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Sample records for advanced therapies cat

  1. 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

  2. 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

  3. Albendazole therapy for experimentally induced Paragonimus kellicotti infection in cats.

    PubMed

    Dubey, J P; Hoover, E A; Stromberg, P C; Toussant, M J

    1978-06-01

    The effect of albendazole therapy was studied in 6 cats with pulmonary paragonimiasis induced by experimental inoculation of metacercariae (25/cat) of Paragonimus kellicotti. At 76 to 101 days after they were inoculated, 5 cats were administered an oral aqueous suspension of albendazole in 2 divided doses totaling 20 mg (2 cats), 50 mg (1 cat), or 100 mg (2 cats)/kg of body weight each day for 14 to 21 days. The 6th cat (control) was not administered albendazole. Nine days after cats were given the 50- and 100-mg/kg dosages, Paragonimus ova were not seen in the feces of 3 cats. There was marked reduction in ova production in the feces of the 2 cats administered 20 mg/kg of albendazole. Live flukes were not recovered from the lungs of 3 cats necropsied 4 or 5 weeks after dosing with 50 or 100 mg/kg, but the lungs of the 2 cats administered 20 mg of albendazole/kg yielded 9 and 7 apparently viable flukes. Seventeen live flukes were recovered from the control cat not treated with albendazole. In 4 noninoculated normal cats administered 20 mg (1 cat), 100 mg (1 cat), and 200 mg (2 cats) of albendazole/kg of body weight each day for 14 days, there were no gross or microscopic lesions attributable to the drug. PMID:666077

  4. [Perioperative pain therapy in dogs and cats - an overview].

    PubMed

    Pieper, Korbinian

    2016-06-16

    Undermanaged pain leads to negative systemic effects that may greatly disturb our patients' welfare. Therefore, a pain assessment tool should be routinely implemented into clinical practice. Validated pain assessment tools are available for dogs and cats. Advanced analgesic therapy follows the principle of a multimodal approach. This means that different analgesic drugs, which act on different targets within the nociceptive pathway, are combined to achieve the desired analgesic effects. In addition to opioids, nonsteroidal anti-inflammatory drugs and local anaesthetics, α2-receptor-agonists, ketamine and gabapentin as well as different nonpharmacologic analgesic techniques are used within the framework of a multimodal analgesic plan. PMID:27223267

  5. 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.

  6. 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 ...

  7. 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.

  8. 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

  9. 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.

  10. Advances in corneal cell therapy.

    PubMed

    Fuest, Matthias; Yam, Gary Hin-Fai; Peh, Gary Swee-Lim; Mehta, Jodhbir S

    2016-09-01

    Corneal integrity is essential for visual function. Transplantation remains the most common treatment option for advanced corneal diseases. A global donor material shortage requires a search for alternative treatments. Different stem cell populations have been induced to express corneal cell characteristics in vitro and in animal models. Yet before their application to humans, scientific and ethical issues need to be solved. The in vitro propagation and implantation of primary corneal cells has been rapidly evolving with clinical practices of limbal epithelium transplantation and a clinical trial for endothelial cells in progress, implying cultivated ocular cells as a promising option for the future. This review reports on the latest developments in primary ocular cell and stem cell research for corneal therapy. PMID:27498943

  11. Advances in optical technologies at Pontificia Universidad Católica del Perú

    NASA Astrophysics Data System (ADS)

    Baldwin, Guillermo; Asmad, Miguel; Romero, Sandra; Gonzales, Franco; Gálvez, Gonzalo; Sánchez, Rubén; Córdova, Darwin

    2011-05-01

    In this work, it is shown a panoramically view of advances and works on fundamental optical technology developed and Physics Section at Pontificia Universidad Católica del Perú PUCP in Lima Peru. This includes works in, precision optics manufacturing, optical testing, and optical design and simulation and also in optical thin film evaporation and its design techniques

  12. 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

  13. Legal basis of the Advanced Therapies Regulation.

    PubMed

    Jekerle, V; Schröder, C; Pedone, E

    2010-01-01

    Advanced therapy medicinal products consist of gene therapy, somatic cell therapy and tissue engineered products. Due to their specific manufacturing process and mode of action these products require specially tailored legislation. With Regulation (EC) No. 1394/2007, these needs have been met. Definitions of gene therapy, somatic cell therapy and tissue engineered products were laid down. A new committee, the Committee for Advanced Therapies, was founded, special procedures such as the certification procedure for small- and medium-sized enterprises were established and the technical requirements for Marketing Authorisation Applications (quality, non-clinical and clinical) were revised. PMID:19940965

  14. Neonatal Gene Therapy With a Gamma Retroviral Vector in Mucopolysaccharidosis VI Cats

    PubMed Central

    Ponder, Katherine P; O'Malley, Thomas M; Wang, Ping; O'Donnell, Patricia A; Traas, Anne M; Knox, Van W; Aguirre, Gustavo A; Ellinwood, N Matthew; Metcalf, Jason A; Wang, Bin; Parkinson-Lawrence, Emma J; Sleeper, Meg M; Brooks, Doug A; Hopwood, John J; Haskins, Mark E

    2012-01-01

    Mucopolysaccharidosis (MPS) VI is due to a deficiency in the activity of N-acetylgalactosamine 4-sulfatase (4S), also known as arylsulfatase B. Previously, retroviral vector (RV)-mediated neonatal gene therapy reduced the clinical manifestations of MPS I and MPS VII in mice and dogs. However, sulfatases require post-translational modification by sulfatase-modifying factors. MPS VI cats were injected intravenously (i.v.) with a gamma RV-expressing feline 4S, resulting in 5 ± 3 copies of RV per 100 cells in liver. Liver and serum 4S activity were 1,450 ± 1,720 U/mg (26-fold normal) and 107 ± 60 U/ml (13-fold normal), respectively, and were directly proportional to the liver 4S protein levels for individual cats. This study suggests that sulfatase-modifying factor (SUMF) activity in liver was sufficient to result in active enzyme despite overexpression of 4S. RV-treated MPS VI cats achieved higher body weights and longer appendicular skeleton lengths, had reduced articular cartilage erosion, and reduced aortic valve thickening and aortic dilatation compared with untreated MPS VI cats, although cervical vertebral bone lengths were not improved. This demonstrates that therapeutic expression of a functional sulfatase protein can be achieved with neonatal gene therapy using a gamma RV, but some aspects of bone disease remain difficult to treat. PMID:22395531

  15. Oral Recombinant Feline Interferon-Omega as an alternative immune modulation therapy in FIV positive cats: clinical and laboratory evaluation.

    PubMed

    Gil, S; Leal, R O; McGahie, D; Sepúlveda, N; Duarte, A; Niza, M M R E; Tavares, L

    2014-02-01

    Recombinant-Feline Interferon-Omega (rFeIFN-ω) is an immune-modulator licensed for use subcutaneously in Feline Immunodeficiency virus (FIV) therapy. Despite oral protocols have been suggested, little is known about such use in FIV-infected cats. This study aimed to evaluate the clinical improvement, laboratory findings, concurrent viral excretion and acute phase proteins (APPs) in naturally FIV-infected cats under oral rFeIFN-ω therapy (0.1 MU/cat rFeIFN-ω PO, SID, 90 days). 11 FIV-positive cats were treated with oral rFeIFN-ω (PO Group). Results were compared to previous data from 7 FIV-positive cats treated with the subcutaneous licensed protocol (SC Group). Initial clinical scores were similar in both groups. Independently of the protocol, rFeIFN-ω induced a significant clinical improvement of treated cats. Concurrent viral excretion and APP's variation were not significant in the PO Group. Oral rFeIFN-ω can be an effective alternative therapy for FIV-infected cats, being also an option for treatment follow-up in cats submitted to the licensed protocol. PMID:24332273

  16. Induction therapy for locally advanced thymoma.

    PubMed

    Riely, Gregory J; Huang, James

    2010-10-01

    Thymomas are the most frequently encountered tumors of the mediastinum and often present with either localized or locally advanced disease. The prognosis in thymoma has been consistently shown to correspond to the invasiveness of the tumor (as represented by the Masaoka stage of the tumor) and the completeness of surgical resection. Because treatment with a variety of different chemotherapy regimens has demonstrated radiographic response rates greater than 50% in patients with advanced thymoma, a number of investigators have explored the use of preoperative (induction, neoadjuvant) therapy for patients with locally advanced thymoma. In this review, we summarize the published experience with preoperative therapy for thymoma and discuss ongoing clinical trials exploring multimodality therapy for treatment of locally advanced thymoma. PMID:20859127

  17. 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

  18. 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

  19. 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

  20. Advances in the targeted therapy of liposarcoma

    PubMed Central

    Guan, Zhonghai; Yu, Xiongfei; Wang, Haohao; Wang, Haiyong; Zhang, Jing; Li, Guangliang; Cao, Jiang; Teng, Lisong

    2015-01-01

    Liposarcoma (LPS) is the most common type of soft-tissue sarcoma. Complete surgical resection is the only curative means for localized disease; however, both radiation and conventional cytotoxic chemotherapy remain controversial for metastatic or unresectable disease. An increasing number of trials with novel targeted therapy of LPS have provided encouraging data during recent years. This review will provide an overview of the advances in our understanding of LPS and summarize the results of recent trials with novel therapies targeting different genetic and molecular aberrations for different subtypes of LPS. PMID:25609980

  1. 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

  2. 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.

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

    NASA Astrophysics Data System (ADS)

    Shu, D.; Benson, C.; Chang, J.; Barraza, J.; Kuzay, T. M.; Alp, E. E.; Sturhahn, W.; Lai, B.; McNulty, I.; Randall, K.; Srajer, G.; Xu, Z.; Yun, W.

    1997-07-01

    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. [Yun et al., Rev. Sci. Instrum. 67(9)(1996)CD-ROM] 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 us 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.

  4. Photodynamic therapy on spontaneous tumors of dogs and cats: a ten-year study

    NASA Astrophysics Data System (ADS)

    Fonda, Diego

    1992-06-01

    Since 1981, more than fifty spontaneous tumors of dogs and cats were treated by photodynamic therapy with hematoporphyrins in the surgery department of the University of Milan. Therapeutic results proved to be successful and promising in certain forms of cancer and will be compared in the future with the effectiveness of other photosensitizer drugs like phatolocyanines derivatives. Applied hematoporphyrins phototherapy methods included: (1) injection of hematoporphyrins derivative (HpD) and irradiation with laser light at 631 nanometers, using a Rhodamine B dye laser; (2) injection of the active component of hematoporphyrin derivative (DHE) and irradiation with a Rhodamine B dye laser; and (3) injection of DHE and irradiation with laser light at 628 nanometers using a gold vapor laser. More frequently treated tumor sites were oral and nasal cavities. Other localizations were mucous membranes of the glans and stomach. Nineteen histological types were diagnosed in treated tumors.

  5. Updates in Therapy for Advanced Melanoma

    PubMed Central

    Singh, Bhavana P.; Salama, April K. S.

    2016-01-01

    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. PMID:26784231

  6. Novel therapy for advanced gastric cancer

    PubMed Central

    Zhang, Yue; Wu, Shenhong

    2015-01-01

    Gastric cancer (GC) is a common lethal malignancy. Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States. Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease. The median overall survival (OS) is less than one year for advanced GC patients; thus, there is an urgent unmet need to develop novel therapy for GC. Although multiple targeted agents were studied, only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit (5.2 mo vs 3.8 mo, P = 0.047) as a single agent; 2.2 mo improvement of survival (9.6 mo vs 7.4 mo, P = 0.017) when combined with paclitaxel in previously treated advanced GC patients. It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab. Even with limited success, targeted therapy may be improved by developing new biomarkers. Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials. More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities. PMID:26600926

  7. 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

  8. Epigenetics Advancing Personalized Nanomedicine in Cancer Therapy

    PubMed Central

    Liu, Shujun

    2012-01-01

    Personalized medicine aims to deliver the right drug to a right patient at the right time. It offers unique opportunities to integrate new technologies and concepts to disease prognosis, diagnosis and therapeutics. While selective personalized therapies are conceptually impressive, the majority of cancer therapies have dismal outcome. Such therapeutic failure could result from no response, drug resistance, disease relapse or severe side effect from improper drug delivery. Nanomedicine, the application of nanotechnology in medicine, has a potential to advance the identification of diagnostic and prognostic biomarkers and the delivery of right drug to disease sites. Epigenetic aberrations dynamically contribute to cancer pathogenesis. Given the individualized traits of epigenetic biomarkers, epigenetic considerations would significantly refine personalized nanomedicine. This review aims to dissect the interface of personalized medicine with nanomedicine and epigenetics. I will outline the progress and highlight challenges and areas that can be further explored perfecting the personalized health care. PMID:22921595

  9. Advances of gene therapy for primary immunodeficiencies

    PubMed Central

    Candotti, Fabio

    2016-01-01

    In the recent past, the gene therapy field has witnessed a remarkable series of successes, many of which have involved primary immunodeficiency diseases, such as X-linked severe combined immunodeficiency, adenosine deaminase deficiency, chronic granulomatous disease, and Wiskott-Aldrich syndrome. While such progress has widened the choice of therapeutic options in some specific cases of primary immunodeficiency, much remains to be done to extend the geographical availability of such an advanced approach and to increase the number of diseases that can be targeted. At the same time, emerging technologies are stimulating intensive investigations that may lead to the application of precise genetic editing as the next form of gene therapy for these and other human genetic diseases. PMID:27508076

  10. 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

  11. 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.

  12. Advances in implantable cardioverter defibrillator therapy.

    PubMed

    Rickard, John; Wilkoff, Bruce L

    2016-03-01

    Since the first implant in 1980, implantable cardioverter defibrillator (ICD) technology has progressed rapidly. Modern ICD's have hundreds of programmable options with the general goal of preventing inappropriate shocks and providing shocks for truly life threatening symptomatic ventricular arrhythmias. New studies on ICD programming have shown the benefits of prolonged detection intervals in reaching this goal. Anti-tachycardia pacing (ATP) therapy has become an important adjunct to defibrillator shocks. Remote monitoring technologies have surfaced which have been shown to identify arrhythmias and problems with the device in an expedient fashion. The subcutaneous ICD offers the advantage of avoiding intravascular leads and their inherent risks. Lastly, the current understanding of the effects of MRI in ICD patients has advanced creating new opportunities to provide MRI safely to such patients. PMID:26653411

  13. 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

  14. Benefits of calcitriol therapy and serum phosphorus control in dogs and cats with chronic renal failure. Both are essential to prevent of suppress toxic hyperparathyroidism.

    PubMed

    Nagode, L A; Chew, D J; Podell, M

    1996-11-01

    Daily oral calcitriol at low doses is safe and effective in the control of renal secondary hyperparathyroidism in dogs and cats. Low doses of calcitriol are most effective when started early in uremia before the advanced stages of renal secondary hyperparathyroidism. At early stages calcitriol both diminishes PTH synthesis in the parathyroid cells present and prevents the hyperplasia that, if unchecked, results in the most extensive an difficult-to-control hyperparathyroidism. The salutary effects on the dog's or cat's sense of well being, appetite, activity, strength, and lifespan as reported by the veterinarians of our survey are attributed primarily to keeping PTH levels below a toxic threshold. Additionally, some of the benefits achieved by calcitriol are likely a direct consequence of calcitriol interacting with the vitamin D receptor in a wide variety of tissues throughout the body. Phosphorus restriction through a combination of diet and intestinal phosphate binders is important to allow calcitriol therapy to successfully lower PTH levels, but it likely has no direct effects that are independent of interactions involving calcitriol. Phosphorus restriction is also important to minimize chances for adverse tissue mineralization. Calcitriol therapy can be considered for treatment of chronic renal failure after serum phosphorus has been decreased to less than 6.0 mg/dL in patients in whom it was initially elevated. Calcitriol supplementation to dogs and cats with chronic renal failure makes good endocrinologic sense. Calcitriol deficits cause increased PTH and, as these two hormones are designed to maintain calcium and phosphorus homeostasis, the PTH increase is initially adaptive. One of the important effects of PTH is to stimulate additional calcitriol formation as a powerful means to raise blood calcium through increased calcium absorption from the diet. With too great an increase in PTH, however, its effects become harmful to many tissues due to the

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. Treatment of advanced thyroid cancer: role of molecularly targeted therapies.

    PubMed

    Covell, Lorinda L; Ganti, Apar Kishor

    2015-09-01

    Advanced thyroid cancer is not amenable to therapy with conventional cytotoxic chemotherapy. However, newer advances in the understanding of the molecular pathogenesis of different subtypes of thyroid cancer have provided new opportunities for the evaluation of molecularly targeted therapies. This has led to multiple clinical trials using various multi-kinase inhibitors and the subsequent US FDA approval of sorafenib for differentiated thyroid cancer and vandetanib and cabozantinib for medullary thyroid carcinoma. This review provides a summary of the current literature for the treatment of advanced thyroid carcinoma and future directions in this disease. PMID:26335853

  20. Advancing Techniques of Radiation Therapy for Rectal Cancer.

    PubMed

    Patel, Sagar A; Wo, Jennifer Y; Hong, Theodore S

    2016-07-01

    Since the advent of radiation therapy for rectal cancer, there has been continual investigation of advancing technologies and techniques that allow for improved dose conformality to target structures while limiting irradiation of surrounding normal tissue. For locally advanced disease, intensity modulated and proton beam radiation therapy both provide more highly conformal treatment volumes that reduce dose to organs at risk, though the clinical benefit in terms of toxicity reduction is unclear. For early stage disease, endorectal contact therapy and high-dose rate brachytherapy may be a definitive treatment option for patients who are poor operative candidates or those with low-lying tumors that desire sphincter-preservation. Finally, there has been growing evidence that supports stereotactic body radiotherapy as a safe and effective salvage treatment for the minority of patients that locally recur following trimodality therapy for locally advanced disease. This review addresses these topics that remain areas of active clinical investigation. PMID:27238474

  1. [Maintenance therapy for advanced non-small-cell lung cancer].

    PubMed

    Saruwatari, Koichi; Yoh, Kiyotaka

    2014-08-01

    Maintenance therapy is a new treatment strategy for advanced non-small-cell lung cancer(NSCLC), and it consists of switch maintenance and continuation maintenance.Switch maintenance is the introduction of a different drug, not included as part of the induction therapy, immediately after completion of 4 cycles of first-line platinum-based chemotherapy.Continuation maintenance is a continuation of at least one of the drugs used in the induction therapy in the absence of disease progression.Several phase III trials have reported survival benefits with continuation maintenance of pemetrexed and switch maintenance of pemetrexed or erlotinib.Therefore, maintenance therapy has become a part of the standard first-line treatment for advanced NSCLC.However, further research is needed to elucidate the selection criteria of patients who may benefit the most from maintenance therapy. PMID:25132023

  2. 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.

  3. 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

  4. 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

  5. Advanced Hodgkin Lymphoma: a New Era of Therapy

    PubMed Central

    Dann, Eldad J.

    2014-01-01

    Therapy of advanced Hodgkin lymphoma (HL) is a rapidly changing field due to a lot of currently emerging data. Treatment approaches are presently based on either the Kairos principle of giving aggressive therapy upfront and considering de-escalation of therapy if the interim PET/CT is negative or the Chronos principle of starting with ABVD followed by escalation of therapy for patients with positive interim PET/CT. The International Prognostic Score (IPS) is still valid for decision-making regarding the type of initial therapy, since patients with a high score do have an inferior progression free survival (PFS) with ABVD compared to those with a low score. Escalated BEACOPP administered upfront improves PFS; however, increase in the overall survival (OS) has not been confirmed yet, and this therapy is accompanied by elevated toxicity and fertility impairment. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients. PMID:25237476

  6. Advances in apheresis therapy for glomerular diseases.

    PubMed

    Yokoyama, Hitoshi; Wada, Takashi; Zhang, Wei; Yamaya, Hideki; Asaka, Mitsuhiro

    2007-06-01

    This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases. PMID:17593511

  7. Recent advances in cardiac resynchronization therapy.

    PubMed

    Steffel, Jan; Holzmeister, Johannes; Abraham, William T

    2011-03-01

    Cardiac resynchronization therapy (CRT) is an integral component of modern heart failure therapy for patients with severe symptoms (New York Heart Association [NYHA] class III or IV), a reduced ejection fraction (≤ 35%), and a wide QRS complex (> 120 ms). Results from recent trials have provided ample evidence that CRT may also reduce morbidity and mortality in patients with mildly symptomatic heart failure (NYHA class II). As a result, the 2010 European guidelines now recommend CRT for this patient population (level of evidence I, class A). This review summarizes and critically evaluates the landmark Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), and Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) studies, which comprise the suite of randomized controlled trials available today on this matter. Furthermore, we discuss the rationale and available evidence for other emerging indications for CRT, including its use in patients with a mildly reduced left ventricular ejection fraction (> 35%), in those with a narrow QRS complex (≤ 130 ms), or in patients with concomitant bradyarrhythmic pacemaker indications. PMID:21474889

  8. Advanced therapies for the treatment of hemophilia: future perspectives

    PubMed Central

    2012-01-01

    Monogenic diseases are ideal candidates for treatment by the emerging advanced therapies, which are capable of correcting alterations in protein expression that result from genetic mutation. In hemophilia A and B such alterations affect the activity of coagulation factors VIII and IX, respectively, and are responsible for the development of the disease. Advanced therapies may involve the replacement of a deficient gene by a healthy gene so that it generates a certain functional, structural or transport protein (gene therapy); the incorporation of a full array of healthy genes and proteins through perfusion or transplantation of healthy cells (cell therapy); or tissue transplantation and formation of healthy organs (tissue engineering). For their part, induced pluripotent stem cells have recently been shown to also play a significant role in the fields of cell therapy and tissue engineering. Hemophilia is optimally suited for advanced therapies owing to the fact that, as a monogenic condition, it does not require very high expression levels of a coagulation factor to reach moderate disease status. As a result, significant progress has been possible with respect to these kinds of strategies, especially in the fields of gene therapy (by using viral and non-viral vectors) and cell therapy (by means of several types of target cells). Thus, although still considered a rare disorder, hemophilia is now recognized as a condition amenable to gene therapy, which can be administered in the form of lentiviral and adeno-associated vectors applied to adult stem cells, autologous fibroblasts, platelets and hematopoietic stem cells; by means of non-viral vectors; or through the repair of mutations by chimeric oligonucleotides. In hemophilia, cell therapy approaches have been based mainly on transplantation of healthy cells (adult stem cells or induced pluripotent cell-derived progenitor cells) in order to restore alterations in coagulation factor expression. PMID:23237078

  9. 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

  10. 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.

  11. 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

  12. Recent advances in therapy for sexual offenders

    PubMed Central

    2009-01-01

    This report focuses on recent policy, and academic and clinical developments in the therapeutic management of sex offenders, including the need for more robust assessment and risk management protocols. Information is provided on current thinking about psychological and pharmacological interventions. Meta-analytic studies clearly indicate that cognitive behavioural and relapse prevention programmes are the most effective intervention, but there is a small amount of literature suggesting that pharmacological treatments may have some utility. With advances in our understanding of the neural substrates of deviant sexual arousal we may be able to develop and trial novel neuropharmacological agents that target dysfunctional neurochemical circuits in this field. PMID:20948736

  13. Recent advances in therapy for sexual offenders.

    PubMed

    Dolan, Mairead

    2009-01-01

    This report focuses on recent policy, and academic and clinical developments in the therapeutic management of sex offenders, including the need for more robust assessment and risk management protocols. Information is provided on current thinking about psychological and pharmacological interventions. Meta-analytic studies clearly indicate that cognitive behavioural and relapse prevention programmes are the most effective intervention, but there is a small amount of literature suggesting that pharmacological treatments may have some utility. With advances in our understanding of the neural substrates of deviant sexual arousal we may be able to develop and trial novel neuropharmacological agents that target dysfunctional neurochemical circuits in this field. PMID:20948736

  14. Advances in Sickle Cell Therapies in the Hydroxyurea Era

    PubMed Central

    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

  15. 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

  16. Targeted therapy in advanced bladder cancer: what have we learned?

    PubMed

    Jordan, Emmet J; Iyer, Gopa

    2015-05-01

    Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been approved by the US Food and Drug Administration for urothelial carcinoma (UC) in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared with cytotoxic therapy. This article outlines representative trials of targeted therapies in UC and discusses the significance of genetic preselection in trial design as a method to optimize responses to these agents, thus, hopefully expanding the armamentarium of treatment options against this lethal disease. PMID:25882566

  17. Advances in target therapy in lung cancer.

    PubMed

    Sculier, Jean-Paul; Berghmans, Thierry; Meert, Anne-Pascale

    2015-03-01

    Herein, we have reviewed and analysed recent literature, published in 2013 and early 2014, in the context of pre-existing data. Considered target therapies were tyrosine kinase inhibitors of active epidermal growth factor receptor mutations (e.g. erlotinib, gefinitib and afatinib), anaplastic lymphoma kinase rearrangements (e.g. crizotinib) or angiogenesis (drugs under development), or monoclonal antibodies against vascular endothelial growth factor (e.g. bevacizumab) or epidermal growth factor receptors (e.g. cetuximab). The therapeutic project has to consider tyrosine kinase inhibitors in the case of nonsmall cell lung cancer with active epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangement. However, these drugs should not be used in the absence of the targeted genetic abnormalities. PMID:25726551

  18. Multimodal therapy in locally advanced breast carcinoma

    SciTech Connect

    Lopez, M.J.; Andriole, D.P.; Kraybill, W.G.; Khojasteh, A. )

    1990-12-01

    Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

  19. 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

  20. Advances in Anti-IgE Therapy

    PubMed Central

    Yalcin, Arzu Didem

    2015-01-01

    Omalizumab depletes free IgE in the blood and interstitial space and inhibits IgE binding to FcεRI on basophils, mast cells, and dendritic cells. We stopped omalizumab treatment after four years. Recurrences of urticaria symptoms were found to be higher in patients with chronic urticaria than recurrences of asthmatic symptoms in severe persistent asthma patients. For the very first time, we used omalizumab in symptomatic therapy of recurrent laryngeal oedema and urticaria attacks in a patient with postoperative pulmonary carcinoid tumor for eight months. During the four years of follow-up, no recurrence was noted in pulmonary carcinoid tumor. Control PET CT results revealed normal findings. After omalizumab treatment, laryngeal oedema and urticaria symptoms were decreased. The most common adverse reaction from omalizumab is injection site induration, injection site itching, injection site pain, and bruising but the package insert contains warnings regarding parasitic infections. While there are no reports of fatal anaphylaxis as a result of omalizumab, some cases have been serious and potentially life-threatening. Therefore, the FDA requires that people receiving omalizumab be monitored in the physician's office for a period of time after their injections. PMID:26075226

  1. 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. PMID:27588746

  2. 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…

  3. Hormonal therapy in advanced or recurrent endometrial cancer

    PubMed Central

    Kokka, Fani; Brockbank, Elly; Oram, David; Gallagher, Chris; Bryant, Andrew

    2014-01-01

    Background Endometrial cancer is a cancer of the lining of the womb and worldwide is the seventh most common cancer in women. Treatment with hormones is thought to be beneficial in patients with endometrial cancer. Objectives To assess the indications, effectiveness and safety of hormone therapy for advanced or recurrent epithelial endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, MEDLINE, EMBASE up to May 2009 and and CENTRAL (Issue 2, 2009). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies, and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) that studied hormonal therapy in adult women diagnosed with advanced or recurrent endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Comparisons were restricted to single-trial analyses so we did not synthesise data in meta-analyses. Main results We found six trials (542 participants) that met our inclusion criteria. These trials assessed the effectiveness of hormonal therapy in women with advanced or recurrent endometrial cancer as a single agent, as part of combination therapy and as low versus high dose. All comparisons were restricted to single-trial analyses, where we found no evidence that hormonal therapy as a single agent or as a combination treatment prolonged overall or five-year disease-free survival of women with advanced or recurrent endometrial cancer. However, low-dose hormonal therapy may have had a benefit in terms of overall and progression-free survival (PFS) compared to high-dose hormonal therapy (HR 1.31, 95% CI 1.04 to 1.66 and HR 1.35, 95% CI 1.07 to 1.71 for overall and PFS, respectively). Authors’ conclusions We found insufficient evidence that hormonal treatment in any form, dose or as part of combination therapy improves the survival of patients with advanced or

  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. Traditional and nontraditional effective and noneffective therapies for cardiac disease in dogs and cats.

    PubMed

    Pion, Paul D

    2004-01-01

    In this article, I presented my (admittedly biased) perspective of the current state of knowledge addressing the role of traditional and non-traditional therapeutics. The focus has been on the nontraditional therapeutics. Among these, the only ones I currently consider to have any documented value are taurine and, less commonly, L-carnitine. The role of taurine (and likely carnitine) remains limited to cases of documented deficiency. In the case of cats with taurine deficiency-induced myocardial failure, it is now clear that most cases are the result of formulation errors by owners and manufacturers. In dogs, it is less clear if the causes of taurine deficiencies represent manifestations of pathologic conditions or dietary formulations errors. Increasingly, it seems the latter may prove to be the case in most, if not all, circumstances. Finally, I would like to reiterate the conclusions of the last time I addressed this topic (with coauthors Kittleson and Sanderson) in this publication. Remember that there is limited evidence to support the therapeutic recommendations you read or hear in most circumstances. The urge to do "something" for patients can be overwhelmingly attractive. Nevertheless, whether it is administration of drugs or prescribing nutraceuticals or prescription diets, strongly consider the source of the information urging you to prescribe, the strength of the evidence presented, the financial costs to the owner, and the potential risks and benefits to the patient. PMID:15032128

  6. Advances in Radiation Therapy in Pediatric Neuro-oncology.

    PubMed

    Bindra, Ranjit S; Wolden, Suzanne L

    2016-03-01

    Radiation therapy remains a highly effective therapy for many pediatric central nervous system tumors. With more children achieving long-term survival after treatment for brain tumors, late-effects of radiation have become an important concern. In response to this problem, treatment protocols for a variety of pediatric central nervous system tumors have evolved to reduce radiation fields and doses when possible. Recent advances in radiation technology such as image guidance and proton therapy have led to a new era of precision treatment with significantly less exposure to healthy tissues. These developments along with the promise of molecular classification of tumors and targeted therapies point to an optimistic future for pediatric neuro-oncology. PMID:26271789

  7. 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

  8. 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

  9. Advancements in gene transfer-based therapy for hemophilia A

    PubMed Central

    Doering, Christopher B; Spencer, H Trent

    2010-01-01

    Gene therapy has promised clinical benefit to those suffering with hemophilia A, but this benefit has not yet been realized. However, during the past two decades, basic and applied gene therapy research has progressed and the goal of gene therapy for hemophilia A is once again in our sights. The hemophilia A patient population suffers from a disease that requires invasive, lifelong management, is exorbitantly expensive to treat, has geographically limited treatment access and can become untreatable due to immune reactions to the treatment product. Subsequent to the cloning of the factor VIII gene and cDNA in the early 1980s, academic and commercial research laboratories began to pursue gene transfer-based therapies to supplement or supplant the available protein replacement therapy. However, to date, clinical trials for gene therapy of hemophilia A have been unsuccessful. Three trials have been conducted with each having tested a different gene-transfer strategy and each demonstrating that there is a considerable barrier to achieving sustained expression of therapeutic amounts of factor VIII. Recent progress has been made in gene-transfer technology and, relevant to hemophilia A, towards increasing the biosynthetic efficiency of factor VIII. These advances are now being combined to develop novel strategies to treat and possibly cure hemophilia A. PMID:20577574

  10. [Concurrent proton therapy and chemotherapy for locally advanced cancers].

    PubMed

    Ishikawa, Hitoshi; Fukumitsu, Nobuyoshi; Ohnishi, Kayoko; Mizumoto, Masashi; Murofushi, Keiko; Numajiri, Haruko; Aihara, Teruhito; Okumura, Toshiyuki; Sakurai, Hideyuki

    2015-02-01

    Charged particles such as protons and carbon-ions offer advantageous physical properties to radiation therapy (RT) for the treatment of various cancers when compared with photons, because they exhibit a spread-out Bragg peak, and may be utilized to achieve a desirable dose distribution to the target volume by using specified beam modulation. Interestingly, the cytocidal effect of protons is almost equal to that of photons, because both protons and photons are considered low-linear energy transfer radiations. Hence, proton beam therapy (PBT) is an attractive RT option, especially in the treatment of locally advanced cancers, as irradiation doses can be safely escalated while sparing the surrounding normal tissues, and because PBT may be concurrently combined with chemotherapy for treating such cancers. Recent advances in PBT techniques including a spot scanning method, as well as an increase in the number of particle therapy institutes are anticipated to yield favorable results through future multi-institutional prospective studies. The University of Tsukuba has carried out several studies to validate the effectiveness of PBT for many types of cancers since 1983. Here, we present our findings on the clinical outcomes of PBT for esophageal cancer, non-small cell lung cancer, intrahepatic biliary tract cancer, pancreas cancer, and bladder cancer; future aspects of PBT concurrently combined with chemotherapy for treating locally advanced cancers are also discussed. PMID:25743133

  11. [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

  12. 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

  13. 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

  14. 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

  15. Advanced Therapies For End-Stage Heart Failure

    PubMed Central

    Katz, Jason N; Waters, Sarah B; Hollis, Ian B; Chang, Patricia P

    2015-01-01

    Management of the advanced heart failure patient can be complex. Therapies include cardiac transplantation and mechanical circulatory support, as well inotropic agents for the short-term. Despite a growing armamentarium of resources, the clinician must carefully weigh the risks and benefits of each therapy to develop an optimal treatment strategy. While cardiac transplantation remains the only true “cure” for end-stage disease, this resource is limited and the demand continues to far outpace the supply. For patients who are transplant-ineligible or likely to succumb to their illness prior to transplant, ventricular assist device therapy has now become a viable option for improving morbidity and mortality. Particularly for the non-operative pa-tient, intravenous inotropes can be utilized for symptom control. Regardless of the treatments considered, care of the heart failure patient requires thoughtful dialogue, multidisciplinary collaboration, and individualized care. While survival is important, most patients covet quality of life above all outcomes. An often overlooked component is the patient’s control over the dying process. It is vital that clinicians make goals-of-care discussions a priority when seeing patients with advanced heart failure. The use of palliative care consultation is well-validated and facilitates these difficult conversations to ensure that all patient needs are ultimately met. PMID:24251460

  16. 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

  17. Targeted therapy in Advanced Bladder cancer- what have we learned?

    PubMed Central

    Jordan, Emmet; Iyer, Gopa

    2016-01-01

    Synopsis Urothelial carcinoma (UC) is the second most common genitourinary malignancy in the United States. In the metastatic setting, cisplatin-based chemotherapy results in a median overall survival (OS) of 12–15 months and remains the only standard of care for this disease. Despite advances in the treatment of other genitourinary malignancies, no novel therapies have been FDA-approved for UC in the last 20 years. To date, no clinical trials of targeted agents in UC have led to improvements in survival compared to cytotoxic therapy. The Cancer Genome Atlas (TCGA) has detected numerous potentially actionable genetic alterations in bladder cancer, providing a roadmap for the use of small molecule inhibitors in this disease. Additionally, the advancement of Next Generation sequencing technologies within the past five years has allowed for rapid, deep sequencing to define the molecular profile of tumors in real time. In this chapter, we outline representative trials of targeted therapies in UC and discuss the significance of genetic pre-selection in trial design as a method to optimize responses to these agents, thus hopefully expanding the armamentarium of treatment options against this lethal disease. PMID:25882566

  18. 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

  19. 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

  20. 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

  1. [Resection for advanced pancreatic cancer following multimodal therapy].

    PubMed

    Kleeff, J; Stöß, C; Yip, V; Knoefel, W T

    2016-05-01

    Pancreatic cancer patients presenting with borderline resectable or locally advanced unresectable tumors remain a therapeutic challenge. Despite the lack of high quality randomized controlled trials, perioperative neoadjuvant treatment strategies are often employed for this group of patients. At present the FOLFIRINOX regimen, which was established in the palliative setting, is the backbone of neoadjuvant therapy, whereas local ablative treatment, such as stereotactic irradiation and irreversible electroporation are currently under investigation. Resection after modern multimodal neoadjuvant therapy follows the same principles and guidelines as upfront surgery specifically regarding the extent of resection, e.g. lymphadenectomy, vascular resection and multivisceral resection. Because it is still exceedingly difficult to predict tumor response after neoadjuvant therapy, a special treatment approach is necessary. In the case of localized stable disease following neoadjuvant therapy, aggressive surgical exploration with serial frozen sections at critical (vascular) margins might be necessary to minimize the risk of debulking procedures and maximize the chance of a curative resection. A multidisciplinary and individualized approach is mandatory in this challenging group of patients. PMID:27138271

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

    ScienceCinema

    Tijana Rajh

    2010-01-08

    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.

  3. [Certain aspects of neoadjuvant therapy of locally advanced breast cancer].

    PubMed

    Voznyĭ, E K; Gurov, S N; Dobrovol'skaia, N Iu

    2001-01-01

    The paper presents the results of a complex investigation of patients with locally-advanced breast cancer who received neoadjuvant chemotherapy or chemoradiation at initial stage. The clinical and pathomorphological effects, nature of neoadjuvant therapy and number of courses were followed up for 5- and 10-year periods. A direct correlation was found between number of courses for chemotherapy-sensitive patients, on the one hand, and greater effect, more intensive medicinal pathomorphism and longer recurrence-free survival, particularly, at later stages, on the other. PMID:11826490

  4. SERA - An Advanced Treatment Planning System for Neutron Therapy

    SciTech Connect

    C. A. Wemple; C. L. Albright; D. W. Nigg; D. W. Wessol; F. J. Wheeler; G. J. Harkin; M. B. Rossmeirer; M. T. Cohen; M. W. Frandsen

    1999-06-01

    The technology for computational dosimetry and treatment planning for Boron Neutron Capture Therapy (BNCT) has advanced significantly over the past few years. Because of the more complex nature of the problem, the computational methods that work well for treatment planning in photon radiotherapy are not applicable to BNCT. The necessary methods have, however, been developed and have been successfully employed both for research applications as well as human trials. Computational geometry for BNCT applications can be constructed directly from tomographic medical imagery and computed radiation dose distributions can be readily displayed in formats that are familiar to the radiotherapy community. The SERA system represents a significant advance in several areas for treatment planning. However further improvements in speed and results presentation are still needed for routine clinical applications, particularly when optimizations of dose pattern is required.

  5. [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

  6. Antibiotic therapy for cat-scratch disease: clinical study of therapeutic outcome in 268 patients and a review of the literature.

    PubMed

    Margileth, A M

    1992-06-01

    During 24 months in an uncontrolled, retrospective study of 268 patients with cat-scratch disease (CSD), 202 were treated with 18 different antimicrobial agents. Criteria for antibiotic effectiveness were established. One or two antibiotics were taken separately for at least 3 to 5 days by 202 patients with CSD. Outcome was determined by follow-up examinations and telephone. Effectiveness of antibiotic therapy was based upon 3 or more days of therapy and clinical improvement of the patient with absence of and/or a decrease in malaise, fatigue, fever, headache, anorexia, lymphadenopathy and, in 90 patients, a declining or normal sedimentation rate. Of 18 different antimicrobials prescribed, 14 commonly used antibiotics were judged to be of little or no value in treatment of CSD. Four antimicrobials were efficacious. Efficacy of the three oral drugs in decreasing order was: rifampin 87%, ciprofloxacin 84%, trimethoprim-sulfamethoxazole 58%. Gentamicin sulfate intramuscular was 73% effective. Antibiotic therapy can be considered for patients with severe cat scratch disease. Conservative, symptomatic treatment is recommended for the majority of patients with mild or moderate CSD. PMID:1608685

  7. 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

  8. 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

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

    PubMed Central

    SUN, RONGRONG; LI, XIANCHI; LIU, MIN; ZENG, YI; CHEN, SHUANG; ZHANG, PEYING

    2016-01-01

    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. PMID:27220939

  10. Sequences and Combinations of Multifaceted Therapy In Advanced Prostate Cancer

    PubMed Central

    Vaishampayan, Ulka

    2015-01-01

    Purpose of Review Multiple agents with very distinct mechanisms of actions and unique toxicities and efficacies have become available for use in advanced prostate cancer. The next wave of investigations is focused on development of combinations and optimal sequences of the currently available agents. The focus of this review paper is to provide an update on clinical developments in advanced prostate cancer occurring within the past year, and to highlight the ongoing investigations of promising novel targets and compounds. Recent Findings The clinical use of enzalutamide prior to chemotherapy, demonstrated improvement in progression free survival (PFS) and overall survival (OS) as compared to placebo in metastatic castrate resistant prostate cancer (CRPC). This report of the PREVAIL trial led to the FDA approval of this agent. Novel agents such as cabozantinib and custirsen that had shown promising results in phase II trials, revealed disappointing results in the phase III setting. The breakthrough report, of the ability of the ARV-7 mutation, detected in circulating tumor cells, to predict lack of response to abiraterone or enzalutamide, and the remarkable responses of poly ADP ribose polymerase (PARP) inhibitors in prostate cancer with BRCA1/2 mutations, have elevated hopes of a bright future in the biomarker driven therapeutic arena. Summary As the clinical application of the recently approved multifaceted therapies widens, trials addressing optimal sequences and combinations are gaining importance. In addition, exploring the utility of therapies in the hormone naïve or non-metastatic settings is an area of active investigation. Early use of available agents, optimal sequencing and aid of biomarkers to guide therapeutic choices will make the achievement of lifetime remissions in advanced prostate cancer a reachable goal. PMID:25811344

  11. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  12. 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.

  13. 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

  14. 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)

  15. Phantom limbs: pain, embodiment, and scientific advances in integrative therapies.

    PubMed

    Lenggenhager, Bigna; Arnold, Carolyn A; Giummarra, Melita J

    2014-03-01

    Research over the past two decades has begun to identify some of the key mechanisms underlying phantom limb pain and sensations; however, this continues to be a clinically challenging condition to manage. Treatment of phantom pain, like all chronic pain conditions, demands a holistic approach that takes into consideration peripheral, spinal, and central neuroplastic mechanisms. In this review, we focus on nonpharmacological treatments tailored to reverse the maladaptive neuroplasticity associated with phantom pain. Recent scientific advances emerging from interdisciplinary research between neuroscience, virtual reality, robotics, and prosthetics show the greatest promise for alternative embodiment and maintaining the integrity of the multifaceted representation of the body in the brain. Importantly, these advances have been found to prevent and reduce phantom limb pain. In particular, therapies that involve sensory and/or motor retraining, most naturally through the use of integrative prosthetic devices, as well as peripheral (e.g., transcutaneous electrical nerve stimulation) or central (e.g., transcranial magnetic stimulation or deep brain stimulation) stimulation techniques, have been found to both restore the neural representation of the missing limb and to reduce the intensity of phantom pain. While the evidence for the efficacy of these therapies is mounting, but well-controlled and large-scale studies are still needed. WIREs Cogn Sci 2014, 5:221-231. doi: 10.1002/wcs.1277 CONFLICT OF INTEREST: The authors have no financial or other relationship that might lead to a conflict of interest. For further resources related to this article, please visit the WIREs website. PMID:26304309

  16. Clinical results of proton beam therapy for advanced neuroblastoma

    PubMed Central

    2013-01-01

    Purpose To evaluate the efficacy of proton beam therapy (PBT) for pediatric patients with advanced neuroblastoma. Methods PBT was conducted at 21 sites in 14 patients with neuroblastoma from 1984 to 2010. Most patients were difficult to treat with photon radiotherapy. Two and 6 patients were classified into stages 3 and 4, respectively, and 6 patients had recurrent disease. Seven of the 8 patients who received PBT as the initial treatment were classified as the high risk group. Twelve patients had gross residual disease before PBT and 2 had undergone intraoperative radiotherapy before PBT. Five patients received PBT for multiple sites, including remote metastases. Photon radiotherapy was used in combination with PBT for 3 patients. The PBT doses ranged from 19.8 to 45.5 GyE (median: 30.6 GyE). Results Seven patients are alive with no evidence of disease, 1 is alive with disease progression, and 6 died due to the tumor. Recurrence in the treatment field was not observed and the 3-year locoregional control rate was 82%. Severe acute radiotoxicity was not observed, but 1 patient had narrowing of the aorta and asymptomatic vertebral compression fracture at 28 years after PBT, and hair loss was prolonged in one patient. Conclusion PBT may be a better alternative to photon radiotherapy for children with advanced neuroblastoma, and may be conducted safely for patients with neuroblastoma that is difficult to manage using photon beams. PMID:23758770

  17. [Advancement of prophylaxis and therapy for venous thromboembolism].

    PubMed

    Kobayashi, Takao

    2008-07-01

    Recently in Japan, venous thromboembolism (VTE) [deep vein thrombosis (DVT)/pulmonary thromboembolism (PTE)] has increased with the Westernization of eating habits and aging of society. In the West, the prophylaxis guidelines have been discussed for many years. Unfortunately, Japan falls far behind the West in this area. Therefore, the necessity of thromboprophylaxis in Japanese people should be emphasized based on reliable VTE studies in Japan. In orthopedic surgery, prospective multicenter studies in Japan indicate that the incidence of DVT/PTE in total hip or knee replacement surgery and hip fracture surgery were almost equal to those in Western people. Furthermore, a multi-center, prospective epidemiological study in Japan revealed that the incidence of VTE following major abdominal surgery was 24.3%. We developed Japanese Guidelines for VTE prophylaxis based on the 6th ACCP guideline in 2004. The incidence of perioperative PTE in Japan has been investigated by the Japanese Society of Anesthesiologists since 2002. The rate of perioperative PTE was estimated to be 4.41 per 10,000 operations in 2002, and 4.76 in 2003; however, it decreased to 3.61 immediately after the guideline for thromboprophylaxis was issued and the management fee for PTE prophylaxis became covered by health insurance in April 2004. Furthermore, it markedly decreased in 2005. However, mechanical prophylaxis is not sufficient to prevent PTE, and advanced prophylaxis by anticoagulants, such as low-molecular-weight heparin/selective Xa inhibitor along with unfractionated heparin (UFH)/vitamin K antagonists (VKA) will be essential. The advanced revised guidelines for VTE prophylaxis based on our clinical evidence will be established in the near future. As for treatment for VTE, anticoagulant and thrombolytic therapies are essential. In cases with VTE, UFH followed by VKA (INR: 1.5-2.5) is standard. In cases of PTE with shock, thrombolytic therapy such as tissue plasminogen activator or urokinase

  18. 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

  19. 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

  20. Progress of Molecular Targeted Therapies for Advanced Renal Cell Carcinoma

    PubMed Central

    Santoni, Matteo; Amantini, Consuelo; Burattini, Luciano; Berardi, Rossana; Santoni, Giorgio; Cascinu, Stefano; Muzzonigro, Giovanni

    2013-01-01

    Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis. VEGF expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia, predominantly via the hypoxia-induced factor (HIF)/Von Hippel-Lindau (VHL) pathway. Advances in our knowledge of VEGF role in tumor angiogenesis, growth, and progression have permitted development of new approaches for the treatment of mRCC, including several agents targeting VEGF and VEGF receptors: tyrosine kinase pathway, serine/threonine kinases, α5β1-integrin, deacetylase, CD70, mammalian target of rapamycin (mTOR), AKT, and phosphatidylinositol 3′-kinase (PI3K). Starting from sorafenib and sunitinib, several targeted therapies have been approved for mRCC treatment, with a long list of agents in course of evaluation, such as tivozanib, cediranib, and VEGF-Trap. Here we illustrate the main steps of tumor angiogenesis process, defining the pertinent therapeutic targets and the efficacy and toxicity profiles of these new promising agents. PMID:24093097

  1. [Recent advance in adjuvant therapy for breast cancer].

    PubMed

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  2. 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.

  3. 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 ...

  4. Cat Scratch Disease

    MedlinePlus

    Cat scratch disease (CSD) is an illness caused by the bacterium Bartonella henselae. Almost half of all cats carry ... infection does not make cats sick. However, the scratch or bite of an infected cat can cause ...

  5. 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 ...

  6. Survival among patients with advanced renal cell carcinoma in the pretargeted versus targeted therapy eras.

    PubMed

    Li, Pengxiang; Wong, Yu-Ning; Armstrong, Katrina; Haas, Naomi; Subedi, Prasun; Davis-Cerone, Margaret; Doshi, Jalpa A

    2016-02-01

    Between December 2005 and October 2009, FDA approved six targeted therapies shown to significantly extend survival for advanced renal cell carcinoma (RCC) patients in clinical trials. This study aimed to examine changes in survival between the pretargeted and targeted therapy periods in advanced RCC patients in a real-world setting. Utilizing the 2000-2010 SEER Research files, a pre-post study design with a contemporaneous comparison group was employed to examine differences in survival outcomes for patients diagnosed with advanced RCC (study group) or advanced prostate cancer (comparison group, for whom no significant treatment innovations happened during this period) across the pretargeted therapy era (2000-2005) and the targeted therapy era (2006-2010). RCC patients diagnosed in the targeted therapy era (N = 6439) showed improved survival compared to those diagnosed in the pretargeted therapy era (N = 7231, hazard ratio (HR) for all-cause death: 0.86, P < 0.01), while the change between the pre-post periods was not significant for advanced prostate cancer patients (HR: 0.97, P = 0.08). Advanced RCC patients had significantly larger improvements in overall survival compared to advanced prostate cancer patients (z = 4.31; P < 0.01). More detailed year-to-year analysis revealed greater survival improvements for RCC in the later years of the posttargeted period. Similar results were seen for cause-specific survival. Subgroup analyses by nephrectomy status, age, and gender showed consistent findings. Patients diagnosed with advanced RCC during the targeted therapy era had better survival outcomes than those diagnosed during the pretargeted therapy era. Future studies should examine the real-world survival improvements directly associated with targeted therapies. PMID:26645975

  7. A dynamic care pathway to coordinate the use of advanced therapy in diabetic foot ulceration.

    PubMed

    Chadwick, P; Haycocks, S; Bielby, A; Milne, J

    2009-10-01

    The non-coordinated use of advanced therapies is not clinically or cost effective. A care pathway for the sequential use of these interventions on complex wounds provides a more restructured approach, and helped improve patient outcomes. PMID:19816383

  8. Advanced Gold Nanomaterials for Photothermal Therapy of Cancer.

    PubMed

    Ahmad, Rasheed; Fu, Juan; He, Nongyue; Li, Song

    2016-01-01

    Photothermal therapy represents a non-invasive therapeutic tool to eradicate cancer tumor with minimum toxic effects. In this ablative therapy, accurate delivery of efficient photothermal conversion agents followed by laser irradiation results in tumor ablation with lower toxicity compared to other cancer therapies. Gold nanomaterials are efficient to passively target and deliver photothermal agents to the cancer tumor. Through surface plasma resonance, gold nanomaterials including nanorods, nanostars, nanoflowers, nanocages and nanoshells exhibited strong NIR absorption and are widely utilized during photothermal ablative therapy of cancer. Currently, researchers have devoted their attention to minimize toxicity of photothermal agents using modified probe design. By developing this noninvasive cancer therapy, expectations to minimize toxicity of cancer treatment may become reality sooner. PMID:27398434

  9. Improvement with ongoing Enzyme Replacement Therapy in advanced late-onset Pompe disease: a case study.

    PubMed

    Case, Laura E; Koeberl, Dwight D; Young, Sarah P; Bali, Deeksha; DeArmey, Stephanie M; Mackey, Joanne; Kishnani, Priya S

    2008-12-01

    Benefits of enzyme replacement therapy with Myozyme (alglucosidase alfa), anecdotally reported in late-onset Pompe disease, range from motor and pulmonary improvement in less severely affected patients, to stabilization with minimal improvement in those with advanced disease. We report a case of a 63-year-old patient with significant morbidity who made notable motor and pulmonary function gains after two years on therapy. Thus, improvements in those with advanced disease may be possible after long-term treatment. PMID:18930676

  10. 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

  11. Primary hypoadrenocorticism in ten cats.

    PubMed

    Peterson, M E; Greco, D S; Orth, D N

    1989-01-01

    Primary hypoadrenocorticism was diagnosed in ten young to middle-aged cats of mixed breeding. Five of the cats were male, and five were female. Historic signs included lethargy (n = 10), anorexia (n = 10), weight loss (n = 9), vomiting (n = 4), and polyuria (n = 3). Dehydration (n = 9), hypothermia (n = 8), prolonged capillary refill time (n = 5), weak pulse (n = 5), collapse (n = 3), and sinus bradycardia (n = 2) were found on physical examination. Results of initial laboratory tests revealed anemia (n = 3), absolute lymphocytosis (n = 2), absolute eosinophilia (n = 1), and azotemia and hyperphosphatemia (n = 10). Serum electrolyte changes included hyponatremia (n = 10), hyperkalemia (n = 9), hypochloremia (n = 9), and hypercalcemia (n = 1). The diagnosis of primary adrenocortical insufficiency was established on the basis of results of adrenocorticotropic hormone (ACTH) stimulation tests (n = 10) and endogenous plasma ACTH determinations (n = 7). Initial therapy for hypoadrenocorticism included intravenous administration of 0.9% saline and dexamethasone and intramuscular administration of desoxycorticosterone acetate in oil. Three cats were euthanatized shortly after diagnosis because of poor clinical response. Results of necropsy examination were unremarkable except for complete destruction of both adrenal cortices. Seven cats were treated chronically with oral prednisone or intramuscular methylprednisolone acetate for glucocorticoid supplementation and with oral fludrocortisone acetate or intramuscular injections of repository desoxycorticosterone pivalate for mineralocorticoid replacement. One cat died after 47 days of therapy from unknown causes; the other six cats are still alive and well after 3 to 70 months of treatment. PMID:2469793

  12. 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

  13. 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. PMID:27178388

  14. Acute phase treatment of venous thromboembolism: advanced therapy. Systemic fibrinolysis and pharmacomechanical therapy.

    PubMed

    Konstantinides, Stavros V; Wärntges, Simone

    2015-06-01

    Venous thromboembolism, which encompasses deep-vein thrombosis and acute pulmonary embolism (PE), represents a major contributor to global disease burden worldwide. For patients who present with cardiogenic shock or persistent hypotension (acute high-risk PE), there is consensus that immediate reperfusion treatment applying systemic fibrinolysis or, in the case of a high bleeding risk, surgical or catheter-directed techniques, is indicated. On the other hand, for the large, heterogeneous group of patients presenting without overt haemodynamic instability, the indications for advanced therapy are less clear. The recently updated guidelines of the European Society of Cardiology emphasise the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for distinguishing between an intermediate and a low risk for an adverse early outcome. In intermediate-high-risk PE defined by the presence of both right ventricular dysfunction on echocardiography (or computed tomography) and a positive troponin (or natriuretic peptide) test, the bleeding risks of full-dose fibrinolytic treatment have been shown to outweigh its potential clinical benefits unless clinical signs of haemodynamic decompensation appear (rescue fibrinolysis). Recently published trials suggest that catheter-directed, ultrasound-assisted, low-dose local fibrinolysis may provide an effective and particularly safe treatment option for some of these patients. PMID:25789580

  15. [Ozone therapy in the advanced stages of arteriosclerosis obliterans].

    PubMed

    Romero Valdés, A; Menéndez Cepero, S; Gómez Moraleda, M; Ley Pozo, J

    1993-01-01

    Fifteen patients with atherosclerosis obliterans at the lower limbs, no candidates to revascularizing surgery were submitted to ozone therapy. An improvement statistically significant was noticed in the treatment groups since amputation ratio decreased (26.7%) and the need of pain's surgery procedures (13.3%) in comparison with the control group (46.7 and 26.7% respectively). Ozone therapy is considered as a good way in the management of the atherosclerosis with obliteration in late period. PMID:8239044

  16. 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

  17. Recent advances in psychological therapies for eating disorders.

    PubMed

    Waller, Glenn

    2016-01-01

    Recent years have seen substantial consolidation and development of the evidence base for psychological therapies for eating disorders. This review summarises the key changes over that time period. Specific forms of cognitive behavioural therapy and family-based treatment have consolidated and extended their positions as treatments of choice despite the development of novel approaches. However, there is still a significant need for further development and testing to improve recovery rates, particularly in anorexia nervosa. PMID:27134740

  18. Recent advances in psychological therapies for eating disorders

    PubMed Central

    Waller, Glenn

    2016-01-01

    Recent years have seen substantial consolidation and development of the evidence base for psychological therapies for eating disorders. This review summarises the key changes over that time period. Specific forms of cognitive behavioural therapy and family-based treatment have consolidated and extended their positions as treatments of choice despite the development of novel approaches. However, there is still a significant need for further development and testing to improve recovery rates, particularly in anorexia nervosa. PMID:27134740

  19. 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.

  20. Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy

    PubMed Central

    Park, Jung Gil; Park, Soo Young; Lee, Hye Won

    2015-01-01

    Sorafenib, a potent multikinase inhibitor, lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma (HCC). Though sorafenib has proven its efficacy in advanced stage HCC, there are limited reports on the role of sorafenib allowing for curative treatment by down-staging. We herein report a case of advanced HCC with vascular invasion, which showed treatment response by sorafenib therapy as to allow for radiofrequency ablation as curative treatment. The patient was followed-up for 6 mo without recurrence with continued sorafenib therapy. PMID:25741170

  1. Targeted therapy for advanced urothelial cancer of the bladder: where do we stand?

    PubMed

    Zhu, Zhaowei; Shen, Zhoujun; Xu, Chen

    2012-11-01

    The treatment of advanced urothelial cancer of the bladder has evolved substantially during recent years. Chemotherapy has been the mainstay of treatment and confers survival advantage. Despite such advances, the chemotherapy of bladder cancer is far from satisfactory due to severe side effects. Targeted therapy with novel drugs directed at specific molecular pathways opens promising new avenues to improve patient outcome. A systematic review examined the clinical data for novel targeted agents in 10 phase II trials, with a focus on bevacizumab, aflibercept, sunitinib, sorafenib, gefitinib, lapatinib and trastuzumab. Besides, we present studies on other novel, promising targeted agents, including pazopanib, cetuximab and everolimus. Although bevacizumab and trastuzumab have shown promising results for patients with advanced bladder cancer, other targeted agents have not achieved the same clinical benefit in this disease as seen in other common epithelial cancers. Ultimately, combination targeted therapy, sequential therapy, adjuvant and neoadjuvant therapy may yield the best outcomes. PMID:22583418

  2. Personalizing Therapy in Advanced Non–Small Cell Lung Cancer

    PubMed Central

    Villaruz, Liza C.; Burns, Timothy F.; Ramfidis, Vasilis S.; Socinski, Mark A.

    2016-01-01

    The recognition that non–small cell lung cancer (NSCLC) is not a single disease entity, but rather a collection of distinct molecularly driven neoplasms, has permanently shifted the therapeutic landscape of NSCLC to a personalized approach. This personalization of NSCLC therapy is typified by the dramatic response rates seen in EGFR mutant NSCLC when treated with targeted tyrosine kinase inhibitor therapy and in ALK translocation–driven NSCLC when treated with ALK inhibitors. Targeted therapeutic approaches in NSCLC necessitate consideration of more invasive biopsy techniques aimed at providing sufficient tissue for both histological determination and molecular profiling in all patients with stage IV disease both at the time of diagnosis and at the time of disease progression. Comprehensive genotyping efforts have identified oncogenic drivers in 62% lung adenocarcinomas and an increasing proportion of squamous cell carcinomas of the lung. The identification of these oncogenic drivers and the triage of patients to clinical trials evaluating novel targeted therapeutic approaches will increasingly mold a landscape of personalized lung cancer therapy where each genotype has an associated targeted therapy. This review outlines the state of personalized lung cancer therapy as it pertains to individual NSCLC genotypes. PMID:24258572

  3. Big cat genomics.

    PubMed

    O'Brien, Stephen J; Johnson, Warren E

    2005-01-01

    Advances in population and quantitative genomics, aided by the computational algorithms that employ genetic theory and practice, are now being applied to biological questions that surround free-ranging species not traditionally suitable for genetic enquiry. Here we review how applications of molecular genetic tools have been used to describe the natural history, present status, and future disposition of wild cat species. Insight into phylogenetic hierarchy, demographic contractions, geographic population substructure, behavioral ecology, and infectious diseases have revealed strategies for survival and adaptation of these fascinating predators. Conservation, stabilization, and management of the big cats are important areas that derive benefit from the genome resources expanded and applied to highly successful species, imperiled by an expanding human population. PMID:16124868

  4. Simplified negative pressure wound therapy with instillation: advances and recommendations.

    PubMed

    Gabriel, Allen; Rauen, Brigitta

    2014-01-01

    Positive results have been demonstrated with the adjunctive use of negative pressure wound therapy (NPWT) and instillation (NPWTi) for stalled and/or complex wounds. With these combined therapies, instillation assists in wound bed preparation and cleansing by loosening soluble material in the wound bed, which can be subsequently removed during the NPWT phase. Previously reported instilled solutions have included saline, topical cleansers, and antiseptics. Recently, a new NPWTi system (V.A.C. VeraFlo™ Therapy, KCI USA, Inc., San Antonio, TX) has been introduced that includes automated, volumetrically controlled delivery of solutions and new foam dressings specifically designed for use with NPWTi. We present the latest NPWTi technologies, provide nursing recommendations for patient management, and conclude with a case study. PMID:24887351

  5. Advances in therapies for non-Hodgkin lymphoma in children.

    PubMed

    Kobos, Rachel; Terry, William

    2015-01-01

    Pediatric patients with newly diagnosed, non-Hodgkin Lymphoma (NHL) have an excellent overall survival. However, therapy regimens are associated with acute toxicity and late effects. Furthermore, patients with relapsed or refractory disease have relatively few options with proven clinical benefit. Both histologic and molecular differences exist between adult and pediatric NHL preventing simple translation of adult NHL successes into improvements in pediatric NHL treatment. This review summarizes the introduction of targeted therapies into frontline treatments for patients with anaplastic large-cell lymphoma and CD20-positive tumors, with the goal of improving overall survival while limiting both short- and long-term toxicities. In addition, newer approaches that have limited data in children but may have a significant role in how we treat pediatric NHL in the future are reviewed, which include CD19 directed therapy, Notch inhibition, the tri-functional antibody, FBTA05, and EZH2 inhibition. PMID:26637768

  6. Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy.

    PubMed

    Luderer, Micah John; de la Puente, Pilar; Azab, Abdel Kareem

    2015-09-01

    Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles. PMID:26033767

  7. 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. PMID:25039267

  8. Recent advances in massage therapy--a review.

    PubMed

    Liu, S-L; Qi, W; Li, H; Wang, Y-F; Yang, X-F; Li, Z-M; Lu, Q; Cong, D-Y

    2015-10-01

    Massage therapy is one of the most widely accepted alternative form of medicine helping patients suffering from varied pathological states including arthritis, anxiety, sleep problems, pain management and injury repair. Besides this, it is one of the safest forms of alternative medicine and has become favorite among various health care professionals. However, there is still a lot of debate is going in medical world pertaining to its certain use in modern medicine. So, the present review shall enlighten all the latest aspects of massage therapy in current medicine. PMID:26531268

  9. Ketogenic Diets: New Advances for Metabolism-Based Therapies

    PubMed Central

    Kossoff, Eric H.; Hartman, Adam L.

    2014-01-01

    Purpose of review Despite myriad anticonvulsants available and in various stages of development, there are thousands of children and adults with epilepsy worldwide still refractory to treatment and not candidates for epilepsy surgery. Many of these patients will now turn to dietary therapies such as the ketogenic diet, medium-chain triglyceride (MCT) diet, modified Atkins diet, and low glycemic index treatment. Recent Findings In the past several years, neurologists are finding new indications to use these dietary treatments, perhaps even as first-line therapy, including infantile spasms, myoclonic-astatic epilepsy (Doose syndrome), Dravet syndrome, and status epilepticus (including FIRES syndrome). Adults are also one of the most rapidly growing populations being treated nowadays; a group of patients previously not typically offered these treatments. In 2009, two controlled trials of the ketogenic diet were published as well as an International Expert Consensus Statement on dietary treatment of epilepsy. Ketogenic diets are also now being increasingly studied for neurologic conditions other than epilepsy, including Alzheimer disease and cancer. Insights from basic science research have helped elucidate the mechanisms by which metabolism-based therapy may be helpful, both in terms of an anticonvulsant and possibly neuroprotective effect. Summary Dietary therapy for epilepsy continues to grow in popularity worldwide, with expanding use for adults and conditions other than epilepsy. PMID:22322415

  10. 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. PMID:26863704

  11. 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…

  12. 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

  13. 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

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

    PubMed

    Wędrychowicz, Andrzej; Zając, Andrzej; Tomasik, Przemysław

    2016-01-21

    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. Recent advances in biological therapy for inflammatory bowel disease.

    PubMed

    Kurtovic, Jelica; Segal, Isidor

    2004-01-01

    Immune system is a major determinant of pathophysiology of inflammatory bowel disease (IBD), and cytokines are well known mediators of immune system. Recently, informations on pro-inflammatory cytokines and their role in IBD have led to development of potential therapeutic approach to manipulate these cytokines and there by inhibiting inflammation in IBD. These therapeutic approaches include inhibitors of the tumour necrosis factor (TNF)-alpha lymphocyte trafficking, type 1 T helper (Th1) cell polarization and nuclear factor type beta; immunoregulatory cytokines and various growth factors. Studies on these therapies have documented variable results and the outcomes of many clinical trials are awaited. However, these potential therapies, if become real may revolutionise approach in patients with IBD. Analysis of the inflammed mucosa from patients with Crohn disease (CD) and ulcerative colitis (UC) have shown increased expression of certain proinflammatory cytokines such as interleukin-1 (IL-1), interleukin 6 (IL-6) and TNF-alpha. The latter is important in the recruitment of neutrophils into inflammed tissue, a process which results from three physiological steps: (i) rolling, (ii) adhesion, and (iii) transendothelial migration. Understanding of the biology of chronic inflammation has expanded the therapies available for IBD and particularly CD. At present, the biological therapies that are being used in clinical practice or investigated for the treatment of IBD are predominantly proteins, usually delivered intravenously or subcutaneously. The therapies used include: 1. TNF-alpha inhibitors: infliximab, CDP 571, etanercept, onercept, CNI- 1493 and thalidomide. 2. Inhibitors of lymphocyte trafficking: natalizumab, LPD-02 and ICAM-1. 3. Inhibitors of Th1 polarization: monoclonal antibodies for IL-12, interferon (IFN)-gamma and anti IFN-gamma. 4. Immunoregulatory cytokines: IL-10 and IL-11. 5. Inhibitors of nuclear factor kappa (beta NF-kbeta.) 6. Growth factors

  16. Advances in graft-versus-host disease biology and therapy

    PubMed Central

    Blazar, Bruce R.; Murphy, William J.; Abedi, Mehrdad

    2013-01-01

    Preface Allogeneic haematopoietic stem cell transplantation is used to treat a variety of disorders, but its efficacy is limited by the occurrence of graft-versus-host disease (GVHD). The past decade has brought impressive advances in our understanding of the role of both donor and host adaptive and innate immune stimulatory and immune suppressive factors that influence GVHD pathogenesis. New insights in basic immunology, preclinical models and clinical studies have led to novel prevention or treatment approaches. This review highlights recent advances in GVHD pathophysiology and its treatment with a focus on immune system manipulations that are amenable to clinical application. PMID:22576252

  17. 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/

  18. 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

  19. 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. PMID:25031967

  20. 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.

  1. Nano Polymeric Carrier Fabrication Technologies for Advanced Antitumor Therapy

    PubMed Central

    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. PMID:24369011

  2. 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

  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. Advances in targeted therapy for unresectable melanoma: new drugs and combinations.

    PubMed

    Hao, Mengze; Song, Fengju; Du, Xiaoling; Wang, Guowen; Yang, Yun; Chen, Kexin; Yang, Jilong

    2015-04-01

    Melanoma is the most deadly cutaneous cancer primarily derived from melanocytes with a poor prognosis in advanced stage. The therapy regimen for early stage melanoma patients is surgical resection with adjuvant IFN-alpha-2b therapy. For metastatic lesions, standard chemotherapy such as dacarbazine (DTIC) has not achieved a satisfying response rate. Therefore, new approaches to manage this deadly disease are highly expected to enhance the cure rate and to extend clinical benefits to patients with unresectable melanoma. Fortunately, the targeted therapeutic drugs and immunotherapy such as vemurafenib, dabrafenib, ipilimumab, and trametinib have shown their special advantage in the treatment of advanced melanoma. This article is to overview the advances in targeted therapy for unresectable melanoma patients. PMID:25578781

  5. Acute renal failure in four cats treated with paromomycin.

    PubMed

    Gookin, J L; Riviere, J E; Gilger, B C; Papich, M G

    1999-12-15

    Acute renal failure was diagnosed in 4 cats receiving paromomycin orally for treatment of infectious enteritis. All 4 cats responded to fluid therapy and recovered normal or near-normal renal function; however, 3 of the cats subsequently became deaf and developed cataracts. Toxicoses were attributed to a combination of an excessive dosage of paromomycin and absorption of the drug across injured intestinal mucosal epithelium. Pharmacokinetic studies are needed to further define the disposition of paromomycin after oral administration to cats. PMID:10613215

  6. Caring for the retrovirus infected cat.

    PubMed

    McCaw, D

    1995-11-01

    No commercial vaccine [correction of vacine] exists for feline immunodeficiency virus (FIV), and although feline leukemia virus (FeLV) vaccines are available, they are neither 100% effective nor used in all cats. These realities clearly indicate the veterinarian will be required to treat either FeLV- or FIV-positive cats for some time to come. The management of FIV- or FeLV-positive cats may require supportive therapies as well as virus-specific therapies such as zidovudine (AZT; Retrovir, Burroughs Wellcome, Research Triangle Park, NC). PMID:8820595

  7. 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.

  8. Advances in percutaneous therapy for upper extremity arterial disease.

    PubMed

    Capers, Quinn; Phillips, John

    2011-08-01

    Upper extremity arteries are affected by occlusive diseases from diverse causes, with atherosclerosis being the most common. Although the overriding principle in managing patients with upper extremity arterial occlusive disease should be cardiovascular risk reduction by noninvasive and pharmacologic means, when target organ ischemia produces symptoms or threatens the patient's well-being, revascularization is necessary. Given their minimally invasive nature and successful outcomes, percutaneous catheter-based therapies are preferred to surgical approaches. The fact that expertise in these techniques resides in not one but several disciplines (vascular surgery, radiology, cardiology, vascular medicine) makes this an area ripe for multidisciplinary collaboration to the benefit of patients. PMID:21803225

  9. 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; de Mello, Ramon Andrade

    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. PMID:26838766

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Endocrine therapy for hormone treatment-naïve advanced breast cancer.

    PubMed

    Martin, Miguel; Lopez-Tarruella, Sara; Gilarranz, Yolanda Jerez

    2016-08-01

    A proportion of patients with hormone receptor-positive locally advanced or metastatic breast cancer will not have received prior endocrine therapy. However, there are limited clinical data specifically in these patients. We conducted a review of randomized phase II and III clinical studies of anastrozole, letrozole, exemestane, palbociclib, and fulvestrant to determine the evidence base supporting use of specific endocrine therapies in this patient population. From our findings, there is a paucity of clinical studies in patients with endocrine therapy-naïve disease; however, it appears that first-line treatment effects are consistent between patients who have and have not received prior endocrine treatment. PMID:27326977

  16. Recent advances for ion beam therapy accelerators using synchrotrons

    NASA Astrophysics Data System (ADS)

    Weinrich, U.

    2011-12-01

    Ion beam therapy has evolved a lot during the last years. After more than a decade of successful clinical studies and first treatment in hospital environment, the carbon beam treatment, which always relies on a synchrotron as main accelerator, has clearly shown its own potential. The clinical success of carbon beam treatment is indicated by the growing number of new fully clinical based facilities. There is a lot of improvement potential for these facilities in order to increase their treatment quality, functionality and capacity as well as the cost effectiveness of the patient treatment. This article focuses on the currently ongoing investigations to fully explore this potential. It can be concluded that synchrotron based ion beam facilities are improving into many directions. This will further improve their impact on the cancer treatment and consequently their benefit to the whole society.

  17. Advance in herpes simplex viruses for cancer therapy.

    PubMed

    Liu, Shanglong; Dai, Meihua; You, Lei; Zhao, Yupei

    2013-04-01

    Oncolytic virotherapy is an attractive approach that uses live viruses to selectively kill cancer cells. Oncolytic viruses can be genetically engineered to induce cell lyses through virus replication and cytotoxic protein expression. Herpes simplex virus (HSV) has become one of the most widely clinically used oncolytic agent. Various types of HSV have been studied in basic or clinical research. Combining oncolytic virotherapy with chemotherapy or radiotherapy generally produces synergic action with unclear molecular mechanisms. Arming HSV with therapeutic transgenes is a promising strategy and can be used to complement conventional therapies. As an efficient gene delivery system, HSV has been successfully used to deliver various immunomodulatory molecules. Arming HSV with therapeutic genes merits further investigation for potential clinical application. PMID:23564184

  18. Novel therapy for locally advanced triple-negative breast cancer

    PubMed Central

    YAMADA, ATSUKO; OSADA, SHINJI; TANAHASHI, TOSHIYUKI; MATSUI, SATOSHI; SASAKI, YOSHIYUKI; TANAKA, YOSHIHIRO; OKUMURA, NAOKI; MATSUHASHI, NOBUHISA; TAKAHASHI, TAKAO; YAMAGUCHI, KAZUYA; YOSHIDA, KAZUHIRO

    2015-01-01

    To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3–25.1 μM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC. PMID:26252842

  19. 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.

  20. 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

  1. Idiopathic pulmonary fibrosis: Recent advances on pharmacological therapy.

    PubMed

    Spagnolo, P; Maher, T M; Richeldi, L

    2015-08-01

    Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF. PMID:25946646

  2. 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

  3. 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

  4. 131I-Metaiodobenzylguanidine therapy in children with advanced neuroblastoma.

    PubMed

    DuBois, S G; Matthay, K K

    2013-03-01

    Neuroblastoma is an aggressive childhood cancer, with a propensity for early widespread metastasis. Approximately 90% of tumors accumulate the norepinephrine analogue metaiodobenzylguanidine (MIBG) avidly, allowing the use of radiolabeled MIBG for targeted imaging and radiotherapy. After preclinical studies demonstrated activity of 131I-MIBG in models of neuroblastoma, clinical development of this agent ensued. Early clinical trials of 131I-MIBG in patients with relapsed or refractory neuroblastoma defined the toxicity profile of this agent, with myelosuppression as the main dose-limiting toxicity. Subsequent trials defined the activity of 131I-MIBG, with response rates of 20-40% in patients with relapsed or refractory disease. More recent clinical trials have tested 131I-MIBG in combination with chemotherapy or as a component of myeloablative therapies. Given the documented activity of 131I-MIBG, future studies will need to evaluate the impact of radiation sensitizers on this activity and define the role of this agent in treating patients with newly diagnosed high-risk neuroblastoma. PMID:23474635

  5. 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…

  6. 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

  7. Cat-Scratch Disease

    MedlinePlus

    ... and how do people get it? Cat-scratch disease is an infection caused by a type of bacteria (germs) carried in cat saliva. This bacteria is called Bartonella henselae and can be passed from a cat to a human. Doctors and ... from fleas. Cat-scratch disease is not a severe illness in people who ...

  8. 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 ...

  9. 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

  10. HER story: the next chapter in HER-2-directed therapy for advanced breast cancer.

    PubMed

    Verma, Sunil; 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

  11. Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies

    PubMed Central

    Teague, Andrea; Lim, Kian-Huat

    2015-01-01

    Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large proportion of patients are diagnosed with locally advanced or metastatic disease at the time of presentation and, unfortunately, this severely limits the number of patients who can undergo surgical resection, which offers the only chance for cure. Recent therapeutic advances for patients with advanced pancreatic cancer have extended overall survival, but prognosis still remains grim. Given that traditional chemotherapy is ineffective in curing advanced pancreatic adenocarcinoma, current research is taking a multidirectional approach in the hopes of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. We also review the current ongoing clinical trials, which include the use of agents targeting the oncogenic network signaling of K-Ras, agents targeting the extracellular matrix, and immune therapies. PMID:25755680

  12. 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).

  13. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  14. 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

  15. MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy

    PubMed Central

    Tran, Khiem A; Cheng, Michelle Y; Mitra, Anupam; Ogawa, Hiromi; Shi, Vivian Y; Olney, Laura P; Kloxin, April M; Maverakis, Emanual

    2016-01-01

    The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. PMID:26730180

  16. Phase 1 Study of Erlotinib Plus Radiation Therapy in Patients With Advanced Cutaneous Squamous Cell Carcinoma

    SciTech Connect

    Heath, C. Hope; Deep, Nicholas L.; Nabell, Lisle; Carroll, William R.; Desmond, Renee; Clemons, Lisa; Spencer, Sharon; Magnuson, J. Scott; Rosenthal, Eben L.

    2013-04-01

    Purpose: To assess the toxicity profile of erlotinib therapy combined with postoperative adjuvant radiation therapy in patients with advanced cutaneous squamous cell carcinoma. Methods and Materials: This was a single-arm, prospective, phase 1 open-label study of erlotinib with radiation therapy to treat 15 patients with advanced cutaneous head-and-neck squamous cell carcinoma. Toxicity data were summarized, and survival was analyzed with the Kaplan-Meier method. Results: The majority of patients were male (87%) and presented with T4 disease (93%). The most common toxicity attributed to erlotinib was a grade 2-3 dermatologic reaction occurring in 100% of the patients, followed by mucositis (87%). Diarrhea occurred in 20% of the patients. The 2-year recurrence rate was 26.7%, and mean time to cancer recurrence was 10.5 months. Two-year overall survival was 65%, and disease-free survival was 60%. Conclusions: Erlotinib and radiation therapy had an acceptable toxicity profile in patients with advanced cutaneous squamous cell carcinoma. The disease-free survival in this cohort was comparable to that in historical controls.

  17. The Advancement of Family Therapy Theory Based on the Science of Self-Organizing Complex Systems.

    NASA Astrophysics Data System (ADS)

    Ramsey-Kemper, Valerie Ann

    1995-01-01

    Problem. The purpose of this study was to review the literature which presents the latest advancements in the field of family therapy theory. Since such advancement has relied on the scientific developments in the study of autopoietic self-organizing complex systems, then the review began with an historical overview of the development of these natural scientific concepts. The study then examined how the latest scientific concepts have been integrated with family therapy practice. The document is built on the theory that individuals are living, complex, self-organizing, autopoietic systems. When individual systems interact with other individual systems (such as in family interaction, or in interaction between therapist and client), then a third system emerges, which is the relationship. It is through interaction in the relationship that transformation of an individual system can occur. Method. The historical antecedents of the field of family therapy were outlined. It was demonstrated, via literature review, that the field of family therapy has traditionally paralleled developments in the hard sciences. Further, it was demonstrated via literature review that the newest understandings of the development of individuals, family systems, and therapeutic systems also parallel recent natural science developments, namely those developments based on the science of self-organizing complex systems. Outcome. The results of the study are twofold. First, the study articulates an expanded theory of the therapist, individual, and family as autopoietic self-organizing complex systems. Second, the study provides an expanded hypothesis which concerns recommendations for future research which will further advance the latest theories of family therapy. More precisely, the expanded hypothesis suggests that qualitative research, rather than quantitative research, is the method of choice for studying the effectiveness of phenomenological therapy.

  18. 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

  19. Review of the economic evaluations of 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

    Androgen deprivation therapy (ADT) is used as first-line therapy for locally advanced or metastatic prostate cancer aiming to reduce testosterone to castrate levels. The authors present an overview of the existing cost-effectiveness studies of ADT in prostate cancer. Cost-effectiveness of ADT was reviewed using a systematic search of the peer-reviewed literature, as well as research abstracts presented at various scientific and industry meetings. Most cost-effectiveness analyses of ADT reported results within the accepted societal threshold of US$50,000 cost/quality-adjusted life year needed to adopt new technology. PMID:23570436

  20. Advances in targeted therapy for the treatment of patients with relapsed/refractory multiple myeloma.

    PubMed

    Le Ray, Emmanuelle; Jagannath, Sundar; Palumbo, Antonio

    2016-01-01

    The development of proteasome inhibitors (PIs) and immunomodulatory drugs has significantly improved outcomes for patients with relapsed/refractory multiple myeloma (RRMM); however, not all patients benefit from treatment with these agents and some patients can become drug refractory over time. Due to the largely incurable nature of multiple myeloma, the development of newer agents is ongoing and includes new oral PIs (ixazomib), immunotherapies (e.g., CD38- or SLAMF7-targeted antibodies), and small molecules. This review provides an overview of the advances in targeted therapy for patients with RRMM, including recently approved agents, with a focus on monotherapy and combined targeted therapies. PMID:26558304

  1. Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies

    PubMed Central

    Flavin, Marisa; Panageas, Katherine S.; Ayers, Gregory D.; Zhao, Zhiguo; Iams, Wade T.; Colgan, Marta; DeNoble, Sarah; Terry, Charles R.; Berry, Elizabeth G.; Iafrate, A. John; Sullivan, Ryan J.; Carvajal, Richard D.; Sosman, Jeffrey A.

    2015-01-01

    Activating NRAS mutations are found in 15-20% of melanomas. Immune therapies have become a mainstay in advanced melanoma treatment. We sought to evaluate whether tumor genotype (e.g. NRAS mutations) correlate with benefit from immune therapy in melanoma. We identified 229 melanoma patients treated with immune therapies (interleukin-2, ipilimumab, or anti-programmed cell-death-1/ligand-1 (PD-1/PD-L1)) at three centers, and compared clinical outcomes following immune therapy for patients with or without NRAS mutations. Of the 229 melanoma patients, 60 had NRAS mutation, 53 had BRAF mutation, and 116 had NRAS/BRAF WT. The NRAS-mutant cohort had superior or a trend to superior outcomes compared to the other cohorts in terms of response to first-line immune therapy (28% vs. 16%, p=0.04), response to any line of immune therapy (32% vs. 20%, p=0.07), clinical benefit (response + stable disease lasting ≥24 weeks; 50% vs. 31%, p<0.01), and progression-free survival (median 4.1 vs. 2.9 months, p=0.09). Benefit from anti-PD-1/PD-L1 was particularly marked in the NRAS cohort (clinical benefit rate 73% vs. 35%). In an independent group of patient samples, NRAS-mutant melanoma had higher PD-L1 expression (although not statistically significant) compared to other genotypes (8/12 vs. 9/20 samples with ≥1% expression; 6/12 vs 6/20 samples with ≥5% expression), suggesting a potential mechanism for the clinical results. This retrospective study suggests that NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared to other genetic subtypes. If confirmed by prospective studies, this may be explained in part by high rates of PD-L1 expression. PMID:25736262

  2. 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

  3. 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

  4. 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. PMID:25997893

  5. 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

  6. 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

  7. Advances in cell and gene-based therapies for cystic fibrosis lung disease.

    PubMed

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

    2012-06-01

    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

  8. [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

  9. 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

  10. 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. PMID:26505885

  11. Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease

    PubMed Central

    Weaver, Frances M.; Follett, Kenneth; Stern, Matthew; Hur, Kwan; Harris, Crystal; Marks, William J.; Rothlind, Johannes; Sagher, Oren; Reda, Domenic; Moy, Claudia S.; Pahwa, Rajesh; Burchiel, Kim; Hogarth, Penelope; Lai, Eugene C.; Duda, John E.; Holloway, Kathryn; Samii, Ali; Horn, Stacy; Bronstein, Jeff; Stoner, Gatana; Heemskerk, Jill; Huang, Grant D.

    2010-01-01

    Context Deep brain stimulation is an accepted treatment for advanced Parkinson disease (PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. Objective To compare 6-month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Design, Setting, and Patients Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age (<70 years vs ≥70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD (Hoehn and Yahr stage ≥2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6-month follow-up visit occurred in May 2006. Intervention Bilateral deep brain stimulation of the subthalamic nucleus (n=60) or globus pallidus (n=61). Patients receiving best medical therapy (n=134) were actively managed by movement disorder neurologists. Main Outcome Measures The primary outcome was time spent in the “on” state (good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Results Patients who received deep brain stimulation gained a mean of 4.6 h/d of on time without troubling dyskinesia compared with 0 h/d for patients who received best medical therapy (between group mean difference, 4.5 h/d [95% CI, 3.7-5.4 h/d]; P<.001). Motor function improved significantly (P<.001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements (≥5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD

  12. Opioid therapy for chronic low back pain: prescribing considerations for advanced practice registered nurses.

    PubMed

    Lall, Maureen Patricia

    2014-12-01

    Chronic low back pain is a common, disabling, and costly condition, and advanced practice registered nurses (APRNs) must carefully evaluate patients before considering long-term opioid therapy as a management strategy. APRNs should refer patients suspected of having a serious condition, or identifiable etiology, for specialist evaluation, as many patients improve with physical therapy, interventional pain management procedures, or surgical intervention. For patients unresponsive to nonopioid treatment, APRNs with an understanding of opioids, and the experience to assess and manage the risks of opioid misuse, abuse, and diversion, may consider long-term opioid therapy as part of a multimodal management plan. Such prescribing necessitates careful patient selection; informed consent; prudent opioid dosing and titration; and monitoring for response to treatment, adverse effects, and aberrant drug-taking behavior. Treatment and regulatory guidelines can assist APRNs in providing safe and effective care to patients with chronic low back pain. PMID:25365050

  13. Advances in intravesical therapy for the treatment of non-muscle invasive bladder cancer (Review).

    PubMed

    Weintraub, Michael D; Li, Qingdi Quentin; Agarwal, Piyush K

    2014-09-01

    The knowledge of tumor biology and the biomechanical properties of the urothelium have led to significant advances in the development of intravesical therapy for the treatment of non-muscle invasive bladder cancer (NMIBC). Targeted therapy improves the efficacy and decreases the side effects of antineoplastic agents. Nanoparticles that target antitumor agents to the urothelial cells have allowed for improved delivery of these agents to tumor cells. Gene therapy is another strategy that has allowed for a targeted induction of an antitumor response. Finally, engineering of the bacillus Calmette-Guérin (BCG) vaccine aimed to minimize the potential side effects associated with this treatment. These novel approaches hold promise for decreasing the rate of progression and recurrence of NMIBC. PMID:25054027

  14. 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

  15. 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

  16. 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 ...

  17. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

    PubMed Central

    Borregales, Leonardo D.; Adibi, Mehrad; Thomas, Arun Z.; Wood, Christopher G.; Karam, Jose A.

    2015-01-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  18. Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

    PubMed

    Raza, Shahzad; Kornblum, Noah; Kancharla, Venkat P; Baig, Mahadi A; Singh, Amrit B; Kalavar, Madhumati

    2011-05-01

    Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs. PMID:21247406

  19. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma.

    PubMed

    Borregales, Leonardo D; Adibi, Mehrad; Thomas, Arun Z; Wood, Christopher G; Karam, Jose A

    2016-04-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  20. [Resection of Advanced Intrahepatic Cholangiocarcinoma after an Effective Response to S-1 and Gemcitabine Combination Therapy].

    PubMed

    Kuga, Yoshio; Moriya, Takashi; Fukuda, Saburo; Nishida, Toshihiro

    2016-06-01

    We report curative resection of an advanced intrahepatic cholangiocarcinoma that responded well to combined S-1 and gemcitabine chemotherapy(GS therapy). A 67-year-old woman was admitted to our hospital in July 2011 for upper right abdominal pain. She was diagnosed with intrahepatic cholangiocarcinoma with abdominal para-aortic lymph node metastasis on the basis of the computed tomography (CT) findings. She was treated with GS therapy. One course of S-1(80 mg/m(3)) consisted of the administration of the drug for 14 days, followed by 14 days of rest; GEM(1,000 mg/m(3)) was administered on days 1 and 15 after initiating S-1. After 2 courses of treatment, the sizes of the primary tumor and the lymph node metastasis were observed to be reduced on CT. In September, partial hepatectomy and regional lymph node dissection were performed. The patient subsequently received 22 postoperative courses of GS therapy. The patient's postoperative course was uneventful, and she remains free of recurrence 49 months since diagnosis. Therefore, GS therapy is a possible option for the management of advanced intrahepatic cholangiocarcinoma. PMID:27306819

  1. Advances in MR image-guided high-intensity focused ultrasound therapy.

    PubMed

    Kim, Young-sun

    2015-05-01

    The clinical role of magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) is rapidly expanding due to its merit of non-invasiveness. MR thermometry based on a proton resonance frequency shift technique is able to accurately measure HIFU-induced temperature changes, which provides considerable advantages over ultrasonography-guided HIFU in terms of safety and therapeutic efficacy. Recent studies and the resulting technological advances in MR-HIFU such as MR thermometry for moving organs, MR-acoustic radiation force imaging, and a volumetric mild hyperthermia technique further will expand its clinical roles from mere ablation therapy to targeted drug delivery and chemo- or radio-sensitisation for cancer treatment. In this article, MR-HIFU therapy is comprehensively reviewed with an emphasis on the roles of MR imaging in HIFU therapy, techniques of MR monitoring, recent advances in clinical MR-HIFU systems, and potential future applications of MR-HIFU therapy. In addition, the pros and cons of MR-HIFU when compared with ultrasonography-guided HIFU are discussed. PMID:25373687

  2. 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. PMID:25682222

  3. 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) Print A A A Text Size en español Obtención de una tomografía computada (video) CAT stands for "computerized axial tomography." Translated, that means ...

  4. Recent Advances in Bone-Targeted Therapies of Metastatic Prostate Cancer

    PubMed Central

    Deng, Xiyun; He, Guangchun; Liu, Junwen; Luo, Feijun; Peng, Xiaoning; Tang, Shigang; Gao, Zhiyong; Lin, Qinlu; Keller, Jill M.; Yang, Tao; Keller, Evan T.

    2014-01-01

    Prostate cancer is one of the most common malignancies affecting men worldwide, with bone being the most common site of metastasis in patients that progress beyond organ confinement. Bone metastases are virtually incurable and result in significant disease morbidity and mortality. Bone provides a unique microenvironment whose local interactions with tumor cells offer novel targets for therapeutic interventions. Several attractive molecules or pathways have been identified as new potential therapeutic targets for bone metastases caused by metastatic castration-resistant prostate cancer. In this review, we present the recent advances in molecular targeted therapies for prostate cancer bone metastasis focusing on therapies that target the bone cells and the bone microenvironment. The therapies covered in this review include agents that inhibit bone resorption, agents that stimulate bone formation, and agents that target the bone matrix. Suggestions to devise more effective molecular targeted therapies are proposed. Hopefully, with better understanding of the biology of the disease and the development of more robust targeted therapies, the survival and quality of life of the affected individuals could be significantly improved. PMID:24767837

  5. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  6. 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

  7. 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

  8. Effects of Qi therapy (external Qigong) on symptoms of advanced cancer: a single case study.

    PubMed

    Lee, M S; Yang, S H; Lee, K K; Moon, S-R

    2005-12-01

    The aim of this study was to examine the effectiveness of Qi therapy (external Qigong) in the management of symptoms of advanced cancer in a man. We used a single case study design to evaluate the effectiveness of Qi therapy (external Qigong) in a 35-year-old man with advanced cancer (Stage IV) involving metastases in the stomach, lung and bone (Karnofsky performance scale: KPS, 40: requires special care and assistance, disabled). Treatment involved six days of pre-assessment, eight treatment sessions on alternate days over 16 days, and a two-week follow-up phase. A visual analogue scale (VAS) was used to assess the patient's self-reported symptoms of cancer over the intervention and follow-up periods. Following treatment, VAS scores' analysis revealed beneficial effects on pain, vomiting, dyspnoea, fatigue, anorexia, insomnia, daily activity and psychological calmness. These improvements were maintained over the two-week follow-up phase. After the first Qi therapy session, the patient discontinued medication and could sit by himself; after the fourth session, the patient was able to walk and use the toilet without assistance (improvement in KPS: 70: care for self, unable to perform normal activity or to do active work). Although limited by the single case study approach, our results support previous studies on this topic and provide reasons to conduct controlled clinical trials. PMID:16274468

  9. Which strategy after first-line therapy in advanced colorectal cancer?

    PubMed Central

    Andrea, Coinu; Fausto, Petrelli; Francesca, Borgonovo Karen; Mary, Cabiddu; Mara, Ghilardi; Veronica, Lonati; Sandro, Barni

    2014-01-01

    Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of “continuum of care” includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies (cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents (bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer. PMID:25083064

  10. Targeted therapy of advanced non-small cell lung cancer: the role of bevacizumab

    PubMed Central

    Stinchcombe, Thomas E

    2007-01-01

    Lung cancer is the leading cause of cancer death in the United States. The majority of patients present with advanced stage disease, and treatment with standard cytotoxic chemotherapy agents have been shown to provide a modest improvement in survival, reduce disease-related symptoms, and improve quality of life. However, with standard chemotherapy treatments the prognosis is poor with the majority of patients dying in less than a year from diagnosis. Treatment with standard chemotherapy agents has reached a therapeutic plateau, and recent investigations have focused on therapies that target a specific pathway within the malignant cell or related to angiogenesis. The most promising of the targeted therapies are agents that target the process of angiogenesis. Bevacizuamab is a monoclonal antibody that binds to circulating vascular endothelial growth factor (VEGF)-A, and prevents binding of VEGF to vascular endothelial growth factor receptors, thus inhibiting activation of the VEGF pathway and angiogenesis. A recent phase III trial of first-line treatment of advanced non-small cell lung cancer revealed a statistically significant improvement in response, progression-free survival, and overall survival with the combination of bevacizumab and standard chemotherapy in comparison to standard chemotherapy alone. Bevacizumab is the only targeted therapy that has been shown to improve survival when combined with standard chemotherapy in the first-line setting. PMID:19707329

  11. Transcatheter Arterial Infusion Therapy in the Treatment of Advanced Pancreatic Cancer: A Feasibility Study

    SciTech Connect

    Shibuya, Keiko; Nagata, Yasushi; Itoh, Tuyoshi; Okajima, Kaoru; Murata, Rumi; Takagi, Takehisa; Hiraoka, Masahiro

    1999-05-15

    Purpose: To evaluate the effects of transcatheter arterial infusion (TAI) therapy in 18 patients with advanced pancreatic cancer. Methods: The drugs infused were epirubicin 60 mg, mitomycin C 20 mg, and 5-fluorouracil 500 mg. The efficacy of TAI was evaluated by a tumor marker (CA19-9), computed tomography (CT) findings, and postoperative histopathological specimens. Results: In 10 of 15 cases, the tumor marker level was decreased after TAI therapy. In 6 of 14 cases, CT showed a decrease in the tumor size, and in 1 case, the tumor disappeared completely. In 6 cases the tumor could be resected. Necrosis, fibrosis, and degeneration of cancer cells were seen in 3 of 4 cases for whom a histopathological evaluation was done. The median survival was 11 months. In 17 patients back pain was the chief complaint, and was reduced to a self-controlled level in 10 patients following TAI therapy. No major complications were encountered. Conclusion: TAI appears to be an effective palliative treatment for advanced pancreatic cancer.

  12. 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

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

    PubMed

    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. PMID:26431849

  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. Advanced BMP Gene Therapies for Temporal and Spatial Control of Bone Regeneration

    PubMed Central

    Wilson, C.G.; Martín-Saavedra, F.M.; Vilaboa, N.; Franceschi, R.T.

    2013-01-01

    Spatial and temporal patterns of bone morphogenetic protein (BMP) signaling are crucial to the assembly of appropriately positioned and shaped bones of the face and head. This review advances the hypothesis that reconstitution of such patterns with cutting-edge gene therapies will transform the clinical management of craniofacial bone defects attributed to trauma, disease, or surgical resection. Gradients in BMP signaling within developing limbs and orofacial primordia regulate proliferation and differentiation of mesenchymal progenitors. Similarly, vascular and mesenchymal cells express BMPs in various places and at various times during normal fracture healing. In non-healing fractures of long bones, BMP signaling is severely attenuated. Devices that release recombinant BMPs promote healing of bone in spinal fusions and, in some cases, of open fractures, but cannot control the timing and localization of BMP release. Gene therapies with regulated expression systems may provide substantial improvements in efficacy and safety compared with protein-based therapies. Synthetic gene switches, activated by pharmacologics or light or hyperthermic stimuli, provide several avenues for the non-invasive regulation of the expression of BMP transgenes in both time and space. Through new gene therapy platforms such as these, active control over BMP signaling can be achieved to accelerate bone regeneration. PMID:23539558

  18. 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.

  19. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    PubMed Central

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  20. 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

  1. ADVANCED MR IMAGING METHODS FOR PLANNING AND MONITORING RADIATION THERAPY IN PATIENTS WITH HIGH GRADE GLIOMA

    PubMed Central

    Lupo, Janine M.; Nelson, Sarah J.

    2016-01-01

    This review explores how the integration of advanced imaging methods with high quality anatomic images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion, perfusion, and susceptibility weighted MR imaging in conjunction with MR spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast enhancing or T2 lesion alone and have a significant impact on targeting resection, planning radiation, and assessing treatment effectiveness. In the long-term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiation-induced vascular injury in otherwise normal appearing brain tissue. PMID:25219809

  2. 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. PMID:24659088

  3. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements

    PubMed Central

    Abdalla, Eddie K; Bauer, Todd W; Chun, Yun S; D'Angelica, Michael; Kooby, David A; Jarnagin, William R

    2013-01-01

    Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location. PMID:23297723

  4. Advanced stages of PD: interventional therapies and related patient-centered care.

    PubMed

    Krüger, Rejko; Hilker, Rüdiger; Winkler, Christian; Lorrain, Michael; Hahne, Matthias; Redecker, Christoph; Lingor, Paul; Jost, Wolfgang H

    2016-01-01

    During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany. PMID:26138439

  5. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements.

    PubMed

    Abdalla, Eddie K; Bauer, Todd W; Chun, Yun S; D'Angelica, Michael; Kooby, David A; Jarnagin, William R

    2013-02-01

    Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location. PMID:23297723

  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. 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

  9. [New advance of research on therapy of severe acute radiation sickness with mesenchymal stem cells].

    PubMed

    Guo, Ling-Ling; Li, Ming; Xing, Shuang; Luo, Qing-Liang

    2011-06-01

    Mesenchymal stem cells (MSC) are a kind of non-hematopoietic adult stem cells with self-renewal and multilineage differentiation potential, which have special biological characteristics, such as secreting various cytokines, promoting hematopoiesis, accelerating stem cells homing and reconstructing hematopoietic microenvironment. MSC are collected and amplified easily, and can be transfected by exogenous gene. Many reports indicated that MSC were applied in therapy for variety of tissues and organs injury, meanwhile the treatment for acute radiation sickness has made significant progress. In this review, the biological characteristics and new research advance on MSC in treatment of severe acute radiation sickness are summarized and discussed. PMID:21729581

  10. 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

  11. 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

  12. Maintenance therapy with capecitabine in patients with locally advanced unresectable pancreatic adenocarcinoma.

    PubMed

    Saif, Muhammad Wasif; Ledbetter, Leslie; Kaley, Kristin; Garcon, Marie Carmel; Rodriguez, Teresa; Syrigos, Kostas N

    2014-09-01

    Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following

  13. Risk of liver injury after α-glucosidase inhibitor therapy in advanced chronic kidney disease patients

    PubMed Central

    Kao, Chih-Chin; Wu, Pei-Chen; Wu, Che-Hsiung; Chen, Li-kwang; Chen, Hsi-Hsien; Wu, Mai-Szu; Wu, Vin-Cent

    2016-01-01

    Although α-glucosidase inhibitors (AGIs) are commonly used for controlling postprandial blood glucose, AGIs-induced liver injuries have been reported. However, the relationship between AGIs and liver injuries in advanced chronic kidney disease (CKD) patients remains unexplored. In this nationwide case-control study, we recruited 1765 advanced diabetic CKD patients, who received AGIs therapy from January 1, 2000 to December 31, 2010 as the study sample and 5295 matched controls. Recent and former AGIs users were defined as patients who received the AGIs prescription for 30–60 d and 30–210 d before the event of liver injury. The risk of AGIs-induced liver injury was examined using time-dependent Cox proportional hazards model. Liver injury occurred in 3.9% of patients in the study group and 3.3% of patients in the control group. AGIs use did not increase the risk of liver injury in advanced CKD patients (P = 0.19). The stratified analysis indicated no increased risk of liver injury in all AGIs-using subgroups (all P > 0.05). The available evidence supports extending the use of AGIs without increasing the risk of liver injury in patients with advanced CKD. Additional randomized controlled trials are warranted to confirm our results. PMID:26751038

  14. 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

  15. ERCC1 protein as a guide for individualized therapy of late-stage advanced non-small cell lung cancer

    PubMed Central

    GAO, ZHIQIANG; HAN, BAOHUI; SHEN, JIE; GU, AIQIN; QI, DAJIANG; HUANG, JINSU; SHI, CHUNLEI; XIONG, LIWEN; ZHAO, YIZHUO; JIANG, LIYAN; WANG, HUIMIN; CHEN, YURONG

    2011-01-01

    Excision repair cross-complementation group 1 (ERCC1) protein has been associated with cisplatin resistance. The objective of this study was to investigate the correlation between ERCC1 protein levels and the therapeutic effect of individualized therapy in advanced non-small cell lung cancer (NSCLC). A total of 190 advanced NSCLC patients were included in this study. Patients were randomized into either the individualized therapy group or the standard therapy group at a ratio of 2:1. Patients in the standard therapy group were treated with either gemcitabine plus cisplatin or vinorelbine plus cisplatin. The expression of ERCC1 protein in lung cancer tissues of patients from the individualized therapy group was detected with immunohistochemistry. Patients with low ERCC1 levels received either gemcitabine plus cisplatin or vinorelbine plus cisplatin, and patients with high levels received gemcitabine plus vinorelbine. The main outcome assessments were response rate (RR), overall survival (OS) and time to progression (TTP). Follow-up data were recorded until September 30, 2010. RR, 1-year survival rate and TTP were not statistically significant. The median survival time was 10.10 months in the standard therapy group (95% CI 8.48–11.92) and 13.59 months in the individualized therapy group (95% CI 11.86–14.74). The difference in median survival time was significantly different between these groups (P=0.036). The median survival time was longer in the individualized group compared to the standard therapy group. ERCC1 protein expression in advanced NSCLC patients, however, was not significantly correlated with RR, OS and TTP in the individualized therapy group. Therefore, this study suggests that ERCC1 protein levels should be assessed in combination with additional biomarkers to determine an optimal index for individualized therapy in advanced NSCLC patients. PMID:22977580

  16. 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.

  17. 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

  18. Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer

    SciTech Connect

    Schneider, Bryan J.; McGinn, Cornelius J.; Chang, Alfred E.; Colletti, Lisa M.; Normolle, Daniel P.; Hejna, Gwen F. P.A.; Zalupski, Mark M. . E-mail: Zalupski@umich.edu

    2005-12-01

    Purpose: The primary objective of this study was to evaluate the tolerance and toxicity of radiation therapy (RT) and capecitabine in patients with advanced, unresectable pancreatic carcinoma. To control micrometastatic disease, combination chemotherapy (gemcitabine and cisplatin) before and after combined modality therapy (CMT) was planned. Methods and Materials: Patients with unresectable or metastatic pancreatic cancer were eligible. Gemcitabine 1000 mg/m{sup 2} and cisplatin 35 mg/m{sup 2} were administered on Days 1 and 8 of a 21-day cycle for two cycles. RT was then given to a dose of 50.4 Gy in 1.8 Gy fractions. Patients were treated with capecitabine 1330 mg/m{sup 2} daily during RT. After CMT, two additional cycles of gemcitabine and cisplatin completed the treatment. Results: Twenty-three patients were treated. Eighteen patients completed CMT. One patient was removed from study during CMT for toxicity issues. Treatment delays and dose reductions were common during the final two cycles of gemcitabine and cisplatin as a result of myelosuppression. Median survival was 10.1 months (95% confidence interval [CI] = 7.6, 13.7) for all 23 patients and 12.8 months (95% CI = 8.2, 18.9) for 18 patients without metastasis. Conclusion: Combined modality therapy with RT and capecitabine was well tolerated. Chemotherapy after CMT was difficult to complete owing to cumulative myelosuppression. Survival, response, and toxicity were comparable to infusional 5-fluorouracil and RT.

  19. 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.

  20. 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.

  1. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    PubMed Central

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-01-01

    Abstract Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients. Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS). The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC. Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts. PMID:26496252

  2. Treatment of advanced thyroid cancer with targeted therapies: ten years of experience.

    PubMed

    Viola, David; Valerio, Laura; Molinaro, Eleonora; Agate, Laura; Bottici, Valeria; Biagini, Agnese; Lorusso, Loredana; Cappagli, Virginia; Pieruzzi, Letizia; Giani, Carlotta; Sabini, Elena; Passannati, Paolo; Puleo, Luciana; Matrone, Antonio; Pontillo-Contillo, Benedetta; Battaglia, Valentina; Mazzeo, Salvatore; Vitti, Paolo; Elisei, Rossella

    2016-04-01

    Thyroid cancer is rare, but it is the most frequent endocrine malignancy. Its prognosis is generally favorable, especially in cases of well-differentiated thyroid cancers (DTCs), such as papillary and follicular cancers, which have survival rates of approximately 95% at 40 years. However, 15-20% of cases became radioiodine refractory (RAI-R), and until now, no other treatments have been effective. The same problems are found in cases of poorly differentiated (PDTC) and anaplastic (ATC) thyroid cancers and in at least 30% of medullary thyroid cancer (MTC) cases, which are very aggressive and not sensitive to radioiodine. Tyrosine kinase inhibitors (TKIs) represent a new approach to the treatment of advanced cases of RAI-R DTC, MTC, PDTC, and, possibly, ATC. In the past 10 years, several TKIs have been tested for the treatment of advanced, progressive, and RAI-R thyroid tumors, and some of them have been recently approved for use in clinical practice: sorafenib and lenvatinib for DTC and PDTC and vandetanib and cabozantinib for MTC. The objective of this review is to present the current status of the treatment of advanced thyroid cancer with the use of innovative targeted therapies by describing both the benefits and the limits of their use based on the experiences reported so far. A comprehensive analysis and description of the molecular basis of these therapies, as well as new therapeutic perspectives, are reported. Some practical suggestions are given for both the choice of patients to be treated and their management, with particular regard to the potential side effects. PMID:27207700

  3. Prolonged complete response following gemcitabine-erlotinib combined therapy in advanced pancreatic cancer

    PubMed Central

    CZARNECKA, ANNA M.; KORZEŃ, PIOTR; NOWAK-DEMENT, ANNA; KUKWA, WOJCIECH; KORNILUK, JAN; SZCZYLIK, CEZARY

    2016-01-01

    Pancreatic cancer is one of the most lethal types of malignant solid tumor and is typically associated with a poor prognosis. The majority of patients are diagnosed with advanced-stage disease, therefore, the median survival period is <6 months. Recently, a number of basic research projects and clinical trials were undertaken with the aim of improving treatment outcomes in pancreatic cancer; however, only one agent, erlotinib, passed the clinical trials. Erlotinib is an inhibitor of epidermal growth factor receptor, which when overexpressed in cancer, promotes angiogenesis, cell proliferation and inhibits apoptosis. The US Food and Drug Administration and European Medicines Agency approved erlotinib in combination with gemcitabine for the first-line treatment of advanced pancreatic cancer. To the best of our knowledge, the current study is the first to report a case of pancreatic cancer treated with this regimen alone to achieve a complete response (CR). A 40-year-old male with a medical history of chronic pancreatitis and hypertension was diagnosed with medically inoperable adenocarcinoma of the pancreas. Following palliative surgery, the patient began palliative gemcitabine and erlotinib chemotherapy. After three months, this treatment strategy resulted in a CR, as determined by imaging studies. Therapy was discontinued after 14 months due to the development of peritoneal metastases and the patient was referred for treatment with the folinic acid, 5-fluorouracil, irinotecan and oxaliplatin regimen. A CR is rarely reported in pancreatic cancer, however, a treatment strategy of gemcitabine and erlotinib may induce rapid regression of advanced-stage disease. PMID:26893699

  4. Successful surgical resection of advanced gastrointestinal stromal tumor post neoadjuvent therapy.

    PubMed

    Kamil, Sm; Biswas, M; Imran, Ak; Islam, R; Mukhtar, Aa; Joshi, Sc

    2009-01-01

    We report a case of a 48-year-old Indian male who presented with swelling and firmness in his left upper part of the abdomen of one month duration with anorexia and weight loss. Initial examination revealed an intra abdominal mass of around 16.8x11.0x24.5cm with minimal left sided pleural effusion. A biopsy from the mass confirmed the diagnosis of gastrointestinal stromal tumour (GISTs) as supported by immmunohistochemistry results which showed strong positivity for c-kit while stains for smooth muscle actin, desmin, myoglobin, S100 Protein and cytokerstin remained negative. The patient was not suitable for surgical intervention in view of advanced tumor, and Imatinib Mesylate 400mg daily was started with the aim of making the tumor operable. Such therapy lasted for twenty months and was tolerated well by the patient. It then resulted in gradual tumor regression, following which the patient underwent successful tumor resection. Post surgical resection patient had no radiological evidence of intra abdominal tumor but mild left sided pleural effusion with left lower lobe atelectasis. The patient had uneventful post operative recovery and he is currently on Imatinib mesylate and tolerating treatment well with mild skin rash. The experience with preoperative imatinib on surgical resection rates and post operative outcomes is limited especially with primary locally advanced GISTs. In our case successful surgical resection was possible for a huge locally advanced GIST with unusually prolonged treatment of twenty months with imatinib preoperatively. PMID:21483516

  5. Chemotherapy for patients with advanced lung cancer receiving long-term oxygen therapy

    PubMed Central

    Suzuki, Hidekazu; Shiroyama, Takayuki; Tamiya, Motohiro; Okamoto, Norio; Tanaka, Ayako; Morishita, Naoko; Nishida, Takuji; Nishihara, Takashi; Hirashima, Tomonori

    2016-01-01

    Background Long-term oxygen therapy (LTOT) is sometimes prescribed for patients with advanced lung cancer who are potential candidates for chemotherapy. The aim of this study was to assess the usefulness of chemotherapy for patients with this disease who require LTOT. Methods The medical records of 40 patients with advanced lung cancer who received LTOT while undergoing systemic chemotherapy at our institution between January 2009 and December 2014 were retrospectively reviewed. Chemotherapy consisted of cytotoxic or molecular-targeted agents. Results Twenty-four patients had adenocarcinoma, 6 had squamous cell carcinoma, and 10 had small cell lung cancer (SCLC). The median survival time from the date of the first chemotherapy cycle performed in conjunction with LTOT was 194 days. In a multivariate analysis, the only factor significantly associated with better prognosis was the line (first or second) of the first chemotherapy with LTOT (hazard ratio =0.42; 95% confidence interval, 0.18 to 0.94). Among the 40 patients, 10 (25%) received chemotherapy during the last 30 days of their lives, 2 of whom died of chemotherapy-related adverse events. Conclusions Chemotherapy for patients with advanced lung cancer who receive LTOT may be acceptable if it is the first- or second-line treatment. However, we should be mindful of the potential overuse of chemotherapy and its negative impact on quality of life. PMID:26904219

  6. 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

  7. Survival of patients with advanced metastatic melanoma: The impact of novel therapies.

    PubMed

    Ugurel, Selma; Röhmel, Joachim; Ascierto, Paolo A; Flaherty, Keith T; Grob, Jean Jacques; Hauschild, Axel; Larkin, James; Long, Georgina V; Lorigan, Paul; McArthur, Grant A; Ribas, Antoni; Robert, Caroline; Schadendorf, Dirk; Garbe, Claus

    2016-01-01

    The survival of advanced metastatic melanoma has been greatly improved within the past few years. New therapeutic strategies like kinase inhibitors for BRAF-mutant melanoma and immune checkpoint blockers proved to prolong survival times within clinical trials, and many of them have already entered routine clinical use. However, these different treatment modalities have not yet been tested against each other, which complicate therapy decisions. We performed an explorative analysis of survival data from recent clinical trials. Thirty-five Kaplan-Meier survival curves from 17 trials were digitised, re-grouped by matching inclusion criteria and treatment line, and averaged by therapy strategy. Notably, the survival curves grouped by therapy strategy revealed a very high concordance, even if different agents were used. The greatest survival improvement was observed with the combination of BRAF plus MEK inhibitors as well as with Programmed-death-1 (PD1) blockers with or without cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockers, respectively, with these two treatment strategies showing similar survival outcomes. For first-line therapy, averaged survival proportions of patients alive at 12 months were 74.5% with BRAF plus MEK inhibitor treatment versus 71.9% with PD-1 blockade. This explorative comparison shows the kinase inhibitors as similarly effective as immune checkpoint blockers with regard to survival. However, to confirm these first trends for implementation into an individualised treatment of melanoma patients, data from prospective clinical trials comparing the different treatment strategies head-to-head have to be awaited. PMID:26707829

  8. 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.

  9. 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…

  10. 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

  11. Cat's claw: an Amazonian vine decreases inflammation in osteoarthritis.

    PubMed

    Hardin, Sonya R

    2007-02-01

    Cat's claw (Uncaria tomentosa and Uncaria guianesis) is a medicinal plant from the Amazon commonly used to treat disorders such as arthritis, gastritis and osteoarthritis. The mechanism of cat's claw appears to be as an inhibitor of TNFalpha and antioxidant. Understanding the processes in osteoarthritis may facilitate and clarify the potential role of cat's claw as a complementary therapy to assist in the reduction of pro-inflammatory mediators and effectors. The clinical relevance of this therapy as a viable modality of intervention will be discussed. PMID:17210508

  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. 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. PMID:21054243

  14. 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

  15. New approach for treatment of advanced malignant tumors: combination of chemotherapy and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wang, Lian-xing; Ju, Hua-lamg; Chem, Zhem-ming

    1995-03-01

    Eighty-three patients suffering from moderate or advanced malignant tumors were treated by combined chemotherapy and photodynamic therapy (PDT) in our hospital. The short term result of such management is very promising, the effectiveness seems to be nearly 100% and the general responsive rate is 79.5% (CR + PR). If compared with another group of 84 similar patients whom were treated with PDT alone, the short term efficacy is 85.7% while the general response rate is 54.7% (P < 0.01), there is a significant statistic. The better result of the combined approach is probably due to the action of the chemotherapeutic agent, potentially blocking the mitosis of the cellular cycle at certain phases of the cancer cells, making the cell membrane become more permeable to the photochemical agent, HPD, and eliciting a better cancerocidal effect.

  16. 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.

  17. 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

  18. Advances in pulmonary therapy and drug development: Lung tissue engineering to lung-on-a-chip.

    PubMed

    Doryab, Ali; Amoabediny, Ghassem; Salehi-Najafabadi, Amir

    2016-01-01

    Lung disease is one of the major causes of death, and the rate of pulmonary diseases has been increasing for decades. Although lung transplantation is the only treatment for majority of patients, this method has been limited due to lack of donors. Therefore, recently, attentions have increased to some new strategies with the aid of tissue engineering and microfluidics techniques not only for the functional analysis, but also for drug screening. In fact, in tissue engineering, the engineered tissue is able to grow by using the patient's own cells without intervention in the immune system. On the other hand, microfluidics devices are applied in order to evaluate drug screenings, function analysis and toxicity. This article reviews new advances in lung tissue engineering and lung-on-a-chip. Furthermore, future directions, difficulties and drawbacks of pulmonary therapy in these areas are discussed. PMID:26875777

  19. 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

  20. 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

  1. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    PubMed Central

    Viola, Joana R.; Rafael, Diana F.; Wagner, Ernst; Besch, Robert; Ogris, Manfred

    2013-01-01

    Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed. PMID:23634303

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Adjuvant role of radiation therapy for locally advanced laryngeal cancer without pathological lymph node metastasis.

    PubMed

    Kim, Sung Hee; Lee, Yoon Se; Kwon, Minsu; Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Kim, Sang Yoon; Lee, Sang-Wook; Nam, Soon Yuhl

    2016-07-01

    Conclusion The application of adjuvant RT to reduce recurrence should be tailored in cases of pathologically negative node metastasis. Objectives The treatment modality following surgical resection of advanced laryngeal cancer is determined by adverse factors. Aside from lymph node metastasis (LNM) or positive margins, definite risk factors supporting adjuvant radiation therapy (RT) have not been clearly suggested. The aim of this study was to analyze the risk factors for advanced laryngeal cancer without LNM and the role of RT. Materials and methods Pathologically T3 and T4-staged laryngeal squamous cell carcinoma without LNM were reviewed. The patients were classified into RT (+) (n = 22) and RT (-) (n = 38) groups. Results Five-year overall survival (OS) of the RT (+) and RT (-) groups was 84.4% and 83.8%, respectively. Five-year disease-specific survival of the RT (+) and RT (-) groups was 88.4% and 93.9%. Five-year local control rate of the RT (+) and RT (-) groups was 94.7% and 91.3%. The factors affecting OS were smoking history and recurrence history (p = 0.02). By multivariate analysis, smoking history and recurrence history were determining factors for 5-year OS (p = 0.024 and p = 0.047, respectively). PMID:26924463

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

    PubMed Central

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

    2015-01-01

    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. PMID:26512656

  13. Intraoperative radiation therapy for advanced cervical metastasis: a single institution experience

    PubMed Central

    2011-01-01

    Background The purpose of this study is to review our experience with the use of IORT for patients with advanced cervical metastasis. Methods Between August 1982 and July 2007, 231 patients underwent neck dissections as part of initial therapy or as salvage treatment for advanced cervical node metastases resulting from head and neck malignancies. IORT was administered as a single fraction to a dose of 15 Gy or 20 Gy in most pts. The majority was treated with 5 MeV electrons (112 pts, 50.5%). Results 1, 3, and 5 years overall survival (OS) after surgery + IORT was 58%, 34%, and 26%, respectively. Recurrence-free survival (RFS) at 1, 3, and 5 years was 66%, 55%, and 49%, respectively. Disease recurrence was documented in 83 (42.8%) pts. The majority of recurrences were regional (38 pts), as compared to local recurrence in 20 pts and distant failures in 25 pts. There were no perioperative fatalities. Conclusions IORT results in effective local disease control at acceptable levels of toxicity. Our results support the initiation of a phase III trial comparing outcomes for patients with cervical metastasis treated with or without IORT. PMID:21676211

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

    PubMed

    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

  15. 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

  16. [Gefitinib therapy in advanced non-small cell lung cancer in patients with EGFR mutations: cost-effectiveness analysis].

    PubMed

    Protsenko, S A; Rudakova, A V

    2015-01-01

    Therapy for advanced non-small cell lung cancer (NSCLC) is very complex clinical problem. The optimal choice of therapy demands not only the analysis of data on clinical effectiveness, but also an assessment of cost-effectiveness of the applied drugs. The current options for first- or second/third-line of lung cancer treatment are tirosine kinase inhibitors (TKI)--gefitinib, erlotinib and afatinib. According to the received results TKI first-line therapy for NSCLC in patients with EGFR mutations is not only clinically effective but also is economically acceptable from a position of the Russian budgetary health care. TKI second-line therapy for NSCLC patients who fail first-line therapy also provides improvement of the quality of life and prolonged time to progression. Comparable clinical effectiveness and safety of erlotinib and gefitinib in patients with EGFR mutations allows making drug choice on the basis of regional price characteristics. Afatinib is highly effective both in the first- and in the second/third-line of therapy in patients with the most frequent mutations (a deletion in exon 19 or a point mutation L858R in exon 21) but first-line therapy demands an increase of financial expenses caused by substantial increase of time to progression and duration of therapy. Thus TKI therapy of both the first-, and second/third-line of patients with NSCLC with EGFR mutations is characterized by acceptable cost-effectiveness. PMID:26571844

  17. 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

  18. 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 Central

    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.

    2014-01-01

    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 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal Dmax 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 Dmean, Dmax, D1cc, D4%, and V20 Gy 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

  19. Thyroid tumors in dogs and cats.

    PubMed

    Barber, Lisa G

    2007-07-01

    The clinical presentation and biologic behavior of thyroid tumors vary widely among dogs, cats, and human beings. Although thyroid tumors in dogs are rare, they are most likely to be malignant. Clinical signs are usually the result of impingement on surrounding structures, and clinical hyperthyroidism is rare. In contrast, hyperthyroidism resulting from benign thyroid proliferation is relatively common among older cats. Malignant tumors are extremely uncommon but have high metastatic potential. Irrespective of the tumor's ability to produce functional thyroid hormone, scintigraphy is often helpful in the diagnosis and staging of thyroid tumors in all three species. Treatment with surgery is a reasonable treatment option for noninvasive tumors. Iodine 131 is a well-established treatment for thyroid nodules in cats, but its effectiveness in dogs is controversial. In dogs, external beam radiation therapy has produced more consistent results in affording local tumor control when surgery is not possible. PMID:17619010

  20. 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.

  1. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  2. Chemoendocrine therapy with prolonged estrogen priming in advanced breast cancer: endocrine pharmacokinetics and toxicity.

    PubMed

    Benz, C; Gandara, D; Miller, B; Drakes, T; Monroe, S; Wilbur, B; DeGregorio, M

    1987-03-01

    Recent efforts to improve response rates in advanced breast cancer have used short, alternating courses of antiestrogen therapy followed by estrogen priming to cytokinetically enhance tumor cell sensitivity to antimetabolites. Based on recent in vitro and in vivo studies, we have introduced a chemoendocrine regimen that uses prolonged courses of estrogen priming. The present protocol consists of alternating monthly cycles of tamoxifen (TAM) and estradiol during which sequential (24-hr) methotrexate, 5-fluorouracil, and leucovorin are administered at 2-week intervals. Twenty-five patients with metastatic breast cancer received greater than 80 endocrine cycles and greater than 300 courses of chemotherapy by this protocol; two-thirds of these patients had previously failed other endocrine or chemotherapy regimens. Most patients experienced grade 1 or 2 myelosuppression or gastrointestinal symptoms during at least one treatment cycle; however, overall toxicity was considered to be mild and therapy was very well tolerated. Serum levels of estradiol, estrone, TAM, and TAM metabolites were measured during all phases of the endocrine cycle in five patients on chronic therapy. Concentrations of TAM and its more abundant metabolite, N-desmethyltamoxifen (N-desTAM), rose twofold during antiestrogen therapy and fell during estrogen priming, with mean levels persisting greater than 100 ng/ml throughout the priming interval. Mean estradiol (E2) and estrone (E1) levels rose during priming and were sustained fivefold and tenfold above the basal postmenopausal levels measured during antiestrogen treatment. Calculating the serum molar ratios of [TAM + N-desTAM]/[E2 + E1] during each phase of the treatment cycle confirmed that estrogen priming was achieved pharmacologically by this endocrine schedule. Clinical remissions were observed in this small patient sample with seven of 18 patients achieving either complete (28%) or partial (11%) responses, and an additional 39% obtaining

  3. 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

  4. 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

  5. The conjoint use of music therapy and reflexology with hospitalized advanced stage cancer patients and their families.

    PubMed

    Magill, Lucanne; Berenson, Susan

    2008-09-01

    Advanced stage cancer patients experience debilitating physical symptoms as well as profound emotional and spiritual struggles. Advanced disease is accompanied by multiple changes and losses for the patient and the family. Palliative care focuses on the relief of overall suffering of patients and families, including symptom control, psychosocial support, and the meeting of spiritual needs. Music therapy and reflexology are complementary therapies that can soothe and provide comfort. When used conjointly, they provide a multifaceted experience that can aid in the reduction of anxiety, pain, and isolation; facilitate communication between patients, family members, and staff; and provide the potential for a more peaceful dying experience for all involved. This article addresses the benefits of the combined use of music therapy and reflexology. Two case studies are presented to illustrate the application and benefits of this dual approach for patients and their families regarding adjustment to the end of life in the presence of anxiety and cognitive impairment. PMID:18662423

  6. 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

  7. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.

    PubMed

    Chuma, Makoto; Terashita, Katsumi; Sakamoto, Naoya

    2015-10-01

    Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents. PMID:25472913

  8. 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

  9. 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

  10. 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

  11. Early efficacy of stereotactic body radiation therapy combined with adoptive immunotherapy for advanced malignancies

    PubMed Central

    WANG, YI-SHAN; YANG, GUIQING; WANG, YUAN-YUAN; YANG, JIA-LIN; YANG, KE

    2013-01-01

    Stereotactic body radiation therapy (SBRT) concentrates radiation to a predefined target, affecting all the cells within it. Adoptive immunotherapy is not restricted by the major histocompatibility complex (MHC) in recognizing and eliminating target cells. We investigated the effects of the combined modality of SBRT and adoptive immunotherapy on patients with advanced malignant tumors. The database of 316 patients with 845 tumors who underwent SBRT between April, 2010 and February, 2012 was retrospectively reviewed. Of the 316 patients, 145 received biological immunotherapy and were assigned into the observation group, whereas the remaining patients constituted the control group. Patients in the two groups were recorded on efficacy assessment, Karnofsky performance status (KPS), cell phenotype expression level in vitro and the percentages of lymphocyte subsets and ratio of CD4+/CD8+ lymphocytes in the peripheral blood. Following treatment, the total effectiveness [complete response (CR) + partial response (PR)], the KPS score, the percentages of lymphocyte subsets and the CD4+/CD8+ lymphocyte ratio in the observation group were higher compared to those in the control group, with a statistically significant difference (P<0.05). The expression of CD3+ and CD3+CD56+ cytokine-induced killer (CIK) cells were increased from 56.76±4.54% and 11.32±2.96% to 94.67±4.46% and 32.65±1.12%, respectively, when cultured in vitro (P<0.01). The percentages of lymphocyte subsets and the CD4+/CD8+ lymphocyte ratio were significantly increased compared to prior to treatment in the observation group (P<0.05). SBRT combined with adoptive immunotherapy may be a novel therapeutic option for patients with advanced malignant tumors. PMID:24649272

  12. 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

  13. 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

  14. Combined therapy of percutaneous cryoablation and traditional Chinese medicine can be a promising strategy for elderly or advanced lung cancer patients based on a retrospective clinical study.

    PubMed

    Gao, Lei; Li, Quanwang; Jiang, Min; Liu, Chuanbo; Song, Zilin; Bao, Xiaoling; Shen, Yang; Liu, Guijian; Hu, Kaiwen

    2014-08-01

    Presently, elderly and advanced lung cancer patients have very limited treatment options. With no promising therapy, treatment of these patients is challenging. We have reviewed 119 primary lung cancer patients who received a combined percutaneous cryoablation and traditional Chinese medicine therapy (Cryo-TCM therapy) between 2005 and 2013. Out of 119 patients, 84.1% patients were elderly or advanced lung cancer when receiving cryoablation. Overall Survival time from the time of Diagnosis (DOS) and Cryoablation (COS) was 19 and 10 months respectively, which were longer than data previously published. Patients who accepted only Cryo-TCM therapy got similar DOS as those who were treated with Cryo-TCM and other classic anticancer therapies. Thus, Cryo-TCM therapy can prolong the survival time and can be used as the main therapy for the elderly or advanced lung cancer patients in China both in quality of life and cost effectiveness. PMID:24859157

  15. 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

  16. [Significance of intermittent CDDP therapy for improving long-term prognosis in patients with advanced ovarian cancer].

    PubMed

    Umesaki, N; Yamamoto, A; Nakano, M; Matsumoto, Y; Tsuda, K; Kawabata, M; Sugawa, T

    1991-12-01

    In cases of advanced ovarian cancer, intermittent CDDP therapy (ICDDPT) was applied after the first operation and induction chemotherapy, and its efficacy and limit were studied. One cycle of this therapy involved consecutive 5 day CDDP treatment (25-30mg/body/day). The therapy was repeated at intervals of 3 months. In many cases, ovarian cancer was histologically rated as epithelial adenocarcinoma. The study included 18 cases in total. ICDDPT was applied to 13 cases in which no tumor mass was detected by second look operation (SLO) or which showed clinical remission after operation. Only 3 of these 13 cases showed recurrence, and all these 13 are still living. Of the 5 cases in which SLO disclosed a tumor mass or which did not show remission after the first operation, 2 died. When the survival rate after ICDDPT was compared by the Kaplan-Meier method with that of controls without CDDP therapy, the effectiveness of ICDDPT was demonstrated. The survival rate could therefore be improved by ICDDPT. The therapy particularly improved the long term prognosis of SLO negative cases and cases in clinical remission. It seems necessary to repeat this therapy for a long period to achieve satisfactory results. In SLO positive cases and cases without clinical remission, the therapy had only a limited effect. PMID:1744459

  17. Feasibility of a Hybrid Brain-Computer Interface for Advanced Functional Electrical Therapy

    PubMed Central

    Savić, Andrej M.; Malešević, Nebojša M.; Popović, Mirjana B.

    2014-01-01

    We present a feasibility study of a novel hybrid brain-computer interface (BCI) system for advanced functional electrical therapy (FET) of grasp. FET procedure is improved with both automated stimulation pattern selection and stimulation triggering. The proposed hybrid BCI comprises the two BCI control signals: steady-state visual evoked potentials (SSVEP) and event-related desynchronization (ERD). The sequence of the two stages, SSVEP-BCI and ERD-BCI, runs in a closed-loop architecture. The first stage, SSVEP-BCI, acts as a selector of electrical stimulation pattern that corresponds to one of the three basic types of grasp: palmar, lateral, or precision. In the second stage, ERD-BCI operates as a brain switch which activates the stimulation pattern selected in the previous stage. The system was tested in 6 healthy subjects who were all able to control the device with accuracy in a range of 0.64–0.96. The results provided the reference data needed for the planned clinical study. This novel BCI may promote further restoration of the impaired motor function by closing the loop between the “will to move” and contingent temporally synchronized sensory feedback. PMID:24616644

  18. 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

  19. 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.

  20. Stem Cells in Liver Diseases and Cancer: Recent Advances on the Path to New Therapies

    PubMed Central

    Rountree, C. Bart; Mishra, Lopa; Willenbring, Holger

    2011-01-01

    Stem cells have potential for therapy of liver diseases, but may also be involved in the formation of liver cancer. Recently, the AASLD Henry M. and Lillian Stratton Basic Research Single Topic Conference “Stem Cells in Liver Diseases and Cancer: Discovery and Promise” brought together a diverse group of investigators to define the status of research on stem cells and cancer stem cells in the liver and identify problems and solutions on the path to clinical translation. This report summarizes the outcomes of the conference and provides an update on recent research advances. Progress in liver stem cell research includes isolation of primary liver progenitor cells (LPC), directed hepatocyte differentiation of primary LPC and pluripotent stem cells, findings of transdifferentiation, disease-specific considerations for establishing a therapeutically effective cell mass, and disease modeling in cell culture. Tumor initiating stem-like cells (TISC) that emerge during chronic liver injury share expression of signaling pathways, including those organized around TGF-β and β-catenin, and surface markers with normal LPC. Recent investigations of the role of TISC in hepatocellular carcinoma have provided insight into the transcriptional and posttranscriptional regulation of hepatocarcinogenesis. Targeted chemotherapies for TISC are in development as a means to overcome cellular resistance and mechanisms driving disease progression in liver cancer. PMID:22030746

  1. [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

  2. 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

  3. 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.

  4. 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

  5. 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. PMID:22175514

  6. 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. PMID:26670806

  7. Plasma cell myeloma--new biological insights and advances in therapy.

    PubMed

    Barlogie, B; Epstein, J; Selvanayagam, P; Alexanian, R

    1989-03-01

    levels) and biology. Further studies of cellular and molecular biology (ie, CAL-LA, H-ras) may reveal those tumor cell features that define clinical entities, response to therapy, and long-term prognosis. The lack of a major advance in prognosis despite the use of more drugs and more intensive regimens justifies the continued use of standard melphalan-prednisone for patients with a highly favorable prognosis, for the very aged, and for those with a short life expectancy due to other major medical problems. However, a radical departure from standard practice is required to improve the prognosis for younger patients with poor risk features.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2465790

  8. Public-health assessment for Advanced Micro Devices No. 915, Sunnyvale, Santa Clara County, California, Region 9. CERCLIS No. CAT080034234. Final report

    SciTech Connect

    Not Available

    1992-07-29

    Advanced Micro Devices, Inc. building 915 (AMD 915) served as an active semiconductor and microprocessor manufacturing facility from 1974 until 1990. AMD 915 is located in Sunnyvale, California in Santa Clara County, approximately four miles south of San Francisco Bay. AMD 915 was included on the National Priorities List (NPL) by the United States Environmental Protection Agency (EPA) in September, 1990. Waste solvents and acid-neutralization liquids contained in two underground storage tanks leaked, causing contamination of subsurface soils and groundwater. The contamination originating from the AMD 915 facility has not migrated off-site and the contaminated groundwater has not impacted any private or municipal drinking water supplies. The underground storage tanks suspected of leaking and some subsurface soils have been removed. A system of groundwater extraction and air stripping/liquid phase carbon adsorption treatment is currently operating at the site to restore groundwater to acceptable drinking water standards. Based on information reviewed, the United States Agency for Toxic Substances and Disease Registry (ATSDR) and the California Department of Health Services (CDHS) conclude that no apparent health hazard exists at the AMD 915 site.

  9. X-ray micro-diffraction studies on biological samples at the BioCAT Beamline 18-ID at the Advanced Photon Source

    PubMed Central

    Barrea, R. A.; Antipova, O.; Gore, D.; Heurich, R.; Vukonich, M.; Kujala, N. G.; Irving, T. C.; Orgel, J. P. R. O.

    2014-01-01

    The small source sizes of third-generation synchrotron sources are ideal for the production of microbeams for diffraction studies of crystalline and non-crystalline materials. While several such facilities have been available around the world for some time now, few have been optimized for the handling of delicate soft-tissue specimens under cryogenic conditions. Here the development of a new X-ray micro-diffraction instrument at the Biophysics Collaborative Access Team beamline 18-ID at the Advanced Photon Source, and its use with newly developed cryo-diffraction techniques for soft-tissue studies, are described. The combination of the small beam sizes delivered by this instrument, the high delivered flux and successful cryo-freezing of rat-tail tendon has enabled us to record data to better than 4 Å resolution. The ability to quickly raster scan samples in the beam allows selection of ordered regions in fibrous samples for markedly improved data quality. Examples of results of experiments obtainable using this instrument are presented. PMID:25178013

  10. 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…

  11. 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. PMID:23570437

  12. Timing of Therapies in the Multidisciplinary Treatment of Locally Advanced Rectal Cancer: Available Evidence and Implications for Routine Practice.

    PubMed

    Sclafani, Francesco; Chau, Ian

    2016-07-01

    A multimodality disciplinary approach is paramount for the management of locally advanced rectal cancer. Over the last decade, (chemo)radiotherapy followed by surgery plus or minus adjuvant chemotherapy has represented the mainstay of treatment for this disease. Nevertheless, robust evidence suggesting the optimal timing and sequence of therapies in this setting has been overall limited. A number of questions are still unsolved including the length of the interval between neoadjuvant radiotherapy and surgery or the timing of systemic chemotherapy. Interestingly, emerging data support the contention that altering sequence or timing or both of the components of this multimodality approach may provide an opportunity to implement treatment strategies that far better address the risk and expectations of individual patients. In this article, we review the available evidence on timing of therapies in the multidisciplinary treatment of locally advanced rectal cancer and discuss the potential implications for routine practice that may derive from a change of the currently accepted treatment paradigm. PMID:27238468

  13. 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.

  14. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

    PubMed Central

    Golan, Talia; Khvalevsky, Elina Zorde; Hubert, Ayala; Gabai, Rachel Malka; Hen, Naama; Segal, Amiel; Domb, Abraham; Harari, Gil; David, Eliel Ben; Raskin, Stephen; Goldes, Yuri; Goldin, Eran; Eliakim, Rami; Lahav, Maor; Kopleman, Yael; Dancour, Alain; Shemi, Amotz; Galun, Eithan

    2015-01-01

    Purpose The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). Methods An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death. Results Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%. Conclusions The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785 PMID:26009994

  15. 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

  16. 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

  17. 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 ...

  18. 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.

  19. 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.

  20. Preoperative induction therapy for locally advanced thymic tumors: a retrospective analysis using the ChART database

    PubMed Central

    Wei, Yucheng; Gu, Zhitao; Fu, Jianhua; Tan, Liejie; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies. Methods Between 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery directly after preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III–IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis. Results Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs. 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs. 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P=0.000), although R0 resection were similar (76.4% vs. 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P=0.000). Conclusions Preoperative neoadjuvant therapy have been used only occasionally in locally advanced thymic malignances. Effective induction therapy leading to tumor downstaging may be beneficial for potentially unresectable diseases, especially in

  1. Diabetic cataracts: different incidence between dogs and cats.

    PubMed

    Salgado, D; Reusch, C; Spiess, B

    2000-06-01

    Diabetes mellitus is one of the most common endocrinopathies in the dog and cat. Diabetic cataract primarily affects the canine species and is rarely observed in the cat. It has been proposed that the incidence of cataracts in diabetic dogs is high because many of these patients have significant hyperglycemia despite insulin therapy. Age, gender, levels of serum glucose (before and during insulin therapy) and cataract formation were evaluated, retrospectively, in 23 dogs and 22 cats with diabetes mellitus. In the canine population, the groups with the highest frequency of presentation were females and sexually intact animals. In contrast, males and neutered animals were the most prevalent groups in the feline diabetic population. Over 80% of diabetic cats and dogs were older than 7 years. Our results confirm the almost total lack of cataracts in diabetic cats, while they were present in more than half of the dogs. A relation between the incidence of cataracts and the correspondent level of hyperglycemia in the canine and feline species could not be established. The estimation of the relative risk for the development of cataracts in diabetic dogs shows that some population groups have a higher probability for suffering from this ocular alteration. A relation between relative risk and the correspondent level of hyperglycemia in the various groups was not found. This fact indicates that other factors are involved in the unequal appearance of diabetic cataracts in dogs and cats. PMID:10892302

  2. Advanced treatment planning methods for efficient radiation therapy with laser accelerated proton and ion beams

    SciTech Connect

    Schell, Stefan; Wilkens, Jan J.

    2010-10-15

    lateral clustering and reduce the number of particles that have to be blocked in the beam delivery system. Furthermore, the optimization routine can be adjusted to reduce the number of dose spots and laser shots. The authors implemented these methods into a research treatment planning system for laser accelerated particles. Results: The authors' proposed methods can decrease the amount of secondary radiation produced when blocking particles with wrong energies or when reducing the total number of particles from one laser shot. Additionally, caused by the efficient use of the beam, the treatment time is reduced considerably. Both improvements can be achieved without extensively changing the quality of the treatment plan since conventional intensity modulated particle therapy usually includes a certain amount of unused degrees of freedom which can be used to adapt to laser specific properties. Conclusions: The advanced beam delivery and treatment planning methods reduce the need to have a perfect laser-based accelerator reproducing the properties of conventional accelerators that might not be possible without increasing treatment time and secondary radiation to the patient. The authors show how some of the differences to conventional beams can be overcome and efficiently used for radiation treatment.

  3. Future directions in risk stratification and therapy for advanced pediatric genitourinary rhabdomyosarcoma.

    PubMed

    Harel, Miriam; Ferrer, Fernando A; Shapiro, Linda H; Makari, John H

    2016-02-01

    Rhabdomyosarcoma (RMS) represents the most common soft tissue sarcoma in infants and children and the third most common pediatric solid tumor, accounting for 5% to 15% of all childhood solid tumors. Of these, 15% to 20% arise from the genitourinary tract, with the most common sites originating from the prostate, bladder, and paratesticular regions, followed by the vagina and uterus. Although upfront radical surgery was used at the initiation of Intergroup RMS Study-I (1972-1978), the treatment paradigm has shifted to include initial biopsy with the goal of organ preservation, systemic chemotherapy for all patients, and local control involving surgical resection with or without radiation therapy for most patients. Collaborative group clinical trials have led to dramatic improvement in survival rates from 1960 to 1996 among patients with low- or intermediate-risk disease; however, outcomes appear to have plateaued in more recent years, and the prognosis for patients with metastatic or relapsed/refractory disease remains poor. Current management goals include minimizing toxicity while maintaining the excellent outcomes in low-risk disease, as well as improving outcomes in patients with intermediate- and high-risk disease. Advances in genetic analysis have allowed further refinement in risk stratification of patients. Perhaps the most significant recent development in RMS research was the discovery of an association of alveolar RMS (ARMS) with translocations t(2;13) and t(1;13). Translocation fusion-positive tumors comprise 80% of ARMS and are more aggressive. Fusion-negative ARMS may have a clinical course similar to embryonal RMS. Future Children's Oncology Group sarcoma studies will likely incorporate fusion status into risk stratification and treatment allocation. Newer radiotherapy modalities hold promise for providing local control of disease while minimizing morbidity. The addition of traditional cytotoxic chemotherapeutic agents does not seem to improve

  4. 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

  5. Current state of ST-segment myocardial infarction: evidence-based therapies and optimal patient outcomes in advanced systems of care.

    PubMed

    Thomas, Joseph L; French, William J

    2014-08-01

    Advances in reperfusion therapy for ST-segment elevation myocardial infarction (STEMI) provide optimal patient outcomes. Reperfusion therapies, including contemporary primary percutaneous coronary intervention, represent decades of clinical evidence development in large clinical trials and national databases. However, rapid identification of STEMI and guideline-directed management of patients across broad populations have been best achieved in advanced systems of care. Current outcomes in STEMI reflect the evolution of both clinical data and idealized health care delivery networks. PMID:25091964

  6. 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

  7. [A patient with unresectable progressive advanced rectal cancer maintained in a state of remission by using combination therapy].

    PubMed

    Kuwabara, Hiroshi; Yamamoto, Yohei; Baba, Hironobu; Mitsuoka, Akito; Nakamura, Hiroshi; Sanada, Takahiro; Baba, Hiroyuki; Goseki, Narihide; Hodotsuka, Masanori; Sano, Tomohiko

    2012-11-01

    We report the case of a patient with unresectable progressive advanced rectal cancer, who has been able to maintain a good quality of life because of combination therapy, including chemoradiotherapy. A 52-year-old woman was diagnosed with progressive locally advanced rectal cancer and invasion of the adnexa of the uterus and the left ureter. No distant metastasis was detected. Colostomy was performed, followed by chemoradiotherapy combined with S-1; then, mFOLFOX6 +bevacizumab (BV) therapy was administered. Aggravation of bilateral hydronephrosis was detected upon completion of 2 courses of treatment, and therefore, percutaneous nephrostomy of the right kidney was performed. After the patient underwent 20 courses of treatment, imaging showed a reduction in the size of the lesion, and the CEA level returned to normal. Later, remission was sustained by sLV5FU2+BV therapy and oral administration of S-1. As a result, we were able to remove the nephrostomy tube from the right kidney in February 2011. Four years after initiation of the treatment, the patient has shown no indication of recurrence. PMID:23267933

  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. 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

  10. Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application.

    PubMed

    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

  11. 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. PMID:25199244

  12. The square cat

    NASA Astrophysics Data System (ADS)

    Putterman, E.; Raz, O.

    2008-11-01

    We present a simple two-dimensional model of a "cat"—a body with zero angular momentum that can rotate itself with no external forces. The model is used to explain the nature of a gauge theory and to illustrate the importance of noncommutative operators. We compare the free-space cat in Newtonian mechanics and the same problem in Aristotelian mechanics at low Reynolds numbers (with the velocity proportional to the force rather than to the acceleration). This example shows the analogy between (angular) momentum in Newtonian mechanics and (torque) force in Aristotelian mechanics. We discuss a topological invariant common to the model in free space and at low Reynolds number.

  13. 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

  14. Targeted therapies for treatment of non-small cell lung cancer-Recent advances and future perspectives.

    PubMed

    Minguet, Joan; Smith, Katherine H; Bramlage, Peter

    2016-06-01

    Non-small cell lung cancer (NSCLC) is one of the most deadly cancers worldwide, with poor prognosis once the disease has progressed past the point at which surgery is a viable option. Whilst chemotherapy has improved survival over recent decades, there is still great need for improvements in treatments for patients with advanced disease. Over the last decade, a variety of such drugs have received market approval for treating NSCLC, with a variety of others in the pipeline. Here, we review the development of targeted therapies for the treatment of advanced or metastatic NSCLC, including those already in clinical practice and those in early trials. The epidermal growth factor receptor (EGFR) inhibitors, gefitinib, erlotinib and afatinib; the anaplastic lymphoma kinase (ALK) inhibitor, crizotinib; and the anti-vascular endothelial growth factor receptor monoclonal antibody, bevacizumab, are already providing improved survival for patients with NSCLC. Moreover, the discovery of EGFR mutations and ALK rearrangements has enabled the identification of patients who are more likely to benefit from a specific drug. The recent approval of the immune checkpoint inhibitor nivolumab, along with the designation of alectinib and MPDL3280A as breakthrough therapies by the FDA, demonstrates how rapidly this area of research is expanding. Over the last decade there has been significant progress made in the treatment of advanced NSCLC, and the large and varied selection of drugs currently undergoing trials provide great promise for improving the prognosis of this highly prevalent and deadly form of cancer. PMID:26537995

  15. Advanced therapies for COPD-What's on the horizon? Progress in lung volume reduction and lung transplantation.

    PubMed

    Trotter, Michael A; Hopkins, Peter M

    2014-11-01

    Advanced chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity. Treatment options beyond conventional medical therapies are limited to a minority of patients. Lung volume reduction surgery (LVRS) although effective in selected subgroups of patients is not commonly undertaken. Morbidity associated with the procedure has contributed to this low utilisation. In response to this, less invasive bronchoscopic lung volume techniques are being developed to attempt to mitigate some of the risks and costs associated with surgery. Of these, endobronchial valve therapy is the most comprehensively studied although the presence of collateral ventilation in a significant proportion of patients has compromised its widespread utility. Bronchial thermal vapour ablation and lung volume reduction (LVR) coils are not dependent on collateral ventilation. These techniques have shown promise in early clinical trials; ongoing work will establish whether they have a role in the management of advanced COPD. Lung transplantation, although effective in selected patients for palliation of symptoms and improving survival, is limited by donor organ availability and economic constraint. Reconditioning marginal organs previously declined for transplantation with ex vivo lung perfusion (EVLP) is one potential strategy in improving the utilisation of donor organs. By increasing the donor pool, it is hoped lung transplantation might be more accessible for patients with advanced COPD into the future. PMID:25478204

  16. Advanced therapies for COPD—What’s on the horizon? Progress in lung volume reduction and lung transplantation

    PubMed Central

    Hopkins, Peter M.

    2014-01-01

    Advanced chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity. Treatment options beyond conventional medical therapies are limited to a minority of patients. Lung volume reduction surgery (LVRS) although effective in selected subgroups of patients is not commonly undertaken. Morbidity associated with the procedure has contributed to this low utilisation. In response to this, less invasive bronchoscopic lung volume techniques are being developed to attempt to mitigate some of the risks and costs associated with surgery. Of these, endobronchial valve therapy is the most comprehensively studied although the presence of collateral ventilation in a significant proportion of patients has compromised its widespread utility. Bronchial thermal vapour ablation and lung volume reduction (LVR) coils are not dependent on collateral ventilation. These techniques have shown promise in early clinical trials; ongoing work will establish whether they have a role in the management of advanced COPD. Lung transplantation, although effective in selected patients for palliation of symptoms and improving survival, is limited by donor organ availability and economic constraint. Reconditioning marginal organs previously declined for transplantation with ex vivo lung perfusion (EVLP) is one potential strategy in improving the utilisation of donor organs. By increasing the donor pool, it is hoped lung transplantation might be more accessible for patients with advanced COPD into the future. PMID:25478204

  17. Device therapy in advanced heart failure: what to put in and what to turn off: remote telemonitoring and implantable hemodynamic devices for advanced heart failure monitoring in the ambulatory setting and the evolving role of cardiac resynchronization therapy.

    PubMed

    Smith, Sakima A; Abraham, William T

    2011-01-01

    Despite evidence based medical and pharmacologic advances the management of heart failure remains challenging, especially in the ambulatory setting. There is an urgent need to develop strategies to reduce hospitalizations and re-admission rates for heart failure in general. This focused review illustrates the potential role for remote telemonitoring and implantable hemodynamic devices to address this significant issue. We also explore the growth of cardiac resynchronization therapy and how it has evolved into another tool in our armamentarium for hemodynamic monitoring. PMID:21906246

  18. [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

  19. [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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances

    PubMed Central

    McLaughlin, Lauren; Cruz, C. Russell; Bollard, Catherine M.

    2015-01-01

    Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

  5. Adoptive T-cell therapies for refractory/relapsed leukemia and lymphoma: current strategies and recent advances.

    PubMed

    McLaughlin, Lauren; Cruz, C Russell; Bollard, Catherine M

    2015-12-01

    Despite significant advancements in the treatment and outcome of hematologic malignancies, prognosis remains poor for patients who have relapsed or refractory disease. Adoptive T-cell immunotherapy offers novel therapeutics that attempt to utilize the noted graft versus leukemia effect. While CD19 chimeric antigen receptor (CAR)-modified T cells have thus far been the most clinically successful application of adoptive T immunotherapy, further work with antigen specific T cells and CARs that recognize other targets have helped diversify the field to treat a broad spectrum of hematologic malignancies. This article will focus primarily on therapies currently in the clinical trial phase as well as current downfalls or limitations. PMID:26622998

  6. Numerical assessment of radiation binary targeted therapy for HER-2 positive breast cancers: advanced calculations and radiation dosimetry

    NASA Astrophysics Data System (ADS)

    Sztejnberg Gonçalves-Carralves, Manuel L.; Jevremovic, Tatjana

    2007-07-01

    In our previous publication (Mundy et al 2006 Phys. Med. Biol. 51 1377) we have described the theoretical assessment of our novel approach in radiation binary targeted therapy for HER-2 positive breast cancers and summarized the future directions in this area of research. In this paper we advanced the numerical analysis to show the detailed radiation dose distribution for various neutron sources in combination with the required boron concentration and allowed radiation skin doses. We once again proved the feasibility of the concept and will use these data and conclusions to start with the experimental verifications.

  7. 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. PMID:26422540

  8. 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.

  9. 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. PMID:26522499

  10. 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

  11. 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

  12. 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

  13. 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

  14. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy

    PubMed Central

    Sultana, A; Tudur Smith, C; Cunningham, D; Starling, N; Tait, D; Neoptolemos, J P; Ghaneh, P

    2007-01-01

    There is no consensus on the management of locally advanced pancreatic cancer, with either chemotherapy or combined modality approaches being employed (Maheshwari and Moser, 2005). No published meta-analysis (Fung et al, 2003; Banu et al, 2005; Liang, 2005; Bria et al, 2006; Milella et al, 2006) has included randomised controlled trials employing radiation therapy. The aim of this systematic review was to compare the following: (i) chemoradiation followed by chemotherapy (combined modality therapy) vs best supportive care (ii) radiotherapy vs chemoradiation (iii) radiotherapy vs combined modality therapy (iv) chemotherapy vs combined modality therapy (v) 5FU-based combined modality treatment vs another-agent-based combined modality therapy. Relevant randomised controlled trials were identified by searching databases, trial registers and conference proceedings. The primary end point was overall survival and secondary end points were progression-free survival/time-to-progression, response rate and adverse events. Survival data were summarised using hazard ratio (HR) and response-rate/adverse-event data with relative risk. Eleven trials involving 794 patients met the inclusion criteria. Length of survival with chemoradiation was increased compared with radiotherapy alone (two trials, 168 patients, HR 0.69; 95% confidence interval (CI) 0.51–0.94), but chemoradiation followed by chemotherapy did not lead to a survival advantage over chemotherapy alone (two trials, 134 patients, HR 0.79; CI 0.32–1.95). Meta-analyses could not be performed for the other comparisons. A survival benefit was demonstrated for chemoradiation over radiotherapy alone. Chemoradiation followed by chemotherapy did not demonstrate any survival advantage over chemotherapy alone, but important clinical differences cannot be ruled out due to the wide CI. PMID:17406358

  15. Cat scratch disease: The story continues

    PubMed Central

    Opavsky, Mary Anne

    1997-01-01

    OBJECTIVE: To present a perspective on the current state of knowledge of cat scratch disease (CSD), including the evidence for Bartonella henselae as the etiological agent, epidemiological and clinical characteristics of the disease, available diagnostic tests and current therapeutic options. DATA SOURCES: MEDLINE search of the literature published from 1966 to 1995 using ‘cat scratch disease’, ‘Bartonella henselae’, ‘Rochalimaea henselae’ as key words and bibliographies of selected papers. DATA EXTRACTION: Selected studies reporting data on etiology, epidemiology, clinical characteristics, diagnosis and therapy of CSD were evaluated. DATA SYNTHESIS AND CONCLUSIONS: Evidence accumulated to date supports B henselae as the etiological agent of CSD. The most significant risk factors for CSD are being licked on the face, scratched or bitten by a kitten and owning a kitten with fleas. Available serological tests can confirm classic CSD and identify B henselae as the cause of more atypical presentations, such as fever of unknown origin, granulomatous hepatitis, encephalitis and osteomyelitis. Symptomatic management is appropriate for isolated lymphadenopathy caused by CSD in healthy individuals; however, antibiotic therapy may be indicated for patients with more severe manifestations of the disease and immunocompromised hosts. Further study of CSD, in particular the epidemiology and therapy, is warranted. A better understanding of the pathogenesis of B henselae infection will have important implications in both immunocompetent and immunocompromised individuals. PMID:22514476

  16. Bone marrow derived stem cells in regenerative medicine as Advanced Therapy Medicinal Products

    PubMed Central

    Astori, Giuseppe; Soncin, Sabrina; Lo Cicero, Viviana; Siclari, Francesco; Sürder, Daniel; Turchetto, Lucia; Soldati, Gianni; Moccetti, Tiziano

    2010-01-01

    Bone marrow derived stem cells administered after minimal manipulation represent an important cell source for cellbased 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 cellbased 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 cellbased 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. PMID:20589167

  17. 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

  18. Sequencing systemic therapies in advanced RCC: is there a best strategy?

    PubMed

    Powles, Tom; Crusz, Shanthini M

    2013-01-01

    There is a strong rationale for sequencing targeted therapy in metastatic clear cell renal cancer. However the timing of the switch and the best agent to switch to remains unclear. Randomized data currently are supportive of the sequence of axitinib, followed by everolimus in those patients in which first-line vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) therapy fails. Everolimus is also justified in the second-line setting, and the overall survival data for sorafenib in VEGF TKI resistant disease is impressive. A degree of cross-resistance appears to exist between all these current agents and has resulted in a drive toward the development of new therapies with novel modes of action. PMID:23714492

  19. Current status of hormone therapy in patients with hormone receptor positive (HR+) advanced breast cancer.

    PubMed

    Dalmau, Elsa; Armengol-Alonso, Alejandra; Muñoz, Montserrat; Seguí-Palmer, Miguel Ángel

    2014-12-01

    The natural history of HR+ breast cancer tends to be different from hormone receptor-negative disease in terms of time to recurrence, site of recurrence and overall aggressiveness of the disease. The developmental strategies of hormone therapy for the treatment of breast cancer have led to the classes of selective estrogen receptor modulators, selective estrogen receptor downregulators, and aromatase inhibitors. These therapeutic options have improved breast cancer outcomes in the metastatic setting, thereby delaying the need for chemotherapy. However, a subset of hormone receptor-positive breast cancers do not benefit from endocrine therapy (intrinsic resistance), and all HR+ metastatic breast cancers ultimately develop resistance to hormonal therapies (acquired resistance). Considering the multiple pathways involved in the HR network, targeting other components of pathologically activated intracellular signaling in breast cancer may prove to be a new direction in clinical research. This review focuses on current and emerging treatments for HR+ metastatic breast cancer. PMID:25311296

  20. Present Advances and Future Perspectives of Molecular Targeted Therapy for Osteosarcoma.

    PubMed

    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

  1. Metastasectomy Following Targeted Therapy in Patients with Advanced Renal Cell Carcinoma

    PubMed Central

    Karam, Jose A.; Rini, Brian I.; Varella, Leticia; Garcia, Jorge A.; Dreicer, Robert; Choueiri, Toni K.; Jonasch, Eric; Matin, Surena F.; Campbell, Steven C.; Wood, Christopher G.; Tannir, Nizar M.

    2015-01-01

    Purpose Metastasectomy is often incorporated in the overall management of patients with metastatic renal cell carcinoma (mRCC). While this approach has been studied in the immunotherapy era, only a few cases have been described in the targeted therapy era. Therefore, we evaluated the role of metastasectomy in patients with mRCC who received prior targeted therapy. Patients and Methods Patients who underwent consolidative metastasectomy following targeted therapy at three institutions from 2004 to 2009 were evaluated in this retrospective study. All patients received at least one cycle of targeted therapy prior to surgical resection of all visible disease. Results Twenty-two patients were identified. Sites of metastasectomy included the retroperitoneum in 12 patients, lung in 6 patients, adrenal gland in 2 patients, bowel in 2 patients, and mediastinum, bone, brain, and IVC thrombus in 1 patient each. A total of 6 postoperative complications were observed in 4 patients within 12 weeks from surgery, all of which resolved with appropriate management. Postoperatively, nine patients received at least one targeted therapy. Eleven patients recurred at a median of 42 weeks from metastasectomy and another eleven patients have not experienced a recurrence at a median of 43 weeks from metastasectomy. Twenty-one patients were alive at a median follow-up of 109 weeks and one patient died of RCC 105 weeks after metastasectomy. Conclusions In a cohort of selected patients with limited tumor burden after treatment with targeted agents, consolidative metastasectomy is feasible with acceptable morbidity. Significant time off targeted therapy and long-term tumor-free status are possible with this approach. PMID:21167518

  2. Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

    PubMed Central

    Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

    2015-01-01

    Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

  3. Advances in adjuvant systemic therapy for non-small-cell lung cancer.

    PubMed

    Leong, David; Rai, Rajat; Nguyen, Brandon; Lee, Andrew; Yip, Desmond

    2014-10-10

    Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies. PMID:25302167

  4. 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

  5. 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.

  6. Prognostic implications of immunohistochemistry markers for EGFR-TKI therapy in Chinese patients with advanced lung adenocarcinoma harboring EGFR mutations

    PubMed Central

    Zhang, Ruiguang; Li, Yan; Nie, Xiu; Dong, Xiaorong; Wu, Gang

    2016-01-01

    Background Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict dramatic clinical responses to tyrosine kinase inhibitor (TKI) treatment. The conclusion on EGFR mutation-specific antibodies by immunohistochemistry (IHC) is not consistent. We evaluated the clinical availability of EGFR mutation-specific antibodies, investigating the prediction role of mutant EGFRs and other IHC markers in TKI therapy in patients with advanced lung adenocarcinoma. Materials and methods We analyzed 637 primary lung adenocarcinomas from an unselected Chinese population. For IHC, antibodies against EGFR exon 19 E746_A750 deletions, exon 21 L858R mutations, thyroid transcription factor-1 (TTF-1), and Napsin-A were applied. Positivity was defined as staining score >0. Results Specificities of E746_A750 and L858R antibodies were 99.6% and 99.3%, while sensitivities were 86.0% and 82.7%, respectively. Tumors with Napsin-A positivity, TTF-1 positivity, EGFR mutations, and lepidic pattern showed a lower marker of proliferation index (Ki67). Higher expression scores of mutant EGFR protein, TTF-1 positivity, lower Ki67 proliferation index, and lepidic pattern were associated with longer progression-free survival. Conclusion High scores of mutant EGFR, Napsin-A positivity, TTF-1 positivity, lower Ki67 index, and lepidic pattern were favorable predictors for TKI therapy in patients with advanced lung adenocarcinoma. PMID:26848271

  7. 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.

  8. Designing post-graduate Master's degree programs: the advanced training program in Dental Functional Analysis and Therapy as one example

    PubMed Central

    Ratzmann, Anja; Ruge, Sebastian; Ostendorf, Kristin; Kordaß, Bernd

    2014-01-01

    Introduction: The decision to consolidate European higher education was reached by the Bologna Conference. Based on the Anglo-American system, a two-cycle degree program (Bachelor and Master) has been introduced. Subjects culminating in a state examination, such as Medicine and Dentistry, were excluded from this reform. Since the state examination is already comparable in its caliber to a Master’s degree in Medicine or Dentistry, only advanced Master’s degree programs with post-graduate specializations come into consideration for these subjects. In the field of dentistry numerous post-graduate study programs are increasingly coming into existence. Many different models and approaches are being pursued. Method: Since the 2004-2005 winter semester, the University of Greifswald has offered the Master’s degree program in Dental Functional Analysis and Therapy. Two and a half years in duration, this program is structured to allow program participation while working and targets licensed dentists who wish to attain certified skills for the future in state-of-the-art functional analysis and therapy. Aim: The design of this post-graduate program and the initial results of the evaluation by alumni are presented here. Conclusion: Our experiences show that the conceptual idea of an advanced Master’s program has proved successful. The program covers a specialty which leads to increased confidence in handling challenging patient cases. The sharing of experiences among colleagues was evaluated as being especially important. PMID:24872853

  9. Persistent high mortality in advanced HIV/TB despite appropriate antiretroviral and antitubercular therapy: an emerging challenge.

    PubMed

    Bisson, Gregory P; Zetola, Nicola; Collman, Ronald G

    2015-03-01

    Approximately 1.1 million, or 13 %, of all TB cases in 2013 were coinfected with HIV, and in some African countries, such as Botswana and Swaziland, 60-80 % of TB cases are coinfected with HIV. Effective therapies for both HIV and TB exist, yet patients presenting with TB and advanced HIV still experience high rates of morbidity and mortality despite initiation of both antitubercular and antiretroviral therapy (ART). Previous reviews and research have focused largely on TB-associated immune reconstitution inflammatory syndrome (TB-IRIS) as a type of complicated outcome on ART in advanced HIV/TB, but recent data indicate that immunologic failure despite suppressive ART is associated with early mortality. In this review, we examine recent findings regarding early mortality in HIV/TB and emerging concepts in the pathophysiology of TB-IRIS, in order to provide an integrated view of factors determining outcomes in coinfected people as well as highlight key needs for future research and therapeutic development. PMID:25772785

  10. 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.

  11. Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

    SciTech Connect

    Willett, C.G.; Shellito, P.C.; Tepper, J.E.; Eliseo, R.; Convery, K.; Wood, W.C. )

    1991-03-15

    A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

  12. Advanced therapies using autologous bone marrow cells for chronic liver disease.

    PubMed

    Takami, Taro; Terai, Shuji; Sakaida, Isao

    2012-07-01

    The radical treatment currently for decompensated liver cirrhosis is still liver transplantation. However, liver transplants are not widely performed worldwide and development of genuine regeneration therapy for liver cirrhosis is an urgent task. We have developed a novel murine model [the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model], and reported that infused GFP-positive bone marrow cells repopulated cirrhotic liver. Moreover, repopulated bone marrow cells ameliorated liver fibrosis through higher expression of matrix metalloproteinase-9, consistent with improved liver functions and better survival rate. Based on these findings, we started a clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhotic patients, and reported the efficacy and the safety of this approach. On the other hand, various other clinical studies for liver disease have been also reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor (G-CSF), portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow derived mesenchymal stem cells (MSCs). Effectiveness of these approaches has been shown in some patients. We provided here an overview of the current status of liver regeneration therapies including our results of the murine GFP/CCl4 model and ABMi therapy for liver cirrhosis and future prospects. PMID:22846198

  13. [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. PMID:21698534

  14. Baseline MELD Score Predicts Hepatic Decompensation during Antiviral Therapy in Patients with Chronic Hepatitis C and Advanced Cirrhosis

    PubMed Central

    Dultz, Georg; Seelhof, Martin; Herrmann, Eva; Welker, Martin-Walter; Friedrich-Rust, Mireen; Teuber, Gerlinde; Kronenberger, Bernd; von Wagner, Michael; Vermehren, Johannes; Sarrazin, Christoph; Zeuzem, Stefan; Hofmann, Wolf Peter

    2013-01-01

    Background and Aims In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined. Methods In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks). Results Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001). Conclusions Our data suggest that the

  15. Gene therapy for cardiovascular disease: advances in vector development, targeting, and delivery for clinical translation

    PubMed Central

    Rincon, Melvin Y.; VandenDriessche, Thierry; Chuah, Marinee K.

    2015-01-01

    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 Ca2+-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. PMID:26239654

  16. 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. PMID:26239654

  17. Original Article A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer

    PubMed Central

    Cohen, Steven J.; Zalupski, Mark M.; Modiano, Manuel R.; Conkling, Paul; Patt, Yehuda Z.; Davis, Peg; Dorr, Robert T.; Boytim, Michelle L.; Hersh, Evan M.

    2010-01-01

    Purpose Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Methods Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n=19; imexon 200 or 280 mg/m2 intravenously (IV) over 30 minutes days 1–5, 15–19 and gemcitabine 800 or 1,000 mg/m2 IV over 30 minutes on days 1,8,15 every 28 days) or regimen B (n=86; imexon 280–1,300 mg/m2 IV over 30–60 minutes days 1, 8, and 15 and gemcitabine 1,000 mg/m2 IV over 30 minutes on days 1, 8, and 15 every 28 days). Results One hundred-five patients received 340 treatment cycles (median 2, range 1–16). Patient characteristics: median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half-life 69 minutes at the MTD and no alteration of gemcitabine pharmacokinetics. Conclusions The recommended phase II dose of imexon is 875 mg/m2 with gemcitabine 1,000 mg/m2. DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer. PMID:19855966

  18. 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.

  19. 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

  20. Folliculogenesis in the domestic cat (Felis catus).

    PubMed

    Bristol-Gould, Sarah; Woodruff, Teresa K

    2006-07-01

    The dynamic regulation of mammalian folliculogenesis is a key component of the reproductive process. Traditionally, the rodent had been used as a model to study ovarian function and reproductive physiology due to the availability of animals, their relatively short cycle length, high rate of fecundity and short generation interval. We maintain that much basic information can be determined using domestic cat ovaries retrieved from local veterinary clinics following routine spaying, without having the expense of maintaining a colony of laboratory cats. Studies of normal feline reproductive physiology and advances in reproductive technology may be extrapolated for use in endangered non-domestic felids. Increased understanding of feline reproduction will be beneficial to veterinary medicine, and to groups working to control feral cat populations. It is important to examine reproductive mechanisms in alternative animal models as there are a vast number of threatened and endangered species in which we lack the critical reproductive information needed to assist in preserving their long-term survival. PMID:16620931

  1. [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

  2. 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…

  3. 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...

  4. Retrobulbar lymphoma associated with a ballistic foreign body in a cat.

    PubMed

    Robat, C; Bemelmans, I; Marescaux, L

    2016-04-01

    A seven-year-old domestic shorthair cat, adopted 5 years previously with a corneal perforation of the left eye, was presented for investigation of a left orbital mass. Computed tomography revealed a metallic foreign body within a contrast-enhancing, heterogeneous orbital mass. Large cell lymphoma was diagnosed from a fine needle aspirate. The cat staged negatively and was treated with L-asparaginase, prednisolone and three fractions of radiation therapy. A rapid clinical remission was obtained and the cat remained in remission for 3 years after therapy. This is the first report of large cell lymphoma likely occurring secondary to a foreign body. PMID:26290463

  5. Practical Guidance on How to Handle Levodopa/Carbidopa Intestinal Gel Therapy of Advanced PD in a Movement Disorder Clinic

    PubMed Central

    Pedersen, Stephen Wørlich; Clausen, Jesper; Gregerslund, Mie Manon

    2012-01-01

    Continuous dopaminergic delivery is recognized for the capacity to ameliorate symptoms in Parkinson’s disease (PD). In advanced PD the short comings of orally administered Levodopa/Carbidopa include fluctuations resulting in unstable effect and dyskinesia. Levodopa/Carbidopa intestinal gel, LCIG, (Duodopa®, Abbott Laboratories) is delivered continuously through a percutaneous endoscopic gastrostomy with the inner tube placed in the duodenum by means of a device (CADD legacy Duodopa pump (CE 0473)). The therapy implies continuous dopaminergic delivery directly to the duodenum and is therefore unaffected by gastric emptying and represents a major adjuvant in the treatment of advanced PD with significant improvement in motor and non-motor symptoms. The aim of this paper is to suggest the prerequisites for a LCIG clinic and propose a feasible set-up and lean organization of a movement disorder clinic. Secondly, the paper proposes practical handling of patients in LCIG treatment for advanced PD based on experience and initiation of LCIG treatment and follow-up in forty patients. PMID:22848335

  6. 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

  7. 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

  8. 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

  9. 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.

  10. Systemic-constructivist couple therapy (SCCT): Description of approach, theoretical advances, and published longitudinal evidence.

    PubMed

    Reid, David W; Doell, Faye K; Dalton, E Jane; Ahmad, Saunia

    2008-12-01

    The systemic-constructivist approach to studying and benefiting couples was derived from qualitative and quantitative research on distressed couples over the past 10 years. Systemic-constructivist couple therapy (SCCT) is the clinical intervention that accompanies the approach. SCCT guides the therapist to work with both the intrapersonal and the interpersonal aspects of marriage while also integrating the social-environmental context of the couple. The theory that underlies SCCT is explained, including concepts such as we-ness and interpersonal processing. The primary components of the therapy are described. Findings described previously in an inaugural monograph containing extensive research demonstrating the long-term utility of SCCT are reviewed. (PsycINFO Database Record (c) 2010 APA, all rights reserved). PMID:22122535

  11. Ewing's Sarcoma: Development of RNA Interference-Based Therapy for Advanced Disease

    PubMed Central

    Simmons, Olivia; Maples, Phillip B.; Senzer, Neil; Nemunaitis, John

    2012-01-01

    Ewing's sarcoma tumors are associated with chromosomal translocation between the EWS gene and the ETS transcription factor gene. These unique target sequences provide opportunity for RNA interference(i)-based therapy. A summary of RNAi mechanism and therapeutically designed products including siRNA, shRNA and bi-shRNA are described. Comparison is made between each of these approaches. Systemic RNAi-based therapy, however, requires protected delivery to the Ewing's sarcoma tumor site for activity. Delivery systems which have been most effective in preclinical and clinical testing are reviewed, followed by preclinical assessment of various silencing strategies with demonstration of effectiveness to EWS/FLI-1 target sequences. It is concluded that RNAi-based therapeutics may have testable and achievable activity in management of Ewing's sarcoma. PMID:22523703

  12. 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

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. Efficacy of RetroNectin-activated cytokine-induced killer cell therapy in the treatment of advanced hepatocelluar carcinoma

    PubMed Central

    LI, WEI; WANG, YAOMEI; KELLNER, DANIEL B.; ZHAO, LINGDI; XU, LINPING; GAO, QUANLI

    2016-01-01

    The present study aimed to investigate the efficacy of RetroNectin-activated cytokine-induced killer cell (R-CIK) therapy in advanced hepatocellular carcinoma patients as compared with conventional chemotherapy, a comparison that has not yet been thoroughly studied. From January 2010 to October 2013, 74 patients with an initial diagnosis of advanced hepatocelluar carcinoma were enrolled in the study. Patients were assigned to one of two treatment arms: patients in arm 1 (n=37) received R-CIK treatment as the first line therapy, whereas those in arm 2 (n=37) received chemotherapy as the first line treatment. The primary end point measured in this study was median overall survival (mOS). Median progression-free survival time (mPFS) and 1- and 2-year survival rates were recorded as secondary end points. Kaplan-Meier analysis was performed on all mOS and mPFS data, and treatment hazard ratios were established using the Cox proportional hazards model. The 1-year survival rate in treatment arm 1 was 42.47% vs. 24.89% in arm 2 (95% CI, 24.91–59.01% vs. 12.10–40.02%, P=0.066); the 2-year survival rates were 21.24 and 5.53% (95% CI, 4.60–45.86 vs. 0.46–21.06%, P=0.106) in arms 1 and 2, respectively; the mPFS in arm 1 was 4.37 vs. 3.90 (x2=0.182, P=0.670) in arm 2; and the mOS in arm 1 was 14.03 months vs. 9.46 months(x2=4.406, P=0.036) in arm 2. Calculations of univariate analyses of arm 1, R-CIK cycles ≥6, KPS >70, AFP ≤400 ng/ml, and findings of no vascular invasion and no extra-hepatic metastasis were potential predictive factors (P<0.05). Calculations from multivariate analyses similarly identified these factors as potentially having predictive value (P<0.05). The main adverse effects of R-CIK therapy included fever and headache pain. R-CIK treatment may prolong mOS in advanced hepatocellular carcinoma patients compared with conventional chemotherapy. Patients who underwent ≥6 cycles of R-CIK, had KPS scores >70, AFP ≤400 ng/ml, displayed no evidence of

  19. 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

  20. Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

    PubMed Central

    Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

    2016-01-01

    Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

  1. Phase II Trial of Goserelin and Exemestane Combination Therapy in Premenopausal Women With Locally Advanced or Metastatic Breast Cancer

    PubMed Central

    Wang, Jiayu; Xu, Binghe; Yuan, Peng; Ma, Fei; Li, Qing; Zhang, Pin; Cai, Ruigang; Fan, Ying; Luo, Yang; Li, Qiao

    2015-01-01

    Abstract A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinizing hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported. We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg goserelin every 4 weeks along with 25 mg exemestane daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for ≥6 months. The median PFS was 13 months (range: 2–42 months). The median DOR was 8 months (range: 2–40 months). Two patients achieved CR (4.5%), and 15 patients experienced PR (34.1%). Fifteen patients (34.1%) had SD ≥6 months. The ORR was 38.6%, and the CBR was 65.9%. Primary progressive disease occurred in 15 patients (34.1%). Five patients (11.4%) died during the study period. Because a few patients have died, the median OS has not been reached. Drug therapy was well tolerated. The most frequent grade-3 adverse events were arthralgia (18.2%), skin rash (6.8%), and myalgia (4.5%). No participants withdrew from the study due to drug toxicity. This study suggested that goserelin and exemestane might be highly effective and well-tolerated regimens in premenopausal women with hormone-responsive, locally advanced or MBC. PMID:26131799

  2. Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice

    PubMed Central

    Liang, Yi-Hsin; Shao, Yu-Yun; Liao, Bin-Chi; Lee, Ho-Sheng; Yang, James Chih-Hsin; Chen, Ho-Min; Chiang, Chun-Ju; Cheng, Ann-Lii; Lai, Mei-Shu

    2016-01-01

    Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan. Methods:We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients. Results:A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001). Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type. PMID:27471567

  3. 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.

  4. Translational research in immune and inflammatory diseases; what are the challenges, expected advances, and innovative therapies?

    PubMed

    Joubert, Jean-Michel; Gottenberg, Jacques-Eric; Paintaud, Gilles; Augendre-Ferrante, Béatrice; Cans, Christophe; Cellier, Dominique; Chevalier, Marie-Pierre; Diaz, Isabelle; Filipecki, Jamila; Kahn, Jean-Emmanuel; Le Men, Johan; Mulleman, Denis; Urbain, Rémi; Vasmant, Daniel

    2014-01-01

    Despite very different aetiologies and clinical expressions, advancing knowledge in the physiopathology and treatment of immune and inflammatory diseases (IID) prompts us to consider them as a whole. These are chronic, often incapacitating and painful illnesses that progress and destroy organs. Management by discipline too often leads to erroneous diagnoses and sometimes inappropriate treatment. More integrated translational research would further understanding of the complex relationships between cytokines and organ damage, which vary with the conditions and patients, making it possible to develop new biomarkers and personalize treatment. The research in France has very many strengths but its organization is fragmented. Better coordinated research into IID, which could be based on creating a strategic valorization field (domaine de valorisation stratégique, DVS) and thematic multi-organization institute (Institut thématique multi-organismes ITMO), would advance patient management. PMID:25099671

  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. Like herding cats.

    PubMed

    Muller-Smith, P

    1997-12-01

    In an effort to be a good manager, it is easy to lose sight of the fact that knowledge workers require a unique approach from their manager. Because nurses are independent and capable individuals that prosper in an environment that recognizes them as knowledge workers, nurse managers often find that traditional management techniques are not sufficient. Trying to manage all of the nurses on a unit as a single group is much like trying to herd cats. It might be less frustrating for the nurse manager to lead gently rather than manage with a firm hand. Warren Bennis suggests that this approach may provide a valuable key to successfully managing in a world of constant change. PMID:9464034

  7. Neurolymphomatosis in a cat.

    PubMed

    Sakurai, Masashi; Azuma, Kazushi; Nagai, Arata; Fujioka, Toru; Sunden, Yuji; Shimada, Akinori; Morita, Takehito

    2016-07-01

    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

  8. Current state-of-the-art of device therapy for advanced heart failure

    PubMed Central

    Lee, Lawrence S.; Shekar, Prem S.

    2014-01-01

    Heart failure remains one of the most common causes of morbidity and mortality worldwide. The advent of mechanical circulatory support devices has allowed significant improvements in patient survival and quality of life for those with advanced or end-stage heart failure. We provide a general overview of past and current mechanical circulatory support devices encompassing options for both short- and long-term ventricular support. PMID:25559828

  9. 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

  10. 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

  11. Human retinal gene therapy for Leber congenital amaurosis shows advancing retinal degeneration despite enduring visual improvement.

    PubMed

    Cideciyan, Artur V; Jacobson, Samuel G; Beltran, William A; Sumaroka, Alexander; Swider, Malgorzata; Iwabe, Simone; Roman, Alejandro J; Olivares, Melani B; Schwartz, Sharon B; Komáromy, András M; Hauswirth, William W; Aguirre, Gustavo D

    2013-02-01

    Leber congenital amaurosis (LCA) associated with retinal pigment epithelium-specific protein 65 kDa (RPE65) mutations is a severe hereditary blindness resulting from both dysfunction and degeneration of photoreceptors. Clinical trials with gene augmentation therapy have shown partial reversal of the dysfunction, but the effects on the degeneration are not known. We evaluated the consequences of gene therapy on retinal degeneration in patients with RPE65-LCA and its canine model. In untreated RPE65-LCA patients, there was dysfunction and degeneration of photoreceptors, even at the earliest ages. Examined serially over years, the outer photoreceptor nuclear layer showed progressive thinning. Treated RPE65-LCA showed substantial visual improvement in the short term and no detectable decline from this new level over the long term. However, retinal degeneration continued to progress unabated. In RPE65-mutant dogs, the first one-quarter of their lifespan showed only dysfunction, and there was normal outer photoreceptor nuclear layer thickness retina-wide. Dogs treated during the earlier dysfunction-only stage showed improved visual function and dramatic protection of treated photoreceptors from degeneration when measured 5-11 y later. Dogs treated later during the combined dysfunction and degeneration stage also showed visual function improvement, but photoreceptor loss continued unabated, the same as in human RPE65-LCA. The results suggest that, in RPE65 disease treatment, protection from visual function deterioration cannot be assumed to imply protection from degeneration. The effects of gene augmentation therapy are complex and suggest a need for a combinatorial strategy in RPE65-LCA to not only improve function in the short term but also slow retinal degeneration in the long term. PMID:23341635

  12. Transoral Laser Microsurgery (TLM) ± Adjuvant Therapy for Advanced Stage Oropharyngeal Cancer: Outcomes and Prognostic Factors

    PubMed Central

    Rich, Jason T.; Milov, Simon; Lewis, James S.; Thorstad, Wade L.; Adkins, Douglas R.; Haughey, Bruce H.

    2013-01-01

    Objectives/Hypothesis Document survival, prognostic variables, and functional outcomes of patients with AJCC stage III or IV oropharyngeal cancer, treated with transoral laser microsurgery (TLM) ± adjuvant therapy. Study Design Analysis of prospectively assembled data pertaining to the above-described patient cohort. Methods Patients treated with TLM for AJCC stage III or IV oropharyngeal cancer at Washington University School of Medicine from 1996 to 2006 were followed for a minimum of 2 years. Recurrence, survival, functional, and human papilloma virus data were analyzed. Results Eighty-four patients met inclusion criteria. Mean follow-up was 52.6 months. Overall AJCC stages were: III 15% and IV 85%. T stages were T1–2, 74%; T3–4, 26%. Eighty-three patients underwent neck dissection, 50 received adjuvant radiotherapy, and 28 received adjuvant chemoradiotherapy. Overall survival at 2 and 5 years was 94% and 88%, respectively. Disease-specific survival at 2 and 5 years was 96% and 92%, respectively. Six patients recurred (7%): locally (one), regionally (four), and distant (five). T stage, positive margins, and p16 status significantly impacted survival. The addition of adjuvant chemo-therapy in high-risk patients did not significantly impact survival. Five patients (6%) had major surgical complications, but without mortality. Eighty-one percent of patients had acceptable swallowing function at last follow-up. Immediately postoperatively, 17% required G-tubes, which dropped to 3.4% of living patients at 3 years. Conclusions In this population, our findings validate TLM ± adjuvant therapy as a highly effective strategy for survival, locoregional control, and swallowing recovery in AJCC stage III and IV oropharyngeal cancer. Our finding also show that p16 positivity improves survival. PMID:19572271

  13. Carbon ion therapy for advanced sinonasal malignancies: feasibility and acute toxicity

    PubMed Central

    2011-01-01

    Purpose To evaluate feasibility and toxicity of carbon ion therapy for treatment of sinonasal malignancies. First site of treatment failure in malignant tumours of the paranasal sinuses and nasal cavity is mostly in-field, local control hence calls for dose escalation which has so far been hampered by accompanying acute and late toxicity. Raster-scanned carbon ion therapy offers the advantage of sharp dose gradients promising increased dose application without increase of side-effects. Methods Twenty-nine patients with various sinonasal malignancies were treated from 11/2009 to 08/2010. Accompanying toxicity was evaluated according to CTCAE v.4.0. Tumor response was assessed according to RECIST. Results Seventeen patients received treatment as definitive RT, 9 for local relapse, 2 for re-irradiation. All patients had T4 tumours (median CTV1 129.5 cc, CTV2 395.8 cc), mostly originating from the maxillary sinus. Median dose was 73 GyE mostly in mixed beam technique as IMRT plus carbon ion boost. Median follow- up was 5.1 months [range: 2.4 - 10.1 months]. There were 7 cases with grade 3 toxicity (mucositis, dysphagia) but no other higher grade acute reactions; 6 patients developed grade 2 conjunctivits, no case of early visual impairment. Apart from alterations of taste, all symptoms had resolved at 8 weeks post RT. Overall radiological response rate was 50% (CR and PR). Conclusion Carbon ion therapy is feasible; despite high doses, acute reactions were not increased and generally resolved within 8 weeks post radiotherapy. Treatment response is encouraging though follow-up is too short to estimate control rates or evaluate potential late effects. Controlled trials are warranted. PMID:21466696

  14. Spinal cord compression after radiolabeled metaiodobenzylguanidine analogue therapy in advanced malignant insulinoma.

    PubMed

    Feitosa, Alina Coutinho Rodrigues; Castro Júnior, Dálvaro Oliveira de; Rocha Filho, José; Moura, Melba; Andrade, Marcony Queiroz; Sanches, Adelina

    2015-04-01

    Malignant insulinomas are frequently diagnosed at a late stage. Medical management is necessary to slow progression of the disease and control of hypoglycemic symptoms when cure by surgical treatment is not possible. Multimodal treatment, in these cases, has been used with variable clinical response. We describe a 68-yr-old woman who presented response failure to usual treatment and was alternatively treated with radiolabeled metaiodobenzylguanidine ([131I]-MIBG) analogue therapy with development of neurologic complications. We also present a review of the current role of [131I]-MIBG treatment in insulinomas. PMID:25993683

  15. [Advances in the research of early goal-directed therapy in severe sepsis and septic shock].

    PubMed

    Sun, W; Yuan, H X; An, Y Z

    2016-05-20

    Nowadays, severe infection has become one of the common problems in clinic. The morbidity of severe sepsis and septic shock is increasing, which becomes a big threat to patients with burn wounds or chronic diseases. It has become a key subject about how to cure severe sepsis and septic shock. In recent years, mortality of patients in such condition has declined slightly, which might be attributed to the application of early goal-directed therapy (EGDT) in certain degree. This article reviews application of EGDT in severe sepsis and septic shock, in order to analyze its effectiveness and boundedness, as well as predict its development. PMID:27188487

  16. 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. PMID:26395136

  17. The legal landscape for advanced therapies: material and institutional implementation of European Union rules in France and the United Kingdom.

    PubMed

    Mahalatchimy, Aurélie; Rial-Sebbag, Emmanuelle; Tournay, Virginie; Faulkner, Alex

    2012-01-01

    In 2007, the European Union adopted a lex specialis, Regulation (EC) No. 1394/2007 on advanced therapy medicinal products (ATMPs), a new legal category of medical product in regenerative medicine. The regulation applies to ATMPs prepared industrially or manufactured by a method involving an industrial process. It also provides a hospital exemption, which means that medicinal products not regulated by EU law do not benefit from a harmonized regime across the European Union but have to respect national laws. This article describes the recent EU laws, and contrasts two national regimes, asking how France and the United Kingdom regulate ATMPs which do and do not fall under the scope of Regulation (EC) No. 1394/2007. What are the different legal categories and their enforceable regimes, and how does the evolution of these highly complex regimes interact with the material world of regenerative medicine and the regulatory bodies and socioeconomic actors participating in it? PMID:22530249

  18. Pathology, Pathogenesis and Therapy of Growth Hormone (GH)-producing Pituitary Adenomas: Technical Advances in Histochemistry and Their Contribution

    PubMed Central

    Osamura, Robert Y.; Egashira, Noboru; Kajiya, Hanako; Takei, Mao; Tobita, Maya; Miyakoshi, Takashi; Inomoto, Chie; Takekoshi, Susumu; Teramoto, Akira

    2009-01-01

    Growth hormone (GH)-producing adenomas (GHomas) are one of the most frequently-occurring pituitary adenomas. Differentiation of hormone-producing cells in the pituitary gland is regulated by transcription factors and co-factors. The transcription factors include Pit-1, Prop-1, NeuroD1, Tpit, GATA-2, SF-1. Aberrant expression of transcription factors such as Pit-1 results in translineage expression of GH in adrenocorticotropic hormone-producing adenomas (ACTHomas). This situation has been substantiated by GFP-Pit-1 transfection expression in the AtT20 cell line. Experimentally, GHomas have been induced in GH-releasing hormone (GHRH) or Prop-1 transgenic animals. Immunohistochemical detection of somatostatin receptor (SSTR2a) has recently emphasized their role in the response of GHomas to somatostatin analogue therapy. In this review, the advances in technology and their contribution to cell biology and medical practice are discussed. PMID:19759870

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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. PMID:24802656

  5. 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

  6. 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

  7. Bottlenecks in the Efficient Use of Advanced Therapy Medicinal Products Based on Mesenchymal Stromal Cells

    PubMed Central

    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. PMID:26273307

  8. Patient-Specific Age: The Other Side of the Coin in Advanced Mesenchymal Stem Cell Therapy.

    PubMed

    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

  9. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    SciTech Connect

    Tey, Jeremy . E-mail: Jeremy_Tey@mail.nhg.com.sg; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-02-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

  10. Advances in Radiation Therapy for Primary and Metastatic Adult Soft Tissue Sarcomas.

    PubMed

    Blumenfeld, Philip; Sen, Neilayan; Abrams, Ross; Wang, Dian

    2016-06-01

    Soft tissue sarcomas (STS) consist of a heterogeneous group of rare malignancies arising from mesenchymal origin. While surgical resection is the primary treatment for STS, the use of radiotherapy (RT) as an adjunctive modality has been shown to improve oncologic outcomes. Technologic improvements, such as image guidance and intensity-modulated radiotherapy that significantly improve both the precision and delivery of RT, have led to the reduction of long-term RT toxicities without compromising outcomes. This review addresses these technologic advancements as well as discussing the most current updates regarding the use of brachytherapy, charged particles, and novel agents with RT. PMID:27113370

  11. Advances in mesenchymal stem cell-mediated gene therapy for cancer

    PubMed Central

    2010-01-01

    Mesenchymal stem cells have a natural tropism for tumours and their metastases, and are also considered immunoprivileged. This remarkable combination of properties has formed the basis for many studies investigating their potential as tumour-specific delivery vehicles for suicide genes, oncolytic viruses and secreted therapeutic proteins. The aim of the present review is to discuss the range of approaches that have been used to exploit the tumour-homing capacity of mesenchymal stem cells for gene delivery, and to highlight advances required to realize the full potential of this promising approach. PMID:20699014

  12. Congenital hypothyroidism of dogs and cats: a review.

    PubMed

    Bojanic, K; Acke, E; Jones, B R

    2011-05-01

    Congenital hypothyroidism is a rare and underdiagnosed congenital endocrine disorder in dogs and cats and the true incidence is unknown. The disorder may cause a range of clinical signs depending on the primary defect, which affect production of thyroid hormones; some cases present when adult. Hallmark clinical signs of congenital hypothyroidism are mental impairment and skeletal developmental abnormalities, resulting in disproportionate dwarfism; goitre may or may not be present. Documented causes of congenital hypothyroidism in dogs include deficiency of, or unresponsiveness to, thyrotropin-releasing hormone (TRH) or thyroid-stimulating hormone (TSH), thyroid dysgenesis, dyshormonogenesis and iodine deficiency. In cats, TSH unresponsiveness, thyroid dysgenesis, dyshormonogenesis and iodine deficiency have been confirmed. Adequate replacement therapy results in a successful outcome in the majority of cases, especially when started early in life, as permanent developmental abnormalities can be prevented. This review describes reported cases in dogs and cats, diagnostic investigation, and recommendations for treatment. PMID:21541884

  13. Actinomyces endogenous endophthalmitis in a cat following multiple dental extractions.

    PubMed

    Westermeyer, Hans D; Ward, Daniel A; Whittemore, Jacqueline C; Lyons, Jeremiah A

    2013-11-01

    An 8-year-old, brachycephalic, mixed breed cat underwent full mouth tooth extractions for the treatment of tooth root abscessation. Subsequently, the cat developed anterior uveitis refractory to topical therapy that eventually necessitated enucleation. Actinomyces species were isolated from both the tooth root abscesses and the anterior chamber after enucleation. Histopathology of the enucleated eye revealed panophthalmitis with abundant intralesional bacteria morphologically consistent with Actinomyces. Between the time of tooth root extraction and enucleation (20 weeks), the cat was diagnosed with hyperthyroidism and treated with oral steroids for inflammatory bowel syndrome. We believe this report represents a rare case of endogenous endophthalmitis secondary to dental disease, possibly precipitated by concurrent immunosuppression. PMID:23281798

  14. 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

  15. Overview of Current Treatment Options and Investigational Targeted Therapies for Locally Advanced Squamous Cell Carcinoma of the Head and Neck.

    PubMed

    Zibelman, Matthew; Mehra, Ranee

    2016-08-01

    Patients with squamous cell carcinoma of the head and neck (SCCHN) typically present with locally advanced (LA) stage III or IV disease and are treated with combined-modality therapy with chemotherapy, radiotherapy, and surgery (if resectable). These aggressive, upfront treatment measures are often associated with substantial morbidity, and about half the patients develop locoregional or distant recurrences. Thus, new therapeutic strategies are needed that offer similar efficacy benefits with less toxicity. Current research is focused on selectively targeting signaling pathways involved in the proliferation and malignant transformation of SCCHN cells and the tumor microenvironment. For example, the ErbB receptor pathway has been implicated in the development and progression of SCCHN, and several agents targeting this pathway and downstream effectors are in various phases of clinical investigation. Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is the only currently approved targeted therapy for the treatment of LA SCCHN. Additional agents targeting EGFR and other ErbB family members, including monoclonal antibodies (eg, panitumumab, nimotuzumab) and small-molecule tyrosine kinase inhibitors (eg, erlotinib, afatinib, lapatinib) are being studied in LA SCCHN with varying results. Other treatment strategies for LA SCCHN include targeting downstream effectors of signaling and resistance mechanisms to EGFR inhibitors (eg, mammalian target of rapamycin, Src family, and Aurora kinase family). Data from ongoing and future clinical trials will continue to refine current treatment paradigms for LA SCCHN and provide new therapeutic options and potential predictive biomarkers to improve patient efficacy and safety and abrogate resistance. PMID:26967327

  16. 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.

  17. 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

  18. 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

  19. MM-398 (nanoliposomal irinotecan): emergence of a novel therapy for the treatment of advanced pancreatic cancer.

    PubMed

    Carnevale, Julia; Ko, Andrew H

    2016-02-01

    While progress in the treatment of advanced pancreatic cancer has accelerated in recent years, this malignancy continues to have an exceedingly poor prognosis, with no standard of care options beyond front-line chemotherapy. Currently, there are a number of new therapeutic agents in varying stages of clinical development, including molecularly targeted agents, immunotherapies, and modified versions of cytotoxics. MM-398, a novel nanoliposomal formulation of irinotecan, was designed to maximize tumor exposure while minimizing systemic toxicity due to its favorable pharmacokinetic profile. Overall, across multiple clinical trials in multiple disease indications, MM-398 has been shown to have a favorable safety and tolerability profile compared with standard irinotecan. Recent results of the Phase III NAPOLI-1 trial in patients with metastatic pancreatic cancer refractory to gemcitabine-based chemotherapy have shown a significant improvement in overall survival of MM-398 when combined with 5-fluorouracil/leucovorin, compared with 5-fluorouracil/leucovorin alone. This review focuses on the development and pharmacokinetic properties of MM-398, followed by evaluation of its safety and efficacy with a primary emphasis on clinical trials in advanced pancreatic cancer. PMID:26685802

  20. Novel Approaches to Treatment of Advanced Melanoma: A Review on Targeted Therapy and Immunotherapy.

    PubMed

    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

  1. Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.

    PubMed

    Swamy, Manjunath N; Wu, Haoquan; Shankar, Premlata

    2016-08-01

    RNA interference (RNAi) provides a powerful tool to silence specific gene expression and has been widely used to suppress host factors such as CCR5 and/or viral genes involved in HIV-1 replication. Newer nuclease-based gene-editing technologies, such as zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system, also provide powerful tools to ablate specific genes. Because of differences in co-receptor usage and the high mutability of the HIV-1 genome, a combination of host factors and viral genes needs to be suppressed for effective prevention and treatment of HIV-1 infection. Whereas the continued presence of small interfering/short hairpin RNA (si/shRNA) mediators is needed for RNAi to be effective, the continued expression of nucleases in the gene-editing systems is undesirable. Thus, RNAi provides the only practical way for expression of multiple silencers in infected and uninfected cells, which is needed for effective prevention/treatment of infection. There have been several advances in the RNAi field in terms of si/shRNA design, targeted delivery to HIV-1 susceptible cells, and testing for efficacy in preclinical humanized mouse models. Here, we comprehensively review the latest advances in RNAi technology towards prevention and treatment of HIV-1. PMID:27013255

  2. 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

  3. Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series.

    PubMed

    Bilen, Mehmet Asim; Lin, Sue-Hwa; Tang, Dean G; Parikh, Kinjal; Lee, Mong-Hong; Yeung, Sai-Ching J; Tu, Shi-Ming

    2015-01-01

    Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend. PMID:25861496

  4. [Case report of advanced breast cancer responding to capecitabine and trastuzumab combination therapy].

    PubMed

    Yoshidome, Katsuhide; Imabun, Shigeru; Nakahara, Masaaki; Hiraoka, Kazuya; Yamagami, Yuko; Tsujimoto, Masahiko; Nakao, Kazuyasu

    2006-10-01

    We conducted a concomitant administration of capecitabine (2,400 mg/day for 21 days followed by a 7-day interval) and trastuzumab (2 mg/kg weekly) to a 73-year-old female patient with impaired lower limb function diagnosed with bilateral breast cancer. The patient had a complete response (CR) to pulmonary metastases, and carcinoembryonic antigen (CEA) level had normalized from 46.4 ng/ml to 0.6 ng/ml. Left mastectomy was performed in order to control bleeding from tumors. No adverse events attributable to medication were observed. The concomitant administration of capecitabine and trastuzumab is a promising therapy with the potential to greatly improve patient quality of life (QOL). PMID:17033236

  5. Advances in drug delivery system for platinum agents based combination therapy

    PubMed Central

    Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

    2015-01-01

    Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy. PMID:26779373

  6. Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series

    PubMed Central

    Bilen, Mehmet Asim; Lin, Sue-Hwa; Tang, Dean G.; Parikh, Kinjal; Lee, Mong-Hong; Yeung, Sai-Ching J.; Tu, Shi-Ming

    2015-01-01

    Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend. PMID:25861496

  7. 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

  8. 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

  9. 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

  10. [Treatment of inter-specific aggression in cats with the selective serotonin reuptake inhibitor fluvoxamine. A case report].

    PubMed

    Sprauer, S

    2012-01-01

    The article describes the redirected, inter-specific aggression of a Maine Coon cat, which was principally directed towards the owners. The cat reacted towards different, nonspecific sounds with abrupt aggressive behaviour and injured the victims at this juncture with moderate scratching and biting. Exclusively using behaviour therapy did not achieve the desired result, thus the therapy was supported with pharmaceuticals. The cat orally received the selective serotonin re-uptake inhibitor fluvoxamine at an initial dosage of 0.5mg/kg BW once daily. After 4 weeks the application rate was increased to 1.0 mg/kg BW once daily. The medication did not cause any side effects. Together with the behaviour-modulating therapy, carried out parallel to the medication therapy, the aggressive behaviour problem of the cat was resolved. After administration for a period of 63 weeks the fluvoxamine therapy was discontinued by gradually reducing the dose without recurrence of the aggressive behaviour. PMID:23242225

  11. 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

  12. AIDS virus restriction factor transgenesis in the domestic cat

    PubMed Central

    Wongsrikeao, Pimprapar; Saenz, Dyana; Rinkoski, Tommy; Otoi, Takeshige; Poeschla, Eric

    2014-01-01

    The domestic cat is a neurobehaviorally complex, accessible species with specific value in research situations where rodents are unsuited on the basis of disease susceptibility, size, or other factors. For example, studies in the cat have revealed much of our present knowledge of the organization of the mammalian brain, in particular the cerebral cortex, and humans and cats are each afflicted with pandemic AIDS lentiviruses that are susceptible to species-specific restriction factors. A capability for feline transgenesis is needed to realize the distinctive potential. Here we introduced a retroviral restriction factor, rhesus macaque TRIMCyp, and GFP, into the domestic cat germline. The method establishes transgenesis by direct gamete genetic modification for the first time in any carnivore. We produced uniformly transgenic outcomes and observed widespread expression, no mosaicism, and germline transmission without F1 silencing. TRIMCyp-transgenic cat lymphocytes resisted FIV replication. The approach yields a first capability to experimentally manipulate AIDS virus restriction factors at the systemic, whole animal level in a susceptible species. In addition to determining if a species can be made genetically immune to its AIDS virus, it can be used to test HIV-1 gene therapy potential, and to build feline models relevant to other diseases. PMID:21909101

  13. Combined surgery and postoperative radiation therapy for advanced laryngeal and hypopharyngeal carcinomas

    SciTech Connect

    Mirimanoff, R.O.; Wang, C.C.; Doppke, K.P.

    1985-03-01

    The survival, pattern of failure and complications in 47 patients with Stage III and IV cancers of the glottis, supraglottis and hypopharynx treated with surgery and postoperative radiotherapy using a new treatment technique referred to as mini-mantle were analyzed. The absolute survival probability of the entire group was 53 and 31% at 3 and 5 years. The local control probability at 3 and 5 years was 63 and 58%, and was higher for the supraglottic/hypopharyngeal than for glottic carcinomas. Five patients developed complications requiring surgical correction, but none experienced mortality. Moderate complications were treated conservatively without lasting sequelae. This technique is a reasonable safe and efficient procedure and can be effectively employed for the management of advanced laryngeal and hypopharyngeal carcinomas after definitive surgery.

  14. 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

  15. 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

  16. Phase I and pharmacologic study of oral Ftorafur and x ray therapy in advanced gastrointestinal cancer

    SciTech Connect

    Byfield, J.E.; Sharp, T.R.; Hornbeck, C.L.; Frankel, S.S.; Floyd, R.A.; Griffiths, J.C.

    1985-03-01

    The authors have treated 15 patients with advanced gastrointestinal carcinoma with a cyclical regimen of combined Ftorafur (N/sub 1/-((2-furanidyl-))-5-Fluorouracil, a 5-FU pro-drug) and external beam radiation. The most common toxicity in general, and the most common limiting toxicity was nausea and vomiting, in contrast to oral FT alone where diarrhea is more prominent. Stomatitis was seen only once and no other form of serious toxicity was encountered. Two-thirds of the patients responded in subjective terms (pain relief). There was 1 partial response of FT alone (pulmonary metastases outside the treatment field). The sole patient whose treatment field was outside the abdomen (chest portals for esophageal carcinoma) developed pneumonitis which contributed to his death. No other delayed effects were noted. Serum FT levels were related to the infested dose and in the microgram range while serum 5-FU levels were in the nanogram range indicating slow decomposition of FT into 5-FU.

  17. High intensity focused ultrasound: a noninvasive therapy for locally advanced pancreatic cancer.

    PubMed

    Wu, Feng

    2014-11-28

    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

  18. Molecularly targeted therapies for advanced or metastatic non-small-cell lung carcinoma

    PubMed Central

    Bayraktar, Soley; Rocha-Lima, Caio M

    2013-01-01

    Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related death in both men and women in the United States. Platinum-based doublet chemotherapy has been a standard for patients with advanced stage disease. Improvements in overall survival and quality of life have been modest. Improved knowledge of the aberrant molecular signaling pathways found in NSCLC has led to the development of biomarkers with associated targeted therapeutics, thus changing the treatment paradigm for many NSCLC patients. In this review, we present a summary of many of the currently investigated biologic targets in NSCLC, discuss their current clinical trial status, and also discuss the potential for development of other targeted agents. PMID:23696960

  19. Successful Treatment of Advanced Ovarian Cancer with Thermochemotherapy and Adjuvant Immune Therapy

    PubMed Central

    Kleef, R.; Kekic, S.; Ludwig, N.

    2012-01-01

    We report on a 4-year progression-free survival of a 54-year-old female first diagnosed in December 2007 with advanced bilateral ovarian cancer FIGO IIIc, disseminated peritoneal carcinosis and malignant diaphragm invasion. Treatment started in January 2008 with 6 cycles of Taxol 175 mg/m2/carboplatin AUC 5 in 3-week intervals. Twenty-four hours following each chemotherapy session, fever-range long-duration whole-body hyperthermia (WBH) was performed at the temperature plateau of 40°C body core temperature for 6 h. Three months after completion of chemotherapy, 4 more long-duration WBH procedures were performed in monthly intervals. Importantly, long-duration WBH was paralleled with intradermal vaccination of autologous dendritic cells. No other treatment was given to the patient. Four years following the first diagnosis, the patient is still in complete remission with no evidence of disease. PMID:22679425

  20. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Methods Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. Results With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Conclusion Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. PMID:23842112

  1. 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

  2. Osteoma of the oral and maxillofacial regions in cats: 7 cases (1999-2009).

    PubMed

    Fiani, Nadine; Arzi, Boaz; Johnson, Eric G; Murphy, Brian; Verstraete, Frank J M

    2011-06-01

    Objective-To describe clinical features of oral and maxillofacial osteomas in cats. Design-Retrospective case series. Animals-7 cats with oral or maxillofacial osteoma or both. Procedures-Medical records were reviewed for information on signalment, history, clinical signs, physical examination findings, diagnostic imaging findings, results of serum biochemical analyses and histologic testing, surgical procedures performed, and perioperative complications. Outcome was determined on the basis of follow-up telephone interviews of owners. Results-Cats ranged from 1 to 23 years of age. Clinical signs were observed in 5 cats and were attributed to the presence of the mass. Diagnostic imaging (radiography and computed tomography) and histologic examination confirmed the diagnosis of osteoma. Three cats were euthanatized; 1 cat was treated by mandibulectomy, 1 was treated by maxillectomy, and 2 were treated by debulking. At the time of follow-up at least 1 year after surgery, all 4 treated cats were alive, with owners reporting an acceptable quality of life. Conclusions and Clinical Relevance-Osteoma of the oral and maxillofacial regions is an uncommon tumor in cats. Most cats are examined during an advanced stage of the disease, when treatment options may be limited. Although osteoma is a benign tumor, the recommendation is to perform a clinical evaluation, diagnostic imaging, biopsy, and treatment early in the disease process, when less invasive surgical approaches may be feasible. PMID:21627511

  3. Acquired retinal folds in the cat.

    PubMed

    MacMillan, A D

    1976-06-01

    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  4. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence

    PubMed Central

    Oladele, Rita O.; Akanmu, Alani S.; Nwosu, Augustina O.; Ogunsola, Folasade T.; Richardson, Malcolm D.; Denning, David W.

    2016-01-01

    Background. Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods. Sera were collected from 214 consenting HIV-infected participants with CD4+ counts <250 cells/mm3, irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results. Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4+ cell count was 160 cells/mm3 (interquartile range, 90–210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4+ cell counts <100 cells/mm3, 4 of 80 (5.0%) in the 100–200 group, and 9 of 73 (12.3%) in 200–250 cells/mm3 group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm3, which was unrelated to CrAg positivity (P = .018). Conclusions. We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We recommend Cr

  5. Cryptococcal Antigenemia in Nigerian Patients With Advanced Human Immunodeficiency Virus: Influence of Antiretroviral Therapy Adherence.

    PubMed

    Oladele, Rita O; Akanmu, Alani S; Nwosu, Augustina O; Ogunsola, Folasade T; Richardson, Malcolm D; Denning, David W

    2016-03-01

    Background.  Cryptococcal meningitis has a high mortality in human immunodeficiency virus (HIV)-infected persons in Africa. This is preventable with early screening and preemptive therapy. We evaluated the prevalence of cryptococcal disease by antigen testing, possible associated factors, and outcomes in HIV-infected patients being managed in a tertiary hospital in Lagos, Nigeria. Methods.  Sera were collected from 214 consenting HIV-infected participants with CD4(+) counts <250 cells/mm(3), irrespective of their antiretroviral therapy (ART) status, between November 2014 and May 2015. A cryptococcal antigen (CrAg) lateral flow assay was used for testing. Pertinent clinical data were obtained from patients and their case notes. Results.  Of the 214 participants, females (124; 57.9%) outnumbered males. Mean age was 41.3 ± 9.4 (standard deviation) years. The majority (204; 95.3%) were ART experienced. The median CD4(+) cell count was 160 cells/mm(3) (interquartile range, 90-210). The overall seroprevalence of cryptococcal antigenemia was 8.9% (19 of 214); 6 of 61 (9.8%) in those with CD4(+) cell counts <100 cells/mm(3), 4 of 80 (5.0%) in the 100-200 group, and 9 of 73 (12.3%) in 200-250 cells/mm(3) group. Among ART-naive patients, 1 of 10 (10%) was CrAg positive. Twenty-seven of 214 (12.6%) had associated oral thrush. Potential baseline meningitis symptoms (3 of 214 [1.4%] experienced neck pain or stiffness and 21 of 214 [9.8%] experienced headache) were common in the study group, but the result was not statistically significant in relation to CrAg positivity. Two of 19 (10.5%) CrAg-positive patients died, 10 of 19 (52.6%) were lost to follow up, and 7 of 19 (36.8%) were alive. Empirical fluconazole was routinely given to those with low CD4 counts <100 cells/mm(3), which was unrelated to CrAg positivity (P = .018). Conclusions.  We report a prevalence of 8.9% cryptococcal antigenemia in a setting where first-line antifungals are not readily available. We

  6. RadCat 3.0 user guide.

    SciTech Connect

    Hinojosa, Daniel; Penisten, Janelle J.; Dennis, Matthew L.; Osborn, Douglas M.; Weiner, Ruth F.; Heames, Terence John; Marincel, Michelle K.

    2009-05-01

    RADTRAN is an internationally accepted program and code for calculating the risks of transporting radioactive materials. The first versions of the program, RADTRAN I and II, were developed for NUREG-0170 (USNRC, 1977), the first environmental statement on transportation of radioactive materials. RADTRAN and its associated software have undergone a number of improvements and advances consistent with improvements in both available data and computer technology. The version of RADTRAN currently bundled with RadCat is RADTRAN 6.0. This document provides a detailed discussion and a guide for the use of the RadCat 3.0 Graphical User Interface input file generator for the RADTRAN code. RadCat 3.0 integrates the newest analysis capabilities of RADTRAN 6.0 which includes an economic model, updated loss-of-lead shielding model, and unit conversion. As of this writing, the RADTRAN version in use is RADTRAN 6.0.

  7. First Human Treatment With Investigational rhGUS Enzyme Replacement Therapy in an Advanced Stage MPS VII Patient

    PubMed Central

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-01-01

    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 60-80 mmHg range, eventually approaching respiratory failure (ETCO2 of 100 mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2 mg/kg over 4 hours 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

  8. 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

  9. 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

  10. Advances in hepatitis C therapy: What is the current state - what come’s next?

    PubMed Central

    Zopf, Steffen; Kremer, Andreas E; Neurath, Markus F; Siebler, Juergen

    2016-01-01

    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 2nd generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or post-transplant patients. These 2nd 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

  11. 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

  12. 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

  13. 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

  14. Maintenance or non-maintenance therapy in the treatment of advanced non-small cell lung cancer: that is the question.

    PubMed

    Galetta, D; Rossi, A; Pisconti, S; Millaku, A; Colucci, G

    2010-11-01

    Lung cancer is the most common cancer worldwide with non-small cell lung cancer (NSCLC), including squamous carcinoma, adenocarcinoma and large cell carcinoma, accounting for about 85% of all lung cancer types with most of the patients presenting with advanced disease at the time of diagnosis. In this setting first-line platinum-based chemotherapy for no more than 4-6 cycles are recommended. After these cycles of treatment, non-progressing patients enter in the so called "watch and wait" period in which no further therapy is administered until there is disease progression. In order to improve the advanced NSCLC outcomes, the efficacy of further treatment in the "watch and wait" period was investigated. This is the "maintenance therapy". Recently, the results coming from randomized phase III trials investigating two new agents, pemetrexed and erlotinib, in this setting led to their registration for maintenance therapy. Here, we report and discuss these results. PMID:21129607

  15. 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

  16. 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

  17. 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

  18. Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse

    PubMed Central

    Tanabe, Katsuyuki; Lanaspa, Miguel A.; Kitagawa, Wataru; Rivard, Christopher J.; Miyazaki, Makoto; Klawitter, Jelena; Schreiner, George F.; Saleem, Moin A.; Mathieson, Peter W.; Makino, Hirofumi; Johnson, Richard J.

    2012-01-01

    Nicorandil is an orally available drug that can act as a nitric oxide donor, an antioxidant, and an ATP-dependent K channel activator. We hypothesized that it may have a beneficial role in treating diabetic nephropathy. We administered nicorandil to a model of advanced diabetic nephropathy (the streptozotocin-induced diabetes in mice lacking endothelial nitric oxide synthase, eNOSKO); controls included diabetic eNOS KO mice without nicorandil and nondiabetic eNOS KO mice treated with either nicorandil or vehicle. Mice were treated for 8 wk. Histology, blood pressure, and renal function were determined. Additional studies involved examining the effects of nicorandil on cultured human podocytes. Here, we found that nicorandil did not affect blood glucose levels, blood pressure, or systemic endothelial function, but significantly reduced proteinuria and glomerular injury (mesangiolysis and glomerulosclerosis). Nicorandil protected against podocyte loss and podocyte oxidative stress. Studies in cultured podocytes showed that nicorandil likely protects against glucose-mediated oxidant stress via the ATP-dependent K channel as opposed to its NO-stimulating effects. In conclusion, nicorandil may be beneficial in diabetic nephropathy by preserving podocyte function. We recommend clinical trials to determine whether nicorandil may benefit diabetic nephropathy or other conditions associated with podocyte dysfunction. PMID:22338086

  19. 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

  20. A randomised trial of lung sealant versus medical therapy for advanced emphysema.

    PubMed

    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

    2015-09-01

    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 hospitalisation (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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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. PMID:26743617

  6. Adult Height in Patients with Advanced CKD Requiring Renal Replacement Therapy during Childhood

    PubMed Central

    Harambat, Jérôme; Bonthuis, Marjolein; van Stralen, Karlijn J.; Ariceta, Gema; Battelino, Nina; Bjerre, Anna; Jahnukainen, Timo; Leroy, Valérie; Reusz, György; Sandes, Ana R.; Sinha, Manish D.; Groothoff, Jaap W.; Combe, Christian; Jager, Kitty J.; Verrina, Enrico; Schaefer, Franz

    2014-01-01

    Summary Background and objectives Growth and final height are of major concern in children with ESRD. This study sought to describe the distribution of adult height of patients who started renal replacement therapy (RRT) during childhood and to identify determinants of final height in a large cohort of RRT children. Design, setting, participants, & measurements A total of 1612 patients from 20 European countries who started RRT before 19 years of age and reached final height between 1990 and 2011 were included. Linear regression analyses were performed to calculate adjusted mean final height SD score (SDS) and to investigate its potential determinants. Results The median final height SDS was −1.65 (median of 168 cm in boys and 155 cm in girls). Fifty-five percent of patients attained an adult height within the normal range. Adjusted for age at start of RRT and primary renal diseases, final height increased significantly over time from −2.06 SDS in children who reached adulthood in 1990–1995 to −1.33 SDS among those reaching adulthood in 2006–2011. Older age at start of RRT, more recent period of start of RRT, cumulative percentage time on a functioning graft, and greater height SDS at initiation of RRT were independently associated with a higher final height SDS. Patients with congenital anomalies of the kidney and urinary tract and metabolic disorders had a lower final height than those with other primary renal diseases. Conclusions Although final height remains suboptimal in children with ESRD, it has consistently improved over time. PMID:24178977

  7. Further advances of chronic renal replacement therapy in eastern Germany, 1994 versus 1989.

    PubMed

    Thieler, H; Kohler, I; Achenbach, H; Goetz, K H; Kraatz, G; Osten, B; Smit, H

    1995-08-01

    Unlike the other former Soviet-block countries, Eastern Germany/the "GDR", had the opportunity to the re-unification with a highly developed western country, the Federal Republic of (West) Germany in 1990. In order to record the following rapid improvements in renal replacement therapy, we performed our own survey in Eastern Germany--excluding Eastern Berlin--by questionnaire, comparing the years 1989/December, and 1994/December. 112 of the 113 dialysis facilities for adult regular dialysis patients replied to our questionnaire (99%). From 1989 to 1994, the number of dialysis centers increased from 53 to 113 (-->213%), reaching 7.9 centres p.m.p. Of these facilities, 29% were hospital centers, 48% were private dialysis units, and 23% were run by nonprofit dialysis organizations. The number of dialysis stations increased from 602 to 1,719 (-->286%), i.e. 120 stations p.m.p. The number of patients in regular dialysis treatment rose from 2,127 to 5,335 (-->251%), that means a prevalence of 373 patients p.m.p. In 1989, 67 new patients (p.m.p.) had been accepted for maintenance treatment (incidence), in contrast to 130 new patients p.m.p. in 1994 (-->194%), now under the conditions of unlimited accessibility to dialysis treatment. Questions referring to this point--the incidence of new patients--were only asked in Thüringen (2.5 mio. inhabitants). Alternative treatment modalities became feasible under the new conditions in Eastern Germany. In contrast to 99% hemodialysis patients in December 1989, at the end of 1994 92.8% of the patients were treated by hemodialysis, 2.0% by hemofiltration, and 5.2% by peritoneal dialysis, predominantly CAPD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8529297

  8. 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

  9. 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

  10. Clinical development of Gene therapy needs a tailored approach: A regulatory perspective from the EU.

    PubMed

    Narayanan, Gopalan; Salmikangas, Paula; Schneider, Christian K; Galli, Maria Cristina; Trouvin, Jean-Hugues; Flory, Egbert; Cossu, Giulio; Ovelgonne, Hans

    2014-02-18

    Gene therapy is a rapidly evolving field, which needs an integrated approach, as acknowledged in the Concept paper on the revision of the guideline on gene transfer medicinal products (Concept paper, EMA, 2009). The first gene therapy application for marketing authorisation was approved in the ICH region in 2012, the product being Alipogene tiparvovec (http, summary for the public, 2012). The regulatory process for this product has been commented on extensively, highlighting the challenges posed by such a novel technology (English, 2011; Flemming, 2012; Melchiorri et al, 2013; Miller, 2012). Here, as current or previous members of the Committee for Advanced Therapies (CAT), we share our perspectives and views on gene therapy as a treatment modality based on current common understanding and regulatory experience of gene therapy products in the EU to date. It is our view that a tailored approach is needed for a given gene therapy product in order to achieve successful Marketing Authorisation. PMID:24547991

  11. Ethical and Professional Issues in Computer-Assisted Therapy.

    ERIC Educational Resources Information Center

    Ford, B. Douglas

    1993-01-01

    Discusses ethical and professional issues in psychology regarding computer-assisted therapy (CAT). Topics addressed include an explanation of CAT; whether CAT is psychotherapy; software, including independent use, validation of effectiveness, and restricted access; clinician resistance; client acceptance; the impact on ethical standards; and a…

  12. Telaprevir- and Boceprevir-Based Triple Therapy for Hepatitis C in Liver Transplant Recipients with Advanced Recurrent Disease: A Multicenter Study

    PubMed Central

    Verna, Elizabeth C.; Saxena, Varun; Burton, James R.; O’Leary, Jacqueline G.; Dodge, Jennifer L.; Stravitz, Richard T.; Levitsky, Joshua; Trotter, James F.; Everson, Gregory T.; Brown, Robert S.; Terrault, Norah A.

    2016-01-01

    Background Antiviral treatment with sustained virologic response (SVR) improves survival in liver transplant (LT) recipients, and is especially relevant to patients with advanced recurrent hepatitis C virus (HCV). We assessed the safety and efficacy of protease inhibitor (PI)-based triple therapy in patients with recurrent advanced fibrosis and cholestatic hepatitis. Methods LT recipients with genotype 1 HCV and advanced fibrosis (F3-4/4) or cholestatic hepatitis treated with telaprevir or boceprevir-based triple therapy at 6 centers (CRUSH-C consortium) were retrospectively assessed. The primary endpoints were sustained virologic response at 12 weeks (SVR12) and safety. Results 45 patients with advanced fibrosis and 9 with cholestatic hepatitis (74% male, 57% with genotype 1a, and 63% prior non-responders) were included. SVR12 occurred in 51% of those with advanced fibrosis and 44% with cholestatic hepatitis, and eRVR was highly predictive of SVR12. Previous null/partial response (OR 0.09, p=0.003), low platelet count (OR 1.02, p=0.004), and steroid use (OR 0.16, p=0.03) were negatively associated with SVR12 in multivariable models. Six (11%) patients died during or after treatment, and hepatic decompensation during treatment occurred in 22% of patients with advanced fibrosis and 33% of patients with cholestatic hepatitis. Hispanic ethnicity (OR 9.37, p=0.03) and low albumin at treatment start (OR 0.01, p=0.001) were predictive of death or decompensation in multivariable models. Conclusions For LT recipients with recurrent advanced HCV and at highest need of effective treatment, PI-based triple therapy achieved sustained viral clearance in ~50% of patients. However, there is significant risk of serious adverse events including hepatic decompensation, arguing for earlier therapeutic intervention. The availability of antiviral drug combinations with higher efficacy and improved safety are of particular importance for post-transplant patients with advanced disease

  13. World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) second edition: guidelines for evaluating the efficacy of parasiticides for the treatment, prevention and control of flea and tick infestations on dogs and cats.

    PubMed

    Marchiondo, A A; Holdsworth, P A; Fourie, L J; Rugg, D; Hellmann, K; Snyder, D E; Dryden, M W

    2013-05-01

    These second edition guidelines, updated from the 2007 version (Marchiondo et al., 2007), are intended to assist the planning and conduct of laboratory and clinical studies to assess the efficacy of ectoparasiticides applied to dogs or cats for the purpose of treating, preventing and controlling flea and tick infestations. Major revisions to this second edition include guidelines on the assessment of systemic flea and tick products, an update of the geographical distribution of the common fleas and ticks species on dogs and cats, determination of flea and tick efficacy based on geometric versus arithmetic means with respect to geographic regulatory agencies, modification of tick categorization in the assessment of efficacy, expanded guidelines on repellency and anti-feeding effects, enhanced practical field study guidance, and considerations on the ranges of flea and ticks for infestations in laboratory studies. The term ectoparasiticide includes insecticidal and acaricidal compounds, as well as insect growth regulators. The range of biological activities from animal treatment that are considered include: repellency and anti-feeding effects, knockdown, speed of kill, immediate and persistent lethal effects, and interference with egg fertility and subsequent development of off-host life cycle stages. Information is provided on the selection of animals, dose determination, dose confirmation and field studies, record keeping, interpretation of results and animal welfare. These guidelines are also intended to assist regulatory authorities involved in the approval and registration of new topical or systemic ectoparasiticides, and to facilitate the worldwide adoption of harmonized procedures. PMID:23741753

  14. Cat Ownership Perception and Caretaking Explored in an Internet Survey of People Associated with Cats.

    PubMed

    Zito, Sarah; Vankan, Dianne; Bennett, Pauleen; Paterson, Mandy; Phillips, Clive J C

    2015-01-01

    People who feed cats that they do not perceive they own (sometimes called semi-owners) are thought to make a considerable contribution to unwanted cat numbers because the cats they support are generally not sterilized. Understanding people's perception of cat ownership and the psychology underlying cat semi-ownership could inform approaches to mitigate the negative effects of cat semi-ownership. The primary aims of this study were to investigate cat ownership perception and to examine its association with human-cat interactions and caretaking behaviours. A secondary aim was to evaluate a definition of cat semi-ownership (including an association time of ≥1 month and frequent feeding), revised from a previous definition proposed in the literature to distinguish cat semi-ownership from casual interactions with unowned cats. Cat owners and semi-owners displayed similar types of interactions and caretaking behaviours. Nevertheless, caretaking behaviours were more commonly displayed towards owned cats than semi-owned cats, and semi-owned cats were more likely to have produced kittens (p<0.01). All interactions and caretaking behaviours were more likely to be displayed towards cats in semi-ownership relationships compared to casual interaction relationships. Determinants of cat ownership perception were identified (p<0.05) and included association time, attachment, perceived cat friendliness and health, and feelings about unowned cats, including the acceptability of feeding unowned cats. Encouraging semi-owners to have the cats they care for sterilized may assist in reducing the number of unwanted kittens and could be a valuable alternative to trying to prevent semi-ownership entirely. Highly accessible semi-owner "gatekeepers" could help to deliver education messages and facilitate the provision of cat sterilization services to semi-owners. This research enabled semi-ownership to be distinguished from casual interaction relationships and can assist welfare and

  15. Pilot study to evaluate the role of Mycoplasma species in cat bite abscesses.

    PubMed

    Torres-Henderson, Camille; Hesser, Jeff; Hyatt, Doreene R; Hawley, Jennifer; Brewer, Melissa; Lappin, Michael R

    2014-12-01

    Mycoplasma species are common inhabitants of the feline oral cavity, and so likely contaminate many cat bite abscesses. The objectives of this study were to determine whether Mycoplasma species are common contaminants of cat bite abscesses and whether they are are associated with β-lactam-resistant clinical disease. Twenty-six privately owned cats with clinical evidence of an abscess suspected to be from a cat bite were included in the study. Samples from each cat were evaluated by aerobic and anaerobic culture, as well as Mycoplasma species culture and polymerase chain reaction (PCR). All cats were initially treated with appropriate wound management and were administered an antibiotic of the β-lactam class (amoxicillin, amoxicillin clavulanate or cefovecin sodium). Mycoplasma species DNA was amplified by PCR from 4/26 samples (15.4%); one of these cases was concurrently culture positive. Adequate DNA for sequencing was present for 2/4 positive PCR samples; one was most homologous with Mycoplasma felis, and the other was most homologous with Mycoplasma equigenitalium and Mycoplasma elephantis. Of the 26 cats, 25 responded to the initial treatment by day 7. The cat that failed initial treatment was positive for M equigenitalium or M elephantis DNA on days 0 and 12, and ultimately responded to administration of enrofloxacin and clindamycin. The results suggest that while Mycoplasma species can contaminate cat bite abscesses, routine wound management and β-lactam antibiotic therapy is adequate for treatment in most cases of abscess. However, as Mycoplasma species infections do not respond to β-lactam class antibiotic therapy, these organisms should be on the differential list for cats with abscesses that fail treatment with this antibiotic class. PMID:24643287

  16. Optimizing Single Agent Panitumumab Therapy in Pre-Treated Advanced Colorectal Cancer12

    PubMed Central

    Gasparini, Giampietro; Buttitta, Fiamma; D'Andrea, Mario Rosario; Tumolo, Salvatore; Buonadonna, Angela; Pavese, Ida; Cordio, Stefano; De Tursi, Michele; Mosconi, Stefania; Stumbo, Luciano; Felicioni, Lara; Marchetti, Antonio

    2014-01-01

    PURPOSE: To improve the selection of advanced colorectal cancer patients to panitumumab by optimizing the assessment of RAS (KRAS-NRAS) mutations. EXPERIMENTAL DESIGN: Using a centralized pyrosequencing RAS assay, we analyzed the tumors of 94 patients, wild-type for KRAS mutations (codons 12 to 13) by Sanger sequencing (SS), treated with panitumumab. RESULTS: By SS analysis, 94 (62%) of 152 patients were wild-type and their objective response rate to panitumumab was 17%. We first optimized the KRAS test, by performing an accurate tissue-dissection step followed by pyrosequencing, a more sensitive method, and found further mutations in 12 (12.8%) cases. Secondly, tumors were subjected to RAS extension analysis (KRAS, exons 3 to 4; NRAS exons 2 to 4) by pyrosequencing that allowed to identify several rare mutations: KRAS codon 61, 5.3%; codon 146, 5.3%; NRAS, 9.5%. Overall, RAS mutation rate was 32.9%. All patients with additional RAS mutations had progressive or stable disease, except 3 patients with mutations at codon 61 of KRAS or NRAS who experienced partial (2 cases) or complete response. By excluding from the analysis 11 cases with mutations at codons 61, no patient was responsive to treatment (P = .021). RAS wild-type versus RAS mutated cases had a significantly better time to progression (P = .044), that resulted improved (p = .004) by excluding codon 61 mutations. CONCLUSION: This study shows that by optimizing the RAS test it is possible to significantly improve the identification of patients who do not gain benefit of panitumumab. Prospective studies are warranted to determine the clinical significance of rare mutations. PMID:25246275

  17. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage.

    PubMed

    Mastellos, Dimitrios C; Reis, Edimara S; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D

    2016-10-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  18. Approximation of Corrected Calcium Concentrations in Advanced Chronic Kidney Disease Patients with or without Dialysis Therapy

    PubMed Central

    Kaku, Yoshio; Ookawara, Susumu; Miyazawa, Haruhisa; Ito, Kiyonori; Ueda, Yuichiro; Hirai, Keiji; Hoshino, Taro; Mori, Honami; Yoshida, Izumi; Morishita, Yoshiyuki; Tabei, Kaoru

    2015-01-01

    Background The following calcium (Ca) correction formula (Payne) is conventionally used for serum Ca estimation: corrected total Ca (TCa) (mg/dl) = TCa (mg/dl) + [4 – albumin (g/dl)]; however, it is inapplicable to advanced chronic kidney disease (CKD) patients. Methods 1,922 samples in CKD G4 + G5 patients and 341 samples in CKD G5D patients were collected. Levels of TCa (mg/day), ionized Ca2+ (iCa2+) (mmol/l) and other clinical parameters were measured. We assumed the corrected TCa to be equal to eight times the iCa2+ value (measured corrected TCa). We subsequently performed stepwise multiple linear regression analysis using the clinical parameters. Results The following formula was devised from multiple linear regression analysis. For CKD G4 + G5 patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 4 × (7.4 – pH) + 0.1 × (6 – P) + 0.22. For CKD G5D patients: approximated corrected TCa (mg/dl) = TCa + 0.25 × (4 – albumin) + 0.1 × (6 – P) + 0.05 × (24 – HCO3-) + 0.35. Receiver operating characteristic analysis showed the high values of the area under the curve of approximated corrected TCa for the detection of measured corrected TCa ≥8.4 mg/dl and ≤10.4 mg/dl for each CKD sample. Both intraclass correlation coefficients for each CKD sample demonstrated superior agreement using the new formula compared to the previously reported formulas. Conclusion Compared to other formulas, the approximated corrected TCa values calculated from the new formula for patients with CKD G4 + G5 and CKD G5D demonstrates superior agreement with the measured corrected TCa. PMID:26557841

  19. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    PubMed Central

    MOMOZONO, HIROYUKI; MIYAKE, HIDEAKI; TEI, HIROMOTO; HARADA, KEN-ICHI; FUJISAWA, MASATO

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC. PMID:27123292

  20. The Cat's Eye Nebula

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This NASA Hubble Space Telescope image shows one of the most complex planetary nebulae ever seen, NGC 6543, nicknamed the 'Cat's Eye Nebula.' Hubble reveals surprisingly intricate structures including concentric gas shells, jets of high-speed gas and unusual shock-induced knots of gas. Estimated to be 1,000 years old, the nebula is a visual 'fossil record' of the dynamics and late evolution of a dying star. A preliminary interpretation suggests that the star might be a double-star system. The suspected companion star also might be responsible for a pair of high-speed jets of gas that lie at right angles to this equatorial ring. If the companion were pulling in material from a neighboring star, jets escaping along the companion's rotation axis could be produced. These jets would explain several puzzling features along the periphery of the gas lobes. Like a stream of water hitting a sand pile, the jets compress gas ahead of them, creating the 'curlicue' features and bright arcs near the outer edge of the lobes. The twin jets are now pointing in different directions than these features. This suggests the jets are wobbling, or precessing, and turning on and off episodically. This color picture, taken with the Wide Field Planetary Camera-2, is a composite of three images taken at different wavelengths. (red, hydrogen-alpha; blue, neutral oxygen, 6300 angstroms; green, ionized nitrogen, 6584 angstroms). The image was taken on September 18, 1994. NGC 6543 is 3,000 light- years away in the northern constellation Draco. The term planetary nebula is a misnomer; dying stars create these cocoons when they lose outer layers of gas. The process has nothing to do with planet formation, which is predicted to happen early in a star's life.