are presently conceived, in which MSC-based therapies potentially unfold beneficial effects, such as amelioration of non-healing conditions after tendon or spinal cord injury, as well as neuropathies. Working along these lines, MSC-based scientific research has been forged ahead to prominently occupy the clinical stage. Aging is to a great deal stochastic by nature bringing forth changes in an individual fashion. Yet, is aging of stem cells or/and their corresponding niche considered a determining factor for outcome and success of clinical therapies? PMID:26696897

  6. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy

    PubMed Central

    Zhao, Baozhong; He, Yu-Ying

    2011-01-01

    Photodynamic therapy (PDT) is a noninvasive procedure that involves a photosensitizing drug and its subsequent activation by light to produce reactive oxygen species that specifically destroy target cells. Recently, PDT has been widely used in treating non-melanoma skin malignancies, the most common cancer in the USA, with superior cosmetic outcomes compared with conventional therapies. The topical ‘photosensitizers’ commonly used are 5-aminolevulinic acid (ALA) and its esterified derivative methyl 5-aminolevulinate, which are precursors of the endogenous photosensitizer protoporphyrin IX. After treatment with ALA or methyl 5-aminolevulinate, protoporphyrin IX preferentially accumulates in the lesion area of various skin diseases, which allows not only PDT treatment but also fluorescence diagnosis with ALA-induced porphyrins. Susceptible lesions include various forms of non-melanoma skin cancer such as actinic keratosis, basal cell carcinoma and squamous cell carcinoma. The most recent and promising developments in PDT include the discovery of new photosensitizers, the exploitation of new drug delivery systems and the combination of other modalities, which will all contribute to increasing PDT therapeutic efficacy and improving outcome. This article summarizes the main principles of PDT and its current clinical use in the management of non-melanoma skin cancers, as well as recent developments and possible future research directions. PMID:21080805

  7. Advances in combination therapies based on nanoparticles for efficacious cancer treatment: an analytical report.

    PubMed

    Mignani, Serge; Bryszewska, Maria; Klajnert-Maculewicz, Barbara; Zablocka, Maria; Majoral, Jean-Pierre

    2015-01-12

    The main objective of nanomedicine research is the development of nanoparticles as drug delivery systems or drugs per se to tackle diseases as cancer, which are a leading cause of death with developed nations. Targeted treatments against solid tumors generally lead to dramatic regressions, but, unfortunately, the responses are often short-lived due to resistant cancer cells. In addition, one of the major challenges of combination drug therapy (called "cocktail") is the crucial optimization of different drug parameters. This issue can be solved using combination nanotherapy. Nanoparticles developed in oncology based on combination nanotherapy are either (a) those designed to combat multidrug resistance or (b) those used to circumvent resistance to clinical cancer drugs. This review provides an overview of the different nanoparticles currently used in clinical treatments in oncology. We analyze in detail the development of combinatorial nanoparticles including dendrimers for dual drug delivery via two strategic approaches: (a) use of chemotherapeutics and chemosensitizers to combat multidrug resistance and (b) use of multiple cytotoxic drugs. Finally, in this review, we discuss the challenges, clinical outlook, and perspectives of the nanoparticle-based combination therapy in cancer.

  8. Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.

    PubMed

    Beik, Jaber; Abed, Ziaeddin; Ghoreishi, Fatemeh S; Hosseini-Nami, Samira; Mehrzadi, Saeed; Shakeri-Zadeh, Ali; Kamrava, S Kamran

    2016-08-10

    In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia. PMID:27264551

  9. Advances of Targeted Therapy in Treatment of Unresectable Metastatic Colorectal Cancer

    PubMed Central

    Lee, Suk-young; Oh, Sang Cheul

    2016-01-01

    Despite being one of the most frequently diagnosed cancers worldwide, prognosis of metastatic colorectal cancer (CRC) was poor. Development and introduction of biologic agents in treatment of patients with metastatic CRC have brought improved outcomes. Monoclonal antibodies directing epidermal growth factor receptors and vascular endothelial growth factor are main biologic agents currently used in treatment of metastatic CRC. Encouraged by results from many clinical trials demonstrating efficacy of those monoclonal antibodies, the combination therapy with those targeted agents and conventional chemotherapeutic agents has been established as the standard therapy for patients with metastatic CRC. However, emergency of resistance to those target agents has limited the efficacy of treatment, and strategies to overcome the resistance are now being investigated by newly developed biological techniques clarifying how to acquire resistance. Here, we introduce mechanisms of action of the biologic agents currently used for treatment of metastatic CRC and several landmark historical clinical studies which have changed the main stream of treatment. The mechanism of resistance to those agents, one of serious problems in treatment metastatic CRC, and ongoing clinical trials to overcome the limitations and improve treatment outcomes will also be presented in this review. PMID:27127793

  10. Recent advances in COPD disease management with fixed-dose long-acting combination therapies.

    PubMed

    Bateman, Eric D; Mahler, Donald A; Vogelmeier, Claus F; Wedzicha, Jadwiga A; Patalano, Francesco; Banerji, Donald

    2014-06-01

    Combinations of two long-acting bronchodilators and long-acting bronchodilators with inhaled corticosteroids (ICS) are recommended therapies in the management of chronic obstructive pulmonary disease (COPD). Three fixed-dose combination products have recently been approved for the treatment of COPD (the long-acting β2-agonist plus long-acting muscarinic antagonist [LABA/LAMA] combinations glycopyrronium/indacaterol [QVA149] and umeclidinium/vilanterol, and the LABA/ICS fluticasone furoate/vilanterol), with others currently in late-stage development. LABA/LAMA and LABA/ICS combination therapies demonstrate positive effects on both lung function and patient-reported outcomes, with significant improvements observed with LABA/LAMA combinations compared with placebo, each component alone and other comparators in current use. No new safety concerns have been observed with combinations of long-acting bronchodilators. Combinations of two long-acting bronchodilators represent a new and convenient treatment option in COPD. This review summarizes published efficacy and safety data from clinical trials of both LABA/LAMA and novel LABA/ICS combinations in patients with COPD.

  11. Advances in Progenitor Cell Therapy Using Scaffolding Constructs for Central Nervous System Injury

    PubMed Central

    Walker, Peter A.; Aroom, Kevin R.; Jimenez, Fernando; Shah, Shinil K.; Harting, Matthew T.; Gill, Brijesh S.

    2010-01-01

    Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and intra arterial infusion have shown low engraftment rates and risk of distal emboli. Novel delivery methods such as nanofiber scaffold implantation could provide the structural and nutritive support required for progenitor cell proliferation, engraftment, and differentiation. The focus of this review is to explore the current state of the art as it relates to current and novel progenitor cell delivery methods. PMID:19644777

  12. Basic Advances and New Avenues in Therapy of Spinal Cord Injury

    PubMed Central

    Dobkin, Bruce H.; Havton, Leif A.

    2014-01-01

    The prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation. PMID:14746521

  13. Bottlenecks in the Efficient Use of Advanced Therapy Medicinal Products Based on Mesenchymal Stromal Cells.

    PubMed

    Escacena, Natalia; Quesada-Hernández, Elena; Capilla-Gonzalez, Vivian; Soria, Bernat; Hmadcha, Abdelkrim

    2015-01-01

    Mesenchymal stromal cells (MSCs) have been established as promising candidate sources of universal donor cells for cell therapy due to their contributions to tissue and organ homeostasis, repair, and support by self-renewal and multidifferentiation, as well as by their anti-inflammatory, antiproliferative, immunomodulatory, trophic, and proangiogenic properties. Various diseases have been treated by MSCs in animal models. Additionally, hundreds of clinical trials related to the potential benefits of MSCs are in progress. However, although all MSCs are considered suitable to exert these functions, dissimilarities have been found among MSCs derived from different tissues. The same levels of efficacy and desired outcomes have not always been achieved in the diverse studies that have been performed thus far. Moreover, autologous MSCs can be affected by the disease status of patients, compromising their use. Therefore, collecting information regarding the characteristics of MSCs obtained from different sources and the influence of the host (patient) medical conditions on MSCs is important for assuring the safety and efficacy of cell-based therapies. This review provides relevant information regarding factors to consider for the clinical application of MSCs.

  14. Genomic Alterations in Advanced Esophageal Cancer May Lead to Subtype-Specific Therapies

    PubMed Central

    Forde, Patrick M.

    2013-01-01

    The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8–12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease. PMID:23853247

  15. Genomic alterations in advanced esophageal cancer may lead to subtype-specific therapies.

    PubMed

    Forde, Patrick M; Kelly, Ronan J

    2013-01-01

    The development of targeted agents for metastatic esophageal or gastroesophageal junction (GEJ) tumors has been limited when compared with that for other common tumors. To date, the anti-human epidermal growth factor receptor-2 (HER-2) antibody, trastuzumab, in combination with chemotherapy, is the only approved novel agent for these cancers, and its use is limited to the small population of patients whose tumors overexpress HER-2. Despite recent progress in the field, median overall survival remains only 8-12 months for patients with stage IV esophageal or GEJ cancer. In this article, we examine the molecular aberrations thought to drive the development and spread of esophageal cancer and identify promising targets for specific tumor inhibition. Data from clinical studies of targeted agents are reviewed, including epidermal growth factor receptor antibodies, tyrosine kinase inhibitors, HER-2, and vascular endothelial growth factor-directed therapy. Current and future targets include MET, fibroblast growth factor receptor, and immune-based therapies. Evidence from trials to date suggests that molecularly unselected patient cohorts derive minimal benefit from most target-specific agents, suggesting that future collaborative investigation should focus on preselected molecular subgroups of patients with this challenging heterogeneous disease.

  16. Replication of cortisol circadian rhythm: new advances in hydrocortisone replacement therapy.

    PubMed

    Chan, Sharon; Debono, Miguel

    2010-06-01

    Cortisol has one of the most distinct and fascinating circadian rhythms in human physiology. This is regulated by the central clock located in the suprachiasmatic nucleus of the hypothalamus. It has been suggested that cortisol acts as a secondary messenger between central and peripheral clocks, hence its importance in the synchronization of body circadian rhythms. Conventional immediate-release hydrocortisone, either at twice- or thrice-daily doses, is not capable of replicating physiological cortisol circadian rhythm and patients with adrenal insufficiency or congenital adrenal hyperplasia still suffer from a poor quality of life and increased mortality. Novel treatments for replacement therapy are therefore essential. Proof-of-concept studies using hydrocortisone infusions suggest that the circadian delivery of hydrocortisone may improve biochemical control and life quality in patients lacking cortisol with an impaired cortisol rhythm. Recently oral formulations of modified-release hydrocortisone are being developed and it has been shown that it is possible to replicate cortisol circadian rhythm and also achieve better control of morning androgen levels. These new drug therapies are promising and potentially offer a more effective treatment with less adverse effects. Definite improvements clearly need to be established in future clinical trials.

  17. How does surgery compare with advanced intra-articular therapies in knee osteoarthritis: current thoughts

    PubMed Central

    Wehling, Peter; Moser, Carsten; Maixner, William

    2016-01-01

    The objectives of osteoarthritis (OA) management are to reduce pain and inflammation, slow cartilage degradation, improve function and reduce disability. Current strategies for managing knee OA include nonpharmacological interventions, oral pharmacological treatments, localized intra-articular injections, and surgery. It has become evident that the inflammatory response is a key contributor to the development and progression of knee OA. Signaling pathways involving growth factors and cytokines are being investigated for the development of new therapies that target the underlying biological processes causing the disease. This concept of ‘molecular orthopedics’ enables more patient-centered diagnostic and treatment strategies. In contrast to other conservative therapies, which ultimately only address OA symptoms, intra-articular injections, in particular autologous conditioned serum (ACS), provide benefits that have the potential to outweigh those of established pharmacological treatments and surgery. Surgery has historically been considered the final solution for treatment of knee OA, both by treating physicians and by patients; however, there are increasing concerns regarding the lack of randomized clinical trials providing evidence to support this opinion. Intra-articular injection of ACS has demonstrated efficacy as a treatment for knee OA in a number of studies, with a very low rate of adverse events and side effects, compared with surgery. Treatment with ACS utilizes the release of anti-inflammatory cytokines and regenerative growth factors to support the natural healing processes in the knee, and has the potential to provide a valuable alternative to surgical intervention. PMID:27247634

  18. College Students and Their Cats

    ERIC Educational Resources Information Center

    Weinstein, Lawrence; Alexander, Ralph

    2010-01-01

    Twenty-two Siamese and 32 mixed breed cats' personalities were rated by their respective college student owners and compared. Further, the owners' self rated personality traits were correlated with the pets'; significant Siamese and Mixed differences and correlations were obtained. These are the first data to examine breed of cat on a personality…

  19. CONTRACT ADMINISTRATIVE TRACKING SYSTEM (CATS)

    EPA Science Inventory

    The Contract Administrative Tracking System (CATS) was developed in response to an ORD NHEERL, Mid-Continent Ecology Division (MED)-recognized need for an automated tracking and retrieval system for Cost Reimbursable Level of Effort (CR/LOE) Contracts. CATS is an Oracle-based app...

  20. [Glomerulonephritis in dogs and cats].

    PubMed

    Reinacher, M; Frese, K

    1991-04-01

    Immunohistology and special staining of plastic sections allow diagnosis and differentiation of subtypes of glomerulonephritis in dogs. Frequency and clinical importance of these forms of glomerulonephritis vary significantly. In cats, glomerulonephritis occurs frequently in FIV-positive cats but is rare in animals suffering from persistent FeLV infection or FIP. PMID:2068715

  1. Malignant histiocytosis in a cat.

    PubMed

    Court, E A; Earnest-Koons, K A; Barr, S C; Gould, W J

    1993-11-01

    A 13-year-old male domestic shorthair cat was found to have normocytic hypochromic regenerative anemia, lymphopenia, eosinopenia, thrombocytopenia, hyperglycemia, hyperbilirubinemia, and a prolonged activated partial thromboplastin time. Transfusions of packed RBC failed to maintain the PCV above 13% for > 8 hours. The cat was euthanatized. At necropsy, the spleen liver, lymph nodes, and bone marrow were infiltrated with malignant histiocytes undergoing erythrophagocytosis.

  2. Endobronchial valve placement as destination therapy for recurrent pneumothorax in the setting of advanced malignancy.

    PubMed

    Gilbert, Christopher R; Toth, Jennifer W; Osman, Umar; Reed, Michael F

    2015-03-01

    The development of a persistent air leak after pneumothorax can be encountered in patients with underlying structural lung disease. In those with advanced malignancy or other comorbidities, the ability to tolerate general anesthesia and thoracoscopic procedures may limit definitive management. We describe the case of a 68-y-old male with refractory acute myelogenous leukemia presenting with recurrent secondary spontaneous pneumothorax and persistent air leak related to an underlying fungal pneumonia. Endobronchial valve placement allowed for timely chest tube removal and discharge from the hospital, as well as avoidance of a thoracoscopic procedure and pleurodesis.

  3. Recent advances in laser therapy for the treatment of port wine stains

    NASA Astrophysics Data System (ADS)

    Lanigan, Sean W.

    2004-09-01

    The pulsed dye laser is the preferred laser for treating port wine stains. It is relatively effective with a low incidence of side effects. However, although considerable lightening of a port wine stain is likely to occur with treatment, complete clearance is achieved in the minority. There has been a number of therapeutic advances over the last few years in the laser treatment of port wine stains. These have come from modification of the original pulsed dye laser, use of other lasers and light sources and a greater understanding of laser - port wine interactions. All of these developments will be discussed in this review.

  4. Renal glomerular fibrosis in a cat.

    PubMed

    Nakamura, S; Shibata, S; Shirota, K; Abe, K; Uetsuka, K; Nakayama, H; Goto, N; Doi, K

    1996-11-01

    Renal glomerular fibrosis was observed in a 1-year-old spayed female Japanese domestic cat that showed clinically advanced renal failure. In the glomeruli, increased homogeneous materials were stained strongly with aniline blue by Masson's trichrome and positive for anti-type III collagen antibody by immunohistochemical staining, causing mesangial sclerosis and capillary collapse. By electron microscopy, randomly arranged fibrils were observed in the expanded subendothelial and mesangial areas, and the fibrils showed periodicity characteristic of collagen fibers in longitudinal sections. These findings of glomerular lesions closely resemble those of human "collagenofibrotic glomerulonephropathy," which has recently been described as a new type of glomerulonephropathy. PMID:8952029

  5. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy.

    PubMed

    Chao, Tzu-I; Tai, Wei-Tien; Hung, Man-Hsin; Tsai, Ming-Hsien; Chen, Min-Hsuan; Chang, Mao-Ju; Shiau, Chung-Wai; Chen, Kuen-Feng

    2016-02-28

    Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC-43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC-43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC. PMID:26679051

  6. Music therapy as a treatment method for improving respiratory muscle strength in patients with advanced multiple sclerosis: a pilot study.

    PubMed

    Wiens, M E; Reimer, M A; Guyn, H L

    1999-01-01

    Respiratory muscle weakness, predominantly of the expiratory muscles, is characteristic of individuals with advanced multiple sclerosis and can result in difficulty in clearing secretions and repeated episodes of pneumonia. This pilot study evaluated the effectiveness of music therapy in strengthening respiratory muscles through an emphasis on diaphragmatic breathing and coordination of breath and speech. Twenty patients were randomly assigned to one of two groups: one that received music therapy or one that attended music appreciation sessions. Participants' inspiratory and expiratory muscle strength was measured by testing mouth pressure before and after the intervention. The experimental group showed some improvement in terms of expiratory muscle strength, in contrast to the control group, which showed deterioration. The results were not statistically significant, however. Patients in both groups exhibited considerable weakness in their expiratory muscles, and results for 79% of the participants were below 30% of the predicted values. Variability, a major confounding factor that resulted in reduced statistical power, led the investigators to suggest an intercenter collaboration to amass sufficient numbers of patients for a future study. Early manifestation of respiratory muscle weakness warrants inclusion of respiratory muscle testing in examination protocols and early intervention efforts.

  7. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  8. Final Report of the Intergroup Randomized Study of Combined Androgen-Deprivation Therapy Plus Radiotherapy Versus Androgen-Deprivation Therapy Alone in Locally Advanced Prostate Cancer

    PubMed Central

    Mason, Malcolm D.; Parulekar, Wendy R.; Sydes, Matthew R.; Brundage, Michael; Kirkbride, Peter; Gospodarowicz, Mary; Cowan, Richard; Kostashuk, Edmund C.; Anderson, John; Swanson, Gregory; Parmar, Mahesh K.B.; Hayter, Charles; Jovic, Gordana; Hiltz, Andrea; Hetherington, John; Sathya, Jinka; Barber, James B.P.; McKenzie, Michael; El-Sharkawi, Salah; Souhami, Luis; Hardman, P.D. John; Chen, Bingshu E.; Warde, Padraig

    2015-01-01

    Purpose We have previously reported that radiotherapy (RT) added to androgen-deprivation therapy (ADT) improves survival in men with locally advanced prostate cancer. Here, we report the prespecified final analysis of this randomized trial. Patients and Methods NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110 was a randomized controlled trial of patients with locally advanced prostate cancer. Patients with T3-4, N0/Nx, M0 prostate cancer or T1-2 disease with either prostate-specific antigen (PSA) of more than 40 μg/L or PSA of 20 to 40 μg/L plus Gleason score of 8 to 10 were randomly assigned to lifelong ADT alone or to ADT+RT. The RT dose was 64 to 69 Gy in 35 to 39 fractions to the prostate and pelvis or prostate alone. Overall survival was compared using a log-rank test stratified for prespecified variables. Results One thousand two hundred five patients were randomly assigned between 1995 and 2005, 602 to ADT alone and 603 to ADT+RT. At a median follow-up time of 8 years, 465 patients had died, including 199 patients from prostate cancer. Overall survival was significantly improved in the patients allocated to ADT+RT (hazard ratio [HR], 0.70; 95% CI, 0.57 to 0.85; P < .001). Deaths from prostate cancer were significantly reduced by the addition of RT to ADT (HR, 0.46; 95% CI, 0.34 to 0.61; P < .001). Patients on ADT+RT reported a higher frequency of adverse events related to bowel toxicity, but only two of 589 patients had grade 3 or greater diarrhea at 24 months after RT. Conclusion This analysis demonstrates that the previously reported benefit in survival is maintained at a median follow-up of 8 years and firmly establishes the role of RT in the treatment of men with locally advanced prostate cancer. PMID:25691677

  9. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy

    PubMed Central

    Niezgoda, Anna; Niezgoda, Piotr; Czajkowski, Rafał

    2015-01-01

    The incidence of malignant melanoma is increasing. The majority of patients are diagnosed in early stages when the disease is highly curable. However, the more advanced or metastatic cases have always been a challenge for clinicians. The poor prognosis for patients with melanoma is now changing as numerous of promising approaches have appeared recently. The discovery of aberrations of pathways responsible for intracellular signal transduction allowed us to introduce agents specifically targeting the mutated cascades. Numerous clinical studies have been conducted to improve effectiveness of melanoma treatment. From 2011 until now, the U.S. FDA has approved seven novel agents, such as BRAF-inhibitors (vemurafenib 2011, dabrafenib 2013), MEK-inhibitors (trametinib 2013), anti-PD1 antibodies (nivolumab 2014, pembrolizumab 2014), anti-CTLA-4 antibody (ipilimumab 2011), or peginterferon-alfa-2b (2011) intended to be used in most advanced cases of melanoma. Nevertheless, clinicians continue working on new possible methods of treatment as resistance to the novel drugs is a commonly observed problem. This paper is based on latest data published until the end of January 2015. PMID:26171394

  10. Recent Advances in Superparamagnetic Iron Oxide Nanoparticles for Cellular Imaging and Targeted Therapy Research

    PubMed Central

    Wang, Yi-Xiang J.; Xuan, Shouhu; Port, Marc; Idee, Jean-Marc

    2013-01-01

    Advances of nanotechnology have led to the development of nanomaterials with both potential diagnostic and therapeutic applications. Among them, superparamagnetic iron oxide (SPIO) nanoparticles have received particular attention. Over the past decade, various SPIOs with unique physicochemical and biological properties have been designed by modifying the particle structure, size and coating. This article reviews the recent advances in preparing SPIOs with novel properties, the way these physicochemical properties of SPIOs influence their interaction with cells, and the development of SPIOs in liver and lymph nodes magnetic resonance imaging (MRI) contrast. Cellular uptake of SPIO can be exploited in a variety of potential clinical applications, including stem cell and inflammation cell tracking and intra-cellular drug delivery to cancerous cells which offers higher intra-cellular concentration. When SPIOs are used as carrier vehicle, additional advantages can be achieved including magnetic targeting and hyperthermia options, as well as monitoring with MRI. Other potential applications of SPIO include magnetofection and gene delivery, targeted retention of labeled stem cells, sentinel lymph nodes mapping, and magnetic force targeting and cell orientation for tissue engineering. PMID:23621536

  11. Dramatic Response to Cisplatin Window Therapy in a Boy With Advanced Metastatic Ewing Sarcoma

    PubMed Central

    Trizzino, Antonino; Ziino, Ottavio; Parafioriti, Antonina; Podda, Marta; Tropia, Serena; Luksch, Roberto

    2013-01-01

    Ewing sarcoma (ES) is the second most common type of primary bone malignancy, and retains a high propensity to metastasize; the prognosis of patients with disseminated disease is very poor, with an event-free survival rate of <20%. Current multimodality treatment for ES consists of combined chemotherapy before and concurrent with surgery and local radiotherapy for the involved bone. Cisplatin is one of the most widely used drugs for the treatment of bone tumors in children, but is not currently used in ES. We describe a child with multifocal ES, treated with a phase II trial including a single-drug window therapy, which displayed a dramatic response to 2 courses of cisplatin and had a favorable outcome. PMID:23892353

  12. Gene Therapy with Helper-Dependent Adenoviral Vectors: Current Advances and Future Perspectives

    PubMed Central

    Vetrini, Francesco; Ng, Philip

    2010-01-01

    Recombinant Adenoviral vectors represent one of the best gene transfer platforms due to their ability to efficiently transduce a wide range of quiescent and proliferating cell types from various tissues and species. The activation of an adaptive immune response against the transduced cells is one of the major drawbacks of first generation Adenovirus vectors and has been overcome by the latest generation of recombinant Adenovirus, the Helper-Dependent Adenoviral (HDAd) vectors. HDAds have innovative features including the complete absence of viral coding sequences and the ability to mediate high level transgene expression with negligible chronic toxicity. This review summarizes the many aspects of HDAd biology and structure with a major focus on in vivo gene therapy application and with an emphasis on the unsolved issues that these vectors still presents toward clinical application. PMID:21994713

  13. Current targeted therapies in the treatment of advanced colorectal cancer: a review

    PubMed Central

    Moriarity, Andrew; O’Sullivan, Jacintha; Kennedy, John; Mehigan, Brian; McCormick, Paul

    2016-01-01

    Treatment strategies for metastatic colorectal cancer (mCRC) patients have undergone dramatic changes in the past decade and despite improved patient outcomes, there still exist areas for continued development. The introduction of targeted agents has provided clinicians with additional treatment options in mCRC, however, results have been mixed at best. These novel therapies were designed to interfere with specific molecules involved in the cellular carcinogenesis pathway and ultimately deliver a more focused treatment. Currently, their use in mCRC has been limited primarily as an adjunct to conventional chemotherapy regimens. This review explores the relevant cell-signaling networks in colorectal cancer, provides focus on the current targeted agent armamentarium approved for use in mCRC and explores the usefulness of predictive mCRC biomarkers. PMID:27482287

  14. Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Durante, Marco; Tommasino, Francesco; Yamada, Shigeru

    2015-01-01

    Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease. PMID:26217585

  15. [Application and advancement of magnetic iron-oxide nanoparticles in tumor-targeted therapy].

    PubMed

    Chen, Yue; Chen, Bao-An

    2010-01-01

    Recently, nanometer-sized magnetic particles have been intensively concerned and investigated due to their particularly large surface-to-volume ratio, quantum-size effect, magnetic character as well as their potential application in the area of bioscience and medicine. The most promising nanoparticles are magnetic iron oxide nanoparticles with appropriate surface modification, which have been widely used experimentally for numerous in vivo applications such as magnetic resonance imaging contrast enhancement, tissue repair, immunoassay, detoxification of biological fluids, drug delivery, hyperthermia and cell separation. To focus on one of the most important and fascinating subjects in nanobiotechnology, this review describes the current situation and development of magnetic iron oxide nanoparticles and their applications in drug delivery and hyperthermia in tumor-targeted therapy. The possible perspectives and some challenges to further development of these nanoparticles are also analyzed and discussed. PMID:20038325

  16. Recent Advances and the Future of Stem Cell Therapies in Amyotrophic Lateral Sclerosis.

    PubMed

    Goutman, Stephen A; Chen, Kevin S; Feldman, Eva L

    2015-04-01

    Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of the motor neurons without a known cure. Based on the possibility of cellular neuroprotection and early preclinical results, stem cells have gained widespread enthusiasm as a potential treatment strategy. Preclinical models demonstrate a protective role of engrafted stem cells and provided the basis for human trials carried out using various types of stem cells, as well as a range of cell delivery methods. To date, no trial has demonstrated a clear therapeutic benefit; however, results remain encouraging and are the basis for ongoing studies. In addition, stem cell technology continues to improve, and induced pluripotent stem cells may offer additional therapeutic options in the future. Improved disease models and clinical trials will be essential in order to validate stem cells as a beneficial therapy.

  17. Advanced cell therapies: targeting, tracking and actuation of cells with magnetic particles.

    PubMed

    Connell, John J; Patrick, P Stephen; Yu, Yichao; Lythgoe, Mark F; Kalber, Tammy L

    2015-01-01

    Regenerative medicine would greatly benefit from a new platform technology that enabled measurable, controllable and targeting of stem cells to a site of disease or injury in the body. Superparamagnetic iron-oxide nanoparticles offer attractive possibilities in biomedicine and can be incorporated into cells, affording a safe and reliable means of tagging. This review describes three current and emerging methods to enhance regenerative medicine using magnetic particles to guide therapeutic cells to a target organ; track the cells using MRI and assess their spatial localization with high precision and influence the behavior of the cell using magnetic actuation. This approach is complementary to the systemic injection of cell therapies, thus expanding the horizon of stem cell therapeutics.

  18. Current advances in biomarkers for targeted therapy in triple-negative breast cancer

    PubMed Central

    Fleisher, Brett; Clarke, Charlotte; Ait-Oudhia, Sihem

    2016-01-01

    Triple-negative breast cancer (TNBC) is a complex heterogeneous disease characterized by the absence of three hallmark receptors: human epidermal growth factor receptor 2, estrogen receptor, and progesterone receptor. Compared to other breast cancer subtypes, TNBC is more aggressive, has a higher prevalence in African-Americans, and more frequently affects younger patients. Currently, TNBC lacks clinically accepted targets for tailored therapy, warranting the need for candidate biomarkers. BiomarkerBase, an online platform used to find biomarkers reported in clinical trials, was utilized to screen all potential biomarkers for TNBC and select only the ones registered in completed TNBC trials through clinicaltrials.gov. The selected candidate biomarkers were classified as surrogate, prognostic, predictive, or pharmacodynamic (PD) and organized by location in the blood, on the cell surface, in the cytoplasm, or in the nucleus. Blood biomarkers include vascular endothelial growth factor/vascular endothelial growth factor receptor and interleukin-8 (IL-8); cell surface biomarkers include EGFR, insulin-like growth factor binding protein, c-Kit, c-Met, and PD-L1; cytoplasm biomarkers include PIK3CA, pAKT/S6/p4E-BP1, PTEN, ALDH1, and the PIK3CA/AKT/mTOR-related metabolites; and nucleus biomarkers include BRCA1, the gluco-corticoid receptor, TP53, and Ki67. Candidate biomarkers were further organized into a “cellular protein network” that demonstrates potential connectivity. This review provides an inventory and reference point for promising biomarkers for breakthrough targeted therapies in TNBC. PMID:27785100

  19. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  20. Advances in levodopa therapy for Parkinson disease: Review of RYTARY (carbidopa and levodopa) clinical efficacy and safety.

    PubMed

    Dhall, Rohit; Kreitzman, David L

    2016-04-01

    Parkinson disease (PD) is a slowly progressive, incurable, neurodegenerative disorder with progressive motor symptoms that can be managed with treatments. Levodopa is generally recognized as the most effective and widely used treatment for PD. It improves function and quality of life, morbidity, and mortality, and therefore reduces individual and societal costs. Levodopa has a relatively short half-life, however, and is quickly metabolized in the plasma, leading to fluctuations, including wearing-off of effect and inconsistent symptomatic relief as well as development of dyskinesias, with both wearing off and dyskinesias worsening with advancing disease. Immediate-release and controlled-release formulations have been used with success, but motor fluctuations remain a problem. RYTARY (levodopa and carbidopa, IPX066) is an oral extended-release therapy composed of carbidopa-levodopa microbeads designed to dissolve at various rates that allows for quick absorption and sustained levodopa release over an extended period. In development studies, RYTARY improved symptoms in patients with both early and advanced PD and offered significantly improved Unified Parkinson Disease Rating Scale scores and "on" times, without worsening troublesome dyskinesias when compared to other levodopa formulations. Tolerability and safety were comparable to other formulations. This section reviews the data that support the use of RYTARY in the treatment of PD.

  1. Phase advance is an actimetric correlate of antidepressant response to sleep deprivation and light therapy in bipolar depression.

    PubMed

    Benedetti, Francesco; Dallaspezia, Sara; Fulgosi, Mara Cigala; Barbini, Barbara; Colombo, Cristina; Smeraldi, Enrico

    2007-01-01

    The combination of total sleep deprivation (TSD) and light therapy (LT) in bipolar depression causes rapid antidepressant effects, and its mechanism of action has been hypothesized to involve the enhancement of all of the monoaminergic systems targeted by antidepressant drugs (serotonin, dopamine, norepinephrine). It is still unknown if the clinical effects are paralleled by changes in biological rhythms. In a before/after design of a study of biological correlates of response, 39 inpatients affected by Type I Bipolar Disorder whose current depressive episode was without psychotic features were treated for one week with repeated TSD combined with morning LT. Wrist actigraphy was recorded throughout the study. Two-thirds of the patients responded to treatment (50% reduction in Hamilton Depression score). Responders showed an increase in daytime activity, phase-advance of the activity-rest rhythm of 57 min compared to the pre-treatment baseline, and reduced nighttime sleep. Non-responders did not show significant changes in the parameters of their activity-rest rhythm. Phase advance of the activity-rest rhythm is an actimetric correlate of the antidepressant response to TSD and LT in bipolar depression. Results are consistent with the known effects of sleep-wake manipulations and neurotransmitter function on the suprachiasmatic nucleus.

  2. Diabetic ketoacidosis and hyperosmolar hyperglycemic state in cats.

    PubMed

    Rand, Jacquie S

    2013-03-01

    Diabetic ketoacidosis and hyperosmolar hyperglycemic state are 2 potentially life-threatening presentations of feline diabetes mellitus. Presentations range from mildly anorexic cats with diabetic ketoacidosis to comatose cats with diabetic ketoacidosis or hyperosmolar hyperglycemic state. Such cases are the result of severe insulin deficiency and/or concurrent disease, resulting in nausea and vomiting, electrolyte and water losses, acidosis, and circulatory collapse. The condition requires careful attention to supportive care to correct fluid and electrolyte abnormalities, treatment of concurrent diseases, and reversal of the effects of insulin deficiency. However, early diagnosis of diabetes mellitus and institution of appropriate insulin therapy prevents these complications.

  3. Duranta erecta poisoning in nine dogs and a cat.

    PubMed

    Scanlan, S N A; Eagles, D A; Vacher, N E; Irvine, M A; Ryan, C J; McKenzie, R A

    2006-10-01

    Four incidents of Duranta erecta (golden dewdrop, Sheena's Gold, Geisha Girl) poisoning affecting nine dogs and a cat produced drowsiness, hyperaesthesia and tetanic seizures in all affected animals with evidence of alimentary tract irritation (vomiting, gastric and intestinal haemorrhage, diarrhoea, melaena) in five dogs and the cat. Fruits and leaves were seen to be eaten by affected animals. Therapy was successful in three of the dogs. Repeated diazepam doses and, in some cases, additional pentobarbitone or propofol anaesthesia, were successful in controlling seizures. PMID:17359477

  4. Long-term Oncologic Outcome Following Preoperative Combined Modality Therapy and Total Mesorectal Excision of Locally Advanced Rectal Cancer

    PubMed Central

    Guillem, Jose G.; Chessin, David B.; Cohen, Alfred M.; Shia, Jinru; Mazumdar, Madhu; Enker, Warren; Paty, Philip B.; Weiser, Martin R.; Klimstra, David; Saltz, Leonard; Minsky, Bruce D.; Wong, W Douglas

    2005-01-01

    Objective: Our aims were to (1) determine the long-term oncologic outcome for patients with rectal cancer treated with preoperative combined modality therapy (CMT) followed by total mesorectal excision (TME), (2) identify factors predictive of oncologic outcome, and (3) determine the oncologic significance of the extent of pathologic tumor response. Summary Background Data: Locally advanced (T3–4 and/or N1) rectal adenocarcinoma is commonly treated with preoperative CMT and TME. However, the long-term oncologic results of this approach and factors predictive of a durable outcome remain largely unknown. Methods: Two hundred ninety-seven consecutive patients with locally advanced rectal adenocarcinoma at a median distance of 6cm from the anal verge (range 0–15 cm) were treated with preoperative CMT (radiation: 5040 centi-Gray (cGy) and 5-fluorouracil (5-FU)-based chemotherapy) followed by TME from 1988 to 2002. A prospectively collected database was queried for long-term oncologic outcome and predictive clinicopathologic factors. Results: With a median follow-up of 44 months, the estimated 10-year overall survival (OS) was 58% and 10 year recurrence-free survival (RFS) was 62%. On multivariate analysis, pathologic response >95%, lymphovascular invasion and/or perineural invasion (PNI), and positive lymph nodes were significantly associated with OS and RFS. Patients with a >95% pathologic response had a significantly improved OS (P = 0.003) and RFS (P = 0.002). Conclusions: Treatment of locally advanced rectal cancer with preoperative CMT followed by TME can provide for a durable 10-year OS of 58% and RFS of 62%. Patients who achieve a >95% response to preoperative CMT have an improved long-term oncologic outcome, a novel finding that deserves further study. PMID:15849519

  5. Neurolymphomatosis in a cat

    PubMed Central

    SAKURAI, Masashi; AZUMA, Kazushi; NAGAI, Arata; FUJIOKA, Toru; SUNDEN, Yuji; SHIMADA, Akinori; MORITA, Takehito

    2016-01-01

    A 9-year-old male mixed breed cat showed chronic progressive neurological symptoms, which are represented by ataxia and seizures. At necropsy, spinal roots and spinal ganglions at the level of sixth cervical nerve to second thoracic nerve were bilaterally swollen and replaced by white mass lesions. Right brachial plexus and cranial nerves (III, V and VII) were also swollen. A mass lesion was found in the right frontal lobe of the cerebrum. Histologically, neoplastic lymphocytes extensively involved the peripheral nerves, and they infiltrated into the cerebral and spinal parenchyma according to the peripheral nerve tract. Immunohistochemically, most neoplastic lymphocytes were positive for CD20. The clinical and histological features in this case resemble those of neurolymphomatosis in humans. PMID:26960326

  6. Targeting mutant p53 protein and the tumor vasculature: an effective combination therapy for advanced breast tumors

    PubMed Central

    Liang, Yayun; Besch-Williford, Cynthia; Benakanakere, Indira; Thorpe, Philip E.

    2010-01-01

    Breast cancer progression depends upon the elaboration of a vasculature sufficient for the nourishment of the developing tumor. Breast tumor cells frequently contain a mutant form of p53 (mtp53), a protein which promotes their survival. The aim of this study was to determine whether combination therapy targeting mtp53 and anionic phospholipids (AP) on tumor blood vessels might be an effective therapeutic strategy for suppressing advanced breast cancer. We examined the therapeutic effects, singly, or in combination, of p53 reactivation and induction of massive apoptosis (PRIMA-1), which reactivates mtp53 and induces tumor cell apoptosis, and 2aG4, a monoclonal antibody that disrupts tumor vasculature by targeting AP on the surface of tumor endothelial cells and causes antibody-dependent destruction of tumor blood vessels, leading to ischemia and tumor cell death. Xenografts from two tumor cell lines containing mtp53, BT-474 and HCC-1428, were grown in nude mice to provide models of advanced breast tumors. After treatment with PRIMA-1 and/or 2aG4, regressing tumors were analyzed for vascular endothelial growth factor (VEGF) expression, blood vessel loss, and apoptotic markers. Individual drug treatment led to partial suppression of breast cancer progression. In contrast, combined treatment with PRIMA-1 and 2aG4 was extremely effective in suppressing tumor growth in both models and completely eradicated approximately 30% of tumors in the BT-474 model. Importantly, no toxic effects were observed in any treatment group. Mechanistic studies determined that PRIMA-1 reactivated mtp53 and also exposed AP on the surface of tumor cells as determined by enhanced 2aG4 binding. Combination treatment led to significant induction of tumor cell apoptosis, loss of VEGF expression, as well as destruction of tumor blood vessels. Furthermore, combination treatment severely disrupted tumor blood vessel perfusion in both tumor models. The observed in vitro PRIMA-1-induced exposure of

  7. Therapy for advanced thyroid cancer: treatment of a high risk case.

    PubMed

    Ceriati, F; Cavicchioni, C; Logroscino, C; Pastore, G; Montemaggi, P; Fabiano, A; Mantovani, M; Marino, I R; Ardito, G; De Luca, G

    1987-01-01

    The treatment of a high risk case of an advanced thyroid cancer is reported. The patient had a thyroid cancer with metastatic lesions of the frontal bone, left temporal bone, left sacroiliac joint, lytic destruction of C6 and lytic lesion of C7. A pre-operative immobilization of the cervical spine was performed by a halo cast set on a corset of gypsum. After this, the patient underwent a thyroidectomy and, at the same time, a metallic plate was applied to immobilize C5-C7. A month after he underwent reoperative surgery to stabilize definitively the cervical spine. Subsequently he was treated by TCT and 131I subdivided in several cycles. The latest total body scan demonstrated a complete regression of secondary lesions.

  8. High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

    PubMed Central

    Wu, Feng

    2014-01-01

    The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound (HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer. PMID:25469016

  9. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

    PubMed

    Verma, Jonathan; Monk, Bradley J; Wolfson, Aaron H

    2016-10-01

    Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC. PMID:27619255

  10. [Advanced and Metastatic Lung Cancer – What is new in the Diagnosis and Therapy?].

    PubMed

    Rothschild, Sacha I

    2015-07-01

    Lung cancer is one of the most common types of malignancies worldwide. The majority of patients are diagnosed with an incurable advanced/metastatic stage disease. Palliative treatment approaches improve the survival and the quality of life of these patients. Lung cancer is subdivided according to histology and molecular biology. The most important classification separates small cell from non-small cell lung cancer. In the subgroup of non-small cell lung cancer novel treatment approaches coming along with an improved prognosis have been established during the last decade. The current manuscript provides an overview on current treatment options for metastatic lung cancer. Furthermore, an outlook on promising future treatment options is provided.

  11. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  12. National Cancer Data Base Analysis of Radiation Therapy Consolidation Modality for Cervical Cancer: The Impact of New Technological Advancements

    SciTech Connect

    Gill, Beant S.; Lin, Jeff F.; Krivak, Thomas C.; Sukumvanich, Paniti; Laskey, Robin A.; Ross, Malcolm S.; Lesnock, Jamie L.; Beriwal, Sushil

    2014-12-01

    Purpose: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. Methods and Materials: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. Results: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61′ 95% confidence interval, 1.27-2.04′ P<.01). Conclusions: Consolidation brachytherapy is a critical treatment component for

  13. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  14. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  15. Phenazopyridine toxicosis in the cat.

    PubMed

    Harvey, J W; Kornick, H P

    1976-08-01

    Severe illness developed after the oral administration of several drugs, including large doses of phenazopyridine (100 mg TID for 4 days) to a cat with dysuria and hematuria. Hemolysis and icterus were evident in blood serum and plasma after day 4 of drug administration, and many hemolyzed red blood cell "ghosts" containing Heinz bodies were observed on a stained blood smear. The cat became anemic and died within 48 hours after the last dose was administered. In an attempt to confirm a cause-and-effect relationship between drug administration and disease, 100 mg of phenazopyridine was given TID (65 mg/kg/day) for 3 days to a clinically normal cat. Nearly 50% of the hemoglobin was oxidized to methemoglobin during the course of phenazopyridine administration. Lower dosages of phenazopyridine (10 and 20 mg/kg/day) for longer periods of administration to 2 other clinically normal cats did not result in illness or anemia; however, the number and size of Heinz bodies and blood methemoglobin content were increased. Evidence of hepatic injury was observed in the clinically affected cat and in 2 of the experimental cats. The relationship between hepatic injury and toxic signs was not determined. Combination products recommeneded for treatment of cystitis in man often contain phenazopyridine. Such products should be avoided in cats unless a safe, effective dosage for phenazopyridine can be established.

  16. Advances in hepatitis C therapy: What is the current state - what come's next?

    PubMed

    Zopf, Steffen; Kremer, Andreas E; Neurath, Markus F; Siebler, Juergen

    2016-01-28

    Chronic hepatitis C virus (HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease. It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin. However, treatment of HCV has undergone a revolutionary change in recent years. The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents (DAA). Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure. High rates of sustained virological response (SVR) rates can be achieved with these novel drugs. Even in difficult to treat populations such as patients with liver cirrhosis, HCV-human immunodeficiency virus co-infections, after liver transplantion, or with chronic kidney disease comparable high rates of SVR can be achieved. The anticipated 2(nd) generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or post-transplant patients. These 2(nd) generations DAAs will have higher resistance barriers, higher antiviral effects and a pan-genotypic spectrum. This review highlights the current state of the art of antiviral treatment in hepatitis C and gives an outlook for upcoming therapies. PMID:26839638

  17. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention.

    PubMed

    Joya, Xavier; Garcia-Algar, Oscar; Salat-Batlle, Judith; Pujades, Cristina; Vall, Oriol

    2015-03-01

    Ethanol is the most common human teratogen, and its consumption during pregnancy can produce a wide range of abnormalities in infants known as fetal alcohol spectrum disorder (FASD). The major characteristics of FASD can be divided into: (i) growth retardation, (ii) craniofacial abnormalities, and (iii) central nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic mental retardation in Western countries. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, the induction of oxidative stress is believed to be one central process linked to the development of the disease. Currently, there is no known effective strategy for prevention (other than alcohol avoidance) or treatment. In the present review we will provide the state of art in the evidence for the use of antioxidants as a potential therapeutic strategy for the treatment using whole-embryo and culture cells models of FASD. We conclude that the imbalance of the intracellular redox state contributes to the pathogenesis observed in FASD models, and we suggest that antioxidant therapy can be considered a new efficient strategy to mitigate the effects of prenatal ethanol exposure.

  18. Atypical teratoid/rhabdoid tumors-current concepts, advances in biology, and potential future therapies.

    PubMed

    Frühwald, Michael C; Biegel, Jaclyn A; Bourdeaut, Franck; Roberts, Charles W M; Chi, Susan N

    2016-06-01

    Atypical teratoid/rhabdoid tumor (AT/RT) is the most common malignant CNS tumor of children below 6 months of age. The majority of AT/RTs demonstrate genomic alterations in SMARCB1 (INI1, SNF5, BAF47) or, to a lesser extent, SMARCA4 (BRG1) of the SWItch/sucrose nonfermentable chromatin remodeling complex. Recent transcription and methylation profiling studies suggest the existence of molecular subgroups. Thus, at the root of these seemingly enigmatic tumors lies a network of factors related to epigenetic regulation, which is not yet completely understood. While conventional-type chemotherapy may have significant survival benefit for certain patients, it remains to be determined which patients will eventually prove resistant to chemotherapy and thus need novel therapeutic strategies. Elucidation of the molecular consequences of a disturbed epigenome has led to the identification of a series of transduction cascades, which may be targeted for therapy. Among these are the pathways of cyclin D1/cyclin-dependent kinases 4 and 6, Hedgehog/GLI1, Wnt/ß-catenin, enhancer of zeste homolog 2, and aurora kinase A, among others. Compounds specifically targeting these pathways or agents that alter the epigenetic state of the cell are currently being evaluated in preclinical settings and in experimental clinical trials for AT/RT. PMID:26755072

  19. The Advance of Personalized and Stratified Therapies in Bronchial Asthma: Phenotypes – Endotypes – Biomarkers

    PubMed Central

    Lauer, Sebastian

    2013-01-01

    Bronchial asthma (BA) is a chronic inflammatory condition with increasing incidence and prevalence worldwide. BA is currently the most prevalent chronic disease in pediatric patients. The majority of BA patients are therapeutically well controlled with guideline based anti-inflammatory therapies; however, there is also a clinically recognized proportion of patients who do not benefit from currently available medication for several reasons. This is the starting point for further investigation into the complexity of the inflammatory phenotype of BA. Recently, the heterogeneity in terms of cellular and molecular pathways underlying BA has been recognized and established. These different pathogenic mechanisms are defined as ‘endotypes’. The best studied endotype so far is the association with T-helper type 2 (TH2) cell eosinophilic airway inflammation. Recently, a number of different therapeutic strategies have been clinically explored which target certain mediators of this pathway, including the interleukins IL-4, IL-5 and IL-13. It is now clear that patients with the TH2-endotype largely benefit from novel biologicals in this area. However, the challenge for diagnostics is to identify patients exhibiting this endotype, and this is the starting point for the search for new biomarkers. One biomarker that has recently been selected based on differential gene expression analysis, and which seems to be strongly associated with the TH2 endotype, is periostin. In this article we will provide a state of the art update on the definition of clinical phenotypes, pathogenetic endotypes and biomarker development for improving BA treatment.

  20. Advances in 4D radiation therapy for managing respiration: part II - 4D treatment planning.

    PubMed

    Rosu, Mihaela; Hugo, Geoffrey D

    2012-12-01

    The development of 4D CT imaging technology made possible the creation of patient models that are reflective of respiration-induced anatomical changes by adding a temporal dimension to the conventional 3D, spatial-only, patient description. This had opened a new venue for treatment planning and radiation delivery, aimed at creating a comprehensive 4D radiation therapy process for moving targets. Unlike other breathing motion compensation strategies (e.g. breath-hold and gating techniques), 4D radiotherapy assumes treatment delivery over the entire respiratory cycle - an added bonus for both patient comfort and treatment time efficiency. The time-dependent positional and volumetric information holds the promise for optimal, highly conformal, radiotherapy for targets experiencing movements caused by respiration, with potentially elevated dose prescriptions and therefore higher cure rates, while avoiding the uninvolved nearby structures. In this paper, the current state of the 4D treatment planning is reviewed, from theory to the established practical routine. While the fundamental principles of 4D radiotherapy are well defined, the development of a complete, robust and clinically feasible process still remains a challenge, imposed by limitations in the available treatment planning and radiation delivery systems.

  1. Advances in 4D Radiation Therapy for Managing Respiration: Part II – 4D Treatment Planning

    PubMed Central

    Rosu, Mihaela; Hugo, Geoffrey D.

    2014-01-01

    The development of 4D CT imaging technology made possible the creation of patient models that are reflective of respiration-induced anatomical changes by adding a temporal dimension to the conventional 3D, spatial-only, patient description. This had opened a new venue for treatment planning and radiation delivery, aimed at creating a comprehensive 4D radiation therapy process for moving targets. Unlike other breathing motion compensation strategies (e.g. breath-hold and gating techniques), 4D radiotherapy assumes treatment delivery over the entire respiratory cycle – an added bonus for both patient comfort and treatment time efficiency. The time-dependent positional and volumetric information holds the promise for optimal, highly conformal, radiotherapy for targets experiencing movements caused by respiration, with potentially elevated dose prescriptions and therefore higher cure rates, while avoiding the uninvolved nearby structures. In this paper, the current state of the 4D treatment planning is reviewed, from theory to the established practical routine. While the fundamental principles of 4D radiotherapy are well defined, the development of a complete, robust and clinically feasible process still remains a challenge, imposed by limitations in the available treatment planning and radiation delivery systems. PMID:22796324

  2. Advances in the development of novel antioxidant therapies as an approach for fetal alcohol syndrome prevention.

    PubMed

    Joya, Xavier; Garcia-Algar, Oscar; Salat-Batlle, Judith; Pujades, Cristina; Vall, Oriol

    2015-03-01

    Ethanol is the most common human teratogen, and its consumption during pregnancy can produce a wide range of abnormalities in infants known as fetal alcohol spectrum disorder (FASD). The major characteristics of FASD can be divided into: (i) growth retardation, (ii) craniofacial abnormalities, and (iii) central nervous system (CNS) dysfunction. FASD is the most common cause of nongenetic mental retardation in Western countries. Although the underlying molecular mechanisms of ethanol neurotoxicity are not completely determined, the induction of oxidative stress is believed to be one central process linked to the development of the disease. Currently, there is no known effective strategy for prevention (other than alcohol avoidance) or treatment. In the present review we will provide the state of art in the evidence for the use of antioxidants as a potential therapeutic strategy for the treatment using whole-embryo and culture cells models of FASD. We conclude that the imbalance of the intracellular redox state contributes to the pathogenesis observed in FASD models, and we suggest that antioxidant therapy can be considered a new efficient strategy to mitigate the effects of prenatal ethanol exposure. PMID:25131946

  3. Embryonic stem cells in companion animals (horses, dogs and cats): present status and future prospects.

    PubMed

    Tecirlioglu, R Tayfur; Trounson, Alan O

    2007-01-01

    Reproductive technologies have made impressive advances since the 1950s owing to the development of new and innovative technologies. Most of these advances were driven largely by commercial opportunities and the potential improvement of farm livestock production and human health. Companion animals live long and healthy lives and the greatest expense for pet owners are services related to veterinary care and healthcare products. The recent development of embryonic stem cell and nuclear transfer technology in primates and mice has enabled the production of individual specific embryonic stem cell lines in a number of species for potential cell-replacement therapy. Stem cell technology is a fast-developing area in companion animals because many of the diseases and musculoskeletal injuries of cats, dogs and horses are similar to those in humans. Nuclear transfer-derived stem cells may also be selected and directed into differentiation pathways leading to the production of specific cell types, tissues and, eventually, even organs for research and transplantaton. Furthermore, investigations into the treatment of inherited or acquired pathologies have been performed mainly in mice. However, mouse models do not always faithfully represent the human disease. Naturally occurring diseases in companion animals can be more ideal as disease models of human genetic and acquired diseases and could help to define the potential therapeutic efficiency and safety of stem cell therapies. In the present review, we focus on the economic implications of companion animals in society, as well as recent biotechnological progress that has been made in horse, dog and cat embryonic stem cell derivation.

  4. Intensity-Modulated Proton Therapy Further Reduces Normal Tissue Exposure During Definitive Therapy for Locally Advanced Distal Esophageal Tumors: A Dosimetric Study

    SciTech Connect

    Welsh, James; Gomez, Daniel; Palmer, Matthew B.; Riley, Beverly A.; Mayankkumar, Amin V.; Komaki, Ritsuko; Dong, Lei; Zhu, X. Ronald; Likhacheva, Anna; Liao, Zhongxing; Hofstetter, Wayne L.; Ajani, Jaffer A.; Cox, James D.

    2011-12-01

    Purpose: We have previously found that {<=} 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Patients and Methods: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Results: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p < .0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p {<=} .0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p < .001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p {<=} .02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p < .0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p {<=} .005), heart (p {<=} .003), and liver (p {<=} .04). Conclusions: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for

  5. Advances in T Helper 17 Cell Biology: Pathogenic Role and Potential Therapy in Multiple Sclerosis

    PubMed Central

    Volpe, Elisabetta; Battistini, Luca; Borsellino, Giovanna

    2015-01-01

    The discovery of the T helper (Th) 17 lineage, involved in the protection against fungal and extracellular bacterial infections, has profoundly revolutionized our current understanding of T cell-mediated responses in autoimmune diseases, including multiple sclerosis (MS). Indeed, recent data demonstrate the pathogenic role of Th17 cells in autoimmune disorders. In particular, studies in MS and in its animal model (EAE, experimental autoimmune encephalomyelitis) have revealed a crucial role of Th17 cells in the pathogenesis of autoimmune demyelinating diseases in both mice and humans. Over the past years, several important aspects concerning Th17 cells have been elucidated, such as the factors which promote or inhibit their differentiation and the effector cytokines which mediate their responses. The identification of the features endowing Th17 cells with high pathogenicity in MS is of particular interest, and discoveries in Th17 cell biology and function could lead to the design of new strategies aimed at modulating the immune response in MS. Here, we will discuss recent advances in this field, with particular focus on the mechanisms conferring pathogenicity in MS and their potential modulation. PMID:26770017

  6. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    ClinicalTrials.gov

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  7. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  8. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    PubMed

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence.

  9. A randomised trial of lung sealant versus medical therapy for advanced emphysema

    PubMed Central

    Come, Carolyn E.; Kramer, Mordechai R.; Dransfield, Mark T.; Abu-Hijleh, Muhanned; Berkowitz, David; Bezzi, Michela; Bhatt, Surya P.; Boyd, Michael B.; Cases, Enrique; Chen, Alexander C.; Cooper, Christopher B.; Flandes, Javier; Gildea, Thomas; Gotfried, Mark; Hogarth, D. Kyle; Kolandaivelu, Kumaran; Leeds, William; Liesching, Timothy; Marchetti, Nathaniel; Marquette, Charles; Mularski, Richard A.; Pinto-Plata, Victor M.; Pritchett, Michael A.; Rafeq, Samaan; Rubio, Edmundo R.; Slebos, Dirk-Jan; Stratakos, Grigoris; Sy, Alexander; Tsai, Larry W.; Wahidi, Momen; Walsh, John; Wells, J. Michael; Whitten, Patrick E.; Yusen, Roger; Zulueta, Javier J.; Criner, Gerard J.; Washko, George R.

    2016-01-01

    Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved by >100%. 44% of treated patients experienced adverse events requiring hospitalization (2.5-fold more than control, p=0.01), with two deaths in the treated cohort. Treatment responders tended to be those experiencing respiratory adverse events. Despite early termination, results show that minimally invasive ELS may be efficacious, yet significant risks (probably inflammatory) limit its current utility. PMID:25837041

  10. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy.

    PubMed

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering-stem cells, scaffolds, and signaling molecules-has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  11. Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies.

    PubMed

    Jafri, Mohammad A; Ansari, Shakeel A; Alqahtani, Mohammed H; Shay, Jerry W

    2016-01-01

    Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase assembly, intracellular trafficking and recruitment to telomeres for completing DNA synthesis, which may provide novel targets for the development of anticancer agents. Here, we summarize telomere organization and function and its role in oncogenesis. We also highlight genomic mutations that lead to reactivation of telomerase, and mechanisms of telomerase reconstitution and trafficking that shed light on its function in cancer initiation and tumor development. Additionally, recent advances in the clinical development of telomerase inhibitors, as well as potential novel targets, will be summarized. PMID:27323951

  12. [A case of advanced esophageal cancer with direct bronchial invasion successfully treated by multidisciplinary therapy].

    PubMed

    Haba, Yusuke; Okamoto, Koichi; Watanabe, Toshifumi; Tsukada, Tomoya; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Oyama, Katsunobu; Ninomiya, Itasu; Fushida, Sachio; Fujimura, Takashi; Ohta, Tetsuo

    2014-11-01

    A 66-year-old man with advanced esophageal cancer (staging Mt, 6.0 cm, cT3N0M0, cStage II) was administered neoadjuvant chemotherapy (NAC: 5-fluorouracil and cisplatin). As the tumor continued to grow after one course of NAC, video-assisted thoracoscopic surgery(VATS) was used to perform an esophagectomy along with 3-field lymph node dissection and retrosternal route reconstruction using a gastric tube. The second course of NAC was not administered. Intraoperative findings showed the direct invasion of the primary esophageal cancer into the membranous portion of the left bronchus. The maximum possible tumor tissue was resected and removed. The tumor tissue was exposed extensively to the surface of the esophageal adventitia and a residual tumor at the surface of the left bronchus was suspected. It was diagnosed as CT-pT4 (left bronchus), N0, M0, CT-pStage III. Subsequently, we administered chemoradiotherapy consisting of weekly low-dose docetaxel with radiation for the residual tumor (60 Gy/30 Fr). The patient is still alive 40 months after surgery without any signs of recurrence. PMID:25731408

  13. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter?

    PubMed Central

    Wong, Hilda

    2013-01-01

    It is increasingly recognized that gastric cancer is a heterogeneous disease which may be divided into subgroups based on histological, anatomical, epidemiological and molecular classifications. Distinct molecular drivers and tumor biology, and thus different treatment targets and predictive biomarkers, may be implicated in each subtype. However, there is little evidence in the literature regarding the correlation among these different classifications, and particularly the molecular aberrations present in each subtype. In this review, we approach advanced gastric cancer (AGC) by presenting aberrant molecular pathways and their potential therapeutic targets in gastric cancer according to histological and anatomical classification, dividing gastric cancer into proximal nondiffuse, distal nondiffuse and diffuse disease. Several pathways are involved predominantly, although not exclusively, in different subtypes. This may help to explain the disappointing results of many published AGC trials in which study populations were heterogeneous regardless of clinicopathological characteristics of the primary tumor. Histological and anatomical classification may provide insights into tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. However, some molecular pathways implicated in gastric cancer have not been studied in correlation with histological or anatomical subtypes. Further studies are necessary to confirm the suggestion that such classification may predict tumor biology and facilitate selection of an enriched patient population for targeted agents in future studies and in the clinic. PMID:23320047

  14. [Platin-containing cytostatic combinations in the therapy of advanced gynecologic carcinomas].

    PubMed

    Schulz, B O; Hof, K; Friedrich, H J; Weppelmann, B; Krebs, D

    1984-01-01

    95 patients with advanced and recurred gynecological carcinomas (57 ovarian carcinoma, 22 cervical carcinoma) were treated by a platinum (CDDP) based polychemotherapy platinum, adriamycine, cyclophosphamide (PAC); platinum, adriamycine, bleomycine (PAB), 22 out of 48 patients with low differentiated epithelial carcinoma of the ovary stage III and IV achieved a remission (13 CR; 9 PR). Today 6 of the CR-patients survive 23 months without recurrence; 7 had a medium survival of 17 months. Medium survival of PR-patients was 15 months. 6 NED-patients survive 22 months without recurrence and 2 NED-patients died after 19,5 months. The overall response rate (CR, PR, NED) was 63%. A retrospective comparison with 78 patients (low differentiated ovarian carcinoma stage III and IV) treated by a cyclophosphamide monotherapy shows an elevated 2-year survival rate of the PAC treated patients. The other patients suffered from carcinoma of the mamma, the tubes, the corpus uteri, the vagina, and the vulva. The therapeutic effect of CDDP based polychemotherapy cannot be judged because of the small number of cases; but the side effects at these patients were registered thoroughly. Side effects of totally 514 therapeutic cycles (460 mg CDDP per patient, 78 mg CDDP per cycle) are presented.

  15. Advances in targeting nucleocapsid-nucleic acid interactions in HIV-1 therapy

    PubMed Central

    Garg, Divita; Torbett, Bruce E.

    2014-01-01

    The continuing challenge of HIV-1 treatment resistance in patients creates a need for the development of new antiretroviral inhibitors. The HIV nucleocapsid (NC) protein is a potential therapeutic target. NC is necessary for viral RNA packaging and in the early stages of viral infection. The high level of NC amino acid conservation among all HIV-1 clades suggests a low tolerance for mutations. Thus, NC mutations that could arise during inhibitor treatment to provide resistance may render the virus less fit. Disruption of NC function provides a unique opportunity to strongly dampen replication at multiple points during the viral life cycle with a single inhibitor. Although NC exhibits desirable features for a potential antiviral target, the structural flexibility, size, and the presence of two zinc fingers makes small molecule targeting of NC a challenging task. In this review, we discuss the recent advances in strategies to develop inhibitors of NC function and present a perspective on potential novel approaches that may help to overcome some of the current challenges in the field. PMID:25026536

  16. Current Advance and Future Prospects of Tissue Engineering Approach to Dentin/Pulp Regenerative Therapy

    PubMed Central

    Gong, Ting; Heng, Boon Chin; Lo, Edward Chin Man; Zhang, Chengfei

    2016-01-01

    Recent advances in biomaterial science and tissue engineering technology have greatly spurred the development of regenerative endodontics. This has led to a paradigm shift in endodontic treatment from simply filling the root canal systems with biologically inert materials to restoring the infected dental pulp with functional replacement tissues. Currently, cell transplantation has gained increasing attention as a scientifically valid method for dentin-pulp complex regeneration. This multidisciplinary approach which involves the interplay of three key elements of tissue engineering—stem cells, scaffolds, and signaling molecules—has produced an impressive number of favorable outcomes in preclinical animal studies. Nevertheless, many practical hurdles need to be overcome prior to its application in clinical settings. Apart from the potential health risks of immunological rejection and pathogenic transmission, the lack of a well-established banking system for the isolation and storage of dental-derived stem cells is the most pressing issue that awaits resolution and the properties of supportive scaffold materials vary across different studies and remain inconsistent. This review critically examines the classic triad of tissue engineering utilized in current regenerative endodontics and summarizes the possible techniques developed for dentin/pulp regeneration. PMID:27069484

  17. Outcomes of chemotherapies and HER2 directed therapies in advanced HER2-mutant lung cancers.

    PubMed

    Eng, Juliana; Hsu, Meier; Chaft, Jamie E; Kris, Mark G; Arcila, Maria E; Li, Bob T

    2016-09-01

    Human epidermal growth factor receptor 2 (HER2, ERBB2) mutations occur in 3% of lung adenocarcinomas. While case reports and series have shown activity of HER2 targeted agents in these patients, little is known about outcomes of chemotherapies. Patients with stage IV HER2-mutant lung cancers at Memorial Sloan Kettering were reviewed. Patient demographics, types of HER2 mutations, duration of systemic treatments and survival were analyzed. We identified 38 patients with HER2-mutant lung cancers: median age 62; majority were women (n=24), never smokers (n=22), and all had adenocarcinomas. A 12 base pair in-frame insertion YVMA in exon 20 (p.A775_G776insYVMA) was present in 24 (63%, 95% CI 46-78%) patients. In addition, there were four 9 base pair insertions, one 6 base pair insertion, and five 3 base pair insertions in exon 20, and four single bp substitutions (exon 20 L755F, V777L, D769H, exon 8 S310F). The median overall survival from date of diagnosis of stage IV disease was 2.3 years (95% CI 1.2-2.6). The median duration of chemotherapy was 4.3 months (68 treatments, range 0-21 months): 6.2 months for pemetrexed ±platinum/bevacizumab, 4 months for taxane ±platinum/bevacizumab, 2.6 months for gemcitabine, 3.5 months for vinorelbine. The median duration of HER2 tyrosine kinase inhibitors was 2.2 months (28 treatments, range 0.3-16.3 months). As we search for better targeted therapies for patients with HER2-mutant lung cancers, chemotherapy remains an important component of care. PMID:27565914

  18. Advances in GBA-associated Parkinson's disease--Pathology, presentation and therapies.

    PubMed

    Barkhuizen, Melinda; Anderson, David G; Grobler, Anne F

    2016-02-01

    therapies are promising for Parkinson's disease, regardless of mutation status. Recently, there has been a boom in studies investigating the role of glucocerebrosidase in the pathology of Parkinson's disease. This merits a comprehensive review of the current cell biological processes and pathological pictures involving Parkinson's disease associated with GBA mutations.

  19. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

    PubMed

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

    This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. PMID:27045432

  20. Evidence-based recommendations on androgen deprivation therapy for localized and advanced prostate cancer

    PubMed Central

    Belsey, Jonathan; Drewa, Tomasz; Kołodziej, Anna; Skoneczna, Iwona; Milecki, Piotr; Dobruch, Jakub; Słojewski, Marcin; Chłosta, Piotr L.

    2016-01-01

    Introduction The management of prostate cancer (PC) is still evolving. Although, androgen deprivation therapy (ADT) is an established treatment option, particularly in patients with disseminated disease, important data regarding hormonal manipulation have recently emerged. The aim of this paper is to review the evidence on ADT, make recommendations and address areas of controversy associated with its use in men with PC. Material and methods An expert panel was convened. Areas related to the hormonal management of patients with PC requiring evidence review were identified and questions to be addressed by the panel were determined. Appropriate literature review was performed and included a search of online databases, bibliographic reviews and consultation with experts. Results The panel was able to provide recommendations on: 1) which patients with localised PC should receive androgen deprivation in conjunction with radiotherapy (RT); 2) what standard initial treatment should be used in metastatic hormone-naïve PC (MHNPC); 3) efficacy of androgen deprivation agents; 4) whether ADT should be continued in patients with castration resistant PC (CRPC). However, no recommendations could be made for combined ADT and very high-dose RT in patients with an intermediate-risk disease. Conclusions ADT remains the cornerstone of treatment for both metastatic hormone-naïve and castration-resistant PC. According to the expert panel's opinion, based on the ERG report, luteinizing hormone-releasing hormone agonists might not be equivalent but this needs to be confirmed in long-term data. The combined use of ADT and RT improves outcome and survival in men with high-risk localised disease. The benefits in patients with intermediate-risk disease, particularly those subject to escalated dose RT are controversial. PMID:27551549