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Sample records for enhanced therapeutic efficacy

  1. Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids

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    Sayeda Yasmin-Karim

    2018-04-01

    Full Text Available Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs, with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT or smart biomaterials toward enhancing therapeutic efficacy during treatment of pancreatic and lung cancers. In in vitro studies, clonogenic assay results showed greater effective tumor cell killing, when combining CBDs and RT. Meanwhile, in vivo study results revealed major increase in survival when employing smart biomaterials for sustained delivery of CBDs to tumor cells. The significance of these findings, considerations for further research, and viable roadmap to clinical translation are discussed.

  2. Agonist anti-GITR antibody significantly enhances the therapeutic efficacy of Listeria monocytogenes-based immunotherapy.

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    Shrimali, Rajeev; Ahmad, Shamim; Berrong, Zuzana; Okoev, Grigori; Matevosyan, Adelaida; Razavi, Ghazaleh Shoja E; Petit, Robert; Gupta, Seema; Mkrtichyan, Mikayel; Khleif, Samir N

    2017-08-15

    We previously demonstrated that in addition to generating an antigen-specific immune response, Listeria monocytogenes (Lm)-based immunotherapy significantly reduces the ratio of regulatory T cells (Tregs)/CD4 + and myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Since Lm-based immunotherapy is able to inhibit the immune suppressive environment, we hypothesized that combining this treatment with agonist antibody to a co-stimulatory receptor that would further boost the effector arm of immunity will result in significant improvement of anti-tumor efficacy of treatment. Here we tested the immune and therapeutic efficacy of Listeria-based immunotherapy combination with agonist antibody to glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) in TC-1 mouse tumor model. We evaluated the potency of combination on tumor growth and survival of treated animals and profiled tumor microenvironment for effector and suppressor cell populations. We demonstrate that combination of Listeria-based immunotherapy with agonist antibody to GITR synergizes to improve immune and therapeutic efficacy of treatment in a mouse tumor model. We show that this combinational treatment leads to significant inhibition of tumor-growth, prolongs survival and leads to complete regression of established tumors in 60% of treated animals. We determined that this therapeutic benefit of combinational treatment is due to a significant increase in tumor infiltrating effector CD4 + and CD8 + T cells along with a decrease of inhibitory cells. To our knowledge, this is the first study that exploits Lm-based immunotherapy combined with agonist anti-GITR antibody as a potent treatment strategy that simultaneously targets both the effector and suppressor arms of the immune system, leading to significantly improved anti-tumor efficacy. We believe that our findings depicted in this manuscript provide a promising and translatable strategy that can enhance the overall

  3. Solid lipid nanoparticle suspension enhanced the therapeutic efficacy of praziquantel against tapeworm

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    Xie S

    2011-10-01

    Full Text Available Shuyu Xie1,*, Baoliang Pan1,*, Baoxin Shi2, Zhuangzhi Zhang2, Xu Zhang2, Ming Wang1, Wenzhong Zhou11Department of Preventive Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, People’s Republic of China; 2Veterinary Research Institute, Xinjiang Academy of Animal Science, Xinjiang, People’s Republic of China *These authors contributed equally to this study Abstract: Hydatid disease caused by tapeworm is an increasing public health and socioeconomic concern. In order to enhance the therapeutic efficacy of praziquantel (PZQ against tapeworm, PZQ-loaded hydrogenated castor oil solid lipid nanoparticle (PZQ-HCO-SLN suspension was prepared by a hot homogenization and ultrasonication method. The stability of the suspension at 4°C and room temperature was evaluated by the physicochemical characteristics of the nanoparticles and in-vitro release pattern of the suspension. Pharmacokinetics was studied after subcutaneous administration of the suspension in dogs. The therapeutic effect of the novel formulation was evaluated in dogs naturally infected with Echinococcus granulosus. The results showed that the drug recovery of the suspension was 97.59% ± 7.56%. Nanoparticle diameter, polydispersivity index, and zeta potential were 263.00 ± 11.15 nm, 0.34 ± 0.06, and -11.57 ± 1.12 mV, respectively and showed no significant changes after 4 months of storage at both 4°C and room temperature. The stored suspensions displayed similar in-vitro release patterns as that of the newly prepared one. SLNs increased the bioavailability of PZQ 5.67-fold and extended the mean residence time of the drug from 56.71 to 280.38 hours. Single subcutaneous administration of PZQ-HCO-SLN suspension obtained enhanced therapeutic efficacy against tapeworm in infected dogs. At the dose of 5 mg/kg, the stool-ova reduction and negative conversion rates and tapeworm removal rate of the suspension were 100%, while the native PZQ were 91

  4. Nanodiamonds enhance therapeutic efficacy of doxorubicin in treating metastatic hormone-refractory prostate cancer.

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    Salaam, Amanee D; Hwang, Patrick T J; Poonawalla, Aliza; Green, Hadiyah N; Jun, Ho-wook; Dean, Derrick

    2014-10-24

    Enhancing therapeutic efficacy is essential for successful treatment of chemoresistant cancers such as metastatic hormone-refractory prostate cancer (HRPC). To improve the efficacy of doxorubicin (DOX) for treating chemoresistant disease, the feasibility of using nanodiamond (ND) particles was investigated. Utilizing the pH responsive properties of ND, a novel protocol for complexing NDs and DOX was developed using a pH 8.5 coupling buffer. The DOX loading efficiency, loading on the NDs, and pH responsive release characteristics were determined utilizing UV-Visible spectroscopy. The effects of the ND-DOX on HRPC cell line PC3 were evaluated with MTS and live/dead cell viability assays. ND-DOX displayed exceptional loading efficiency (95.7%) and drug loading on NDs (23.9 wt%) with optimal release at pH 4 (80%). In comparison to treatment with DOX alone, cell death significantly increased when cells were treated with ND-DOX complexes demonstrating a 50% improvement in DOX efficacy. Of the tested treatments, ND-DOX with 2.4 μg mL(-1) DOX exhibited superior efficacy (60% cell death). ND-DOX with 1.2 μg mL(-1) DOX achieved 42% cell death, which was comparable to cell death in response to 2.4 μg mL(-1) of free DOX, suggesting that NDs aid in decreasing the DOX dose necessary to achieve a chemotherapeutic efficacy. Due to its enhanced efficacy, ND-DOX can be used to successfully treat HRPC and potentially decrease the clinical side effects of DOX.

  5. HemoHIM enhances the therapeutic efficacy of ionizing radiation treatment in tumor-bearing mice.

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    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho

    2010-02-01

    Although radiotherapy is commonly used for a variety of cancers, radiotherapy alone does not achieve a satisfactory therapeutic outcome. In this study, we examined the possibility that HemoHIM can enhance the anticancer effects of ionizing radiation (IR) in melanoma-bearing mice. The HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of three edible herbs-Angelica Radix, Cnidium Rhizoma, and Paeonia Radix. Anticancer effects of HemoHIM were evaluated in melanoma-bearing mice exposed to IR. IR treatment (5 Gy at 7 days after melanoma cell injection) reduced the weight of the solid tumors, and HemoHIM supplementation with IR enhanced the decreases in tumor weight (P HemoHIM administration also increased the activity of natural killer cells and cytotoxic T cells, although the proportions of these cells in spleen were not different. In addition, HemoHIM administration increased the interleukin-2 and tumor necrosis factor-alpha secretion from lymphocytes stimulated with concanavalin A, which seemed to contribute to the enhanced efficacy of HemoHIM in tumor-bearing mice treated with IR. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy for enhancing the antitumor efficacy.

  6. Lactobionic acid-conjugated TPGS nanoparticles for enhancing therapeutic efficacy of etoposide against hepatocellular carcinoma

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    Tsend-Ayush, Altansukh; Zhu, Xiumei; Ding, Yu; Yao, Jianxu; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-05-01

    Many effective anti-cancer drugs have limited use in hepatocellular carcinoma (HCC) therapy due to the drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and the inhibition of drug-resistance-related mechanisms has become an integrated strategy for effectively combating chemo-resistant cancer. Herein, lactobionic acid-conjugated d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) has been developed as a potential asialoglycoprotein receptor (ASGPR)-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. The main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after being prepared using the nanoprecipitation method and characterized by dynamic light scattering (DLS). According to the results, smaller (˜141.43 nm), positively charged ETO-loaded TPGS-LA NPs were more suitable for providing efficient delivery to hepatoma cells by avoiding the clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs were noticeably able to enhance the cytotoxicity of ETO in HepG2 cells. Besides this, markedly higher internalization by the ASGPR-overexpressed HepG2 cells and efficient accumulation at the tumor site in vivo were revealed in the TPGS-LA NP group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to the ETO-loaded TPGS NPs. These results suggest that TPGS-LA NPs could be used as a potential ETO delivery system against HCC.

  7. Development and Evaluation of Mouth Dissolving Films of Amlodipine Besylate for Enhanced Therapeutic Efficacy

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    K. M. Maheswari

    2014-01-01

    Full Text Available The present investigation was undertaken with an objective of formulating mouth dissolving films (MDFs of Amlodipine Besylate (AMLO to enhance convenience and compliance of the elderly and pediatric patients for better therapeutic efficacy. Film formers like hydroxy propyl methyl cellulose (HPMC and methyl cellulose (MC along with film modifiers like poly vinyl pyrrolidone K30 (PVP K30, and sodium lauryl sulphate (SLS as solubilizing agents were evaluated. The prepared MDFs were evaluated for in vitro dissolution characteristics, in vitro disintegration time, and their physicomechanical properties. All the prepared MDFs showed good mechanical properties like tensile strength, folding endurance, and % elongation. MDFs were evaluated by means of FTIR, SEM, and X-RD studies. MDFs with 7.5% (w/w of HPMC E3 gave better dissolution properties when compared to HPMC E5, HPMC E15, and MC. MDFs with PVP K30 and SLS gave superior dissolution properties when compared to MDFs without PVP K30 and SLS. The dissolution properties of MDFs with PVP K30 were superior when compared to MDFs with SLS. In the case of F3 containing 7.5% of HPMC E3 and 0.04% of PVP K30, complete and faster release was observed within 60 sec when compared to other formulations. Release kinetics data reveals diffusion is the release mechanism.

  8. Systemic Administration of Interleukin 2 Enhances the Therapeutic Efficacy of Dendritic Cell-Based Tumor Vaccines

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    Shimizu, K.; Fields, R. C.; Giedlin, M.; Mule, J. J.

    1999-03-01

    We have reported previously that murine bone marrow-derived dendritic cells (DC) pulsed with whole tumor lysates can mediate potent antitumor immune responses both in vitro and in vivo. Because successful therapy was dependent on host immune T cells, we have now evaluated whether the systemic administration of the T cell stimulatory/growth promoting cytokine interleukin-2 (IL-2) could enhance tumor lysate-pulsed DC-based immunizations to further promote protective immunity toward, and therapeutic rejection of, syngeneic murine tumors. In three separate approaches using a weakly immunogenic sarcoma (MCA-207), the systemic administration of non-toxic doses of recombinant IL-2 (20,000 and 40,000 IU/dose) was capable of mediating significant increases in the potency of DC-based immunizations. IL-2 could augment the efficacy of tumor lysate-pulsed DC to induce protective immunity to lethal tumor challenge as well as enhance splenic cytotoxic T lymphocyte activity and interferon-γ production in these treated mice. Moreover, treatment with the combination of tumor lysate-pulsed DC and IL-2 could also mediate regressions of established pulmonary 3-day micrometastases and 7-day macrometastases as well as established 14- and 28-day s.c. tumors, leading to either significant cure rates or prolongation in overall survival. Collectively, these findings show that nontoxic doses of recombinant IL-2 can potentiate the antitumor effects of tumor lysate-pulsed DC in vivo and provide preclinical rationale for the use of IL-2 in DC-based vaccine strategies in patients with advanced cancer.

  9. Therapeutic Strategies to Enhance the Anticancer Efficacy of Histone Deacetylase Inhibitors

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    Claudia P. Miller

    2011-01-01

    Full Text Available Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.

  10. Anticancer Drug-Incorporated Layered Double Hydroxide Nanohybrids and Their Enhanced Anticancer Therapeutic Efficacy in Combination Cancer Treatment

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    Tae-Hyun Kim

    2014-01-01

    Full Text Available Objective. Layered double hydroxide (LDH nanoparticles have been studied as cellular delivery carriers for anionic anticancer agents. As MTX and 5-FU are clinically utilized anticancer drugs in combination therapy, we aimed to enhance the therapeutic performance with the help of LDH nanoparticles. Method. Anticancer drugs, MTX and 5-FU, and their combination, were incorporated into LDH by reconstruction method. Simply, LDHs were thermally pretreated at 400°C, and then reacted with drug solution to simultaneously form drug-incorporated LDH. Thus prepared MTX/LDH (ML, 5-FU/LDH (FL, and (MTX + 5-FU/LDH (MFL nanohybrids were characterized by X-ray diffractometer, scanning electron microscopy, infrared spectroscopy, thermal analysis, zeta potential measurement, dynamic light scattering, and so forth. The nanohybrids were administrated to the human cervical adenocarcinoma, HeLa cells, in concentration-dependent manner, comparing with drug itself to verify the enhanced therapeutic efficacy. Conclusion. All the nanohybrids successfully accommodated intended drug molecules in their house-of-card-like structures during reconstruction reaction. It was found that the anticancer efficacy of MFL nanohybrid was higher than other nanohybrids, free drugs, or their mixtures, which means the multidrug-incorporated LDH nanohybrids could be potential drug delivery carriers for efficient cancer treatment via combination therapy.

  11. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells.

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    Reenu Punia

    doxorubicin influx and efflux was mediated through downregulation of MDR1 treansporter in NSCLC cells.These findings suggested that acacetin augments the cytotoxicity of doxorubicin at lower concentrations in lung cancer cells. Their combination leads to more retention of doxorubicin in the cells by modulating drug trasporter and thus enhances its therapeutic potential.

  12. Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy.

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    Järnum, Sofia; Runström, Anna; Bockermann, Robert; Winstedt, Lena; Crispin, Max; Kjellman, Christian

    2017-09-01

    Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887-97. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.

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    Ning, Shoucheng; Bednarski, Mark; Oronsky, Bryan; Scicinski, Jan; Knox, Susan J

    2014-05-09

    Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Design of dendrimer-based drug delivery nanodevices with enhanced therapeutic efficacies

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    Kannan, Rangaramanujam

    2007-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorable, `peripheral' functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug delivery. They have significant potential compared to liposomes and nanoparticles, because of the reduced macrophage update, increased cellular transport, and the ability to modulate the local environment through functional groups. We are developing nanodevices based on dendritic systems for drug delivery, that contain a high drug payload, ligands, and imaging agents, resulting in `smart' drug delivery devices that can target, deliver, and signal. In collaboration with the Children's Hospital of Michigan, Karmanos Cancer Institute, and College of Pharmacy, we are testing the in vitro and in vivo response of these nanodevices, by adapting the chemistry for specific clinical applications such as asthma and cancer. These materials are characterized by UV/Vis spectroscopy, flow cytometry, fluorescence/confocal microscopy, and appropriate animal models. Our results suggest that: (1) We can prepare drug-dendrimer conjugates with drug payloads of greater than 50%, for a variety of drugs; (2) The dendritic polymers are capable of transporting and delivering drugs into cells faster than free drugs, with superior therapeutic efficiency. This can be modulated by the surface functionality of the dendrimer; (3) For chemotherapy drugs, the conjugates are a factor of 6-20 times more effective even in drug-resistant cell lines; (4) For corticosteroidal drugs, the dendritic polymers provide higher drug residence times in the lung, allowing for passive targeting. The ability of the drug-dendrimer-ligand conjugates to target specific asthma and cancer cells is currently being explored using in vitro and in vivo animal models.

  15. Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

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    Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke; Kajikawa, Shu-hei [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Uesato, Shin-ichi [Department of Biotechnology, Faculty of Engineering, Kansai University, Osaka 564-8680 (Japan); Watanabe, Kazushi [Proubase Technology Inc., Kanagawa 211-0063 (Japan); Tanimura, Susumu [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Koji, Takehiko [Department of Histology and Cell Biology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523 (Japan); Kohno, Michiaki, E-mail: kohnom@nagasaki-u.ac.jp [Laboratory of Cell Regulation, Department of Pharmaceutical Sciences, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Proubase Technology Inc., Kanagawa 211-0063 (Japan); Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501 (Japan)

    2013-04-19

    Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showed that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.

  16. A theranostic prodrug delivery system based on Pt(IV) conjugated nano-graphene oxide with synergistic effect to enhance the therapeutic efficacy of Pt drug.

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    Li, Jingwen; Lyv, Zhonglin; Li, Yanli; Liu, Huan; Wang, Jinkui; Zhan, Wenjun; Chen, Hong; Chen, Huabing; Li, Xinming

    2015-05-01

    Due to their high NIR-optical absorption and high specific surface area, graphene oxide and graphene oxide-based nanocomposites have great potential in both drug delivery and photothermal therapy. In the work reported herein we successfully integrate a Pt(IV) complex (c,c,t-[Pt(NH3)2Cl2(OH)2]), PEGylated nano-graphene oxide (PEG-NGO), and a cell apoptosis sensor into a single platform to generate a multifunctional nanocomposite (PEG-NGO-Pt) which shows potential for targeted drug delivery and combined photothermal-chemotherapy under near infrared laser irradiation (NIR), and real-time monitoring of its therapeutic efficacy. Non-invasive imaging using a fluorescent probe immobilized on the GO shows an enhanced therapeutic effect of PEG-NGO-Pt in cancer treatment via apoptosis and cell death. Due to the enhanced cytotoxicity of cisplatin and the highly specific tumor targeting of PEG-NGO-Pt at elevated temperatures, this nanocomposite displays a synergistic effect in improving the therapeutic efficacy of the Pt drug with complete destruction of tumors, no tumor recurrence and minimal systemic toxicity in comparison with chemotherapy or photothermal treatment alone, highlighting the advantageous effects of integrating Pt(IV) with GO for anticancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Preconditioning mesenchymal stem cells with the mood stabilizers lithium and valproic acid enhances therapeutic efficacy in a mouse model of Huntington's disease.

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    Linares, Gabriel R; Chiu, Chi-Tso; Scheuing, Lisa; Leng, Yan; Liao, Hsiao-Mei; Maric, Dragan; Chuang, De-Maw

    2016-07-01

    Huntington's disease (HD) is a fatal neurodegenerative disorder caused by CAG repeat expansions in the huntingtin gene. Although, stem cell-based therapy has emerged as a potential treatment for neurodegenerative diseases, limitations remain, including optimizing delivery to the brain and donor cell loss after transplantation. One strategy to boost cell survival and efficacy is to precondition cells before transplantation. Because the neuroprotective actions of the mood stabilizers lithium and valproic acid (VPA) induce multiple pro-survival signaling pathways, we hypothesized that preconditioning bone marrow-derived mesenchymal stem cells (MSCs) with lithium and VPA prior to intranasal delivery to the brain would enhance their therapeutic efficacy, and thereby facilitate functional recovery in N171-82Q HD transgenic mice. MSCs were treated in the presence or absence of combined lithium and VPA, and were then delivered by brain-targeted single intranasal administration to eight-week old HD mice. Histological analysis confirmed the presence of MSCs in the brain. Open-field test revealed that ambulatory distance and mean velocity were significantly improved in HD mice that received preconditioned MSCs, compared to HD vehicle-control and HD mice transplanted with non-preconditioned MSCs. Greater benefits on motor function were observed in HD mice given preconditioned MSCs, while HD mice treated with non-preconditioned MSCs showed no functional benefits. Moreover, preconditioned MSCs reduced striatal neuronal loss and huntingtin aggregates in HD mice. Gene expression profiling of preconditioned MSCs revealed a robust increase in expression of genes involved in trophic effects, antioxidant, anti-apoptosis, cytokine/chemokine receptor, migration, mitochondrial energy metabolism, and stress response signaling pathways. Consistent with this finding, preconditioned MSCs demonstrated increased survival after transplantation into the brain compared to non-preconditioned cells

  18. Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction.

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    Xue, Xiaodong; Liu, Yu; Zhang, Jian; Liu, Tao; Yang, Zhonglu; Wang, Huishan

    2015-01-01

    Objectives. Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation. Methods. Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISA in vitro. In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery. Results. In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs. In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery. Conclusions. Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

  19. How music training enhances working memory: a cerebrocerebellar blending mechanism that can lead equally to scientific discovery and therapeutic efficacy in neurological disorders.

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    Vandervert, Larry

    2015-01-01

    Following in the vein of studies that concluded that music training resulted in plastic changes in Einstein's cerebral cortex, controlled research has shown that music training (1) enhances central executive attentional processes in working memory, and (2) has also been shown to be of significant therapeutic value in neurological disorders. Within this framework of music training-induced enhancement of central executive attentional processes, the purpose of this article is to argue that: (1) The foundational basis of the central executive begins in infancy as attentional control during the establishment of working memory, (2) In accordance with Akshoomoff, Courchesne and Townsend's and Leggio and Molinari's cerebellar sequence detection and prediction models, the rigors of volitional control demands of music training can enhance voluntary manipulation of information in thought and movement, (3) The music training-enhanced blending of cerebellar internal models in working memory as can be experienced as intuition in scientific discovery (as Einstein often indicated) or, equally, as moments of therapeutic advancement toward goals in the development of voluntary control in neurological disorders, and (4) The blending of internal models as in (3) thus provides a mechanism by which music training enhances central executive processes in working memory that can lead to scientific discovery and improved therapeutic outcomes in neurological disorders. Within the framework of Leggio and Molinari's cerebellar sequence detection model, it is determined that intuitive steps forward that occur in both scientific discovery and during therapy in those with neurological disorders operate according to the same mechanism of adaptive error-driven blending of cerebellar internal models. It is concluded that the entire framework of the central executive structure of working memory is a product of the cerebrocerebellar system which can, through the learning of internal models

  20. Histatin 5-spermidine conjugates have enhanced fungicidal activity and efficacy as a topical therapeutic for oral candidiasis.

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    Tati, Swetha; Li, Rui; Puri, Sumant; Kumar, Rohitashw; Davidow, Peter; Edgerton, Mira

    2014-01-01

    Oropharyngeal candidiasis (OPC) is caused by the opportunistic fungi Candida albicans and is prevalent in immunocompromised patients, individuals with dry mouth, or patients with prolonged antibiotic therapies that reduce oral commensal bacteria. Human salivary histatins, including histatin 5 (Hst 5), are small cationic proteins that are the major source of fungicidal activity of saliva. However, Hsts are rapidly degraded in vivo, limiting their usefulness as therapeutic agents despite their lack of toxicity. We constructed a conjugate peptide using spermidine (Spd) linked to the active fragment of Hst 5 (Hst 54-15), based upon our findings that C. albicans spermidine transporters are required for Hst 5 uptake and fungicidal activity. We found that Hst 54-15-Spd was significantly more effective in killing C. albicans and Candida glabrata than Hst 5 alone in both planktonic and biofilm growth and that Hst 54-15-Spd retained high activity in both serum and saliva. Hst 54-15-Spd was not bactericidal against streptococcal oral commensal bacteria and had no hemolytic activity. We tested the effectiveness of Hst 54-15-Spd in vivo by topical application to tongue surfaces of immunocompromised mice with OPC. Mice treated with Hst 54-15-Spd had significant clearance of candidal tongue lesions macroscopically, which was confirmed by a 3- to 5-log fold reduction of C. albicans colonies recovered from tongue tissues. Hst 54-15-Spd conjugates are a new class of peptide-based drugs with high selectivity for fungi and potential as topical therapeutic agents for oral candidiasis.

  1. Endothelial Protein C–Targeting Liposomes Show Enhanced Uptake and Improved Therapeutic Efficacy in Human Retinal Endothelial Cells

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    Arta, Anthoula; Eriksen, Anne Z.; Melander, Fredrik

    2018-01-01

    PURPOSE. To determine whether human retinal endothelial cells (HRECs) express the endothelial cell protein C receptor (EPCR) and to realize its potential as a targeting moiety by developing novel single and dual corticosteroid–loaded functionalized liposomes that exhibit both enhanced uptake by H...... of cell tube formations in contrast to nontargeting liposomes. CONCLUSIONS. We show that HRECs express EPCR and this receptor could be a promising nanomedicine target in ocular diseases where the endothelial barrier of the retina is compromised....

  2. Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells

    OpenAIRE

    2009-01-01

    Abstract Purpose The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management...

  3. Enhanced therapeutic efficacy of budesonide in experimental colitis with enzyme/pH dual-sensitive polymeric nanoparticles

    Directory of Open Access Journals (Sweden)

    Naeem M

    2015-07-01

    Full Text Available Muhammad Naeem, Jiafu Cao, Moonjeong Choi, Woo Seong Kim, Hyung Ryong Moon, Bok Luel Lee, Min-Soo Kim, Yunjin Jung, Jin-Wook Yoo College of Pharmacy, Pusan National University, Busan, South Korea Abstract: Current colon-targeted drug-delivery approaches for colitis therapy often utilize single pH-triggered systems, which are less reliable due to the variation of gut pH in individuals and in disease conditions. Herein, we prepared budesonide-loaded dual-sensitive nanoparticles using enzyme-sensitive azo-polyurethane and pH-sensitive methacrylate copolymer for the treatment of colitis. The therapeutic potential of the enzyme/pH dual-sensitive nanoparticles was evaluated using a rat colitis model and compared to single pH-triggered nanoparticles. Clinical activity scores, colon/body weight ratios, myeloperoxidase activity, and proinflammatory cytokine levels were markedly decreased by dual-sensitive nanoparticles compared to single pH-triggered nanoparticles and budesonide solution. Moreover, dual-sensitive nanoparticles accumulated selectively in inflamed segments of the colon. In addition, dual-sensitive nanoparticle plasma concentrations were lower than single pH-triggered nanoparticles, and no noticeable in vitro or in vivo toxicity was observed. Our results demonstrate that enzyme/pH dual-sensitive nanoparticles are an effective and safe colon-targeted delivery system for colitis therapy. Keywords: azo-polyurethane, methacrylate copolymer, budesonide, colon-targeted nanoparticles, colitis

  4. Enhancement of the efficacy of therapeutic proteins by formulation with PEGylated liposomes; a case of FVIII, FVIIa and G-CSF.

    Science.gov (United States)

    Yatuv, Rivka; Robinson, Micah; Dayan, Inbal; Baru, Moshe

    2010-02-01

    Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.

  5. Poly(ethylene glycol-block-poly(ε-caprolactone– and phospholipid-based stealth nanoparticles with enhanced therapeutic efficacy on murine breast cancer by improved intracellular drug delivery

    Directory of Open Access Journals (Sweden)

    He XD

    2015-03-01

    Full Text Available Xiaodan He,1 Li Li,2 Hong Su,1 Dinglun Zhou,3 Hongmei Song,4 Ling Wang,1 Xuehua Jiang1 1West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3West China School of Public Health, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 4HitGen Ltd., Chengdu, Sichuan, People’s Republic of China Background: Effective anticancer drug delivery to the tumor site without rapid body clearance is a prerequisite for successful chemotherapy. 1,2-distearoyl-sn-glycero-3-phospho-ethanolamine-N-(methoxy[polyethyleneglycol]-2000 (DSPE-PEG2000 has been widely used in the preparation of stealth liposomes. Although PEG chains can efficiently preserve liposomes from rapid clearance by the reticuloendothelial system (RES, its application has been hindered by poor cellular uptake and unsatisfactory therapeutic effect.Methods: To address the dilemma, we presented a facile approach to fabricate novel stealth nanoparticles generated by poly(ethylene glycol-block-poly(ε-caprolactone (PEG-b-PCL, soybean phosphatidylcholine (SPC, and cholesterol, namely LPPs (L represented lipid and PP represented PEG-b-PCL, for the delivery of anticancer drug paclitaxel (PTX. LPPs were prepared using the thin film hydration method. Two PEG-b-PCL polymers with different molecular weights (MW; PEG2000-b-PCL2000, MW: 4,000 Da and PEG5000-b-PCL5000, MW: 10,000 Da were used to fabricate stealth nanoparticles. Conventional PEGylated liposome (LDP2000, L represented lipid and DP2000 represented DSPE-PEG2000 composed of SPC, cholesterol, and DSPE-PEG2000 was used as the control. The physical properties, cellular uptake, endocytosis pathway, cytotoxicity, pharmacokinetics, tumor accumulation, and anticancer efficacy of free PTX, PTX-loaded LPPs, and LDP2000 were systemically investigated after injection into 4T1

  6. Therapeutic efficacy of antibodies lacking Fcγ receptor binding against lethal dengue virus infection is due to neutralizing potency and blocking of enhancing antibodies [corrected].

    Directory of Open Access Journals (Sweden)

    Katherine L Williams

    2013-02-01

    Full Text Available Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS are life-threatening complications following infection with one of the four serotypes of dengue virus (DENV. At present, no vaccine or antiviral therapies are available against dengue. Here, we characterized a panel of eight human or mouse-human chimeric monoclonal antibodies (MAbs and their modified variants lacking effector function and dissected the mechanism by which some protect against antibody-enhanced lethal DENV infection. We found that neutralizing modified MAbs that recognize the fusion loop or the A strand epitopes on domains II and III of the envelope protein, respectively, act therapeutically by competing with and/or displacing enhancing antibodies. By analyzing these relationships, we developed a novel in vitro suppression-of-enhancement assay that predicts the ability of modified MAbs to act therapeutically against antibody-enhanced disease in vivo. These studies provide new insight into the biology of DENV pathogenesis and the requirements for antibodies to treat lethal DENV disease.

  7. MicroRNA-126 Priming Enhances Functions of Endothelial Progenitor Cells under Physiological and Hypoxic Conditions and Their Therapeutic Efficacy in Cerebral Ischemic Damage

    Directory of Open Access Journals (Sweden)

    Qunwen Pan

    2018-01-01

    Full Text Available Endothelial progenitor cells (EPCs have shown the potential for treating ischemic stroke (IS, while microRNA-126 (miR-126 is reported to have beneficial effects on endothelial function and angiogenesis. In this study, we investigated the effects of miR-126 overexpression on EPCs and explore the efficacy of miR-126-primed EPCs (EPCmiR-126 in treating IS. The effects of miR-126 overexpression on EPC proliferation, migratory, tube formation capacity, reactive oxygen species (ROS production, and nitric oxide (NO generation were determined. In in vivo study, the effects of EPCmiR-126 on the cerebral blood flow (CBF, neurological deficit score (NDS, infarct volume, cerebral microvascular density (cMVD, and angiogenesis were determined. Moreover, the levels of circulating EPCs (cEPCs and their contained miR-126 were measured. We found (1 miR-126 overexpression promoted the proliferation, migration, and tube formation abilities of EPCs; decreased ROS; and increased NO production of EPCs via activation of PI3K/Akt/eNOS pathway; (2 EPCmiR-126 was more effective than EPCs in attenuating infarct volume and NDS and enhancing cMVD, CBF, and angiogenesis; and (3 infusion of EPCmiR-126 increased the number and the level of miR-126 in cEPCs. Our data indicate that miR-126 overexpression enhanced the function of EPCs in vitro and in vivo.

  8. Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (− and ER (+ Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ibrahim Tekedereli

    2013-01-01

    Full Text Available Bcl-2 is overexpressed in about a half of human cancers and 50–70% of breast cancer patients, thereby conferring resistance to conventional therapies and making it an excellent therapeutic target. Small interfering RNA (siRNA offers novel and powerful tools for specific gene silencing and molecularly targeted therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically administered nanoliposomal (NL-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous twice a week leads to significant antitumor activity and suppression of growth in both estrogen receptor-negative (ER(− MDA-MB-231 and ER-positive (+ MCF7 breast tumors in orthotopic xenograft models (P < 0.05. A single intravenous injection of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231 and MCF-7 animal models (P < 0.05. NL-Bcl-2-siRNA treatment-induced apoptosis and autophagic cell death, and inhibited cyclin D1, HIF1α and Src/Fak signaling in tumors. In conclusion, our data provide the first evidence that in vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA significantly inhibits growth of both ER(− and ER(+ breast tumors and enhances the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by siRNA is a viable approach in breast cancers.

  9. Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

    2014-03-15

    To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

  10. Enhancing Teacher Efficacy in Special Education.

    Science.gov (United States)

    McDaniel, Elizabeth A.; McCarthy, Holly DiBella

    1989-01-01

    A special education teacher's sense of teaching efficacy and personal teaching efficacy influences teacher motivation and effort, teacher-student interactions, and student achievement. Methods for enhancing teachers' sense of efficacy are suggested. (JDD)

  11. Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated ...

    African Journals Online (AJOL)

    Therapeutic efficacy of sulfadoxine-pyrimethamine in uncomplicated Plasmodium falciparum malaria 3 years after introduction in Mpumalanga. Aaron Mabuza, John Govere, David Durrheim, Nicros Mangomezulu, Barry Bredenkamp, Karen Barnes, Brian Sharp ...

  12. Repeated tumor pO2 measurements by multi-site EPR oximetry as a prognostic marker for enhanced therapeutic efficacy of fractionated radiotherapy

    International Nuclear Information System (INIS)

    Hou Huagang; Lariviere, Jean P.; Demidenko, Eugene; Gladstone, David; Swartz, Harold; Khan, Nadeem

    2009-01-01

    Purpose: To investigate the temporal effects of single or fractionated radiotherapy on subcutaneous RIF-1 tumor pO 2 and to determine the therapeutic outcomes when the timing of fractionations is guided by tumor pO 2 . Methods: The time-course of the tumor pO 2 changes was followed by multi-site electron paramagnetic resonance (EPR) oximetry. The tumors were treated with single 10, 20, and 10 Gy x 2 doses, and the tumor pO 2 was measured repeatedly for six consecutive days. In the 10 Gy x 2 group, the second dose of 10 Gy was delivered at a time when the tumors were either relatively oxygenated or hypoxic. The changes in tumor volumes were followed for nine days to determine the therapeutic outcomes. Results: A significant increase in tumor pO 2 was observed at 24 h post 10 Gy, while 20 Gy resulted in a significant increase in tumor pO 2 at 72-120 h post irradiation. The tumors irradiated with a second dose of 10 Gy at 24 h, when the tumors were oxygenated, had a significant increase in tumor doubling times (DTs), as compared to tumors treated at 48 h when they were hypoxic (p 2 repeatedly during fractionated schemes to optimize radiotherapeutic outcome. This technique could also be used to identify responsive and non-responsive tumors, which will facilitate the design of other therapeutic approaches for non-responsive tumors at early time points during the course of therapy.

  13. Localized sequence-specific release of a chemopreventive agent and an anticancer drug in a time-controllable manner to enhance therapeutic efficacy.

    Science.gov (United States)

    Pan, Wen-Yu; Lin, Kun-Ju; Huang, Chieh-Cheng; Chiang, Wei-Lun; Lin, Yu-Jung; Lin, Wei-Chih; Chuang, Er-Yuan; Chang, Yen; Sung, Hsing-Wen

    2016-09-01

    Combination chemotherapy with multiple drugs commonly requires several injections on various schedules, and the probability that the drug molecules reach the diseased tissues at the proper time and effective therapeutic concentrations is very low. This work elucidates an injectable co-delivery system that is based on cationic liposomes that are adsorbed on anionic hollow microspheres (Lipos-HMs) via electrostatic interaction, from which the localized sequence-specific release of a chemopreventive agent (1,25(OH)2D3) and an anticancer drug (doxorubicin; DOX) can be thermally driven in a time-controllable manner by an externally applied high-frequency magnetic field (HFMF). Lipos-HMs can greatly promote the accumulation of reactive oxygen species (ROS) in tumor cells by reducing their cytoplasmic expression of an antioxidant enzyme (superoxide dismutase) by 1,25(OH)2D3, increasing the susceptibility of cancer cells to the cytotoxic action of DOX. In nude mice that bear xenograft tumors, treatment with Lipos-HMs under exposure to HFMF effectively inhibits tumor growth and is the most effective therapeutic intervention among all the investigated. These empirical results demonstrate that the synergistic anticancer effects of sequential release of 1,25(OH)2D3 and DOX from the Lipos-HMs may have potential for maximizing DOX cytotoxicity, supporting more effective cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Neurodevelopmental Treatment (NDT): Therapeutic Intervention and Its Efficacy.

    Science.gov (United States)

    Stern, Francine Martin; Gorga, Delia

    1988-01-01

    Use of neurodevelopmental treatment, also known as the Bobath method, is discussed, including its history, philosophy, goals, and treatment emphasis with infants and children with movement disorders. Examples of children before and after therapeutic intervention illustrate use of the technique, and controversies in measuring therapy efficacy are…

  15. Understanding Music's Therapeutic Efficacy with Implications for Why Music Matters

    Science.gov (United States)

    Thram, Diane

    2015-01-01

    In this essay, I focus on how attention to music's therapeutic efficacy is important to the praxial music education philosophy espoused by Elliott and Silverman. I note, despite the use of the term praxis from Aristotle's philosophy dating back to antiquity, there is no mention in Music Matters 2 of what historical evidence tells us about how…

  16. Therapeutic Efficacy Of Cotecxin (R) alone and Its Combination with ...

    African Journals Online (AJOL)

    The therapeutic efficacy of Cotecxin(R) (Dihydroartemisinin) alone and its combination with diminazene aceturate (Berenil(R)) was studied in rats infected with Federe strain of Trypanosoma brucei brucei. Fifty healthy adult albino rats of both sexes weighing between 100-180g used were divided into five groups (A-E) of 10 ...

  17. Therapeutic benefits of enhancing permeability barrier for atopic eczema

    Directory of Open Access Journals (Sweden)

    George Man

    2015-06-01

    Full Text Available The regulatory role of epidermal permeability barrier function in cutaneous inflammation has been well appreciated. While barrier disruption induces cutaneous inflammation, improvement of permeability barrier function alleviates inflammation. Studies have demonstrated that improvement of epidermal permeability barrier function not only prevents the development of atopic eczema, but also delays the relapse of these diseases. Moreover, enhancing the epidermal permeability barrier also alleviates atopic eczema. Furthermore, co-applications of barrier enhancing products with glucocorticoids can increase the therapeutic efficacy and reduce the adverse effects of glucocorticoids in the treatment of atopic eczema. Therefore, utilization of permeability barrier enhancing products alone or in combination with glucocorticoids could be a valuable approach in the treatment of atopic eczema. In this review, we discuss the benefits of improving the epidermal permeability barrier in the management of atopic eczema.

  18. Therapeutic efficacy of Chymotrypsin in acute bovine mastitis

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    Marco Leal G

    2016-05-01

    Full Text Available Objective. To evaluate the therapeutic efficacy of a proteolytic drug “chymotrypsin” combined with beta-lactam antibiotics in cows with acute mastitis. Material and Methods. Fourteen cows with acute mastitis. Three cows were treated with a beta-latam antibiotic (BLA and the other eleven cows were treated with chymotrypsin plus beta-lactam antibiotic (C+BLA. The response was evaluated according to the semiological findings, somatic cell count (SCC and a microbiological culture. Results. There was a therapeutic efficacy comparing the pre and post treatment period (SCC reduction, p<0.01 and a reduction of clinical signs in 84.7% of treated quarters in the first day of treatment (C+BLA compared with (BLA. Conclusions. Chymotrypsin improves the treatment of acute mastitis when is combined with BLA, controlling the infected mammary glands, compared with the group treated only with amoxicilina and clavulanic acid.

  19. An Enhanced Understanding of Therapeutic Communities Worldwide.

    Science.gov (United States)

    Tiburcio, Nelson Jose; Kressel, David

    2011-01-01

    Therapeutic communities posit favorable treatment outcomes by relying on the community as the healing agent (Deleon 2000). Active treatment participation and treatment tenure are two domains that are positive predictors of positive treatment outcomes over time. Some of the more important domains that remain to be thoroughly investigated in international research on therapeutic community (TC) treatment outcome studies are the underlying effects of culture on the treatment process. Cultural components play a significant role, as also reported by various TC participants over the years (such as the effects of health literacy on sustaining abstinence from drug use over the long term, Tiburcio 2008). In recent years, health literacy has taken on a significant role in order for individuals to readily understand their needs (Schillinger et al 2002; Jorm et al 1997); or as pertains to feeling shamed in the process (Parikh et al 1996). As these and other studies suggest, the cultural competence of the providers is equally important. To our knowledge the " International TC Study " and findings presented herein constitute one of only a few studies that have conducted investigations comparing therapeutic community treatment modifications internationally, from the perspective of the participants themselves and which consider cultural components of this process. One key advantage of the resulting Qualitative datasets and analyses is that it not only includes residents' perspectives, and staff experiential elements, but importantly, incorporates staff debriefings about their respective interactions at each of the international treatment modalities, presenting well rounded depictions of each of these milieus. To that end, the data examined here presents an enhanced portrait of the provider-patient treatment dynamic, and lends voice to the various aspects of treatment participation in light of these cultural issues, and from the perspective of providers, as well as the participants.

  20. Therapeutic efficacy of self-ligating brackets: A systematic review.

    Science.gov (United States)

    Dehbi, Hasnaa; Azaroual, Mohamed Faouzi; Zaoui, Fatima; Halimi, Abdelali; Benyahia, Hicham

    2017-09-01

    Over the last few years, the use of self-ligating brackets in orthodontics has progressed considerably. These systems have been the subject of numerous studies with good levels of evidence making it possible to evaluate their efficacy and efficiency compared to conventional brackets. The aim of this study was to evaluate the therapeutic efficacy of self-ligating brackets by means of a systematic review of the scientific literature. A systematic study was undertaken in the form of a recent search of the electronic Pubmed database, oriented by the use of several keywords combined by Boolean operators relating to the therapeutic efficacy of self-ligating brackets through the study of tooth alignment, space closure, expansion, treatment duration and degree of discomfort. The search was limited to randomized controlled studies, and two independent readers identified studies corresponding to the selection criteria. The chosen articles comprised 20 randomized controlled trials. The studies analyzed revealed the absence of significant differences between the two types of system on the basis of the clinical criteria adopted, thereby refuting the hypothesis of the superiority of self-ligating brackets over conventional systems. Copyright © 2017 CEO. Published by Elsevier Masson SAS. All rights reserved.

  1. Therapeutic enhancement of protective immunity during experimental leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Senad Divanovic

    2011-09-01

    Full Text Available Leishmaniasis remains a significant cause of morbidity and mortality in the tropics. Available therapies are problematic due to toxicity, treatment duration and emerging drug resistance. Mouse models of leishmaniasis have demonstrated that disease outcome depends critically on the balance between effector and regulatory CD4(+ T cell responses, something mirrored in descriptive studies of human disease. Recombinant IL-2/diphtheria toxin fusion protein (rIL-2/DTx, a drug that is FDA-approved for the treatment of cutaneous T cell lymphoma, has been reported to deplete regulatory CD4(+ T cells.We investigated the potential efficacy of rIL-2/DTx as adjunctive therapy for experimental infection with Leishmania major. Treatment with rIL-2/DTx suppressed lesional regulatory T cell numbers and was associated with significantly increased antigen-specific IFN-γ production, enhanced lesion resolution and decreased parasite burden. Combined administration of rIL-2/DTx and sodium stibogluconate had additive biological and therapeutic effects, allowing for reduced duration or dose of sodium stibogluconate therapy.These data suggest that pharmacological suppression of immune counterregulation using a commercially available drug originally developed for cancer therapy may have practical therapeutic utility in leishmaniasis. Rational reinvestigation of the efficacy of drugs approved for other indications in experimental models of neglected tropical diseases has promise in providing new candidates to the drug discovery pipeline.

  2. Therapeutic efficacy of uterine arterial embolization for intractable uterine hemorrhage

    International Nuclear Information System (INIS)

    Liu Lang; Lu Lianwei; Ke Mengjia; Zhao Ru'en; Zeng Shaolan

    2010-01-01

    Objective: To evaluate the therapeutic efficacy of uterine arterial embolization (UAE) for intractable uterine hemorrhage. Methods: 16 patients with intractable uterine hemorrhage underwent bilateral UAE after failed conventional conservative treatment. Results: Uterine hemorrhage ceased within 12 hours in 15 patients (93.8%) after bilateral super-selective UAE. Internal iliac artery embolization was performed on one patient (6.2%) and hysterectomy was eventually carried out because of recurrent hemorrhage. Conclusion: UAE is a rapid and effective treatment method obviating hysterectomy for intractable uterine hemorrhage. (authors)

  3. Transient Treg depletion enhances therapeutic anti‐cancer vaccination

    Science.gov (United States)

    Aston, Wayne J.; Chee, Jonathan; Khong, Andrea; Cleaver, Amanda L.; Solin, Jessica N.; Ma, Shaokang; Lesterhuis, W. Joost; Dick, Ian; Holt, Robert A.; Creaney, Jenette; Boon, Louis; Robinson, Bruce; Lake, Richard A.

    2016-01-01

    Abstract Introduction Regulatory T cells (Treg) play an important role in suppressing anti‐ immunity and their depletion has been linked to improved outcomes. To better understand the role of Treg in limiting the efficacy of anti‐cancer immunity, we used a Diphtheria toxin (DTX) transgenic mouse model to specifically target and deplete Treg. Methods Tumor bearing BALB/c FoxP3.dtr transgenic mice were subjected to different treatment protocols, with or without Treg depletion and tumor growth and survival monitored. Results DTX specifically depleted Treg in a transient, dose‐dependent manner. Treg depletion correlated with delayed tumor growth, increased effector T cell (Teff) activation, and enhanced survival in a range of solid tumors. Tumor regression was dependent on Teffs as depletion of both CD4 and CD8 T cells completely abrogated any survival benefit. Severe morbidity following Treg depletion was only observed, when consecutive doses of DTX were given during peak CD8 T cell activation, demonstrating that Treg can be depleted on multiple occasions, but only when CD8 T cell activation has returned to base line levels. Finally, we show that even minimal Treg depletion is sufficient to significantly improve the efficacy of tumor‐peptide vaccination. Conclusions BALB/c.FoxP3.dtr mice are an ideal model to investigate the full therapeutic potential of Treg depletion to boost anti‐tumor immunity. DTX‐mediated Treg depletion is transient, dose‐dependent, and leads to strong anti‐tumor immunity and complete tumor regression at high doses, while enhancing the efficacy of tumor‐specific vaccination at low doses. Together this data highlight the importance of Treg manipulation as a useful strategy for enhancing current and future cancer immunotherapies. PMID:28250921

  4. Therapeutic efficacy of cyclic home elemental enteral alimentation in Crohn's disease: Japanese cooperative Crohn's disease study.

    Science.gov (United States)

    Matsueda, K; Shoda, R; Takazoe, M; Hiwatashi, N; Bamba, T; Kobayashi, K; Saito, T; Terano, A; Yao, T

    1995-11-01

    Crohn's disease (CD) often flares up and requires frequent hospitalization and/or surgery. Cyclic home elemental enteral alimentation (C-HEEA) was developed to prevent flare-up of CD and to minimize patient hospitalization. However, its therapeutic efficacy has not been studied in a large patient population. Therefore, questionnaires were sent to members of the Inflammatory Bowel Disease (IBD) Research Group of Japan to evaluate the therapeutic efficacy of C-HEEA and to define the factors that may affect the efficacy of the treatment. Data for 410 patients (C-HEEA-treated n = 322; drug-treated n = 88) were collected from 29 institutions and analysis showed the following results. The cumulative remission and non-hospitalization rates of the C-HEEA treated group were significantly higher than the rates of the drug-treated group in all patients and in those with ileitis and ileo-colitis (P < 0.0001, P < 0.001, and P < 0.01, respectively), but no significant difference was noted in patients with colitis. Cumulative remission and non-hospitalization rates were also influenced by the daily calorie content of the elemental diet (ED); more than 1200 kcal of the ED per day was found to be more effective than lower amounts to maintain remission and to prevent hospitalization. The therapeutic efficacy of C-HEEA was shown to be superior to that of drug treatment in patients with CD with ileal involvement, and it is suggested that more than 1200kcal per day should be supplied by the ED to enhance its therapeutic efficacy.

  5. Therapeutic efficacy of a therapeutic cooking group from the patients' perspective.

    Science.gov (United States)

    Hill, Kimberly H; O'Brien, Kimberly A; Yurt, Roger W

    2007-01-01

    The purpose of this study was to evaluate the therapeutic efficacy of the cooking group from the burn survivors' perspective. By incorporating concepts of kitchen skills, energy conservation, and desensitization techniques, the cooking group can assist patients with the functional use of their hands, standing tolerance, return to former vocational activities, and socialization with other patients. A questionnaire was developed based on commonly expressed benefits of cooking group. Areas of interest included decreasing anxiety in the kitchen, distraction from their burns, socializing with other burn survivors, and the physical benefits of participating in the group. The results of this study indicate that participants regard the therapeutic cooking group as a valuable treatment modality that effectively combines functional activities with socialization to decrease burn related anxiety and increase motion in a supportive environment for patients with burns.

  6. Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12.

    Science.gov (United States)

    Bozeman, Erica N; He, Sara; Shafizadeh, Yalda; Selvaraj, Periasamy

    2016-01-01

    Immunotherapeutic approaches have emerged as promising strategies to treat various cancers, including breast cancer. A single approach, however, is unlikely to effectively combat the complex, immune evasive strategies found within the tumor microenvironment, thus novel, effective combination treatments must be explored. In this study, we investigated the efficacy of a combination therapy consisting of PD-L1 immune checkpoint blockade and whole cell vaccination in a HER-2 positive mouse model of breast cancer. We demonstrate that tumorigenicity is completely abrogated when adjuvanted with immune stimulatory molecules (ISMs) B7-1 and a cell-surface anchored (GPI) form of IL-12 or GM-CSF. Irradiated cellular vaccines expressing the combination of adjuvants B7-1 and GPI-IL-12 completely inhibited tumor formation which was correlative with robust HER-2 specific CTL activity. However, in a therapeutic setting, both cellular vaccination and PD-L1 blockade induced only 10-20% tumor regression when administered alone but resulted in 50% tumor regression as a combination therapy. This protection was significantly hindered following CD4 or CD8 depletion indicating the essential role played by cellular immunity. Collectively, these pre-clinical studies provide a strong rationale for further investigation into the efficacy of combination therapy with tumor cell vaccines adjuvanted with membrane-anchored ISMs along with PD-L1 blockade for the treatment of breast cancer.

  7. Therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia

    Directory of Open Access Journals (Sweden)

    Ekta Atul Thakkar

    2014-12-01

    Full Text Available Aim: The aim was to determine therapeutic efficacy of different Hemodialysis prescriptions in canine azotemia. Materials and Methods: Patients (n=9 with acute onset of renal dysfunction or chronic patients with superimposed acute factor (component or patients with known chronic nature of the disease were dialyzed with Fresenius 4008S hemodialysis machine after jugular catheterization. Patients were randomly divided into two groups, one group (n=3 was dialyzed every day and second (n=4 was dialyzed on alternate days. The patients were evaluated for following parameters to compare the efficacy of the dialysis prescription: Urea reduction ratio (URR, creatinine reduction ratio (CRR, Kt/V, time averaged concentration of urea (TAC urea. Result and Discussion: Increasing both dialysis frequency and duration is the superior dialysis schedule. Patient dialyzed every day with total processed blood volume 1.79 L/Kg for 4 h 26 min/session had the lowest TAC of 36.82 mg/dl, thereby was considered it as a better prescription.

  8. Understanding music’s therapeutic efficacy: Implications for music education

    Directory of Open Access Journals (Sweden)

    Diane Thram

    2014-11-01

    Full Text Available In the current era of electronic domination of human experience, be it via cell phone and/or computer addiction, or the ubiquitous television, actual participation in music- making is less and less common for the average person, child or adult. Passive participation through listening is most often cited by people as their major experience with music in their lives. When asked if listening has therapeutic effects, it is rare for anyone to respond in the negative. Likewise, for performers/active participants in music- making, be it solitary or as part of a group, invariably an enhanced sense of well-being from the act of making music is reported. This paper addresses therapeutic aspects of musical participation (singing, clapping, playing an instrument, dancing, listening by providing a historical overview (12th c to present of attitudes toward music’s therapeutic effects. It argues that music exists through the interaction of our biological capacity to make music with our cultural circumstances. How individuals benefit in all aspects their being – physical, mental and emotional – from engaging in the act of making music is illustrated with examples from field research in southern Africa. Finally implications for Music Education are explored which emphasize how more comprehensive integration of music into the curriculum can serve as an antidote to the increasing isolation and alienation of modern life.

  9. Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.

    Science.gov (United States)

    Kelly, Cynthia W

    2008-04-01

    To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.

  10. Stealth Properties to Improve Therapeutic Efficacy of Drug Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stefano Salmaso

    2013-01-01

    Full Text Available Over the last few decades, nanocarriers for drug delivery have emerged as powerful tools with unquestionable potential to improve the therapeutic efficacy of anticancer drugs. Many colloidal drug delivery systems are underdevelopment to ameliorate the site specificity of drug action and reduce the systemic side effects. By virtue of their small size they can be injected intravenously and disposed into the target tissues where they release the drug. Nanocarriers interact massively with the surrounding environment, namely, endothelium vessels as well as cells and blood proteins. Consequently, they are rapidly removed from the circulation mostly by the mononuclear phagocyte system. In order to endow nanosystems with long circulation properties, new technologies aimed at the surface modification of their physicochemical features have been developed. In particular, stealth nanocarriers can be obtained by polymeric coating. In this paper, the basic concept underlining the “stealth” properties of drug nanocarriers, the parameters influencing the polymer coating performance in terms of opsonins/macrophages interaction with the colloid surface, the most commonly used materials for the coating process and the outcomes of this peculiar procedure are thoroughly discussed.

  11. The Slaying of a Beautiful Hypothesis: The Efficacy of Counseling and the Therapeutic Process

    Science.gov (United States)

    Hauser, Mike; Hays, Danica G.

    2010-01-01

    Although the efficacy of counseling has been empirically linked to the therapeutic process, the emphasis in much of the literature remains on technique use. This article discusses 3 components of therapeutic efficacy (i.e., common factors, working alliance, and counselor attributes) and provides implications for counselors and counselor training.…

  12. Exogenous Restoration of TUSC2 Expression Induces Responsiveness to Erlotinib in Wildtype Epidermal Growth Factor Receptor (EGFR Lung Cancer Cells through Context Specific Pathways Resulting in Enhanced Therapeutic Efficacy.

    Directory of Open Access Journals (Sweden)

    Bingbing Dai

    Full Text Available Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC cell lines resistant to the epidermal growth factor receptor (EGFR tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.

  13. Integrin-binding elastin-like polypeptide as an in situ gelling delivery matrix enhances the therapeutic efficacy of adipose stem cells in healing full-thickness cutaneous wounds.

    Science.gov (United States)

    Choi, Seong-Kyoon; Park, Jin-Kyu; Kim, Jung-Hee; Lee, Kyeong-Min; Kim, Enjoo; Jeong, Kyu-Shik; Jeon, Won Bae

    2016-09-10

    One crucial issue in stem cell therapy used for tissue repair is often the lack of selective carriers to deliver stem cells to the site of injury where the native extracellular matrix is pathologically damaged or lost. Therefore, it is necessary to develop a biomaterial that is permissive to stem cells and is suitable to replace injured or missing matrix. The major aim of this study is to investigate the potential of an RGD-containing elastin-like polypeptide (REP) with the structure TGPG[VGRGD(VGVPG)6]20WPC to engraft adipose stem cells (ASC) to full-thickness excisional wounds in mice. We implanted REP into the wound defects via body temperature-induced in situ aggregation. Engrafted REP exhibited a half-life of 2.6days in the wounds and did not elicit any pathological immune responses. REP itself significantly accelerated wound closure and reepithelialization and upregulated the expression of dermal tissue components. A combined administration of REP and ASC formed a hydrogel-like ASC/REP composite, which provided better neovascularization than the use of ASCs alone and increased the viability of transplanted ASC, improving overall wound healing. In vitro and in vivo mechanistic investigations suggested that REP enhances ASC survival at least in part via the Fak/Src adhesion-induced upregulation of Mek/Erk and PI3K/Akt survival pathways. We conclude that REP is a promising therapeutic agent for the improvement of stem cell-based therapy for enhanced tissue regeneration and repair. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Therapeutic efficacy of hydro-kinesiotherapy Programs in lumbar spondylosis

    Directory of Open Access Journals (Sweden)

    Ana-Maria BOTEZAN

    2015-12-01

    Full Text Available Lumbar spondylarthrosis is a degenerative disease that affects the joint structures of the lumbar spine. In the course of time, numerous studies on the role of hydro-kinesiotherapy in the treatment of lumbar spondylosis have been conducted. The aim of this research is motivated by the significantly high number of patients with chronic pain in the lumbar spine due to lumbar spondylosis, as well as by the negative impact on their quality of life through the impairment of the activities of daily living. The prospective longitudinal study was carried out at the Clinical Rehabilitation Hospital Cluj-Napoca. The study included 35 patients with chronic low back pain and mobility limitation in the lumbar spine. The patients were assigned to two groups: the study group formed by 20 patients and the control group consisting of 15 patients aged between 40-70 years. The treatment of the patients included in the study was performed over a two week period and consisted of a hydro-kinesiotherapy program, for the patients of the study group, the duration of a treatment session being 40 minutes. Both the subjects of the study group and of the control group also benefited from sedative massage of the lumbosacral spine, kinesiotherapy, laser therapy of the lumbar spine. The patients were evaluated using Schober’s test, the Visual Analogue Scale, the Oswestry index. These evaluation methods were applied to the patients of both groups at the beginning of the rehabilitation programs and after two weeks. The results of the study demonstrated the therapeutic efficacy of the medical rehabilitation programs that included hydro-kinesiotherapy programs. The patients of both groups had improvements through a decrease of lumbar pain, an increase in lumbar spine mobility, as well as in the patients’ ability to organize themselves in the activities of daily living. However, the patients of the study group, with a hydro-kinesiotherapy program performed for two weeks, had

  15. Efficacy of therapeutic ultrasound and exercise therapy in the ...

    African Journals Online (AJOL)

    Results: Findings of the study revealed no significant difference in VAS, ROM and WOMAC scores in the study and control groups. Conclusions: This study confirms that therapeutic ultrasound is of no additional benefit to exercise therapy in the management of chronic osteoarthritis. Key words: Ultrasound; Exercise; ...

  16. Therapeutic Efficacy of Intermittent Cryotherapy in the Management ...

    African Journals Online (AJOL)

    This study was therefore, designed to investigate the efficacy of intermittent cryotherapy in the management of pain among human subjects who sustained closed soft tissue injuries (CSTIs). Subjects' pre- and post-treatment pain perception scores (PPS) using visual analogue scale (VAS) and the sessions of treatment were ...

  17. Efficacy of enhanced external counterpulsation: our experience

    Directory of Open Access Journals (Sweden)

    Chandra Mani Adhikari

    2014-11-01

    Full Text Available Aims Enhanced external counterpulsation therapy is a non-invasive, non-pharmacological outpatient treatment option for refractory angina pectoris. Our aim is to evaluate its efficacy in Nepalese refractory angina pectoris patients. Materials and methods It was single centre prospective study conducted from 2010 August to 2013 December. All thirty one (n=31 consecutive patients, referred for and received 35 hours of treatment were included in this study. The distance covered in six minute walk test before and after the treatment was recorded and compared. Patients were followed each with the questionnaires about their anginal symptoms before and after the treatment. Results In our study 19(61.3% were male and 12(38.7% female. The mean age was 65.7±9.3 years. Most patients had multi vessel disease. Twelve patients had previous history of revascularization. In 6 minute walk test there was significant difference in mean distance covered before and after the treatment. Most patients experienced decrease in the angina symptom. They had decreased in severity and frequency of angina, resulting in decreased use of sublingual nitrates. Conclusion EECP can be safe and effective treatment option for patients with RAP.

  18. Zoledronic acid enhances antitumor efficacy of liposomal doxorubicin.

    Science.gov (United States)

    Hattori, Yoshiyuki; Shibuya, Kazuhiko; Kojima, Kaori; Miatmoko, Andang; Kawano, Kumi; Ozaki, Kei-Ichi; Yonemochi, Etsuo

    2015-07-01

    Previously, we found that the injection of zoledronic acid (ZOL) into mice bearing tumor induced changes of the vascular structure in the tumor. In this study, we examined whether ZOL treatment could decrease interstitial fluid pressure (IFP) via change of tumor vasculature, and enhance the antitumor efficacy of liposomal doxorubicin (Doxil®). When ZOL solution was injected at 40 µg/mouse per day for three consecutive days into mice bearing murine Lewis lung carcinoma LLC tumor, depletion of macrophages in tumor tissue and decreased density of tumor vasculature were observed. Furthermore, ZOL treatments induced inflammatory cytokines such as interleukin (IL)-10 and -12, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF)-α in serum of LLC tumor-bearing mice, but not in normal mice, indicating that ZOL treatments might induce an inflammatory response in tumor tissue. Furthermore, ZOL treatments increased antitumor activity by Doxil in mice bearing a subcutaneous LLC tumor, although they did not significantly increase the tumor accumulation of doxorubicin (DXR). These results suggest that ZOL treatments might increase the therapeutic efficacy of Doxil via improvement of DXR distribution in a tumor by changing the tumor vasculature. ZOL treatment can be an alternative approach to increase the antitumor effect of liposomal drugs.

  19. Experimental study of plasmapheresis therapeutic efficacy in severe radiation damage

    International Nuclear Information System (INIS)

    Legeza, V.I.; Abdul', Yu.A.; Chigareva, N.G.; Petkevich, N.V.; Myasoedov, A.F.; Andryukhin, V.I.; Artemenko, A.G.

    1994-01-01

    In experiments with dogs exposed to 2.9 Gy (LD 80/45 ) it was found that plasmapheresis treatment 4-6 h after irradiation reduce the severity of the radiation sickness clinical manifestations and post-radiation toxemia thus increasing the rate of animal survival up to 60 %. Sham plasmapheresis included all the manipulations of plasmapheretic treatment except plasma substitution and had no detoxication effect and did not affect the irradiated animals survival. This is evidence for leading role of detoxiation in the mechanisms of th therapeutic action of plasmapheresis in acute irradiation

  20. Therapeutic enhancement of newly derived bacteriocins against Giardia lamblia.

    Science.gov (United States)

    Amer, Eglal I; Mossallam, Shereen F; Mahrous, Hoda

    2014-11-01

    Trials for identifying efficient anti-giardial agents are still ongoing. Nowadays, bacteriocins have attracted the attention as potential antimicrobial compounds. For the first time, the current study evaluated the therapeutic efficacy of bacteriocins derived from newly isolated Egyptian strains of probiotics Lactobacilli; L. acidophilus (P106) and L. plantarum (P164) against Giardia lamblia. Bacteriocins' efficacy was evaluated both in vitro; by growth inhibition and adherence assays, and in vivo; through estimation of parasite density, intestinal histopathological examination and ultrastructural analysis of Giardia trophozoites. In vivo bacteriocins' clinical safety was assessed. In vitro results proved that 50 µg of L. acidophilus bacteriocin induced reduction of the mean Giardia lamblia trophozoites by 58.3 ± 4.04%, while at lower concentrations of 10 and 20 µg of both L. acidophilus and L. plantarum, non significant reduction of the mean parasite density was achieved. In vitro trophozoites adherence was susceptible to the tested bacteriocins at all studied concentrations with variable degrees, while the highest adherence reduction was demonstrated using 50 µg of L acidophilus bacteriocin. In vivo, oral inoculation of 50 µg/mouse L. acidophilus bacteriocin for 5 successive days resulted in a noteworthy decline of the intestinal parasite density, along with amelioration of intestinal pathology of infected mice. Ultrastructural examination proved thatfive doses of L. acidophilus bacteriocin showed marked changes in cellular architecture of the trophozoites with evident disorganization of the cell membrane, adhesive disc and cytoplasmic components. This is the first reported study of the safe anti-giardial efficacy of L. acidophilus (P106) derived bacteriocin, hence highlighting its great promise as a potential therapeutic safe alternative to existing commercial drugs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis

    Science.gov (United States)

    Loos, Julia A.; Dávila, Valeria A.; Rodrígues, Christian R.; Petrigh, Romina; Zoppi, Jorge A.; Crocenzi, Fernando A.; Cumino, Andrea C.

    2017-01-01

    Metformin (Met) is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day) in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day) was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy. PMID:28182659

  2. Metformin exhibits preventive and therapeutic efficacy against experimental cystic echinococcosis.

    Directory of Open Access Journals (Sweden)

    Julia A Loos

    2017-02-01

    Full Text Available Metformin (Met is an anti-hyperglycemic and potential anti-cancer agent which may exert its anti-proliferative effects via the induction of energetic stress. In this study we investigated the in vitro and in vivo efficacy of Met against the larval stage of Echinococcus granulosus. Metformin showed significant dose- and time-dependent killing effects on in vitro cultured protoscoleces and metacestodes. Notably, the combination of Met together with the minimum effective concentration of ABZSO had a synergistic effect after days 3 and 12 on metacestodes and protoscoleces, respectively. Oral administration of Met (50 mg/kg/day in E. granulosus-infected mice was highly effective in reducing the weight and number of parasite cysts, yet its combination with the lowest recommended dose of ABZ (5 mg/kg/day was even more effective. Coincidentally, intracystic Met accumulation was higher in animals treated with both drugs compared to those administered Met alone. Furthermore, the safe plant-derived drug Met exhibited remarkable chemopreventive properties against secondary hydatidosis in mice. In conclusion, based on our experimental data, Met emerges as a promising anti-echinococcal drug as it has proven to efficiently inhibit the development and growth of the E. granulosus larval stage and its combination with ABZ may improve the current anti-parasitic therapy.

  3. The Therapeutic Efficacy of Domestic Violence Victim Interventions.

    Science.gov (United States)

    Hackett, Shannon; McWhirter, Paula T; Lesher, Susan

    2016-04-01

    A meta-analysis on domestic violence interventions was conducted to determine overall effectiveness of mental health programs involving women and children in joint treatment. These interventions were further analyzed to determine whether outcomes are differentially affected based on the outcome measure employed. To date, no meta-analyses have been published on domestic violence victim intervention efficacy. The 17 investigations that met study criteria yielded findings indicating that domestic violence interventions have a large effect size (d = .812), which decreases to a medium effect size when compared to control groups (d = .518). Effect sizes were assessed to determine whether treatment differed according to the focus of the outcome measure employed: (a) external stress (behavioral problems, aggression, or alcohol use); (b) psychological adjustment (depression, anxiety, or happiness); (c) self-concept (self-esteem, perceived competence, or internal locus of control); (d) social adjustment (popularity, loneliness, or cooperativeness); (e) family relations (mother-child relations, affection, or quality of interaction); and (f) maltreatment events (reoccurrence of violence, return to partner). Results reveal that domestic violence interventions across all outcome categories yield effects in the medium to large range for both internalized and externalized symptomatology. Implications for greater awareness and support for domestic violence treatment and programming are discussed. © The Author(s) 2015.

  4. Immunogenicity to therapeutic proteins: impact on PK/PD and efficacy.

    Science.gov (United States)

    Chirmule, Narendra; Jawa, Vibha; Meibohm, Bernd

    2012-06-01

    The development of therapeutic proteins requires the understanding of the relationship between the dose, exposure, efficacy, and toxicity of these molecules. Several intrinsic and extrinsic factors contribute to the challenges for measuring therapeutic proteins in a precise and accurate manner. In addition, induction of an immune response to therapeutic protein results in additional complexities in the analysis of the pharmacokinetic profile, toxicity, safety, and efficacy of this class of molecules. Assessment of immunogenicity of therapeutic proteins is a required aspect of regulatory filings for a licensing application and for the safe and efficacious use of these compounds. A systematic strategy and well-defined criteria for measuring anti-drug antibodies (ADA) have been established, to a large extent, through coordinated efforts. These recommendations are based on risk assessment and include the determination of ADA content (concentration/titer), affinity, immunoglobulin isotype/subtype, and neutralization capacity. This manuscript reviews the requirements necessary for understanding the nature of an ADA response in order to discern the impact of immunogenicity on pharmacokinetics/pharmacodynamics and efficacy.

  5. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    International Nuclear Information System (INIS)

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended

  6. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of (131)I in Hyperthyroidism.

    Science.gov (United States)

    Kartamihardja, A Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended.

  7. The Influence of Antithyroid Drug Discontinuation to the Therapeutic Efficacy of 131I in Hyperthyroidism

    Science.gov (United States)

    Kartamihardja, A. Hussein Sundawa; Massora, Stepanus

    2016-01-01

    The influence of antithyroid drugs (ATDs) on the therapeutic efficacy of radioactive iodine in hyperthyroidism is still controversial. The aim of this study was to evaluate the effect of ATD discontinuation to the therapeutic efficacy of I-131 in hyperthyroidism patients with long-term ATD treatment. Retrospective study was done to 39 subjects with hyperthyroidism who had been treated with doses of 300 MBq radioactive iodine. The subjects were divided into three groups: Group I (n = 14) had been using ATDs for more than one year and discontinued more than three days; group II (n = 14) had been using ATDs for more than one year but discontinued only for three days or less, and group III (n = 11) has never been used any ATD before radioactive iodine treatment. There was a significant difference in the therapeutic efficacy after three months of radioactive iodine treatment between group I and group II (P = 0.018), group II and group III (P = 0.017), but not between group I and group III (P = 1.0). There was no observed difference on the therapeutic efficacy between the three groups at 6 months after radioactive iodine therapy (P = 0.143). Administration of ATDs more than 1 year without discontinuation decreased response of radioactive iodine treatment in 3 months follow-up. Discontinuation of ATDs for more than 3 days before radioactive iodine treatment is recommended. PMID:27134556

  8. Self-Efficacy for Therapeutic Mode Use among Occupational Therapy Students in Norway

    Science.gov (United States)

    Opseth, Thea Moos; Carstensen, Tove; Yazdani, Farzaneh; Ellingham, Brian; Thørrisen, Mikkel Magnus; Bonsaksen, Tore

    2017-01-01

    Background: The intentional relationship model (IRM) proposes six distinct ways of relating to clients. A new instrument for measuring self-efficacy for using the therapeutic modes in occupational therapy practice was recently found to have good psychometric properties. To date, however, no research has investigated factors associated with…

  9. Nanoparticle-mediated delivery of pioglitazone enhances therapeutic neovascularization in a murine model of hindlimb ischemia.

    Science.gov (United States)

    Nagahama, Ryoji; Matoba, Tetsuya; Nakano, Kaku; Kim-Mitsuyama, Shokei; Sunagawa, Kenji; Egashira, Kensuke

    2012-10-01

    Critical limb ischemia is a severe form of peripheral artery disease (PAD) for which neither surgical revascularization nor endovascular therapy nor current medicinal therapy has sufficient therapeutic effects. Peroxisome proliferator activated receptor-γ agonists present angiogenic activity in vitro; however, systemic administration of peroxisome proliferator-activated receptor-γ agonists is hampered by its side effects, including heart failure. Here, we demonstrate that the nanoparticle (NP)-mediated delivery of the peroxisome proliferator activated receptor-γ agonist pioglitazone enhances its therapeutic efficacy on ischemia-induced neovascularization in a murine model. In a nondiabetic murine model of hindlimb ischemia, a single intramuscular injection of pioglitazone-incorporated NP (1 µg/kg) into ischemic muscles significantly improved the blood flow recovery in the ischemic limbs, significantly increasing the number of CD31-positive capillaries and α-smooth muscle actin-positive arterioles. The therapeutic effects of pioglitazone-incorporated NP were diminished by the peroxisome proliferator activated receptor-γ antagonist GW9662 and were not observed in endothelial NO synthase-deficient mice. Pioglitazone-incorporated NP induced endothelial NO synthase phosphorylation, as demonstrated by Western blot analysis, as well as expression of multiple angiogenic growth factors in vivo, including vascular endothelial growth factor-A, vascular endothelial growth factor-B, and fibroblast growth factor-1, as demonstrated by real-time polymerase chain reaction. Intramuscular injection of pioglitazone (1 µg/kg) was ineffective, and oral administration necessitated a >500 μg/kg per day dose to produce therapeutic effects equivalent to those of pioglitazone-incorporated NP. NP-mediated drug delivery is a novel modality that may enhance the effectiveness of therapeutic neovascularization, surpassing the effectiveness of current treatments for peripheral artery

  10. Good News in Bad News: How Negativity Enhances Economic Efficacy

    OpenAIRE

    Svensson, H.M.; Albæk, E.; van Dalen, A.; de Vreese, C.

    2017-01-01

    Negativity is a news ideology, and its negative effects on attitude formation are widely documented. Contrary to this view, the present study demonstrates that negative economic news can in fact be good news. Based on a two-wave national panel survey and a media content analysis, we show that individual exposure to negative economic news enhances internal economic efficacy, a sense of competence in and understanding of the economy. This is good news as internal economic efficacy may facilitat...

  11. Therapeutic Efficacy of Meropenem for Treatment of Experimental Penicillin-Resistant Pneumococcal Meningitis

    Science.gov (United States)

    Kim, Shin-Woo; Jin, Joung Hwa; Kang, Soo Jung; Jung, Sook-In; Kim, Yeon-Sook; Kim, Choon-Kwan; Lee, Hyuck; Oh, Won Sup; Kim, Sungmin; Peck, Kyong Ran

    2004-01-01

    With the widespread emergence of antimicrobial resistance, combination regimens of ceftriaxone and vancomycin (C+V) or ceftriaxone and rifampin (C+R) are recommended for empirical treatment of pneumococcal meningitis. To evaluate the therapeutic efficacy of meropenem (M), we compared various treatment regimens in arabbit model of meningitis caused by penicillin-resistant Streptococcus pneumoniae (PRSP). Therapeutic efficacy was also evaluated by the final bacterial concentration in the cerebrospinal fluid (CSF) at 24 hr. Each group consisted of six rabbits. C+V cleared the CSF at 10 hr, but regrowth was noted in 3 rabbits at 24 hr. Meropenem monotherapy resulted in sterilization at 10 hr, but regrowth was observed in all 6 rabbits at 24 hr. M+V also resulted in sterilization at 10 hr, but regrowth was observed in 2 rabbits at 24 hr. M+V was superior to the meropenem monotherapy at 24 hr (reduction of 4.8 vs. 1.8 log10 cfu/mL, respectively; p=0.003). The therapeutic efficacy of M+V was comparable to that of C+V (reduction of 4.8 vs. 4.0 log10 cfu/mL, respectively; p=0.054). The meropenem monotherapy may not be a suitable choice for PRSP meningitis, while combination of meropenem and vancomycin could be a possible alternative in the treatment of PRSP meningitis. PMID:14966336

  12. A dynamical systems model for combinatorial cancer therapy enhances oncolytic adenovirus efficacy by MEK-inhibition.

    Science.gov (United States)

    Bagheri, Neda; Shiina, Marisa; Lauffenburger, Douglas A; Korn, W Michael

    2011-02-01

    Oncolytic adenoviruses, such as ONYX-015, have been tested in clinical trials for currently untreatable tumors, but have yet to demonstrate adequate therapeutic efficacy. The extent to which viruses infect targeted cells determines the efficacy of this approach but many tumors down-regulate the Coxsackievirus and Adenovirus Receptor (CAR), rendering them less susceptible to infection. Disrupting MAPK pathway signaling by pharmacological inhibition of MEK up-regulates CAR expression, offering possible enhanced adenovirus infection. MEK inhibition, however, interferes with adenovirus replication due to resulting G1-phase cell cycle arrest. Therefore, enhanced efficacy will depend on treatment protocols that productively balance these competing effects. Predictive understanding of how to attain and enhance therapeutic efficacy of combinatorial treatment is difficult since the effects of MEK inhibitors, in conjunction with adenovirus/cell interactions, are complex nonlinear dynamic processes. We investigated combinatorial treatment strategies using a mathematical model that predicts the impact of MEK inhibition on tumor cell proliferation, ONYX-015 infection, and oncolysis. Specifically, we fit a nonlinear differential equation system to dedicated experimental data and analyzed the resulting simulations for favorable treatment strategies. Simulations predicted enhanced combinatorial therapy when both treatments were applied simultaneously; we successfully validated these predictions in an ensuing explicit test study. Further analysis revealed that a CAR-independent mechanism may be responsible for amplified virus production and cell death. We conclude that integrated computational and experimental analysis of combinatorial therapy provides a useful means to identify treatment/infection protocols that yield clinically significant oncolysis. Enhanced oncolytic therapy has the potential to dramatically improve non-surgical cancer treatment, especially in locally advanced

  13. Enhanced photodynamic efficacy of zinc phthalocyanine by conjugating to heptalysine.

    Science.gov (United States)

    Li, Linsen; Luo, Zhipu; Chen, Zhuo; Chen, Jincan; Zhou, Shanyong; Xu, Peng; Hu, Ping; Wang, Jundong; Chen, Naisheng; Huang, Jinling; Huang, Mingdong

    2012-11-21

    Zinc phthalocyanine (ZnPc) is a promising photosensitizer for photodynamic therapy, but faces some challenges: ZnPc is insoluble in water and thus requires either special formulation of ZnPc by, e.g., liposome or Cremophor EL, or chemical modification of Pc ring to enhance its bioavailability and photodynamic efficacy. Here, we conjugated monosubstituted ZnPc-COOH with a series of oligolysine moieties with different numbers of lysine residues (ZnPc-(Lys)(n) (n = 1, 3, 5, 7, 9) to improve the water solubility of the ZnPc conjugates. We measured the photosensitizing efficacies and the cellular uptakes of this series of conjugates on a normal and a cancerous cell line. In addition, we developed a sensitive in situ method to distinguish the difference in photodynamic efficacy among conjugates. Our results showed that ZnPc-(Lys)(7) has the highest photodynamic efficacy compared to the other conjugates investigated.

  14. Enhancing of Self-Efficacy in Teacher Education Students

    Science.gov (United States)

    Malinauskas, Romualdas K.

    2017-01-01

    In this study, the effectiveness of training module on enhancing self-efficacy in teacher education students was investigated. Sixty-eight (68) teacher education students (M age = 22.74; SD = 0.57) participated in this study, 36 of whom were assigned to an experimental group and the other 32 were assigned to a control group. The training module on…

  15. Factors Associated with Therapeutic Efficacy of Intravesical OnabotulinumtoxinA Injection for Overactive Bladder Syndrome.

    Directory of Open Access Journals (Sweden)

    Sheng-Mou Hsiao

    Full Text Available To analyze the predictors of therapeutic efficacy after intravesical botulinum toxin A injection for overactive bladder syndrome (OAB refractory to antimuscarinic therapy.All consecutively OAB patients, who visited the urologic outpatient clinics of a medical center and refractory to antimuscarinic treatment, were prospectively enrolled. All enrolled patients received intravesical injection of 100 U onabotulinumtoxinA (Botox. The Global Response Assessment (GRA score ≥ 2 at 3 months after Botox injection was defined as a successful treatment, otherwise failed.Overall, 89 patients received intravesical injection. Eighty patients, including 42 men and 38 women, had received follow-up at 3 months. The overall success rate was 63.8%. The global response assessment, urgency severity score, urgency, urgency urinary incontinence and frequency episodes, and functional bladder capacity improved after treatment. However, post-void residual volume (PVR increased, and voiding efficiency (VE decreased after treatment. Female gender (odds ratio = 3.75 was the only independent factor associated with the success. Female gender (coefficient = 0.74, low baseline overactive bladder symptoms score (coefficient = -0.12 and the presence of OAB-wet (coefficient = 0.79 were independent factors associated with therapeutic efficacy (i.e., GRA score. VE (odds ratio = 0.062 was the only predictor for a large PVR at 3 months. The optimum cutoff value of VE was <87% with the area under the ROC curve being 0.64 (sensitivity = 63.8%, specificity = 57.1%.The therapeutic effects of Botox can persist till 6 months after treatment. Female gender, low overactive bladder symptoms score and OAB-wet are associated better therapeutic efficacy, and low baseline VE is associated with large PVR. These findings can serve as an initial guide or assist in consultation regarding the treatment of OAB patients with Botox injection.ClinicalTrials.gov NCT01657409.

  16. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target.

    Science.gov (United States)

    Hiu, Takeshi; Farzampour, Zoya; Paz, Jeanne T; Wang, Eric Hou Jen; Badgely, Corrine; Olson, Andrew; Micheva, Kristina D; Wang, Gordon; Lemmens, Robin; Tran, Kevin V; Nishiyama, Yasuhiro; Liang, Xibin; Hamilton, Scott A; O'Rourke, Nancy; Smith, Stephen J; Huguenard, John R; Bliss, Tonya M; Steinberg, Gary K

    2016-02-01

    Ischaemic stroke is the leading cause of severe long-term disability yet lacks drug therapies that promote the repair phase of recovery. This repair phase of stroke occurs days to months after stroke onset and involves brain remapping and plasticity within the peri-infarct zone. Elucidating mechanisms that promote this plasticity is critical for the development of new therapeutics with a broad treatment window. Inhibiting tonic (extrasynaptic) GABA signalling during the repair phase was reported to enhance functional recovery in mice suggesting that GABA plays an important function in modulating brain repair. While tonic GABA appears to suppress brain repair after stroke, less is known about the role of phasic (synaptic) GABA during the repair phase. We observed an increase in postsynaptic phasic GABA signalling in mice within the peri-infarct cortex specific to layer 5; we found increased numbers of α1 receptor subunit-containing GABAergic synapses detected using array tomography, and an associated increased efficacy of spontaneous and miniature inhibitory postsynaptic currents in pyramidal neurons. Furthermore, we demonstrate that enhancing phasic GABA signalling using zolpidem, a Food and Drug Administration (FDA)-approved GABA-positive allosteric modulator, during the repair phase improved behavioural recovery. These data identify potentiation of phasic GABA signalling as a novel therapeutic strategy, indicate zolpidem's potential to improve recovery, and underscore the necessity to distinguish the role of tonic and phasic GABA signalling in stroke recovery. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  17. Eugenol nanocapsule for enhanced therapeutic activity against periodontal infections.

    Science.gov (United States)

    Pramod, Kannissery; Aji Alex, M R; Singh, Manisha; Dang, Shweta; Ansari, Shahid H; Ali, Javed

    2016-01-01

    Eugenol is a godsend to dental care due to its analgesic, local anesthetic, and anti-inflammatory and antibacterial effects. The aim of the present research work was to prepare, characterize and evaluate eugenol-loaded nanocapsules (NCs) against periodontal infections. Eugenol-loaded polycaprolactone (PCL) NCs were prepared by solvent displacement method. The nanometric size of the prepared NCs was confirmed by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The in vitro drug release was found to follow a biphasic pattern and followed Michaelis-Menten like model. The percentage cell viability values near to 100 in the cell viability assay indicated that the NCs are not cytotoxic. In the in vivo studies, the eugenol NC group displayed significant difference in the continuity of epithelium of the interdental papilla in comparison to the untreated, pure eugenol and placebo groups. The in vivo performance of the eugenol-loaded NCs using ligature-induced periodontitis model in rats indicated that eugenol-loaded NCs could prevent septal bone resorption in periodontitis. On the basis of our research findings it could be concluded that eugenol-loaded PCL NCs could serve as a novel colloidal drug delivery system for enhanced therapeutic activity of eugenol in the treatment of periodontal infections.

  18. Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure.

    Science.gov (United States)

    Campos, Cécile; Perrey, Antoine; Lambert, Céline; Pereira, Bruno; Goutte, Marion; Dubois, Anne; Goutorbe, Felix; Dapoigny, Michel; Bommelaer, Gilles; Hordonneau, Constance; Buisson, Anthony

    2017-06-01

    Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

  19. Predictive markers of efficacy for an angiopoietin-2 targeting therapeutic in xenograft models.

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    Gallen Triana-Baltzer

    Full Text Available The clinical efficacy of anti-angiogenic therapies has been difficult to predict, and biomarkers that can predict responsiveness are sorely needed in this era of personalized medicine. CVX-060 is an angiopoietin-2 (Ang2 targeting therapeutic, consisting of two peptides that bind Ang2 with high affinity and specificity, covalently fused to a scaffold antibody. In order to optimize the use of this compound in the clinic the construction of a predictive model is described, based on the efficacy of CVX-060 in 13 cell line and 2 patient-derived xenograft models. Pretreatment size tumors from each of the models were profiled for the levels of 27 protein markers of angiogenesis, SNP haplotype in 5 angiogenesis genes, and somatic mutation status for 11 genes implicated in tumor growth and/or vascularization. CVX-060 efficacy was determined as tumor growth inhibition (TGI% at termination of each study. A predictive statistical model was constructed based on the correlation of these efficacy data with the marker profiles, and the model was subsequently tested by prospective analysis in 11 additional models. The results reveal a range of CVX-060 efficacy in xenograft models of diverse tissue types (0-64% TGI, median = 27% and define a subset of 3 proteins (Ang1, EGF, Emmprin, the levels of which may be predictive of TGI by Ang2 blockade. The direction of the associations is such that better efficacy correlates with high levels of target and low levels of compensatory/antagonizing molecules. This effort has revealed a set of candidate predictive markers for CVX-060 efficacy that will be further evaluated in ongoing clinical trials.

  20. Therapeutic efficacy and mechanism of action of ethamsylate, a long-standing hemostatic agent.

    Science.gov (United States)

    Garay, Ricardo P; Chiavaroli, Carlo; Hannaert, Patrick

    2006-01-01

    Ethamsylate (2,5-dihydroxy-benzene-sulfonate diethylammonium salt) is a synthetic hemostatic drug indicated in cases of capillary bleeding. This review covers more than 40 years of intensive clinical and fundamental research with ethamsylate. First, we summarize the large medical literature concerning its clinical efficacy. Of these, well-controlled clinical trials clearly showed the therapeutic efficacy of ethamsylate in dysfunctional uterine bleeding, with the magnitude of blood-loss reduction being directly proportional to the severity of the menorrhagia. Other well-controlled clinical trials showed therapeutic efficacy of ethamsylate in periventricular hemorrhage in very low birth weight babies and surgical or postsurgical capillary bleeding. Second, we review the numerous investigations performed to elucidate the mechanism of action of ethamsylate. Ethamsylate acts on the first step of hemostasis by improving platelet adhesiveness and restoring capillary resistance. Recent studies showed that ethamsylate promotes P-selectin-dependent, platelet adhesive mechanisms. Finally, we compare ethamsylate with other recent hemostatic agents. It is suggested that the place of ethamsylate as a hemostatic agent is that of a mild but well-tolerated drug, particularly useful in dysfunctional uterine bleeding when contraception is not needed.

  1. Correlation between paclitaxel Tc > 0.05 and its therapeutic efficacy and severe toxicities in ovarian cancer patients

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    Shuyao Zhang

    2016-01-01

    Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.

  2. New class of monoclonal antibodies against severe influenza: prophylactic and therapeutic efficacy in ferrets.

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    Robert H E Friesen

    2010-02-01

    Full Text Available The urgent medical need for innovative approaches to control influenza is emphasized by the widespread resistance of circulating subtype H1N1 viruses to the leading antiviral drug oseltamivir, the pandemic threat posed by the occurrences of human infections with highly pathogenic avian H5N1 viruses, and indeed the evolving swine-origin H1N1 influenza pandemic. A recently discovered class of human monoclonal antibodies with the ability to neutralize a broad spectrum of influenza viruses (including H1, H2, H5, H6 and H9 subtypes has the potential to prevent and treat influenza in humans. Here we report the latest efficacy data for a representative antibody of this novel class.We evaluated the prophylactic and therapeutic efficacy of the human monoclonal antibody CR6261 against lethal challenge with the highly pathogenic avian H5N1 virus in ferrets, the optimal model of human influenza infection. Survival rates, clinically relevant disease signs such as changes in body weight and temperature, virus replication in lungs and upper respiratory tract, as well as macro- and microscopic pathology were investigated. Prophylactic administration of 30 and 10 mg/kg CR6261 prior to viral challenge completely prevented mortality, weight loss and reduced the amount of infectious virus in the lungs by more than 99.9%, abolished shedding of virus in pharyngeal secretions and largely prevented H5N1-induced lung pathology. When administered therapeutically 1 day after challenge, 30 mg/kg CR6261 prevented death in all animals and blunted disease, as evidenced by decreased weight loss and temperature rise, reduced lung viral loads and shedding, and less lung damage.These data demonstrate the prophylactic and therapeutic efficacy of this new class of human monoclonal antibodies in a highly stringent and clinically relevant animal model of influenza and justify clinical development of this approach as intervention for both seasonal and pandemic influenza.

  3. Shangri-La revisited: an exploration of therapeutic efficacy among intentional communities.

    Science.gov (United States)

    Francis, T L

    1992-04-01

    Field and literature surveys were employed to explore the therapeutic efficacy of a reportedly common set of social structures found among some Intentional Communities (ICs). Substance misuse served as an example of social problems plausibly related to the examined social structures, which included: (1) meditative practices, (2) progressive education, (3) holistic health practices, (4) nutritional diet, (5) open policy making, (6) equally or equitably shared resources, (7) integrating membership processes, and (8) environmental concern. The field survey identified and examined 11 such ICs, and the literature exploration concerning the structures found that they appear to be therapeutic. Future research should focus on refining the study of structural and antecedent variables and on finding relationships between these variables to communities in the larger society.

  4. The mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization

    International Nuclear Information System (INIS)

    Li Weiduo; Yang Jianyong; Zhuang Wenquan; Chen Wei; Li Heping

    2002-01-01

    Objective: To explore the mid-to-long term therapeutic efficacy of Graves' disease after interventional embolization. Methods: Twenty-five patients of Graves' disease treated with interventional embolization were followed up for 24-57 months. T 3 and T 4 were monitored at pre-operation, six months, 12 months, 2, 3 and 4 years after operation, respectively. Other references included pulse, thyroid size, and vessel's murmur. Results: Twenty-two patients completely relieved from the hyperthyroidism during the follow-up. Only one patient suffered from recurrence. Other two patients were still on maintaining dosage of antithyroid drug therapy. No hypothyroidism or hypoparathyroidism was found during this term. Conclusion: Mid-to-long term follow-up showed satisfactory efficacy of interventional therapy, offering another alternative for treatment of refractory Graves' disease

  5. Biofilm disruption with rotating microrods enhances antimicrobial efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Mair, Lamar O., E-mail: Lamar.Mair@gmail.com [Weinberg Medical Physics, Inc., North Bethesda, MD (United States); Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar [Weinberg Medical Physics, Inc., North Bethesda, MD (United States); Hausfeld, Jeffrey [School of Medicine and Health Sciences, George Washington University, WA (United States); Karlsson, Amy J. [Department of Chemical and Biomolecular Engineering, University of Maryland, College Park, MD (United States); Shirtliff, Mark E. [School of Dentistry, University of Maryland, Baltimore, MD (United States); Shapiro, Benjamin [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Weinberg, Irving N. [Weinberg Medical Physics, Inc., North Bethesda, MD (United States)

    2017-04-01

    Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms. - Highlights: • Fungal biofilms have been implicated in a variety of medical ailments. • Magnetic microrods, grown via electroplating, were rotated in and around fungal biofilms. • Rotating microrods potentiate the effectiveness of antimicrobial drug. • Antimicrobial efficacy may be enhanced due to increased mixing.

  6. Biofilm disruption with rotating microrods enhances antimicrobial efficacy

    International Nuclear Information System (INIS)

    Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

    2017-01-01

    Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms. - Highlights: • Fungal biofilms have been implicated in a variety of medical ailments. • Magnetic microrods, grown via electroplating, were rotated in and around fungal biofilms. • Rotating microrods potentiate the effectiveness of antimicrobial drug. • Antimicrobial efficacy may be enhanced due to increased mixing.

  7. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.

    Science.gov (United States)

    Roseman, Leor; Nutt, David J; Carhart-Harris, Robin L

    2017-01-01

    < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.

  8. Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression

    Directory of Open Access Journals (Sweden)

    Leor Roseman

    2018-01-01

    ASC (p < 0.05.Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety.Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797

  9. Administration of BMSCs with muscone in rats with gentamicin-induced AKI improves their therapeutic efficacy.

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    Pengfei Liu

    Full Text Available The therapeutic action of bone marrow-derived mesenchymal stem cells (BMSCs in acute kidney injury (AKI has been reported by several groups. However, recent studies indicated that BMSCs homed to kidney tissues at very low levels after transplantation. The lack of specific homing of exogenously infused cells limited the effective implementation of BMSC-based therapies. In this study, we provided evidence that the administration of BMSCs combined with muscone in rats with gentamicin-induced AKI intravenously, was a feasible strategy to drive BMSCs to damaged tissues and improve the BMSC-based therapeutic effect. The effect of muscone on BMSC bioactivity was analyzed in vitro and in vivo. The results indicated that muscone could promote BMSC migration and proliferation. Some secretory capacity of BMSC still could be improved in some degree. The BMSC-based therapeutic action was ameliorated by promoting the recovery of biochemical variables in urine or blood, as well as the inhibition of cell apoptosis and inflammation. In addition, the up-regulation of CXCR4 and CXCR7 expression in BMSCs could be the possible mechanism of muscone amelioration. Thus, our study indicated that enhancement of BMSCs bioactivities with muscone could increase the BMSC therapeutic potential and further developed a new therapeutic strategy for the treatment of AKI.

  10. Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins

    Directory of Open Access Journals (Sweden)

    Alison Smith

    2016-01-01

    Full Text Available Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.

  11. Therapeutic orientations, professional efficacy, and burnout among substance abuse social workers in Israel.

    Science.gov (United States)

    Tartakovsky, Eugene; Kovardinsky, Slava

    2013-07-01

    This study investigates the therapeutic orientations of substance abuse social workers and the relationship between these orientations and burnout. Ninety-two social workers who provided outpatient treatment to people suffering from substance-related disorders in Israel participated in the study. The results obtained demonstrated that the substance abuse social workers adhere more to the psychodynamic and ecosystemic therapeutic orientations than to the cognitive-behavioral orientation. A greater adherence to the cognitive-behavioral orientation was associated with a higher sense of professional efficacy; a greater adherence to the psychodynamic orientation was associated with a higher level of exhaustion; and greater adherence to the ecosystemic orientation was associated with lower levels of exhaustion and cynicism. Female social workers reported lower levels of exhaustion and cynicism. The cognitive-behavioral orientation mediated the connection between the social workers' experience in the field of substance abuse and two dimensions of burnout-exhaustion and professional efficacy. Significance of the findings for improving the well-being of substance abuse social workers and for the advancement of psychosocial services is discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The in vivo therapeutic efficacy of the oncolytic adenovirus Delta24-RGD is mediated by tumor-specific immunity.

    Directory of Open Access Journals (Sweden)

    Anne Kleijn

    Full Text Available The oncolytic adenovirus Delta24-RGD represents a new promising therapeutic agent for patients with a malignant glioma and is currently under investigation in clinical phase I/II trials. Earlier preclinical studies showed that Delta24-RGD is able to effectively lyse tumor cells, yielding promising results in various immune-deficient glioma models. However, the role of the immune response in oncolytic adenovirus therapy for glioma has never been explored. To this end, we assessed Delta24-RGD treatment in an immune-competent orthotopic mouse model for glioma and evaluated immune responses against tumor and virus. Delta24-RGD treatment led to long-term survival in 50% of mice and this effect was completely lost upon administration of the immunosuppressive agent dexamethasone. Delta24-RGD enhanced intra-tumoral infiltration of F4/80+ macrophages, CD4+ and CD8+ T-cells, and increased the local production of pro-inflammatory cytokines and chemokines. In treated mice, T cell responses were directed to the virus as well as to the tumor cells, which was reflected in the presence of protective immunological memory in mice that underwent tumor rechallenge. Together, these data provide evidence that the immune system plays a vital role in the therapeutic efficacy of oncolytic adenovirus therapy of glioma, and may provide angles to future improvements on Delta24-RGD therapy.

  13. Transferrin-Modified Nanoparticles for Photodynamic Therapy Enhance the Antitumor Efficacy of Hypocrellin A

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    Xi Lin

    2017-11-01

    Full Text Available Photodynamic therapy (PDT has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA and carboxymethyl chitosan (CMC nanoparticle loaded with a photosensitizer hypocrellin A (HA, named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.

  14. Prophylactic and therapeutic efficacy of human monoclonal antibodies against H5N1 influenza.

    Directory of Open Access Journals (Sweden)

    Cameron P Simmons

    2007-05-01

    Full Text Available New prophylactic and therapeutic strategies to combat human infections with highly pathogenic avian influenza (HPAI H5N1 viruses are needed. We generated neutralizing anti-H5N1 human monoclonal antibodies (mAbs and tested their efficacy for prophylaxis and therapy in a murine model of infection.Using Epstein-Barr virus we immortalized memory B cells from Vietnamese adults who had recovered from infections with HPAI H5N1 viruses. Supernatants from B cell lines were screened in a virus neutralization assay. B cell lines secreting neutralizing antibodies were cloned and the mAbs purified. The cross-reactivity of these antibodies for different strains of H5N1 was tested in vitro by neutralization assays, and their prophylactic and therapeutic efficacy in vivo was tested in mice. In vitro, mAbs FLA3.14 and FLD20.19 neutralized both Clade I and Clade II H5N1 viruses, whilst FLA5.10 and FLD21.140 neutralized Clade I viruses only. In vivo, FLA3.14 and FLA5.10 conferred protection from lethality in mice challenged with A/Vietnam/1203/04 (H5N1 in a dose-dependent manner. mAb prophylaxis provided a statistically significant reduction in pulmonary virus titer, reduced associated inflammation in the lungs, and restricted extrapulmonary dissemination of the virus. Therapeutic doses of FLA3.14, FLA5.10, FLD20.19, and FLD21.140 provided robust protection from lethality at least up to 72 h postinfection with A/Vietnam/1203/04 (H5N1. mAbs FLA3.14, FLD21.140 and FLD20.19, but not FLA5.10, were also therapeutically active in vivo against the Clade II virus A/Indonesia/5/2005 (H5N1.These studies provide proof of concept that fully human mAbs with neutralizing activity can be rapidly generated from the peripheral blood of convalescent patients and that these mAbs are effective for the prevention and treatment of H5N1 infection in a mouse model. A panel of neutralizing, cross-reactive mAbs might be useful for prophylaxis or adjunctive treatment of human cases of H5N1

  15. Osmotic Compounds Enhance Antibiotic Efficacy against Acinetobacter baumannii Biofilm Communities.

    Science.gov (United States)

    Falghoush, Azeza; Beyenal, Haluk; Besser, Thomas E; Omsland, Anders; Call, Douglas R

    2017-10-01

    Biofilm-associated infections are a clinical challenge, in part because a hydrated matrix protects the bacterial community from antibiotics. Herein, we evaluated how different osmotic compounds (maltodextrin, sucrose, and polyethylene glycol [PEG]) enhance antibiotic efficacy against Acinetobacter baumannii biofilm communities. Established (24-h) test tube biofilms (strain ATCC 17978) were treated with osmotic compounds in the presence or absence of 10× the MIC of different antibiotics (50 μg/ml tobramycin, 20 μg/ml ciprofloxacin, 300 μg/ml chloramphenicol, 30 μg/ml nalidixic acid, or 100 μg/ml erythromycin). Combining antibiotics with hypertonic concentrations of the osmotic compounds for 24 h reduced the number of biofilm bacteria by 5 to 7 log ( P baumannii strains were similarly treated with 400-Da PEG and tobramycin, resulting in a mean 2.7-log reduction in recoverable bacteria compared with tobramycin treatment alone. Multivariate regression models with data from different osmotic compounds and nine antibiotics demonstrated that the benefit from combining hypertonic treatments with antibiotics is a function of antibiotic mass and lipophilicity ( r 2 > 0.82; P baumannii and Escherichia coli K-12. Augmenting topical antibiotic therapies with a low-mass hypertonic treatment may enhance the efficacy of antibiotics against wound biofilms, particularly when using low-mass hydrophilic antibiotics. IMPORTANCE Biofilms form a barrier that protects bacteria from environmental insults, including exposure to antibiotics. We demonstrated that multiple osmotic compounds can enhance antibiotic efficacy against Acinetobacter baumannii biofilm communities, but viscosity is a limiting factor, and the most effective compounds have lower molecular mass. The synergism between osmotic compounds and antibiotics is also dependent on the hydrophobicity and mass of the antibiotics. The statistical models presented herein provide a basis for predicting the optimal combination of

  16. Percutaneous Radiofrequency Ablation for the Hepatocellular Carcinoma Abutting the Diaphragm: Assessment of Safety and Therapeutic Efficacy

    International Nuclear Information System (INIS)

    Kang, Tae Wook; Rhim, Hyun Chul; Kim, Eun Young; Kim, Young Sun; Choi, Dong Il; Lee, Won Jae; Lim, Hyo K.

    2009-01-01

    To assess the safety and therapeutic efficacy of a percutaneous radiofrequency (RF) ablation for the hepatocellular carcinoma (HCC) abutting the diaphragm. We retrospectively assessed 80 patients who underwent a percutaneous RF ablation for a single nodular (< 4 cm) HCC over the last four years. Each patient underwent an ultrasound-guided RF ablation using internally cooled electrodes for the first-line treatment. We divided patients into two subgroups based on whether the index tumor was abutting (less than 5 mm) the diaphragm or not: group A (abutting; n = 31) versus group B (non-abutting; n = 49). We compared the two subgroups for complications and therapeutic efficacy using image and the review of medical records. The statistical assessment included an independent t-test, Fisher's exact test, and chi-square test. The assessment of the diaphragmatic swelling at CT immediately following the procedure was more severe in group A than group B (mean thickness change:1.44 vs. 0.46 mm, p = 0.00). Further, right shoulder pain was more common in group A than B (p = 0.01). Although minor complications (hemothorax 1 case, pleural effusion 1 case) were noted only in group A, no major thoracic complication occurred in either group. The technical success rate was lower in group A than group B (84% vs. 98%, p = 0.03). As well, the primary and secondary technique effectiveness rates in group A and group B were 90% versus 98% (p = 0.29) and 79% versus 91% (p = 0.25), respectively. The local tumor progression rate was higher in group A than in group B (29% vs. 6%, p = 0.02). We found that the percutaneous RF ablation for the HCC abutting the diaphragm is a safe procedure without major complications. However, it is less effective with regard to technical success and local tumor control

  17. Improved oral bioavailability and therapeutic efficacy of dabigatran etexilate via Soluplus-TPGS binary mixed micelles system.

    Science.gov (United States)

    Hu, Mei; Zhang, Jinjie; Ding, Rui; Fu, Yao; Gong, Tao; Zhang, Zhirong

    2017-04-01

    The clinical use of dabigatran etexilate (DABE) is limited by its poor absorption and relatively low bioavailability. Our study aimed to explore the potential of a mixed micelle system composed of Soluplus ® and D-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) to improve the oral absorption and bioavailability of DBAE. DBAE was first encapsulated into Soluplus/TPGS mixed micelles by a simple thin film hydration method. The DBAE loaded micelles displayed an average size distribution of around 83.13 nm. The cellular uptake of DBAE loaded micelles in Caco-2 cell monolayer was significantly enhanced by 2-2.6 fold over time as compared with DBAE suspension. Both lipid raft/caveolae and macropinocytosis-mediated the cell uptake of DBAE loaded micelles through P-glycoprotein (P-gp)-independent pathway. Compared with the DBAE suspension, the intestinal absorption of DBAE from DBAE mixed micelles in rats was significantly improved by 8 and 5-fold in ileum at 2 h and 4 h, respectively. Moreover, DBAE mixed micelles were absorbed into systemic circulation via both portal vein and lymphatic pathway. The oral bioavailability of DBAE mixed micelles in rats was 3.37 fold higher than that of DBAE suspension. DBAE mixed micelles exhibited a comparable anti-thrombolytic activity with a thrombosis inhibition rate of 63.18% compared with DBAE suspension in vivo. Thus, our study provides a promising drug delivery system to enhance the oral bioavailability and therapeutic efficacy of DBAE.

  18. Improving therapeutic outcomes in autism spectrum disorders: Enhancing social communication and sensory processing through the use of interactive robots.

    Science.gov (United States)

    Sartorato, Felippe; Przybylowski, Leon; Sarko, Diana K

    2017-07-01

    For children with autism spectrum disorders (ASDs), social robots are increasingly utilized as therapeutic tools in order to enhance social skills and communication. Robots have been shown to generate a number of social and behavioral benefits in children with ASD including heightened engagement, increased attention, and decreased social anxiety. Although social robots appear to be effective social reinforcement tools in assistive therapies, the perceptual mechanism underlying these benefits remains unknown. To date, social robot studies have primarily relied on expertise in fields such as engineering and clinical psychology, with measures of social robot efficacy principally limited to qualitative observational assessments of children's interactions with robots. In this review, we examine a range of socially interactive robots that currently have the most widespread use as well as the utility of these robots and their therapeutic effects. In addition, given that social interactions rely on audiovisual communication, we discuss how enhanced sensory processing and integration of robotic social cues may underlie the perceptual and behavioral benefits that social robots confer. Although overall multisensory processing (including audiovisual integration) is impaired in individuals with ASD, social robot interactions may provide therapeutic benefits by allowing audiovisual social cues to be experienced through a simplified version of a human interaction. By applying systems neuroscience tools to identify, analyze, and extend the multisensory perceptual substrates that may underlie the therapeutic benefits of social robots, future studies have the potential to strengthen the clinical utility of social robots for individuals with ASD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Therapeutic efficacy of rose oil: A comprehensive review of clinical evidence

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    Safieh Mohebitabar

    2017-04-01

    Full Text Available Objective: Rose oil is obtained from the petals of difference Rosa species especially Rosa centifolia L. and Rosa damascena Mill. Various pharmacological properties have been attributed to rose oil. The aim of the present study was to review the rose oil therapeutic effects which had been clinically evaluated in trial studies. Materials and Methods: Google scholar, PubMed, Cochrane Library, and Scopus were searched for human studies which have evaluated the therapeutic effects of rose oil and published in English language until August 2015. Results: Thirteen clinical trials (772 participants were included in this review. Rose oil was administered via inhalation or used topically. Most of the studies (five trials evaluated the analgesic effect of rose oil. Five studies evaluated the physiological relaxation effect of rose oil. Anti-depressant, psychological relaxation, improving sexual dysfunction, and anti-anxiety effects were the other clinical properties reported for rose oil. Conclusion: Numerous studies on the pharmacological properties of rose oil have been done in animals, but studies in humans are few.  In this study, it was observed that rose oil had physiological and psychological relaxation, analgesic and anti-anxiety effects. To obtain conclusive results on the efficacy and safety of rose oil, further clinical trials with larger sample size and better designation are required.

  20. Therapeutic efficacy of natural prostaglandin in the treatment of pyometra in bitches

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    Basanti Jena

    2013-12-01

    Full Text Available Aim: The current study was done to study the therapeutic effect of natural prostaglandin in treatment of canine pyometra. Materials and Methods: Seven bitches were treated with natural PGF2 á i.e. dinoprost tromethamine at the dose rate of 100 μg/kg body weight subcutaneously once daily for 7 days with supportive therapies. The physiological, haematological and biochemical parameters were studied before (0th day and after treatment (8th day. Therapeutic efficacy was assessed in terms of return of abnormal parameters to either normal or near normal value as compared to the untreated control group, intensity of side effects and post treatment reproductive status. Results: All physiological, haematological and biochemical parameters in the seven treated bitches returned to normal range at the end of treatment. The intensity of side effects was quite severe in the treatment group. Six bitches came to estrus within 2 months of treatment and out of them four conceived on subsequent mating. In rest three bitches there was recurrence of pyometra within 4 months of treatment. Conclusion: Though conception rate of recovered bitches is decreased when compared with that of normal healthy bitches still this treatment protocol can be used successfully in treatment of canine pyometra to conserve the breeding capability of bitches. [Vet World 2013; 6(6.000: 295-299

  1. Therapeutic Drug Monitoring of Lacosamide in Norway: Focus on Pharmacokinetic Variability, Efficacy and Tolerability.

    Science.gov (United States)

    Svendsen, Torleiv; Brodtkorb, Eylert; Baftiu, Arton; Burns, Margrete Larsen; Johannessen, Svein I; Johannessen Landmark, Cecilie

    2017-07-01

    Lacosamide (LCM) is a new antiepileptic drug (AED). Experience from therapeutic drug monitoring (TDM) in clinical practice is limited. The purpose of this study is to evaluate the pharmacokinetic variability of LCM in relation to efficacy and tolerability in patients with refractory epilepsy in a real-life setting. Variables included age, gender, daily doses and serum concentrations of LCM and other AEDs from the TDM-database at the National Center for Epilepsy in Norway. Clinical data regarding efficacy and tolerability were collected from medical records. The Norwegian Prescription Database (NorPD) was used to include population-based numbers of users. TDM-data from 344 patients were included. The median dose, serum concentration, and concentration/dose (C/D)-ratio of LCM was 350 (range 25-700) mg/day, 19.7 (range 8.1-56.2) µmol/L, and 0.06 (0.02-0.82) µmol/L/mg, respectively. Serum concentrations were reduced by 28% by concomitant use of enzyme inducers and increased by 30% in patients aged >65 years. Efficacy and tolerability were assessed in 227 patients: 29% had >50% seizure reduction (eight seizure free), 30% had no effect, and 44% reported adverse effects. In Norway, there were on average 500 patients per year using LCM in this period based on NorPD. The study demonstrated pharmacokinetic variability and use of TDM of LCM in Norway. Data were collected from multiple sources for improved pharmacovigilance. Serum concentrations were influenced by enzyme inducers and ageing, indicating the usefulness of TDM. Effect and tolerability were favorable within a suggested reference range of 10-40 µmol/L given drug-fasting conditions.

  2. Therapeutic Ultrasound Enhancement of Drug Delivery to Soft Tissues

    Science.gov (United States)

    Lewis, George; Wang, Peng; Lewis, George; Olbricht, William

    2009-04-01

    Effects of exposure to 1.58 MHz focused ultrasound on transport of Evans Blue Dye (EBD) in soft tissues are investigated when an external pressure gradient is applied to induce convective flow through the tissue. The magnitude of the external pressure gradient is chosen to simulate conditions in brain parenchyma during convection-enhanced drug delivery (CED) to the brain. EBD uptake and transport are measured in equine brain, avian muscle and agarose brain-mimicking phantoms. Results show that ultrasound enhances EBD uptake and transport, and the greatest enhancement occurs when the external pressure gradient is applied. The results suggest that exposure of the brain parenchyma to ultrasound could enhance penetration of material infused into the brain during CED therapy.

  3. Praziquantel synergistically enhances paclitaxel efficacy to inhibit cancer cell growth.

    Directory of Open Access Journals (Sweden)

    Zhen Hua Wu

    Full Text Available The major challenges we are facing in cancer therapy with paclitaxel (PTX are the drug resistance and severe side effects. Massive efforts have been made to overcome these clinical challenges by combining PTX with other drugs. In this study, we reported the first preclinical data that praziquantel (PZQ, an anti-parasite agent, could greatly enhance the anticancer efficacy of PTX in various cancer cell lines, including PTX-resistant cell lines. Based on the combination index value, we demonstrated that PZQ synergistically enhanced PTX-induced cell growth inhibition. The co-treatment of PZQ and PTX also induced significant mitotic arrest and activated the apoptotic cascade. Moreover, PZQ combined with PTX resulted in a more pronounced inhibition of tumor growth compared with either drug alone in a mouse xenograft model. We tried to investigate the possible mechanisms of this synergistic efficacy induced by PZQ and PTX, and we found that the co-treatment of the two drugs could markedly decrease expression of X-linked inhibitor of apoptosis protein (XIAP, an anti-apoptotic protein. Our data further demonstrated that down-regulation of XIAP was required for the synergistic interaction between PZQ and PTX. Together, this study suggested that the combination of PZQ and PTX may represent a novel and effective anticancer strategy for optimizing PTX therapy.

  4. Leadership and Leader Developmental Self-Efficacy: Their Role in Enhancing Leader Development Efforts.

    Science.gov (United States)

    Murphy, Susan Elaine; Johnson, Stefanie K

    2016-01-01

    This chapter describes the role of two types of self-efficacy-leader self-efficacy and leader developmental efficacy-for enhancing leadership development. Practical implications for designing and developing leadership programs that take into account these two types of self-efficacy are discussed. © 2016 Wiley Periodicals, Inc., A Wiley Company.

  5. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer's disease mouse models.

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    Scott B Raymond

    Full Text Available Alzheimer's disease is a neurodegenerative disorder typified by the accumulation of a small protein, beta-amyloid, which aggregates and is the primary component of amyloid plaques. Many new therapeutic and diagnostic agents for reducing amyloid plaques have limited efficacy in vivo because of poor transport across the blood-brain barrier. Here we demonstrate that low-intensity focused ultrasound with a microbubble contrast agent may be used to transiently disrupt the blood-brain barrier, allowing non-invasive, localized delivery of imaging fluorophores and immunotherapeutics directly to amyloid plaques. We administered intravenous Trypan blue, an amyloid staining red fluorophore, and anti-amyloid antibodies, concurrently with focused ultrasound therapy in plaque-bearing, transgenic mouse models of Alzheimer's disease with amyloid pathology. MRI guidance permitted selective treatment and monitoring of plaque-heavy anatomical regions, such as the hippocampus. Treated brain regions exhibited 16.5+/-5.4-fold increase in Trypan blue fluorescence and 2.7+/-1.2-fold increase in anti-amyloid antibodies that localized to amyloid plaques. Ultrasound-enhanced delivery was consistently reproduced in two different transgenic strains (APPswe:PSEN1dE9, PDAPP, across a large age range (9-26 months, with and without MR guidance, and with little or no tissue damage. Ultrasound-mediated, transient blood-brain barrier disruption allows the delivery of both therapeutic and molecular imaging agents in Alzheimer's mouse models, which should aid pre-clinical drug screening and imaging probe development. Furthermore, this technique may be used to deliver a wide variety of small and large molecules to the brain for imaging and therapy in other neurodegenerative diseases.

  6. Dual-therapeutic reporter genes fusion for enhanced cancer gene therapy and imaging.

    Science.gov (United States)

    Sekar, T V; Foygel, K; Willmann, J K; Paulmurugan, R

    2013-05-01

    Two of the successful gene-directed enzyme prodrug therapies include herpes simplex virus-thymidine kinase (HSV1-TK) enzyme-ganciclovir prodrug and the Escherichia coli nitroreductase (NTR) enzyme-CB1954 prodrug strategies; these enzyme-prodrug combinations produce activated cytotoxic metabolites of the prodrugs capable of tumor cell death by inhibiting DNA synthesis and killing quiescent cells, respectively. Both these strategies also affect significant bystander cell killing of neighboring tumor cells that do not express these enzymes. We have developed a dual-combination gene strategy, where we identified HSV1-TK and NTR fused in a particular orientation can effectively kill tumor cells when the tumor cells are treated with a fusion HSV1-TK-NTR gene- along with a prodrug combination of GCV and CB1954. In order to determine whether the dual-system demonstrate superior therapeutic efficacy than either HSV1-TK or NTR systems alone, we conducted both in vitro and in vivo tumor xenograft studies using triple negative SUM159 breast cancer cells, by evaluating the efficacy of cell death by apoptosis and necrosis upon treatment with the dual HSV1-TK genes-GCV-CB1954 prodrugs system, and compared the efficiency to HSV1-TK-GCV and NTR-CB1954. Our cell-based studies, tumor regression studies in xenograft mice, histological analyses of treated tumors and bystander studies indicate that the dual HSV1-TK-NTR-prodrug system is two times more efficient even with half the doses of both prodrugs than the respective single gene-prodrug system, as evidenced by enhanced apoptosis and necrosis of tumor cells in vitro in culture and xenograft of tumor tissues in animals.

  7. Augmenting the Efficacy of Immunotoxins and Other Targeted Protein Toxins by Endosomal Escape Enhancers

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    Hendrik Fuchs

    2016-07-01

    Full Text Available The toxic moiety of almost all protein-based targeted toxins must enter the cytosol of the target cell to mediate its fatal effect. Although more than 500 targeted toxins have been investigated in the past decades, no antibody-targeted protein toxin has been approved for tumor therapeutic applications by the authorities to date. Missing efficacy can be attributed in many cases to insufficient endosomal escape and therefore subsequent lysosomal degradation of the endocytosed toxins. To overcome this drawback, many strategies have been described to weaken the membrane integrity of endosomes. This comprises the use of lysosomotropic amines, carboxylic ionophores, calcium channel antagonists, various cell-penetrating peptides of viral, bacterial, plant, animal, human and synthetic origin, other organic molecules and light-induced techniques. Although the efficacy of the targeted toxins was typically augmented in cell culture hundred or thousand fold, in exceptional cases more than million fold, the combination of several substances harbors new problems including additional side effects, loss of target specificity, difficulties to determine the therapeutic window and cell type-dependent variations. This review critically scrutinizes the chances and challenges of endosomal escape enhancers and their potential role in future developments.

  8. Plasma microRNAs serve as biomarkers of therapeutic efficacy and disease progression in hypertension-induced heart failure

    NARCIS (Netherlands)

    Dickinson, Brent A; Semus, Hillary M; Montgomery, Rusty L; Stack, Christianna; Latimer, Paul A; Lewton, Steven M; Lynch, Joshua M; Hullinger, Thomas G; Seto, Anita G; van Rooij, Eva

    AIMS: Recent studies have shown that microRNAs (miRNAs), besides being potent regulators of gene expression, can additionally serve as circulating biomarkers of disease. The aim of this study is to determine if plasma miRNAs can be used as indicators of disease progression or therapeutic efficacy in

  9. Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs

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    Ildiko Barabasi

    2016-11-01

    Full Text Available Therapeutic efficacy and safety evaluation of erythrocyte concentrate used in dogs 1Ildikó BARABÁSI, 1Cristina ȘTEFǍNUȚ, 1Laurenţ OGNEAN 1University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400037, Manastur street, no.3-5, Cluj-Napoca, Romania *Corresponding author: lognean@yahoo.com   Keywords: dogs, erythrocyte concentrate, hematocrit, immune-mediated hemolytic anemia, transfusion therapy Introduction: The minimum dose of whole blood products as well as erythrocyte concentrate has been under a lot of debate, new equations for calculating the optimal dose being made up from a large variety of hematologists (Kisielewicz et al 2014; Helm and Knottenbelt, 2010; Gibson, 2007. Aim: The therapeutical efficacy of erythrocyte concentrates in dogs with different types of anemia by measuring the hematocrit level 6 hours after the transfusion and a complete blood count 5 days post-transfusion therapy. Materials and methods: Blood tests were performed with ADIVA hematological analyzer; the 6 hour post-transfusion hematocrit was determined by a micro hematocrit. On admission every patient received a routine blood test that included 40 hematological parameters and 21 biochemical parameters. In addition, a detailed examination of the blood smears was also performed by the ADIVA hematological analyzer with 26 parameters that mostly referred to red blood cell and white blood cell morphology. Blood typing was done using the RapidVet quick test kit. Patients received only type specific blood and to limit transfusion reaction occurrences, in addition, a crossmatch test was performed before every transfusion. Statistical analysis was accomplished with GraphPadInStat 3.0 and the graphical depiction of the obtained results was made using the Origin 8.5. graphics program. Results: Statistical analysis reveal that the total red blood cell count underwent very significant changes (p=0.0052 as well as the hemoglobin (p=0.0085. The hematocrit

  10. Transplantation of autologous adipose stem cells lacks therapeutic efficacy in the experimental autoimmune encephalomyelitis model.

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    Xiujuan Zhang

    Full Text Available Multiple sclerosis (MS, characterized by chronic inflammation, demyelination, and axonal damage, is a complicated neurological disease of the human central nervous system. Recent interest in adipose stromal/stem cell (ASCs for the treatment of CNS diseases has promoted further investigation in order to identify the most suitable ASCs. To investigate whether MS affects the biologic properties of ASCs and whether autologous ASCs from MS-affected sources could serve as an effective source for stem cell therapy, cells were isolated from subcutaneous inguinal fat pads of mice with established experimental autoimmune encephalomyelitis (EAE, a murine model of MS. ASCs from EAE mice and their syngeneic wild-type mice were cultured, expanded, and characterized for their cell morphology, surface antigen expression, osteogenic and adipogenic differentiation, colony forming units, and inflammatory cytokine and chemokine levels in vitro. Furthermore, the therapeutic efficacy of the cells was assessed in vivo by transplantation into EAE mice. The results indicated that the ASCs from EAE mice displayed a normal phenotype, typical MSC surface antigen expression, and in vitro osteogenic and adipogenic differentiation capacity, while their osteogenic differentiation capacity was reduced in comparison with their unafflicted control mice. The ASCs from EAE mice also demonstrated increased expression of pro-inflammatory cytokines and chemokines, specifically an elevation in the expression of monocyte chemoattractant protein-1 and keratin chemoattractant. In vivo, infusion of wild type ASCs significantly ameliorate the disease course, autoimmune mediated demyelination and cell infiltration through the regulation of the inflammatory responses, however, mice treated with autologous ASCs showed no therapeutic improvement on the disease progression.

  11. Efficacy of a therapeutic vaccine using mutated β-amyloid sensitized dendritic cells in Alzheimer's mice.

    Science.gov (United States)

    Luo, Zhongqiu; Li, Jialin; Nabar, Neel R; Lin, Xiaoyang; Bai, Ge; Cai, Jianfeng; Zhou, Shu-Feng; Cao, Chuanhai; Wang, Jinhuan

    2012-09-01

    Despite FDA suspension of Elan's AN-1792 amyloid beta (Aβ) vaccine in phase IIb clinical trials, the implications of this study are the guiding principles for contemporary anti-Aβ immunotherapy against Alzheimer's disease (AD). AN-1792 showed promising results with regards to Aβ clearance and cognitive function improvement, but also exhibited an increased risk of Th1 mediated meningoencephalitis. As such, vaccine development has continued with an emphasis on eliciting a notable anti-Aβ antibody titer, while avoiding the unwanted Th1 pro-inflammatory response. Previously, we published the first report of an Aβ sensitized dendritic cell vaccine as a therapeutic treatment for AD in BALB/c mice. Our vaccine elicited an anti-Aβ titer, with indications that a Th1 response was not present. This study is the first to investigate the efficacy and safety of our dendritic cell vaccine for the prevention of AD in transgenic mouse models (PDAPP) for AD. We also used Immunohistochemistry to characterize the involvement of LXR, ABCA1, and CD45 in order to gain insight into the potential mechanisms through which this vaccine may provide benefit. The results indicate that (1) the use of mutant Aβ1-42 sensitized dendritic cell vaccine results in durable antibody production, (2) the vaccine provides significant benefits with regards to cognitive function without the global (Th1) inflammation seen in prior Aβ vaccines, (3) histological studies showed an overall decrease in Aβ burden, with an increase in LXR, ABCA1, and CD45, and (4) the beneficial results of our DC vaccine may be due to the LXR/ABCA1 pathway. In the future, mutant Aβ sensitized dendritic cell vaccines could be an efficacious and safe method for the prevention or treatment of AD that circumvents problems associated with traditional anti-Aβ vaccines.

  12. An HDAC-dependent epigenetic mechanism that enhances the efficacy of the antidepressant drug fluoxetine

    Science.gov (United States)

    Schmauss, C.

    2015-01-01

    Depression is a prevalent and debilitating psychiatric illnesses. However, currently prescribed antidepressant drugs are only efficacious in a limited group of patients. Studies on Balb/c mice suggested that histone deacetylase (HDAC) inhibition may enhance the efficacy of the widely-prescribed antidepressant drug fluoxetine. This study shows that reducing HDAC activity in fluoxetine-treated Balb/c mice leads to robust antidepressant and anxiolytic effects. While reducing the activity of class I HDACs 1 and 3 led to antidepressant effects, additional class II HDAC inhibition was necessary to exert anxiolytic effects. In fluoxetine-treated mice, HDAC inhibitors increased enrichment of acetylated histone H4 protein and RNA polymerase II at promotor 3 of the brain-derived neurotrophic factor (Bdnf) gene and increased Bdnf transcription from this promotor. Reducing Bdnf-stimulated tropomyosin kinase B receptor activation in fluoxetine-treated mice with low HDAC activity abolished the behavioral effects of fluoxetine, suggesting that the HDAC-triggered epigenetic stimulation of Bdnf expression is critical for therapeutic efficacy. PMID:25639887

  13. Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC

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    Thangjam Davis Singh

    2015-01-01

    Full Text Available BACKGROUND: Clinical use of chemotherapeutic drug, cisplatin is limited by its toxicity and drug resistance. Therefore, efforts continue for the discovery of novel combination therapies with cisplatin, to increase efficacy and reduce its toxicity. Here, we screened 16 medicinal plant extracts from Northeast part of India and found that leaf extract of Zanthoxylum armatum DC. (ZALE induced cytotoxicity as well as an effect on the increasing of the efficiency of chemotherapeutic drugs (cisplatin, mitomycin C and camptothecin. This work shows detail molecular mechanism of anti-cancer activity of ZALE and its potential for combined treatment regimens to enhance the apoptotic response of chemotherapeutic drugs. RESULTS: ZALE induced cytotoxicity, nuclear blebbing and DNA fragmentation in HeLA cells suggesting apoptosis induction in human cervical cell line. However, the apoptosis induced was independent of caspase 3 activation and poly ADP ribose polymerase (PARP cleavage. Further, ZALE activated Mitogen-activated protein kinases (MAPK pathway as revealed by increased phosphorylation of extracellular-signal-regulated kinases (ERK, p38 and c-Jun N-ter-minal kinase (JNK. Inhibition of ERK activation but not p38 or JNK completely blocked the ZALE induced apoptosis suggesting an ERK dependent apoptosis. Moreover, ZALE generated DNA double strand breaks as suggested by the induction γH2AX foci formation. Interestingly, pretreatment of certain cancer cell lines with ZALE, sensitized the cancer cells to cisplatin and other chemotherapeutic drugs. Enhanced caspase activation was observed in the synergistic interaction among chemotherapeutic drugs and ZALE. CONCLUSION: Purification and identification of the bio-active molecules from the ZALE or as a complementary treatment for a sequential treatment of ZALE with chemotherapeutic drugs might be a new challenger to open a new therapeutic window for the novel anti-cancer treatment.

  14. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

    Science.gov (United States)

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

    2009-03-17

    Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

  15. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

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    Kim Sung-Ho

    2009-03-01

    Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

  16. Low-dose radiation potentiates the therapeutic efficacy of folate receptor-targeted hapten therapy.

    Science.gov (United States)

    Sega, Emanuela I; Lu, Yingjuan; Ringor, Michael; Leamon, Christopher P; Low, Philip S

    2008-06-01

    Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm(3) before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Mice bearing 300-mm(3) subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon alpha) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm(3). More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice.

  17. Low-Dose Radiation Potentiates the Therapeutic Efficacy of Folate Receptor-Targeted Hapten Therapy

    International Nuclear Information System (INIS)

    Sega, Emanuela I.; Lu Yingjuan; Ringor, Michael; Leamon, Christopher P.; Low, Philip S.

    2008-01-01

    Purpose: Human cancers frequently overexpress a high-affinity cell-surface receptor for the vitamin folic acid. Highly immunogenic haptens can be targeted to folate receptor-expressing cell surfaces by administration of folate-hapten conjugates, rendering the decorated tumor cell surfaces more recognizable by the immune system. Treatment of antihapten-immunized mice with folate-hapten constructs results in elimination of moderately sized tumors by the immune system. However, when subcutaneous tumors exceed 300 mm 3 before initiation of therapy, antitumor activity is significantly decreased. In an effort to enhance the efficacy of folate-targeted hapten immunotherapy (FTHI) against large tumors, we explored the combination of targeted hapten immunotherapy with low-dose radiotherapy. Methods and Materials: Mice bearing 300-mm 3 subcutaneous tumors were treated concurrently with FTHI (500 nmol/kg of folate conjugated to fluorescein isothiocyanate, 20,000 U/dose of interleukin 2, and 25,000 U/dose of interferon α) and low-dose radiotherapy (3 Gy/dose focused directly on the desired tumor mass). The efficacy of therapy was evaluated by measuring tumor volume. Results: Tumor growth analyses show that radiotherapy synergizes with FTHI in antihapten-immunized mice, thereby allowing for cures of animals bearing tumors greater than 300 mm 3 . More importantly, nonirradiated distal tumor masses in animals containing locally irradiated tumors also showed improved response to hapten immunotherapy, suggesting that not all tumor lesions must be identified and irradiated to benefit from the combination therapy. Conclusions: These results suggest that simultaneous treatment with FTHI and radiation therapy can enhance systemic antitumor activity in tumor-bearing mice

  18. Chemical modifications of antisense morpholino oligomers enhance their efficacy against Ebola virus infection.

    Science.gov (United States)

    Swenson, Dana L; Warfield, Kelly L; Warren, Travis K; Lovejoy, Candace; Hassinger, Jed N; Ruthel, Gordon; Blouch, Robert E; Moulton, Hong M; Weller, Dwight D; Iversen, Patrick L; Bavari, Sina

    2009-05-01

    Phosphorodiamidate morpholino oligomers (PMOs) are uncharged nucleic acid-like molecules designed to inactivate the expression of specific genes via the antisense-based steric hindrance of mRNA translation. PMOs have been successful at knocking out viral gene expression and replication in the case of acute viral infections in animal models and have been well tolerated in human clinical trials. We propose that antisense PMOs represent a promising class of therapeutic agents that may be useful for combating filoviral infections. We have previously shown that mice treated with a PMO whose sequence is complementary to a region spanning the start codon of VP24 mRNA were protected against lethal Ebola virus challenge. In the present study, we report on the abilities of two additional VP24-specific PMOs to reduce the cell-free translation of a VP24 reporter, to inhibit the in vitro replication of Ebola virus, and to protect mice against lethal challenge when the PMOs are delivered prior to infection. Additionally, structure-activity relationship evaluations were conducted to assess the enhancement of antiviral efficacy associated with PMO chemical modifications that included conjugation with peptides of various lengths and compositions, positioning of conjugated peptides to either the 5' or the 3' terminus, and the conferring of charge modifications by the addition of piperazine moieties. Conjugation with arginine-rich peptides greatly enhanced the antiviral efficacy of VP24-specific PMOs in infected cells and mice during lethal Ebola virus challenge.

  19. Diagnostic efficacy and therapeutic impact of computed tomography in the evaluation of clinically suspected otosclerosis

    International Nuclear Information System (INIS)

    Dudau, Cristina; Salim, Fakhruddin; Jiang, Dan; Connor, Steve E.J.

    2017-01-01

    To assess the diagnostic efficacy and therapeutic impact of CT in evaluating patients with clinically suspected otosclerosis. CT scans performed over a 5-year period for clinically suspected otosclerosis were retrospectively reviewed. CT diagnoses were correlated with subsequent surgical management. For otosclerosis positive cases, clinically significant extensions of otosclerosis were correlated with audiometry and the diagnosis was correlated with surgical findings. Of 259 CT studies, 46 % of patients were positive, 49 % negative and 5 % equivocal for otosclerosis. A relevant alternative CT diagnosis was evident in 33 % of the negative studies. One targeted surgery was performed for every four CT studies. CT outcome influenced the decision to perform stapedectomy in 41 % CT-positive versus 4 % CT-negative patients. CT-positive ears for otosclerosis could not be predicted from baseline clinical or audiometric criteria. Those with endosteal extension demonstrated lower bone conduction thresholds presurgically. The positive predictive value of CT diagnosis of otosclerosis was 100 %. CT demonstrated a high rate of clinically relevant diagnoses in both CT-positive and -negative for otosclerosis patients, and this frequently influenced surgical management. CT also added value by demonstrating relevant extensions of the otosclerotic foci, some of which were predictive of audiometric parameters. (orig.)

  20. Do ABO blood group antigens hamper the therapeutic efficacy of mesenchymal stromal cells?

    Science.gov (United States)

    Moll, Guido; Hult, Annika; von Bahr, Lena; Alm, Jessica J; Heldring, Nina; Hamad, Osama A; Stenbeck-Funke, Lillemor; Larsson, Stella; Teramura, Yuji; Roelofs, Helene; Nilsson, Bo; Fibbe, Willem E; Olsson, Martin L; Le Blanc, Katarina

    2014-01-01

    Investigation into predictors for treatment outcome is essential to improve the clinical efficacy of therapeutic multipotent mesenchymal stromal cells (MSCs). We therefore studied the possible harmful impact of immunogenic ABO blood groups antigens - genetically governed antigenic determinants - at all given steps of MSC-therapy, from cell isolation and preparation for clinical use, to final recipient outcome. We found that clinical MSCs do not inherently express or upregulate ABO blood group antigens after inflammatory challenge or in vitro differentiation. Although antigen adsorption from standard culture supplements was minimal, MSCs adsorbed small quantities of ABO antigen from fresh human AB plasma (ABP), dependent on antigen concentration and adsorption time. Compared to cells washed in non-immunogenic human serum albumin (HSA), MSCs washed with ABP elicited stronger blood responses after exposure to blood from healthy O donors in vitro, containing high titers of ABO antibodies. Clinical evaluation of hematopoietic stem cell transplant (HSCT) recipients found only very low titers of anti-A/B agglutination in these strongly immunocompromised patients at the time of MSC treatment. Patient analysis revealed a trend for lower clinical response in blood group O recipients treated with ABP-exposed MSC products, but not with HSA-exposed products. We conclude, that clinical grade MSCs are ABO-neutral, but the ABP used for washing and infusion of MSCs can contaminate the cells with immunogenic ABO substance and should therefore be substituted by non-immunogenic HSA, particularly when cells are given to immunocompentent individuals.

  1. Diagnostic efficacy and therapeutic impact of computed tomography in the evaluation of clinically suspected otosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Dudau, Cristina [King' s College Hospital NHS Foundation Trust, Department of Neuroradiology, London (United Kingdom); Salim, Fakhruddin; Jiang, Dan [Department of Otolaryngology, Head and Neck Surgery, Auditory Implantation Centre, London (United Kingdom); Connor, Steve E.J. [Department of Radiology, Guy' s and St Thomas' NHS Foundation Trust, London (United Kingdom)

    2017-03-15

    To assess the diagnostic efficacy and therapeutic impact of CT in evaluating patients with clinically suspected otosclerosis. CT scans performed over a 5-year period for clinically suspected otosclerosis were retrospectively reviewed. CT diagnoses were correlated with subsequent surgical management. For otosclerosis positive cases, clinically significant extensions of otosclerosis were correlated with audiometry and the diagnosis was correlated with surgical findings. Of 259 CT studies, 46 % of patients were positive, 49 % negative and 5 % equivocal for otosclerosis. A relevant alternative CT diagnosis was evident in 33 % of the negative studies. One targeted surgery was performed for every four CT studies. CT outcome influenced the decision to perform stapedectomy in 41 % CT-positive versus 4 % CT-negative patients. CT-positive ears for otosclerosis could not be predicted from baseline clinical or audiometric criteria. Those with endosteal extension demonstrated lower bone conduction thresholds presurgically. The positive predictive value of CT diagnosis of otosclerosis was 100 %. CT demonstrated a high rate of clinically relevant diagnoses in both CT-positive and -negative for otosclerosis patients, and this frequently influenced surgical management. CT also added value by demonstrating relevant extensions of the otosclerotic foci, some of which were predictive of audiometric parameters. (orig.)

  2. Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

    Science.gov (United States)

    Bradbury, Allison M; Gray-Edwards, Heather L; Shirley, Jamie L; McCurdy, Victoria J; Colaco, Alexandria N; Randle, Ashley N; Christopherson, Pete W; Bird, Allison C; Johnson, Aime K; Wilson, Diane U; Hudson, Judith A; De Pompa, Nicholas L; Sorjonen, Donald C; Brunson, Brandon L; Jeyakumar, Mylvaganam; Platt, Frances M; Baker, Henry J; Cox, Nancy R; Sena-Esteves, Miguel; Martin, Douglas R

    2014-01-01

    The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme β-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated GM2 patients and those in future clinical trials. PMID:25284324

  3. Therapeutic efficacy of chemotherapy with ACNU and radiation therapy for malignant glioma in the cerebral hemisphere

    Energy Technology Data Exchange (ETDEWEB)

    Miyagami, Mitsusuke; Katayama, Yoichi; Nakamura, Saburo [Nihon Univ., Tokyo (Japan). School of Medicine

    2000-10-01

    Seventy-two patients with malignant gliomas (57 with glioblastoma and 15 with anaplastic astrocytoma) in the cerebral hemisphere were studied retrospectively to evaluate the therapeutic efficacy of chemotherapy with nimustine and radiation after surgery. Survival was analyzed with the Kaplan-Meier method in 21 patients treated with radiotherapy after surgery and 51 patients treated with nimustine and radiotherapy after surgery. Histological classification age, and the extent of resection of the tumors were significantly correlated with survival. The median survival time was 8 months in patients treated with radiotherapy and 15 months in patients treated with nimustine and radiotherapy. The 2- and 5-year survival rates were 12% and 0% in patients treated with radiotherapy and 33% and 22% in patients treated with nimustine and radiotherapy. Thus, a significant difference in survival was recognized, and chemotherapy with nimustine was found to be useful as an adjuvant therapy for glioblastoma after surgery. However, survival time did not differ between intravenous and intra-arterial infusion of nimustine. (author)

  4. Efficacy of Morin as a Potential Therapeutic Phytocomponent: Insights into the Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Amarendranath Choudhury

    2017-11-01

    Full Text Available Morin (3,5,7,29,49-pentahydroxyflavone is a yellow colour natural bioflavonoid abundantly available in different species of Moraceae family. Besides this, Morin is also harvested from several other sources like tea, coffee, cereals, fruits and red wine. Anti-oxidant, anti-inflammatory, and antiproliferative potency of Morin is well established in both in vivo and in vitro experiments. Among all major sources of Morin, Almond (Prunus dulcis, Fig (Chlorophora tinctoria, and Indian guava (Psidium guajava contains high quantity of it. Easy availability, less side effects and robust functional properties have encouraged the use of these plants in the traditional herbal medicine. In last few decades, the studies on Morin have opened up a whole new era in the therapeutic medicine. Besides anti-oxidant, anti-inflammatory, and antiproliferative activity, Morin has also been reported as a potential neuroprotective agent against many neurological diseases including Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. According to published reports, the underlying neuroprotective mechanism of Morin is focused mainly on its capacity to inhibit oxidative stress in brain. However, recent data also supports its efficacy in neuroprotection by effectively interacting in the β‒amyloid pathways, inflammatory pathways, and apoptotic pathways. In the present review, we have accumulated all the protective contributions of Morin and intended to drag a mechanistic pathway containing the molecular events leading to the protection against various anomalies.

  5. Therapeutic efficacy and safety of propylthiouracil in psoriasis: An open-label study

    Directory of Open Access Journals (Sweden)

    Pushpa Gnanaraj

    2011-01-01

    Full Text Available Background: Psoriasis is a common hyperproliferative disorder of the skin associated with significant morbidity. Most of the drugs used in psoriasis provide only a temporary relief, whereas they are riddled with potential toxicities and cost concerns. Hence, there is a constant need to explore newer, effective, orally administered, and cost-effective drugs with minimal adverse effects. In this scenario, propylthiouracil (PTU, an antithyroid thioureylene has been shown to be effective in psoriasis which satisfies the above criteria. Aim: The objective of our study is to assess the clinical efficacy of PTU in psoriasis. Methods: A total of 25 patients with plaque psoriasis were treated with oral PTU for 12 weeks. Clinical response was assessed using the "Psoriasis Area and Severity Index" (PASI score. Routine blood analyses and thyroid function tests were carried out periodically during the study. Results: Oral PTU produced significant clearing of lesions at 6 weeks and 12 weeks of the study period in all patients, as demonstrated by the reduction in PASI scores (33.9% in 6 weeks and 74.1% reduction in 12 weeks. Four patients experienced near complete clearing of the lesions. One patient developed mild elevation of liver enzymes which reversed on withdrawal of PTU. None of the patients had hypothyroidism or cytopenias. Conclusion: PTU significantly clears the lesions in psoriasis with minimal adverse effects. Hence, it can be considered as a therapeutic option in psoriasis, especially when the standard drugs cannot be used due to their toxicities or forbidding cost.

  6. Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement

    Directory of Open Access Journals (Sweden)

    Yum S

    2015-08-01

    Full Text Available Soohwan Yum, Seongkeun Jeong, Sunyoung Lee, Joon Nam, Wooseong Kim, Jin-Wook Yoo, Min-Soo Kim, Bok Luel Lee, Yunjin Jung College of Pharmacy, Pusan National University, Busan, Republic of Korea Abstract: Piceatannol (PCT, an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT were compared with PCT in a gelatin capsule (conventional PCT in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2 p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products. Keywords: piceatannol, colitis, colon-targeted delivery, multitarget, polypharmacology

  7. Using PEGylated magnetic nanoparticles to describe the EPR effect in tumor for predicting therapeutic efficacy of micelle drugs.

    Science.gov (United States)

    Chen, Ling; Zang, Fengchao; Wu, Haoan; Li, Jianzhong; Xie, Jun; Ma, Ming; Gu, Ning; Zhang, Yu

    2018-01-25

    Micelle drugs based on a polymeric platform offer great advantages over liposomal drugs for tumor treatment. Although nearly all of the nanomedicines approved in the clinical use can passively target to the tumor tissues on the basis of an enhanced permeability and retention (EPR) effect, the nanodrugs have shown heterogenous responses in the patients. This phenomenon may be traced back to the EPR effect of tumor, which is extremely variable in the individuals from extensive studies. Nevertheless, there is a lack of experimental data describing the EPR effect and predicting its impact on therapeutic efficacy of nanoagents. Herein, we developed 32 nm magnetic iron oxide nanoparticles (MION) as a T 2 -weighted contrast agent to describe the EPR effect of each tumor by in vivo magnetic resonance imaging (MRI). The MION were synthesized by a thermal decomposition method and modified with DSPE-PEG2000 for biological applications. The PEGylated MION (Fe 3 O 4 @PEG) exhibited high r 2 of 571 mM -1 s -1 and saturation magnetization (M s ) of 94 emu g -1 Fe as well as long stability and favorable biocompatibility through the in vitro studies. The enhancement intensities of the tumor tissue from the MR images were quantitatively measured as TNR (Tumor/Normal tissue signal Ratio) values, which were correlated with the delay of tumor growth after intravenous administration of the PLA-PEG/PTX micelle drug. The results demonstrated that the group with the smallest TNR values (TNR EPR effect in patients for accurate medication guidance of micelle drugs in the future treatment of tumors.

  8. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases.

    Science.gov (United States)

    Oh, Doo-Byoung

    2015-08-01

    Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy.

  9. [Therapeutic efficacy of compound Xuanju capsule on autoimmune prostatitis in rats: an experimental study].

    Science.gov (United States)

    Li, Tian-Fu; Wu, Qiu-Yue; Li, Wei-Wei; Zhang, Cui; Li, Na; Shang, Xue-Jun; Xia, Xin-Yi; Xu, Hao-Qin; Huang, Yu-Feng

    2014-05-01

    To evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on autoimmune prostatitis in rat models. Sixty healthy male Wistar rats were randomly divided into five groups of equal number: blank control, low-concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment. Autoimmune prostatitis models were established by intragastric administration of PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30 days after modeling, the rats in the blank control and low-conc and hi-conc PPP model groups were treated with normal saline, and those in the other two groups with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals were sacrificed for observation of pathological changes in the prostate tissue and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum. Compared with the PPP models, the hi-conc PPP + CXC group showed significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63 +/- 2.91] pg/ml, P microscope. Compound Xuanju Capsule is efficacious on autoimmune prostatis in rats by reducing inflammatory changes in the prostate tissue and improving the expression of inflammatory factors.

  10. Therapeutic efficacy of autologous platelet-rich plasma and polydeoxyribonucleotide on female pattern hair loss.

    Science.gov (United States)

    Lee, Si-Hyung; Zheng, Zhenlong; Kang, Jin-Soo; Kim, Do-Young; Oh, Sang Ho; Cho, Sung Bin

    2015-01-01

    Autologous platelet-rich plasma (PRP) exerts positive therapeutic effects on hair thickness and density in patients with pattern hair loss. The aim of our study was to evaluate the efficacy of intra-perifollicular autologous PRP and polydeoxyribonucleotide (PDRN) injections in treating female pattern hair loss (FPHL). Twenty FPHL patients were treated with a single session of PRP injection, followed by 12 sessions of PDRN intra-perifollicular injection, along the scalp at weekly intervals. Additionally, another 20 FPHL patients were treated with 12 sessions of PDRN injection only. Meanwhile, one half of the backs of two rabbits was injected with the PRP preparation, while the other half was injected with phosphate buffered saline as a control. Tissue samples from the rabbits were analyzed by real-time polymerase chain reaction and Western blotting. Compared with baseline values, patients treated with PRP and PDRN injections exhibited clinical improvement in mean hair counts (23.2 ± 15.5%; p hair thickness (16.8 ± 10.8%; p hair counts (17.9 ± 13.2%; p hair thickness (13.5 ± 10.7%; p hair thickness than treatment with PDRN therapy alone (p = 0.031), but not in hair counts (p > 0.05). The pilot animal study revealed significant up-regulation of WNT, platelet-derived growth factor, and fibroblast growth factor expression in rabbit skin treated with the PRP preparation, compared with control skin. In conclusion, intra-perifollicular injections of autologous PRP and/or PDRN generate improvements in hair thickness and density in FPHL patients. © 2014 by the Wound Healing Society.

  11. Neuroprotective efficacy and therapeutic window of curcuma oil: in rat embolic stroke model

    Science.gov (United States)

    Dohare, Preeti; Garg, Puja; sharma, Uma; Jagannathan, NR; Ray, Madhur

    2008-01-01

    Background Among the naturally occurring compounds, turmeric from the dried rhizome of the plant Curcuma longa has long been used extensively as a condiment and a household remedy all over Southeast Asia. Turmeric contains essential oil, yellow pigments (curcuminoids), starch and oleoresin. The present study was designed for investigating the neuroprotective efficacy and the time window for effective therapeutic use of Curcuma oil (C. oil). Method In the present study, the effect of post ischemic treatment of C.oil after ischemia induced by occlusion of the middle cerebral artery in the rat was observed. C.oil (500 mg/kg body wt) was given 4 hrs post ischemia. The significant effect on lesion size as visualized by using diffusion-weighted magnetic resonance imaging and neuroscore was still evident when treatment was started 4 hours after insult. Animals were assessed for behavioral deficit scores after 5 and 24 hours of ischemia. Subsequently, the rats were sacrificed for evaluation of infarct and edema volumes and other parameters. Results C.oil ameliorated the ischemia induced neurological functional deficits and the infarct and edema volumes measured after 5 and 24 hrs of ischemia. After 24 hrs, immunohistochemical and Western blot analysis demonstrated that the expression of iNOS, cytochrome c and Bax/Bcl-2 were altered after the insult, and antagonized by treatment with C.oil. C.oil significantly reduced nitrosative stress, tended to correct the decreased mitochondrial membrane potential, and also affected caspase-3 activation finally apoptosis. Conclusion Here we demonstrated that iNOS-derived NO produced during ischemic injury was crucial for the up-regulation of ischemic injury targets. C.oil down-regulates these targets this coincided with an increased survival rate of neurons. PMID:18826584

  12. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    Science.gov (United States)

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  13. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    Directory of Open Access Journals (Sweden)

    Jan B W J Cornelissen

    Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.

  14. Tumor blood vessel "normalization" improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Nigg

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  15. Tumor blood vessel 'normalization' improves the therapeutic efficacy of boron neutron capture therapy (BNCT) in experimental oral cancer

    International Nuclear Information System (INIS)

    Nigg, D.W.

    2012-01-01

    We previously demonstrated the efficacy of BNCT mediated by boronophenylalanine (BPA) to treat tumors in a hamster cheek pouch model of oral cancer with no normal tissue radiotoxicity and moderate, albeit reversible, mucositis in precancerous tissue around treated tumors. It is known that boron targeting of the largest possible proportion of tumor cells contributes to the success of BNCT and that tumor blood vessel normalization improves drug delivery to the tumor. Within this context, the aim of the present study was to evaluate the effect of blood vessel normalization on the therapeutic efficacy and potential radiotoxicity of BNCT in the hamster cheek pouch model of oral cancer.

  16. Potentiating therapeutic effects by enhancing synergism based on active constituents from traditional medicine.

    Science.gov (United States)

    Zhang, Aihua; Sun, Hui; Wang, Xijun

    2014-04-01

    Shifting current drug discovery tide from 'finding new drugs' to 'screening natural products' may be helpful for overcoming the 'more investment, fewer drugs' challenge. Traditional Chinese medicine (TCM), relying on natural products, has been playing a very important role in health protection and disease control for thousands of years in Asia, whose therapeutic efficacy is based on the 'synergism', that is, the combinational effects to be greater than that of the individual drug. Based on syndromes and patient characteristics and guided by the theories of TCM, formulae are designed to contain a combination of various kinds of crude drugs that, when combined, generally assume that a synergism of all ingredients will bring about the maximum of therapeutic efficacy. The increasing evidence has shown that multiple active component combinations of TCM could amplify the therapeutic efficacy of each agent, representing a new trend for modern medicine. However, the precise mechanism of synergistic action remains poorly understood. The present review highlights the concept of synergy and gives some examples of synergistic effects of TCM, and provides an overview of the recent and potential developments of advancing drug discovery towards more agile development of targeted combination therapies from TCM. Copyright © 2013 John Wiley & Sons, Ltd.

  17. Therapeutic Efficacy of Bipolar Radiofrequency Thermotherapy for Patients with Chronic Prostatitis: A Retrospective Analysis of 26 Cases

    OpenAIRE

    Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

    2012-01-01

    Purpose Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. Materials and Methods A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 year...

  18. Poly-epsilon-caprolactone nanoparticles enhance ursolic acid in vivo efficacy against Trypanosoma cruzi infection.

    Science.gov (United States)

    Abriata, Juliana Palma; Eloy, Josimar O; Riul, Thalita Bachelli; Campos, Patricia Mazureki; Baruffi, Marcelo Dias; Marchetti, Juliana Maldonado

    2017-08-01

    Despite affecting millions of people worldwide, Chagas disease is still neglected by the academia and industry and the therapeutic option available, benznidazole, presents limited efficacy and side effects. Within this context, ursolic acid may serve as an option for treatment, however has low bioavailability, which can be enhanced through the encapsulation in polymeric nanoparticles. Therefore, herein we developed ursolic acid-loaded nanoparticles with poly-ε-caprolactone by the nanoprecipitation method and characterized them for particle size, zeta potential, polydispersity, encapsulation efficiency, morphology by scanning electron microscopy and thermal behavior by differential scanning calorimetry. Results indicated that an appropriate ratio of organic phase/aqueous phase and polymer/drug is necessary to produce smaller particles, with low polydispersity, negative zeta potential and high drug encapsulation efficiency. In vitro studies indicated the safety of the formulation against fibroblast culture and its efficacy in killing T. cruzi. Very importantly, the in vivo study revealed that the ursolic acid-loaded nanoparticle is as potent as the benznidazole group to control parasitemia, which could be attributed to improved bioavailability of the encapsulated drug. Finally, the toxicity evaluation showed that while benznidazole group caused liver toxicity, the nanoparticles were safe, indicating that this formulation is promising for future evaluation. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. The Role of Therapeutic Mentoring in Enhancing Outcomes for Youth in Foster Care

    Science.gov (United States)

    Johnson, Sara B.; Pryce, Julia M.; Martinovich, Zoran

    2011-01-01

    Effective service interventions greatly enhance the well-being of foster youth. A study of 262 foster youth examined one such intervention, therapeutic mentoring. Results showed that mentored youth improved significantly in the areas of family and social functioning, school behavior, and recreational activities, as well as in the reduction of…

  20. Therapeutic efficacy of different brands of albendazole against soil transmitted helminths among students of Mendera Elementary School, Jimma, Southwest Ethiopia.

    Science.gov (United States)

    Tefera, Ephrem; Belay, Tariku; Mekonnen, Seleshi Kebede; Zeynudin, Ahmed; Belachew, Tefera

    2015-01-01

    Different brands Albendazole are commercially available and the efficacious brand/s is/are required for effective control of STHs infection. Thus, this study is aimed at determining the therapeutic efficacy of different brands of albendazole against soil transmitted helminths among school children of Jimma town. A cross sectional survey for prevalence of geohelminths and a randomized trial for efficacy study of different brands of albendazole was conducted among students Mendera Elementary School from March 29 to April 29, 2010. Positive subjects were randomized into three treatment arms using lottery method. The collected stool samples were examined by the McMaster method. CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula. Of the 715 school children who had their stools examined, 326 were positive for STHs with a prevalence rate of 45.6%. The cure rates (CR) for A. lumbricoides, T. trichiura and Hookworm were 99.4, 59.9 and 93.7%, respectively. Similarly, the egg reduction rates (ERR) were 97, 99.9 and 99.9% respectively. A statistical significant mean STH egg count difference were observed between pre and post-intervention study (p 0.05). All the three brands of Albendazole tested regardless of the brand type were therapeutically efficacious for Ascariasis, Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple.

  1. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    OpenAIRE

    Thomas L. Chenevert; Charles R. Meyer; Bradford A. Moffat; Alnawaz Rehemtulla; Suresh K. Mukherji; Stephen S. Gebarski; Douglas J. Quint; Patricia L. Robertson; Theodore S. Lawrence; Larry Junck; Jeremy M. G. Taylor; Timothy D. Johnson; Qian Dong; Karin M. Muraszko; James A. Brunberg

    2002-01-01

    The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular ...

  2. Therapeutic efficacy of percutaneous radiofrequency ablation versus microwave ablation for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Lei Zhang

    Full Text Available The aim of this study was to investigate the therapeutic efficacy of percutaneous radiofrequency (RF ablation versus microwave (MW ablation for hepatocellular carcinoma (HCC measuring ≤ 5 cm in greatest diameter. From January 2006 to December 2006, 78 patients had undergone RF ablation whereas 77 had undergone MW ablation. Complete ablation (CA, local tumour progression (LTP and distant recurrence (DR were compared. The overall survival curves were calculated with the Kaplan-Meier technique and compared with the log-rank test. The CA rate was 83.4% (78/93 for RF ablation and 86.7%(91/105 for MW ablation. The LTP rate was 11.8% (11/93 for RF ablation and 10.5% (11/105 for MW ablation. DR was found in 51 (65.4% in the RF ablation and 62 (80.5% in the MW ablation. There was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.780 and the 1-, 3-, and 5-year disease-free survival rates (P = 0.123 between RF and MW ablation. At subgroup analyses, for patients with tumors ≤ 3.0 cm, there was no significant difference in the 1-, 3-, and 5-year overall survival rates (P = 0.067 and the corresponding disease-free survival rates(P = 0.849. For patients with tumor diameters of 3.1-5.0 cm, the 1-, 3-, and 5-year overall survival rates were 87.1%, 61.3%, and 40.1% for RF ablation and 85.4%, 36.6%, and 22% for MW ablation, with no significant difference (P = 0.068. The corresponding disease-free survival rates were 74.2%, 54.8%, and 45.2% for the RF ablation group and 53.3%, 26.8%, and 17.1% for the MW ablation group. The disease-free survival curve for the RF ablation group was significantly better than that for the MW ablation group (P = 0.018. RF ablation and MW ablation are both effective methods in treating hepatocellular carcinomas, with no significant differences in CA, LTP, DR, and overall survival.

  3. Therapeutic Efficacy of Endometrial Scratching in Repeated Controlled Ovarian Stimulation (COS) Failure Cycles

    Science.gov (United States)

    Wadhwa, Leena; Mishra, Mona

    2018-01-01

    Objective: The objective of the study was (1) “to evaluate the therapeutic efficacy of endometrial scratching in repeated controlled ovarian stimulation (COS) failure cycles.” And (2) “to compare differences in pregnancy outcome by endometrial scratching in early (D2–D4) and late follicular phases (D7–D9) of the same stimulation cycle.” Materials and Methods: Women attending infertility clinic in a tertiary care center and who have two or more repeated COS failure cycles and planned for COS with intrauterine insemination (IUI) were included in the study which is a prospective parallel, interventional, single-blinded, randomized control study, in 1:1 allocation ratio. A total of 165 patients were recruited and randomly allocated into three groups: Group A (n = 55) underwent endometrial scratching on D2–D4 of the same COS cycle, Group B (n = 55) on D7–D9, and Group C (n = 55) no intervention done. All the patients underwent COS according to standard protocol followed by IUI. Results: Clinical pregnancy rate was 12.73% (odds ratio [OR] =0.87 95% confidence interval [CI] =0.288–2.55, P = 1), 16.36% (OR = 1.15; 95% CI = 0.40–3.23, P = 1), and 14.54%, respectively, in Group A, B, and C, respectively (P = 0.86), as per intention to treat analysis. Using Chi-square test, P value between Group A and B was 0.787, between Group A and C was 1.000, and between Group B and C was 1.000. As per protocol analysis, clinical pregnancy rate was 13.46% (OR = 0.83; 95% CI = 0.27–2.5, P = 0.74), 19.57% (OR = 1.3 95%; CI = 0.45–3.73, P = 0.41), and 15.69%. Using Chi-square test, Pvalue between Group A and B was 0.588, between Group A and C was 0.967, and between Group B and C was 0.815. No abortions and multiple pregnancies occurred in either of the groups. Conclusion: The effect found was of good quantum in Group B as per protocol analysis which could be of clinical relevance if larger sample size would have been taken. Endometrial scratching is a cost

  4. Therapeutic efficacy of fibroblast growth factor 10 in a rabbit model of dry eye.

    Science.gov (United States)

    Zheng, Wenjing; Ma, Mingming; Du, Ergang; Zhang, Zhengwei; Jiang, Kelimu; Gu, Qing; Ke, Bilian

    2015-11-01

    The aim of the present study was to investigate the therapeutic efficacy of fibroblast growth factor 10 (FGF10) in the promotion of healing, survival and expression of mucin in corneal epithelial cells in a rabbit dry eye model. A total of 12 healthy female New Zealand white rabbits were divided randomly into three groups. The lacrimal glands were injected with saline either alone (normal control group) or with concanavalin A (Con A), with either topical phosphate‑buffered saline (PBS; PBS control group) or 25 µg/ml FGF10 (FGF10 treatment group). Lacrimal gland inflammation, tear function, corneal epithelial cell integrity, cell apoptosis and mucin expression were subsequently assessed. Lacrimal gland tissue biopsies were performed in conjunction with histology and electron microscopy observations. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured using Fourier domain‑optical coherence tomography. Tear membrane break‑up time (TBUT) was also assessed and corneal fluorescein staining was performed. The percentages of apoptotic corneal and conjunctival (Cj) epithelial cells (ECs) were counted using a terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. The mRNA expression levels of Muc1 were determined using reverse transcription‑quantitative polymerase chain reaction analyses. The TMH and TMA values of the PBS and treatment groups were found to be significantly reduced, compared with those of the normal control group 3 days after Con A injection. However, the TMH and TMA of the FGF10 treatment group were higher, compared with those of the PBS group 3 and 7 days after treatment, respectively. Furthermore, the FGF10 treatment group exhibited prolonged TBUT, reduced corneal fluorescein staining and repaired epithelial cell ultrastructure7 days after treatment. The percentages of apoptotic corneal‑ and Cj‑ECs in the FGF10 treatment group were significantly reduced, compared with those in the PBS group. FGF10

  5. Radiofrequency ablation of liver cancer: early evaluation of therapeutic response with contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Choi, Dong Gil; Lim, Hyo K.; Lee, Won Jae; Kim, Seung Hoon; Kim, Min Ju; Kim, Seung Kwon; Jang, Kyung Mi; Lee, Ji Yeon; Lim, Jae Hoon

    2004-01-01

    The early assessment of the therapeutic response after percutaneous radiofrequency (RF) ablation is important, in order to correctly decide whether further treatment is necessary. The residual unablated tumor is usually depicted on contrast-enhanced multiphase helical computed tomography (CT) as a focal enhancing structure during the arterial and portal venous phases. Contrast-enhanced color Doppler and power Doppler ultrasonography (US) have also been used to detect residual tumors. Contrast-enhanced gray-scale US, using a harmonic technology which has recently been introduced, allows for the detection of residual tumors after ablation, without any of the blooming or motion artifacts usually seen on contrast-enhanced color or power Doppler US. Based on our experience and reports in the literature, we consider that contrast-enhanced gray-scale harmonic US constitutes a reliable alternative to contrast-enhanced multiphase CT for the early evaluation of the therapeutic response to RF ablation for liver cancer. This technique was also useful in targeting any residual unablated tumors encountered during additional ablation

  6. Validation of an instrument for mathematics enhancement teaching efficacy of Pacific Northwest agricultural educators

    Science.gov (United States)

    Jansen, Daniel J.

    Teacher efficacy continues to be an important area of study in educational research. This study tested an instrument designed to assess the perceived efficacy of agricultural education teachers when engaged in lessons involving mathematics instruction. The study population of Oregon and Washington agricultural educators utilized in the validation of the instrument revealed important demographic findings and specific results related to teacher efficacy for the study population. An instrument was developed from the assimilation of three scales previously used and validated in efficacy research. Participants' mathematics teaching efficacy was assessed using a portion of the Mathematics Teaching Efficacy Beliefs Instrument (MTEBI), and personal mathematics efficacy was evaluated by the mathematics self-belief instrument which was derived from the Betz and Hackett's Mathematics Self-Efficacy Scale. The final scale, the Teachers' Sense of Efficacy Scale (TSES) created by Tschannen-Moran and Woolfolk Hoy, examined perceived personal teaching efficacy. Structural equation modeling was used as the statistical analyses tool to validate the instrument and examine correlations between efficacy constructs used to determine potential professional development needs of the survey population. As part of the data required for validation of the Mathematics Enhancement Teaching Efficacy instrument, demographic information defining the population of Oregon and Washington agricultural educators was obtained and reported. A hypothetical model derived from teacher efficacy literature was found to be an acceptable model to verify construct validity and determine strength of correlations between the scales that defined the instrument. The instrument produced an alpha coefficient of .905 for reliability. Both exploratory and confirmatory factor analyses were used to verify construct and discriminate validity. Specifics results related to the survey population of agricultural educators

  7. Strategy to prime the host and cells to augment therapeutic efficacy of progenitor cells for patients with myocardial infarction

    Directory of Open Access Journals (Sweden)

    Jeehoon Kang

    2016-11-01

    Full Text Available Cell therapy in myocardial infarction (MI is an innovative strategy that is regarded as a rescue therapy to repair the damaged myocardium and to promote neovascularization for the ischemic border zone. Among several stem cell sources for this purpose, autologous progenitors from bone marrow or peripheral blood would be the most feasible and safest cell-source. Despite the theoretical benefit of cell therapy, this method is not widely adopted in the actual clinical practice due to its low therapeutic efficacy. Various methods have been used to augment the efficacy of cell therapy in MI, such as using different source of progenitors, genetic manipulation of cells, or priming of the cells or hosts (patients with agents. Among these methods, the strategy to augment the therapeutic efficacy of the autologous peripheral blood mononuclear cells by priming agents may be the most feasible and the safest method that can be applied directly to the clinic. In this review, we will discuss the current status and future directions of priming peripheral blood mononuclear cells or patients, as for cell therapy of MI.

  8. Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

    Science.gov (United States)

    Wolbring, Gregor; Diep, Lucy; Yumakulov, Sophya; Ball, Natalie; Leopatra, Verlyn; Yergens, Dean

    2013-01-01

    So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE). We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a) healthcare, healthcare policy, and healthcare ethics, (b) disability and (c) health consumers and how visible various assessment fields are within Neuro/Cogno/Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers) is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements. PMID:27429129

  9. Emerging Therapeutic Enhancement Enabling Health Technologies and Their Discourses: What Is Discussed within the Health Domain?

    Directory of Open Access Journals (Sweden)

    Gregor Wolbring

    2013-07-01

    Full Text Available So far, the very meaning of health and therefore, treatment and rehabilitation is benchmarked to the normal or species-typical body. We expect certain abilities in members of a species; we expect humans to walk but not to fly, but a bird we expect to fly. However, increasingly therapeutic interventions have the potential to give recipients beyond species-typical body related abilities (therapeutic enhancements, TE. We believe that the perfect storm of TE, the shift in ability expectations toward beyond species-typical body abilities, and the increasing desire of health consumers to shape the health system will increasingly influence various aspects of health care practice, policy, and scholarship. We employed qualitative and quantitative methods to investigate among others how human enhancement, neuro/cognitive enhancement, brain machine interfaces, and social robot discourses cover (a healthcare, healthcare policy, and healthcare ethics, (b disability and (c health consumers and how visible various assessment fields are within Neuro/Cogno/ Human enhancement and within the BMI and social robotics discourse. We found that health care, as such, is little discussed, as are health care policy and ethics; that the term consumers (but not health consumers is used; that technology, impact and needs assessment is absent; and that the imagery of disabled people is primarily a medical one. We submit that now, at this early stage, is the time to gain a good understanding of what drives the push for the enhancement agenda and enhancement-enabling devices, and the dynamics around acceptance and diffusion of therapeutic enhancements.

  10. Therapeutic efficacy and dosimetric aspects of Rhenium-188-HEDP in bone pain palliation

    International Nuclear Information System (INIS)

    Liepe, Knut

    2005-01-01

    Full text: Bone metastases are a frequent complication of cancer, occurring in up 70% of patients suffering from advanced breast or prostate cancer and often present with severe bone pain. In this purpose the radionuclide therapy is a useful option for cancer patients. Different radionuclides are described, such as 89 Sr, 32 P, 153 Sm-EDTMP, 186 Re-HEDP, 131 I-BDP3, 90 Y, 117mSn-DTPA, 188 Re-HEDP and 188 Re-DMSA. The most experiences are available for 89 Sr. An indication for the treatment are patients with osteoblastic metastases, bone pain, sufficient bone marrow function and at least of three bone metastases visualized in bone scan. A bisphosphonate therapy, a chemotherapy with lower bone marrow toxicity or a local field external beam radiotherapy represent no contraindications, especially because the reported synergistic effects to the systemic radionuclide therapy. In 33 treated patients (breast and prostate cancer) we investigated the effect of 188 Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function. There were an improvement on the Karnofsky performance scale from 74 7% to 85 9% 12 weeks after therapy (p= 0.001). The pain score showed a maximum decrease from 44 ± 18% to 27 ± 20% in the 3rd to the 8th week after therapy (p = .009) and 76% had a pain relief (20% were pain free). The maximal differences between the values of platelets and leukocytes before and after therapy were not statistically significant (p = 0.021 and p = 0.094). In 105 investigated patients treated with different radionuclides ( 89 Sr, 153 Sm-EDTMP, 186 Re-HEDP, 188 Re-HEDP and 89 Sr in combination with chemotherapy) no different therapeutic efficacy of the treatments were observed. In dose calculation of 188 Re-HEDP a radiation dose of 3.83 ± 2.01 mGy/MBq (12.6 Gy for 3300 MBq) for bone metastases and 0.61 ± 0.21 mGy/MBq (2 Gy for 3300 MBq) were found. With the introducing of radionuclide treatments with chemotherapy and repeated treatments, the

  11. Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    DEFF Research Database (Denmark)

    Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

    2012-01-01

    The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

  12. Therapeutic efficacy of Artemether/Lumefantrine (Coartem® against Plasmodium falciparum in Kersa, South West Ethiopia

    Directory of Open Access Journals (Sweden)

    Animut Abebe

    2010-01-01

    Full Text Available Abstract Background Artemether/Lumefantrine (Coartem® has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2004 in Ethiopia. In the present study the therapeutic efficacy of artemether/lumefantrine for the treatment of uncomplicated P. falciparum infection at Kersa, Jima zone, South-west Ethiopia, has been assessed. Methods A 28 day therapeutic efficacy study was conducted between November 2007 and January 2008, in accordance with the 2003 WHO guidelines. Outcomes were classified as early treatment failure (ETF, late clinical failure (LCF, late parasitological failure (LPF and adequate clinical and parasitological response (ACPR. Results 90 patients were enrolled and completed the 28 day follow-up period after treatment with artemether/lumefantrine. Cure rate was very high, 96.3%, with 95% CI of 0.897-0.992 (PCR uncorrected. Age-stratified data showed adequate clinical and parasitological response (ACPR to be 100% for children under 5 and 97.4% and 87.3% for children aged 5-14, and adults, respectively. There was no early treatment failure (ETF in all age groups. Fever was significantly cleared on day 3 (P 0.05. No major side effect was observed in the study except the occurrence of mouth ulcers in 7% of the patients. Conclusions The current study proved the excellent therapeutic efficacy of artemether/lumefantrine in the study area and the value of using it. However, the proper dispensing and absorption of the drug need to be emphasized in order to utilize the drug for a longer period of time. This study recommends further study on the toxicity of the drug with particular emphasis on the development of oral ulcers in children.

  13. Diffusion MRI: A New Strategy for Assessment of Cancer Therapeutic Efficacy

    Directory of Open Access Journals (Sweden)

    Thomas L. Chenevert

    2002-10-01

    Full Text Available The use of anatomical imaging in clinical oncology practice traditionally relies on comparison of patient scans acquired before and following completion of therapeutic intervention. Therapeutic success is typically determined from inspection of gross anatomical images to assess changes in tumor size. Imaging could provide significant additional insight into therapeutic impact if a specific parameter or combination of parameters could be identified which reflect tissue changes at the cellular or physiologic level. This would provide an early indicator of treatment response/outcome in an individual patient before completion of therapy. Moreover, response of a tumor to therapeutic intervention may be heterogeneous. The use of imaging could assist in delineating therapeutic-induced spatial heterogeneity within a tumor mass by providing information related to specific regions that are resistant or responsive to treatment. Largely untapped potential resides in exploratory methods such as diffusion MRI, which is a non-volumetric intravoxel measure of tumor response based upon water molecular mobility. Alterations in water mobility reflect changes in tissue structure at the cellular level. While the clinical utility of diffusion MRI for oncologic practice is still under active investigation, this overview on the use of diffusion MRI for the evaluation of brain tumors will serve to introduce how this approach may be applied in the future for the management of patients with solid tumors.

  14. Nano-Engineered Mesenchymal Stem Cells Increase Therapeutic Efficacy of Anticancer Drug Through True Active Tumor Targeting.

    Science.gov (United States)

    Layek, Buddhadev; Sadhukha, Tanmoy; Panyam, Jayanth; Prabha, Swayam

    2018-06-01

    Tumor-targeted drug delivery has the potential to improve therapeutic efficacy and mitigate non-specific toxicity of anticancer drugs. However, current drug delivery approaches rely on inefficient passive accumulation of the drug carrier in the tumor. We have developed a unique, truly active tumor-targeting strategy that relies on engineering mesenchymal stem cells (MSC) with drug-loaded nanoparticles. Our studies using the A549 orthotopic lung tumor model show that nano-engineered MSCs carrying the anticancer drug paclitaxel (PTX) home to tumors and create cellular drug depots that release the drug payload over several days. Despite significantly lower doses of PTX, nano-engineered MSCs resulted in significant inhibition of tumor growth and superior survival. Anticancer efficacy of nano-engineered MSCs was confirmed in immunocompetent C57BL/6 albino female mice bearing orthotopic Lewis Lung Carcinoma (LL/2-luc) tumors. Furthermore, at doses that resulted in equivalent therapeutic efficacy, nano-engineered MSCs had no effect on white blood cell count, whereas PTX solution and PTX nanoparticle treatments caused leukopenia. Biodistribution studies showed that nano-engineered MSCs resulted in greater than 9-fold higher AUC lung of PTX (1.5 μg.day/g) than PTX solution and nanoparticles (0.2 and 0.1 μg.day/g tissue, respectively) in the target lung tumors. Furthermore, the lung-to-liver and the lung-to-spleen ratios of PTX were several folds higher for nano-engineered MSCs relative to those for PTX solution and nanoparticle groups, suggesting that nano-engineered MSCs demonstrate significantly less off-target deposition. In summary, our results demonstrate that nano-engineered MSCs can serve as an efficient carrier for tumor-specific drug delivery and significantly improved anti-cancer efficacy of conventional chemotherapeutic drugs. Mol Cancer Ther; 17(6); 1196-206. ©2018 AACR . ©2018 American Association for Cancer Research.

  15. Biofilm disruption with rotating microrods enhances antimicrobial efficacy

    Science.gov (United States)

    Mair, Lamar O.; Nacev, Aleksandar; Hilaman, Ryan; Stepanov, Pavel Y.; Chowdhury, Sagar; Jafari, Sahar; Hausfeld, Jeffrey; Karlsson, Amy J.; Shirtliff, Mark E.; Shapiro, Benjamin; Weinberg, Irving N.

    2017-04-01

    Biofilms are a common and persistent cause of numerous illnesses. Compared to planktonic microbes, biofilm residing cells often demonstrate significant resistance to antimicrobial agents. Thus, methods for dislodging cells from the biofilm may increase the antimicrobial susceptibility of such cells, and serve as a mechanical means of increasing antimicrobial efficacy. Using Aspergillus fumigatus as a model microbe, we magnetically rotate microrods in and around biofilm. We show that such rods can improve the efficacy of antimicrobial Amphotericin B treatments in vitro. This work represents a first step in using kinetic magnetic particle therapy for disrupting fungal biofilms.

  16. Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

    Science.gov (United States)

    Etame, Arnold B.

    The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

  17. Enhancing Students' Self-Efficacy in Making Positive Career Decisions

    Science.gov (United States)

    Reddan, Gregory

    2015-01-01

    Field Project A is an elective course in the Bachelor of Exercise Science program at Griffith University and includes elements of both career development learning and work-integrated learning. This paper aims to determine the effects of the learning activities and assessment items developed for the course on students' self-efficacy in making…

  18. In Vitro Evaluation of Biofilm Dispersal as a Therapeutic Strategy To Restore Antimicrobial Efficacy

    DEFF Research Database (Denmark)

    Roizman, Dan; Vidaillac, Celine; Givskov, Michael

    2017-01-01

    As a proof-of-concept study, the direct impact of biofilm dispersal on the in vitro efficacy of imipenem and tobramycin was evaluated against 3-day-old biofilms of Pseudomonas aeruginosa. Arabinose induction of biofilm dispersal via activation of the phosphodiesterase YhjH in the P. aeruginosa en...

  19. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats

    NARCIS (Netherlands)

    Cornelissen, J.B.W.J.; Giessen, van der J.W.B.; Takumi, K.; Teunis, P.F.M.; Wisselink, H.J.

    2014-01-01

    High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment.

  20. Glycoengineering of therapeutic antibodies enhances monocyte/macrophage-mediated phagocytosis and cytotoxicity.

    Science.gov (United States)

    Herter, Sylvia; Birk, Martina C; Klein, Christian; Gerdes, Christian; Umana, Pablo; Bacac, Marina

    2014-03-01

    Therapeutic Abs possess several clinically relevant mechanisms of action including perturbation of tumor cell signaling, activation of complement-dependent cytotoxicity, Ab-dependent cellular cytotoxicity (ADCC), Ab-dependent cellular phagocytosis (ADCP), and induction of adaptive immunity. In view of the important role of phagocytic lineage cells in the mechanism of action of therapeutic Abs, we analyzed FcγR receptor-dependent effector functions of monocytes and macrophages triggered by glycoengineered (GE) Abs (having enhanced FcγRIIIa [CD16a] binding affinity) versus their wild-type (WT) counterparts under different experimental conditions. We first defined the precise FcγR repertoire on classical and nonclassical intermediate monocytes--M1 and M2c macrophage populations. We further show that WT and GE Abs display comparable binding and induce similar effector functions (ADCC and ADCP) in the absence of nonspecific, endogenous IgGs. However, in the presence of these IgGs (i.e., in a situation that more closely mimics physiologic conditions), GE Abs display significantly superior binding and promote stronger monocyte and macrophage activity. These data show that in addition to enhancing CD16a-dependent NK cell cytotoxicity, glycoengineering also enhances monocyte and macrophage phagocytic and cytotoxic activities through enhanced binding to CD16a under conditions that more closely resemble the physiologic setting.

  1. The Course of Self-Efficacy for Therapeutic Use of Self in Norwegian Occupational Therapy Students: A 10-Month Follow-Up Study

    Directory of Open Access Journals (Sweden)

    Kathrin Schwank

    2018-01-01

    Full Text Available Background. Occupational therapy students need to develop self-efficacy for managing the therapeutic relationship in practice. This study examined the 10-month trajectories of Norwegian students’ self-efficacy for use of self. Methods. Eighty-nine students completed self-efficacy questionnaires related to the use of self after a workshop and at 3- and 10-month follow-up. Changes on the three outcome measures (self-efficacy for therapeutic mode use, for recognizing clients’ interpersonal characteristics, and for managing interpersonal events were analyzed with repeated measures ANOVA. Results. Across the follow-up period, the students improved their self-efficacy for therapeutic mode use (partial η2 = 0.44, p<0.001, for recognizing clients’ interpersonal characteristics (partial η2 = 0.81, p<0.001, and for managing interpersonal events (partial η2=0.32, p<0.001. Conclusion. The increased self-efficacy for use of self that was found at 3-month follow-up was maintained at 10-month follow-up. The results indicate that students may experience a boost in self-efficacy for therapeutic use of self after a brief workshop and that these changes can be sustained over time.

  2. Signal integration: a framework for understanding the efficacy of therapeutics targeting the human EGFR family

    Science.gov (United States)

    Shepard, H. Michael; Brdlik, Cathleen M.; Schreiber, Hans

    2008-01-01

    The human EGFR (HER) family is essential for communication between many epithelial cancer cell types and the tumor microenvironment. Therapeutics targeting the HER family have demonstrated clinical success in the treatment of diverse epithelial cancers. Here we propose that the success of HER family–targeted monoclonal antibodies in cancer results from their ability to interfere with HER family consolidation of signals initiated by a multitude of other receptor systems. Ligand/receptor systems that initiate these signals include cytokine receptors, chemokine receptors, TLRs, GPCRs, and integrins. We further extrapolate that improvements in cancer therapeutics targeting the HER family are likely to incorporate mechanisms that block or reverse stromal support of malignant progression by isolating the HER family from autocrine and stromal influences. PMID:18982164

  3. Quantifying the importance of pMHC valency, total pMHC dose and frequency on nanoparticle therapeutic efficacy.

    Science.gov (United States)

    Sugarman, Jordan; Tsai, Sue; Santamaria, Pere; Khadra, Anmar

    2013-05-01

    Nanoparticles (NPs) coated with β-cell-specific peptide major histocompatibility complex (pMHC) class I molecules can effectively restore normoglycemia in spontaneously diabetic nonobese diabetic mice. They do so by expanding pools of cognate memory autoreactive regulatory CD8+ T cells that arise from naive low-avidity T-cell precursors to therapeutic levels. Here we develop our previously constructed mathematical model to explore the effects of compound design parameters (NP dose and pMHC valency) on therapeutic efficacy with the underlying hypothesis that the functional correlates of the therapeutic response (expansion of autoregulatory T cells and deletion of autoantigen-loaded antigen-presenting cells by these T cells) are biphasic. We show, using bifurcation analysis, that the model exhibits a 'resonance'-like behavior for a given range of NP dose in which bistability between the healthy state (possessing zero level of effector T-cell population) and autoimmune state (possessing elevated level of the same population) disappears. A heterogeneous population of model mice subjected to several treatment protocols under these new conditions is conducted to quantify both the average percentage of autoregulatory T cells in responsive and nonresponsive model mice, and the average valency-dependent minimal optimal dose needed for effective therapy. Our results reveal that a moderate increase (≥1.6-fold) in the NP-dependent expansion rate of autoregulatory T-cell population leads to a significant increase in the efficacy and the area corresponding to the effective treatment regimen, provided that NP dose ≥8 μg. We expect the model developed here to generalize to other autoimmune diseases and serve as a computational tool to understand and optimize pMHC-NP-based therapies.

  4. The Novel IκB Kinase β Inhibitor, IMD-0560, Has Potent Therapeutic Efficacy in Ovarian Cancer Xenograft Model Mice.

    Science.gov (United States)

    Sawada, Ikuko; Hashimoto, Kae; Sawada, Kenjiro; Kinose, Yasuto; Nakamura, Koji; Toda, Aska; Nakatsuka, Erika; Yoshimura, Akihiko; Mabuchi, Seiji; Fujikawa, Tomoyuki; Itai, Akiko; Kimura, Tadashi

    2016-05-01

    Aberrant activation of nuclear factor-kappa β (NF-κB) signaling has been correlated with poor outcome among patients with ovarian cancer. Although the therapeutic potential of NF-κB pathway disruption in cancers has been extensively studied, most classical NF-κB inhibitors are poorly selective, exhibit off-target effects, and have failed to be applied in clinical use. IMD-0560, N-[2,5-bis (trifluoromethyl) phenyl]-5-bromo-2-hydroxybenzamide, is a novel low-molecular-weight compound that selectively inhibits the IκB kinase complex and works as an inhibitor of NF-κB signaling. The aim of this study was to assess the therapeutic potential of IMD-0560 against ovarian cancer in vitro and in vivo. NF-κB activity (phosphorylation) was determined in 9 ovarian cancer cell lines and the inhibitory effect of IMD-0560 on NF-κB activation was analyzed by Western blotting. Cell viability, cell cycle, vascular endothelial growth factor (VEGF) expression, and angiogenesis were assessed in vitro to evaluate the effect of IMD-0560 on ovarian cancer cells. In vivo efficacy of IMD-0560 was also investigated using an ovarian cancer xenograft mouse model. The NF-κB signaling pathway was constitutively activated in 8 of 9 ovarian cancer cell lines. IMD-0560 inhibited NF-κB activation and suppressed ovarian cancer cell proliferation by inducing G1 phase arrest. IMD-0560 decreased VEGF secretion from cancer cells and inhibited the tube formation of human umbilical vein endothelial cells. IMD-0560 significantly inhibited peritoneal metastasis and prolonged the survival in an ovarian cancer xenograft mice model. Immunohistochemical staining of excised tumors revealed that IMD-0560 suppressed VEGF expression, tumor angiogenesis, and cancer cell proliferation. IMD-0560 showed promising therapeutic efficacy against ovarian cancer xenograft mice by inducing cell cycle arrest and suppressing VEGF production from cancer cells. IMD-0560 may be a potential future option in regimens for the

  5. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability

    Energy Technology Data Exchange (ETDEWEB)

    Gulati, Karan [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia); Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M. [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Atkins, Gerald J., E-mail: gerald.atkins@adelaide.edu.au [Discipline of Orthopaedics and Trauma, The University of Adelaide, SA 5005 (Australia); Losic, Dusan, E-mail: dusan.losic@adelaide.edu.au [School of Chemical Engineering, The University of Adelaide, SA 5005 (Australia)

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements. - Highlights: • Ti wire with titania nanotubes (TNTs) are proposed as ‘in-bone’ therapeutic implants. • 3D cell culture model is used to confirm therapeutic efficacy of drug releasing implants. Osteoblasts migrated and firmly attached to the TNTs and the micro-scale cracks. • Tailorable drug loading from few nanograms to several hundred

  6. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis

    Science.gov (United States)

    Cohan, Stanley

    2016-01-01

    Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit–risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56bright natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS. The clinical pharmacology, efficacy, and safety of subcutaneous daclizumab have been evaluated extensively in a large clinical study program. In pivotal studies, daclizumab demonstrated superior efficacy in reducing clinical and radiologic measures of MS disease activity compared with placebo or intramuscular interferon beta-1a, a standard-of-care therapy for relapsing MS. The risk of hepatic disorders, cutaneous events, and infections was modestly increased. The monthly subcutaneous self-injection dosing regimen of daclizumab may be advantageous in maintaining patient adherence to treatment, which is important for optimal outcomes with MS disease-modifying therapy. Daclizumab has been approved in the US and in the European Union and represents an effective new treatment option for patients with relapsing forms of MS, and is currently under review by other regulatory agencies. PMID:27672308

  7. The therapeutic efficacy of sacroiliac joint blocks with triamcinolone acetonide in the treatment of sacroiliac joint dysfunction without spondyloarthropathy.

    Science.gov (United States)

    Liliang, Po-Chou; Lu, Kang; Weng, Hui-Ching; Liang, Cheng-Loong; Tsai, Yu-Duan; Chen, Han-Jung

    2009-04-20

    Prospective case series. The study aimed to investigate the therapeutic efficacy of sacroiliac joint (SIJ) blocks with triamcinolone acetonide in patients with SIJ pain without spondyloarthropathy. Numerous studies have demonstrated that SIJ blocks with corticosteroid/anesthetic provide long-term pain relief in seronegative spondyloarthropathy. However, only one report on SIJ dysfunction patients without spondyloarthropathy shows promising results. We conducted a prospective observational study of patients at a University Spine Center from March 2005 to May 2006. The above mentioned SIJ blocks were performed in 150 patients, and dual SIJ blocks confirmed SIJ pain in 39 patients (26%). Twenty-six patients (66.7%) experienced significant pain reduction for more than 6 weeks; the overall mean duration of pain reduction in these responders was 36.8 +/- 9.9 weeks. SIJ blocks were ineffective in 13 patients (33.3%); the mean duration of pain reduction in these patients was 4.4 +/- 1.8 weeks. Univariate analysis revealed that treatment failure was significantly associated with a history of lumbar/lumbosacral fusion (P = 0.03). SIJ blocks with triamcinolone acetonide are beneficial for some patients with SIJ pain without spondyloarthropathy. The SIJ blocks showed a long-lasting efficacy in two-thirds of the patients; however, the duration of its efficacy was shorter in patients with a history of lumbar/lumbosacral fusion. These findings suggest the need for further studies.

  8. Curcumin's Neuroprotective Efficacy in Drosophila Model of Idiopathic Parkinson's Disease Is Phase Specific: Implication of its Therapeutic Effectiveness

    Science.gov (United States)

    Phom, Limamanen; Achumi, Bovito; Alone, Debasmita P.; Muralidhara

    2014-01-01

    Abstract Selective degeneration of dopaminergic neurons in the substantia nigra underlies the basic motor impairments of Parkinson's disease (PD). Curcumin has been used for centuries in traditional medicines in India. Our aim is to understand the efficacy of genotropic drug curcumin as a neuroprotective agent in PD. Analysis of different developmental stages in model organisms revealed that they are characterized by different patterns of gene expression which is similar to that of developmental stages of human. Genotropic drugs would be effective only during those life cycle stages for which their target molecules are available. Hence there exists a possibility that targets of genotropic compounds such as curcumin may not be present in all life stages. However, no reports are available in PD models illustrating the efficacy of curcumin in later phases of adult life. This is important because this is the period during which late-onset disorders such as idiopathic PD set in. To understand this paradigm, we tested the protective efficacy of curcumin in different growth stages (early, late health stage, and transition phase) in adult Drosophila flies. Results showed that it can rescue the motor defects during early stages of life but is ineffective at later phases. This observation was substantiated with the finding that curcumin treatment could replenish depleted brain dopamine levels in the PD model only during early stages of life cycle, clearly suggesting its limitation as a therapeutic agent in late-onset neurodegenerative disorders such as PD. PMID:25238331

  9. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

  10. Efficacy of Gd-DTPA-enhanced MRI in hypertrophic cardiomyopathy

    International Nuclear Information System (INIS)

    Okamoto, Shinya; Aoki, Toshikazu; Konishi, Tokuji; Nakano, Takeshi; Yamakado, Kyoichiro; Sakuma, Hajime; Takeda, Kann; Nakagawa, Takashi

    1991-01-01

    The cabability of magnetic resonance (MR) imaging to detect tissue characterization or myocardial degeneration process of the hypertrophied myocardium was evaluated in 15 patients with hypertrophic cardiomyopathy. T1-weighted MR images were obtained with a 1.5 T MR unit by using ECG-gated spin-echo techniques. MR images were visually reviewed before and after enhancement of Gd-DTPA. Four patients had an increase in signal intensity mainly in the endocardium of the left ventricular septum on non-enhanced MR images, 3 of whom had widespread high intensity in addition to two-thirds of the wall. Gd-DTPA enhanced-MR images showed high intensity over the whole septum in 5 patients and also in the antero-lateral endocardium in 4 patients. Decreased intensity on non-enhanced MR images, as shown in 4 patients, became clear on enhanced-MR images. According to findings on enhanced-MR images, signal intensity was defined as normal (N), septum (S), and diffuse (D). Patients in Group D tended to be younger and have more frequently family history. Regarding both interventricular septum thickness and left ventricular posterior wall thickness, there was no significant difference among the three groups. Both left ventricular diastolic diameter and left ventricular systolic diameter were significantly larger in Group D than the other two groups. Left ventricular ejection fraction was significantly lower in both Group S and Group D. Widespread abnormal intensity on Gd-DTPA enhanced MR images was associated with findings similar to dilated cardiomyopathy, such as dilated left ventricular lumen and decreased ejection fraction. Gd-DTPA enhanced MR imaging seemed to be useful for visualizing myocardial degeneration in hypertrophic cardiomyopathy.(N.K.)

  11. Enhanced antitumor efficacy of doxorubicin-encapsulated halloysite nanotubes

    Directory of Open Access Journals (Sweden)

    Li K

    2017-12-01

    Full Text Available Kai Li,1,* Yongxing Zhang,2,* Mengting Chen,1 Yangyang Hu,1 Weiliang Jiang,1 Li Zhou,1 Sisi Li,1 Min Xu,1 Qinghua Zhao,2 Rong Wan1 1Department of Gastroenterology, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Department of Orthopaedics, Shanghai First People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the antitumor efficacy of doxorubicin (DOX and provide novel clinical treatment of gastric cancer, halloysite nanotubes (HNTs loaded with DOX were encapsulated by soybean phospholipid (LIP and the formed HNTs/DOX/LIP was systematically characterized via different techniques. The in vitro anticancer activity of HNTs/DOX/LIP was examined using an MTT assay. The antitumor efficacy and biocompatibility were monitored by measuring the tumor volume and assessing the blood routine and serum biochemistry using an ectopic implantation cancer model. The results show that when the concentration of HNTs was 3 mg/mL and the concentration of DOX was 1 mg/mL the optimal DOX loading efficiency was as high as 22.01%±0.43%. In vitro drug release behavior study demonstrated that HNTs/DOX/LIP shows a pH-responsive release property with fast drug release under acidic conditions (pH =5.4. MTT assays and in vivo experimental results revealed that HNTs/DOX/LIP exhibits a significantly higher inhibitory efficacy on the growth of mouse gastric cancer cells than free DOX at the same drug concentration. In addition, the life span of tumor-bearing mice in the HNTs/DOX/LIP-treated group was obviously prolonged compared with the control groups. Moreover, HNTs/DOX/LIP possessed excellent hemocompatibility as shown in the blood and histology studies. These findings indicated that the formed HNTs/DOX/LIP possesses higher antitumor efficacy and may be used as a targeted

  12. Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

    Science.gov (United States)

    Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

    2016-10-04

    Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

  13. Effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on oxcarbazepine concentrations and therapeutic efficacy in patients with epilepsy.

    Science.gov (United States)

    Shen, Chunhong; Zhang, Bijun; Liu, Zhirong; Tang, Yelei; Zhang, Yinxi; Wang, Shan; Guo, Yi; Ding, Yao; Wang, Shuang; Ding, Meiping

    2017-10-01

    The aim of the study is to investigate the effects of ABCB1, ABCC2, UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P<0.05). As for UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  14. Network Meta-Analysis Comparing the Efficacy of Therapeutic Treatments for Bronchiolitis in Children.

    Science.gov (United States)

    Guo, Caili; Sun, Xiaomin; Wang, Xiaowen; Guo, Qing; Chen, Dan

    2018-01-01

    This study aims to compare placebo (PBO) and 7 therapeutic regimens-namely, bronchodilator agents (BAs), hypertonic saline (HS), BA ± HS, corticosteroids (CS), epinephrine (EP), EP ± CS, and EP ± HS-to determine the optimal bronchiolitis treatment. We plotted networks using the curative outcome of several studies and specified the relations among the experiments by using mean difference, standardized mean difference, and corresponding 95% credible interval. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each therapy on clinical severity score (CSS) and length of hospital stay (LHS). This network meta-analysis included 40 articles from 1995 to 2016 concerning the treatment of bronchiolitis in children. All 7 therapeutic regimens displayed no significant difference to PBO with regard to CSS in our study. Among the 7 therapies, BA performed better than CS. As for LHS, EP and EP ± HS had an advantage over PBO. Moreover, EP and EP ± HS were also more efficient than BA. The SUCRA results showed that EP ± CS is most effective, and EP ± HS is second most effective with regard to CSS. With regard to LHS, EP ± HS ranked first, EP ± CS ranked second, and EP ranked third. We recommend EP ± CS and EP ± HS as the first choice for bronchiolitis treatment in children because of their outstanding performance with regard to CSS and LHS. © 2017 American Society for Parenteral and Enteral Nutrition.

  15. [Therapeutic efficacy of nootropil different doses in attention deficit hyperactivity disorder].

    Science.gov (United States)

    Zavadenko, N N; Suvorinova, S Iu

    2004-01-01

    Attention Deficit Hyperactivity Disorder (ADHD) is the most common cause of behavioral and learning problems in childhood. Therapeutic efficiency of nootropil (piracetam) in two different doses has been evaluated in the open control study of 80 children with ADHD, 70 boys and 10 girls, aged 6-11 years, being divided into 3 groups. Two groups received nootropil, as a monotherapy, for a month: 1st group (30 patients)--in the dosage of 70 mg/kg daily and 2nd group (30 patients)--40 mg/kg daily orally. The control group of 20 patients did not receive any treatment. All children were examined twice with one month interval. A procedure of assessment included of structured questionnaire to parents, neurological examination with scored evaluation of subtle signs and psychological testing. Nootropil therapy in ADHD children resulted in the improvement of behavioral characteristics, motor coordination as well as continuous, selective and divided attention. A response rate was 60% in patients received 70 mg/kg of nootropil and 43% for nootropil dosage of 40 mg/kg. The results of the study suggest more considerable positive therapeutic effects of nootropil higher dose on behavioral, motor and attention characteristics in children with ADHD.

  16. Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    Energy Technology Data Exchange (ETDEWEB)

    Rabussay, Dietmar [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Dev, Nagendu B [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Fewell, Jason [Valentis, Inc., 8301 New Trails Drive, The Woodlands, TX (United States); Smith, Louis C [Valentis, Inc., 8301 New Trails Drive, The Woodlands, TX (United States); Widera, Georg [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States); Zhang Lei [Genetronics, Inc., Department of Research and Development, 11199 Sorrento Valley Road, San Diego, CA (United States)

    2003-02-21

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as 'electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing 'pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm{sup -1} generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes

  17. Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    International Nuclear Information System (INIS)

    Rabussay, Dietmar; Dev, Nagendu B; Fewell, Jason; Smith, Louis C; Widera, Georg; Zhang Lei

    2003-01-01

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as 'electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing 'pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm -1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco

  18. Therapeutic efficacy of the Qing Dai in patients with intractable ulcerative colitis.

    Science.gov (United States)

    Suzuki, Hideo; Kaneko, Tsuyoshi; Mizokami, Yuji; Narasaka, Toshiaki; Endo, Shinji; Matsui, Hirofumi; Yanaka, Akinori; Hirayama, Aki; Hyodo, Ichinosuke

    2013-05-07

    Ulcerative colitis (UC) is a chronic inflammatory bowel disease that may become intractable when treated with conventional medications such as aminosalicylates, corticosteroids, and azathioprine. The herbal medicine Qing Dai has traditionally been used in Chinese medicine to treat UC patients, but there is a lack of published data on the efficacy of Qing Dai in UC treatment. We report several cases of patients with intractable UC who take Qing Dai in a retrospective observational study. Furthermore, we explore the mechanisms of action of Qing Dai. Nine patients with active UC who received conventional medications but wished to receive Qing Dai as an alternative medication were included in our analysis. The UC severity level was determined based on the clinical activity index (CAI). Additionally, 5 of the 9 patients were endoscopically evaluated according to the Matts grading system. Each patient received 2 g/d of Qing Dai orally and continued taking other medications for UC as prescribed. Electron spin resonance was applied to explore the mechanisms of action of Qing Dai. After 4 mo of treatment with Qing Dai, the CAI score decreased from 8.3 ± 2.4 to 2.4 ± 3.4 (mean ± SD; P Qing Dai possesses strong hydroxyl radical scavenging activity. Qing Dai showed significant clinical and endoscopic efficacy in patients who failed to respond to conventional medications. Scavenging of hydroxyl radicals appears to be a potential mechanism through which Qing Dai acts, but the significance of the scavenging ability of Qing Dai with respect to the anti-inflammatory effect in UC patients warrants further investigation.

  19. Therapeutic efficacy of aldoxorubicin in an intracranial xenograft mouse model of human glioblastoma.

    Science.gov (United States)

    Marrero, Luis; Wyczechowska, Dorota; Musto, Alberto E; Wilk, Anna; Vashistha, Himanshu; Zapata, Adriana; Walker, Chelsey; Velasco-Gonzalez, Cruz; Parsons, Christopher; Wieland, Scott; Levitt, Daniel; Reiss, Krzysztof; Prakash, Om

    2014-10-01

    Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo), aldoxorubicin (Aldoxo), which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc) was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents-3/4 maximum tolerated dose (MTD)], Doxo [6 mg/kg (3/4 MTD)], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67) and abundant intratumoral programmed cell death (cleaved caspase-3). Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.

  20. Therapeutic Efficacy of Aldoxorubicin in an Intracranial Xenograft Mouse Model of Human Glioblastoma

    Directory of Open Access Journals (Sweden)

    Luis Marrero

    2014-10-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive primary brain tumor with a median survival of 12 to 15 months after diagnosis. Acquired chemoresistance, high systemic toxicity, and low penetration of the blood brain barrier by many anticancer drugs contribute to the failure of anti-GBM therapies. To circumvent some of these obstacles, we tested a novel prodrug approach to evaluate anti-GBM efficacy by utilizing serum albumin-binding doxorubicin (Doxo, aldoxorubicin (Aldoxo, which is less toxic, is released from albumin in an acidic environment and accumulates in tumor tissues. A human GBM cell line that expresses a luciferase reporter (U87-luc was stereotactically injected into the left striatum of the brain of immunodeficient mice. Following initial tumor growth for 12 days, mice were injected once a week in the tail-vein with Aldoxo [24 mg/kg or 18 mg/kg of doxorubicin equivalents—3/4 maximum tolerated dose (MTD], Doxo [6 mg/kg (3/4 MTD], or vehicle. Aldoxo-treated mice demonstrated significantly slower growth of the tumor when compared to vehicle-treated or Doxo-treated mice. Five out of eight Aldoxo-treated mice remained alive more than 60 days with a median survival of 62 days, while the median survival of vehicle- and Doxo-treated mice was only 26 days. Importantly, Aldoxo-treated mice exhibited high levels of Doxo within the tumor tissue, accompanied by low tumor cell proliferation (Ki67 and abundant intratumoral programmed cell death (cleaved caspase-3. Effective accumulation of Aldoxo in brain tumor tissues but not normal brain, its anti-tumor efficacy, and low toxicity, provide a strong rationale for evaluating this novel drug conjugate as a treatment for patients afflicted with GBM.

  1. [Epidemiologic and therapeutic study on gonococcal infections--clinical efficacy of cefetamet pivoxil].

    Science.gov (United States)

    Nishimura, M; Kumamoto, Y; Hirose, T; Hayashi, K; Tsukamoto, T; Gohro, T; Ikegaki, S; Kamito, H; Inoke, T; Henmi, I

    1990-07-01

    We studied the epidemiology of 109 cases of gonococcal infections (105 males with urethritis and 4 females with cervicitis), together with the basic and clinical effects of cefetamet pivoxil in the cases. The peak of age distribution of the male patients was in the younger half of their twenties, and all of the 4 female cases were between 20 and 39 years old. The major source of infections in the males younger than 25 years old was their girl friends or so-called pick-up friends, and that of the males older than 25 years old workers serving at an amusement center, for example, bars and so-called special massage parlor, which accounted for about three fourths of the male cases between 35 and 44 years old. The distribution of the MIC (inoculum size; 10(6) CFU/ml) of Cefetamet against beta-lactamase non penicillinase producing Neisseria gonorrhoeae (non-PPNG) ranged from 0.025 to 0.1 microgram/ml and that against beta-lactamase producing Neisseria gonorrhoeae ranged from 0.025 to 0.05 microgram/ml. The isolation rate of PPNG was 10.2% (9/88). In male patients with gonococcal urethritis, the efficacy rate was 100% on days 3 and 7 for 1,000 mg single dose and 7-day treatment and 500 mg single dose treatment. One of the cases treated with 250 mg single dose therapy was unchanged at 3, but the efficacy rate of the remaining cases was 100% at day 7. Complicated urethritis with C. trachomatis was noticed in 25.7% (5/105) of the male urethritis and in 25.0% (1/4) of the female cervicitis cases. The only side effect was diarrhea observed in 1 of the 124 case (0.8%).

  2. Therapeutic efficacy of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome.

    Science.gov (United States)

    Kajiwara, Mitsuru; Inoue, Shougo; Kobayashi, Kanao; Ohara, Shinya; Teishima, Jun; Matsubara, Akio

    2014-04-01

    Narrow band imaging cystoscopy can increase the visualization and detection of Hunner's lesions. A single-center, prospective clinical trial was carried out aiming to show the effectiveness of narrow band imaging-assisted transurethral electrocoagulation for ulcer-type interstitial cystitis/painful bladder syndrome. A total of 23 patients (19 women and 4 men) diagnosed as having ulcer-type interstitial cystitis/painful bladder syndrome were included. All typical Hunner's lesions and suspected areas identified by narrow band imaging were electrocoagulated endoscopically after the biopsy of those lesions. Therapeutic efficacy was assessed prospectively by using visual analog scale score of pain, O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score. The mean follow-up period was 22 months. All patients (100%) experienced a substantial improvement in pain. The average visual analog scale pain scores significantly decreased from 7.3 preoperatively to 1.2 1 month postoperatively. A total of 21 patients (91.3%) who reported improvement had at least a 50% reduction in bladder pain, and five reported complete resolution. Daytime frequency was significantly decreased postoperatively. O'Leary-Sant's symptom index, O'Leary-Sant's problem index and overactive bladder symptom score were significantly decreased postoperatively. However, during the follow-up period, a total of six patients had recurrence, and repeat narrow band imaging-assisted transurethral electrocoagulation of the recurrent lesions was carried out for five of the six patients, with good response in relieving bladder pain. Our results showed that narrow band imaging-assisted transurethral electrocoagulation could be a valuable therapeutic alternative in patients with ulcer-type interstitial cystitis/painful bladder syndrome, with good efficacy and reduction of recurrence rate. © 2014 The Japanese Urological Association.

  3. Metronomic Doses of Temozolomide Enhance the Efficacy of Carbon Nanotube CpG Immunotherapy in an Invasive Glioma Model.

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    Mao Ouyang

    Full Text Available Even when treated with aggressive current therapies, most patients with glioblastoma survive less than two years. Rapid tumor growth, an invasive nature, and the blood-brain barrier, which limits the penetration of large molecules into the brain, all contribute to the poor tumor response associated with conventional therapies. Immunotherapy has emerged as a therapeutic approach that may overcome these challenges. We recently reported that single-walled carbon nanotubes (SWCNTs can be used to dramatically increase the immunotherapeutic efficacy of CpG oligonucleotides in a mouse model of glioma. Following implantation in the mouse brain, the tumor cell line used in these previous studies (GL261 tends to form a spherical tumor with limited invasion into healthy brain. In order to evaluate SWCNT/CpG therapy under more clinically-relevant conditions, here we report the treatment of a more invasive mouse glioma model (K-Luc that better recapitulates human disease. In addition, a CpG sequence previously tested in humans was used to formulate the SWCNT/CpG which was combined with temozolomide, the standard of care chemotherapy for glioblastoma patients. We found that, following two intracranial administrations, SWCNT/CpG is well-tolerated and improves the survival of mice bearing invasive gliomas. Interestingly, the efficacy of SWCNT/CpG was enhanced when combined with temozolomide. This enhanced anti-tumor efficacy was correlated to an increase of tumor-specific cytotoxic activity in splenocytes. These results reinforce the emerging understanding that immunotherapy can be enhanced by combining it with chemotherapy and support the continued development of SWCNT/CpG.

  4. EFFICACY OF SOFT TISSUE APPLICATION, MANUALLY-THERAPEUTICAL TECHNIQUES FOR KNEE ARTHROKINEMATICS RECOVERY COMPLEX IN PATIENTS AFTER ARTHROSCOPIC MENISCECTOMY

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    Kostov Rostislav V

    2015-07-01

    Full Text Available Introduction: In this article we present the final effect of the application of complex soft tissue manually-treatment system for recovery of joint kinematics in patients with moderate and minimal protective period of rehabilitation after arthroscopic meniscectomy. Material and Methods: The study was conducted in 2005-2012 into three medical centers in Bulgaria: Blagoevgrad, Sofia and Pleven. The study included a total of 110 patients divided into three groups (Control and Experimental I and Experimental Group II who studied the effect of topical application of the manual therapeutic techniques compared to traditional rehabilitation methods applied. For testing the efficacy of a treatment approach in the three groups of patients, the results have processed by the method of variational analysis. Results: After analysis of results we find significantly more fully and without residual short violations recovery for all controlled parameters in patients who have implemented comprehensive manually-therapeutic treatment compared with control group patients. Conclusion: Application of adequate physiological and pedagogically grounded complex rehabilitation is required in patients after arthroscopic meniscectomy model with motor deficits in tractable routine rehabilitation. Observations allow us to offer a methodology for implementation in general practice rehabilitation in patients after meniscal ruptures treated by arthroscopic meniscectomy and motor deficits, intractable routine rehabilitation.

  5. EVALUATION OF THE THERAPEUTIC EFFICACY OF HIGH-INTENSITY PULSED-PERIODIC LASER RADIATION (CLINICAL AND EXPERIMENTAL OBSERVATIONS

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    V. V. Sokolov

    2016-01-01

    Full Text Available From the experience of clinical observations, we have shown a high therapeutic effectiveness of the medical laser KULON-MED in: cosmetics, non-cancer inflammatory diseases of the gastrointestinal tract and cancer (cancer of the stomach and colon as at different wavelengths, and with different types of photosensitizers. In the area of anti-tumor photodynamic therapy (PDT, based on experimental studies, we have showed the high antitumor (sarcoma S‑37 effectiveness of the laser (with the inhibition of tumor growth of up to 100% for repetitively pulsed irradiation mode, and for mode fractionation doses laser radiation. In addition, significant differences are shown in the effectiveness of anticancer PDT methods in the application of high-intensity lasers, continuous and pulsed caused fundamental properties of laser radiation characteristics – time structure of the radiation pulses. Thus, for the first time we have shown that the time of high-intensity laser pulses structure significantly affects therapeutic efficacy laser system, and hence on the mechanisms of interaction of laser radiation with biological tissue.

  6. Does the addition of Serenoa repens to tamsulosin improve its therapeutical efficacy in benign prostatic hyperplasia?

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    Argirović Aleksandar

    2013-01-01

    Full Text Available Background/Aim. It has been observed that a large number of patients with low urinary tract symptoms due to benign prostatic hyperplasia (LUTS/BPH has been treated with a combination of tamsulosin (TAM + Serenoa repens (SR (TAM + SR. The aim of this study was to compare a combination TAM + SR with TAM and SR alone, to see if there was any difference in efficacy and tolerance of each in patients with LUTS/BPH. Methods. In this prospective study patients had to have prostate volume (PV 3, a maximal flow rate (Qmax of 5-15 mL/s, with post voiding residual volume (PVR < 150 mL and serum prostatic antigen (PSA < 4 ng/mL. TAM (0.4 mg was administered once a day, SR (320 mg daily or SR (320 mg + TAM (0.4 mg daily for a median period of 6 months. Results. A total of 297 patients were recruited, whereas 265 patients were fully available: 87 into the group TAM, 97 into the group SR and 81 into the group TAM + SR. There was no statistically significant difference between the treatment groups in the sense of demographic and other baseline parameters. No difference was found among the 3 treatment groups, neither in the major endpoint of the study in the sense of a change between baseline and final evaluation in total IPSS, obstructive and irritative subscores, improvement of QoLs, increase in Qmax, nor for the second endpoint including diminution of PV, PSA and PVR. During the treatment period 20 (23% of the patients managed with TAM and 17 (21% with TAM + SR had drug-treated with related adverse reactions. No adverse effect was detected in the group SR. Conclusion. Treatment of BPH by both SR and TAM seems to be efficacious alone. None of them had superiority over another and, additionally, a combined therapy (TAM + SR does not provide extra benefits. Furthermore, SR is a well-tolerated agent that can be used alternatively in the treatment of LUTS/BPH.

  7. Therapeutic Efficacy of Vectored PGT121 Gene Delivery in HIV-1-Infected Humanized Mice.

    Science.gov (United States)

    Badamchi-Zadeh, Alexander; Tartaglia, Lawrence J; Abbink, Peter; Bricault, Christine A; Liu, Po-Ting; Boyd, Michael; Kirilova, Marinela; Mercado, Noe B; Nanayakkara, Ovini S; Vrbanac, Vladimir D; Tager, Andrew M; Larocca, Rafael A; Seaman, Michael S; Barouch, Dan H

    2018-04-01

    Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies. However, administration of purified bNAbs poses challenges in resource-poor settings, where the HIV-1 disease burden is greatest. In vivo vector-based production of bNAbs represents an alternative strategy. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121 in wild-type and immunocompromised C57BL/6 mice as well as in HIV-1-infected bone marrow-liver-thymus (BLT) humanized mice. Ad5.PGT121 and AAV1.PGT121 produced functional antibody in vivo Ad5.PGT121 produced PGT121 rapidly within 6 h, whereas AAV1.PGT121 produced detectable PGT121 in serum by 72 h. Serum PGT121 levels were rapidly reduced by the generation of anti-PGT121 antibodies in immunocompetent mice but were durably maintained in immunocompromised mice. In HIV-1-infected BLT humanized mice, Ad5.PGT121 resulted in a greater reduction of viral loads than did AAV1.PGT121. Ad5.PGT121 also led to more-sustained virologic control than purified PGT121 IgG. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Further evaluation of vector delivery of HIV-1 bNAbs is warranted, although approaches to prevent the generation of antiantibody responses may also be required. IMPORTANCE Broadly neutralizing antibodies (bNAbs) are being explored for HIV-1 prevention and cure strategies, but delivery of purified antibodies may prove challenging. We investigated adenovirus serotype 5 (Ad5) and adeno-associated virus serotype 1 (AAV1) vectors to deliver the HIV-1-specific bNAb PGT121. Ad5.PGT121 afforded more rapid, robust, and durable antiviral efficacy than AAV1.PGT121 and purified PGT121 IgG in HIV-1-infected humanized mice. Copyright © 2018 Badamchi-Zadeh et al.

  8. Synergistic efficacy of salicylic acid with a penetration enhancer on human skin monitored by OCT and diffuse reflectance spectroscopy

    Science.gov (United States)

    Zhao, Qingliang; Dai, Cuixia; Fan, Shanhui; Lv, Jing; Nie, Liming

    2016-10-01

    Salicylic acid (SA) has been frequently used as a facial chemical peeling agent (FCPA) in various cosmetics for facial rejuvenation and dermatological treatments in the clinic. However, there is a tradeoff between therapeutic effectiveness and possible adverse effects caused by this agent for cosmetologists. To optimize the cosmetic efficacy with minimal concentration, we proposed a chemical permeation enhancer (CPE) azone to synergistically work with SA on human skin in vivo. The optical properties of human skin after being treated with SA alone and SA combined with azone (SA@azone) were successively investigated by diffuse reflectance spectroscopy (DRS) and optical coherence tomography (OCT). Our results revealed that as the SA concentration increased, the light reflectance decreased and the absorption increased. We also found that SA@azone exhibited a synergistic effect on enhancing light penetration and OCT imaging depth. We demonstrated that the combination of DRS and OCT techniques could be used as a noninvasive, rapid and accurate measurement method to monitor the subtle changes of skin tissue after treatment with FCPA and CPE. The approach will greatly benefit the development of clinical cosmetic surgery, dermatosis diagnosis and therapeutic effect inspection in related biomedical studies.

  9. Therapeutic Efficacy of the Combined Extract of Herbal Medicine Against Infectious Bursal Disease in Chickens

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    Changbo Ou, Ningning Shi1, Qing Pan, Deyu Tian, Wenshu Zeng and Cheng He*

    2013-07-01

    Full Text Available Currently, infectious bursal disease (IBD is a highly contagious disease leading to huge economic losses in poultry industry. Our objective was to investigate potential therapeutic effects of the combined extracts of Rhizoma Dryopteridis crassirhizomatis and Fructus mume (RDCFM against IBDV infection. Seventy-two 4-week-old SPF chickens were randomly divided into six groups and inoculated intranasally with 0.2 ml of 102.5 EID50 of IBDV strain CJ801. Twenty-four hours post infection, the birds were orally administered with 400, 200 and 100 mg/kg BW of RDCFM, respectively, 125 mg/kg Astragalus polysaccharide (ASP and saline water, respectively for 5 days and then monitored daily for 10 days. Finally, the remaining birds were euthanized to collect the sera for detecting antibodies and immune organs for determining the immune organs index as well as virus loads. The herbal extracts improved survival rate and relative body gain rate. Virus loads in bursa of Fabricius in herbal treated groups decreased significantly while higher antibody levels were detected in the three RDCFM groups as compared to those of ASP and infection group. These results implied that chickens administered with 100-200 mg/kg of RDCFM for 5 days could improve protection against IBDV infection and RDCFM may be a promising alternative to ASP and egg yolk antibody.

  10. Therapeutic efficacy of neuromuscular electrical stimulation and electromyographic biofeedback on Alzheimer's disease patients with dysphagia.

    Science.gov (United States)

    Tang, Yi; Lin, Xiang; Lin, Xiao-Juan; Zheng, Wei; Zheng, Zhi-Kai; Lin, Zhao-Min; Chen, Jian-Hao

    2017-09-01

    To study the therapeutic effect of neuromuscular electrical stimulation and electromyographic biofeedback (EMG-biofeedback) therapy in improving swallowing function of Alzheimer's disease patients with dysphagia.A series of 103 Alzheimer's disease patients with dysphagia were divided into 2 groups, among which the control group (n = 50) received swallowing function training and the treatment group (n = 53) received neuromuscular electrical stimulation plus EMG-biofeedback therapy. The mini-mental state scale score was performed in all patients along the treatment period. Twelve weeks after the treatment, the swallowing function was assessed by the water swallow test. The nutritional status was evaluated by Mini Nutritional Assessment (MNA) as well as the levels of hemoglobin and serum albumin. The frequency and course of aspiration pneumonia were also recorded.No significant difference on mini-mental state scale score was noted between 2 groups. More improvement of swallowing function, better nutritional status, and less frequency and shorter course of aspiration pneumonia were presented in treatment group when compared with the control group.Neuromuscular electrical stimulation and EMG-biofeedback treatment can improve swallowing function in patients with Alzheimer's disease and significantly reduce the incidence of adverse outcomes. Thus, they should be promoted in clinical practice.

  11. Therapeutic Efficacy of Allyl Isothiocyanate Evaluated on N-Nitrosodiethylamine/Phenobarbitol induced Hepatocarcinogenesis in Wistar Rats

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    G. Thiyagarajan

    2010-07-01

    Full Text Available N-nitrosodiethylamine (NDEA is a potential carcinogenic agent that induces liver cancer. To evaluate the chemotherapeutic effect of Allyl isothiocyanate in the experimental model, Wistar male rats were administered single dose of intraperitoneal (IP injection of NDEA. Two weeks after administration of NDEA, Phenobarbital at the concentration of 0.05% was incorporated in rat chow for up to 14 successive weeks to promote liver cancer. Allyl isothiocyanate (AITC (2mg/kg body weight in addition with 0.5ml of corn oil was given orally on a daily basis. At the end of this experimental period, the rats were sacrificed and the blood samples were taken for biochemical studies. The levels of the marker enzymes for liver function were measured in serum. The results of the biochemical studies showed that NDEA administration followed by phenobarbital induces macro and microscopic liver tumors that increase the levels of marker enzymes and decreases the level of antioxidant in the serum in addition to loss of body weight. Conclusively, the administration of AITC as therapeutic treatment for hepatocarcinoma has significantly reduced the tumor development and counteracted all the biochemical effects induced by NDEA.

  12. Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.

    Science.gov (United States)

    Pensel, Patricia E; Ullio Gamboa, Gabriela; Fabbri, Julia; Ceballos, Laura; Sanchez Bruni, Sergio; Alvarez, Luis I; Allemandi, Daniel; Benoit, Jean Pierre; Palma, Santiago D; Elissondo, María C

    2015-12-01

    Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

    Science.gov (United States)

    Bentzley, Brandon S.; Jhou, Thomas C.; Aston-Jones, Gary

    2014-01-01

    Development of new treatments for drug addiction will depend on high-throughput screening in animal models. However, an addiction biomarker fit for rapid testing, and useful in both humans and animals, is not currently available. Economic models are promising candidates. They offer a structured quantitative approach to modeling behavior that is mathematically identical across species, and accruing evidence indicates economic-based descriptors of human behavior may be particularly useful biomarkers of addiction severity. However, economic demand has not yet been established as a biomarker of addiction-like behavior in animals, an essential final step in linking animal and human studies of addiction through economic models. We recently developed a mathematical approach for rapidly modeling economic demand in rats trained to self-administer cocaine. We show here that economic demand, as both a spontaneous trait and induced state, predicts addiction-like behavior, including relapse propensity, drug seeking in abstinence, and compulsive (punished) drug taking. These findings confirm economic demand as a biomarker of addiction-like behavior in rats. They also support the view that excessive motivation plays an important role in addiction while extending the idea that drug dependence represents a shift from initially recreational to compulsive drug use. Finally, we found that economic demand for cocaine predicted the efficacy of a promising pharmacotherapy (oxytocin) in attenuating cocaine-seeking behaviors across individuals, demonstrating that economic measures may be used to rapidly identify the clinical utility of prospective addiction treatments. PMID:25071176

  14. Therapeutic efficacy of AS2077715 against experimental tinea pedis in guinea pigs in comparison with terbinafine.

    Science.gov (United States)

    Ohsumi, Keisuke; Murai, Hidetsugu; Nakamura, Ikko; Watanabe, Masato; Fujie, Akihiko

    2014-10-01

    AS2077715 is a novel antifungal metabolite produced by the newly isolated fungal strain Capnodium sp. 339855. This compound has potent inhibitory activity against Trichophyton mentagrophytes mitochondrial cytochrome bc1 complex (complex III) and potent fungicidal activity against T. mentagrophytes, as measured in vitro. Here, we compared the effects of AS2077715 and terbinafine in a guinea pig model of tinea pedis. In a treatment regimen started from the day 7 after infection, 10 daily oral doses of 10 and 20 mg kg(-1) AS2077715 and 20 mg kg(-1) of terbinafine significantly decreased fungal colony-forming units (CFUs) in foot pad skin. In a treatment regimen started from the day 11 after infection, 20 mg kg(-1) AS2077715 significantly reduced fungal CFUs in foot pad skin after 7 daily doses in comparison with 20 mg kg(-1) terbinafine-treated guinea pigs. Our findings suggest that in vivo potency and efficacy of AS2077715 are equal to or greater than that of terbinafine, positioning AS2077715 as a good candidate for use in treating trichophytosis.

  15. Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

    Science.gov (United States)

    Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

    2014-06-16

    Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma

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    Girard, N.; Courel, M.N.; Vera, P.; Delpech, B. [Centre Henri-Becquerel, Rouen (France). Laboratoire d' Oncologie Moleculaire

    2000-07-01

    The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 {mu}Ci/{mu}gHN, 1 {mu}g chloramine-T/{mu}gHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 {mu}Ci 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment (six animals per group). Tumour volumes were evaluated every second day from treatment day and the rate of tumour growth was expressed as a ratio of tumour size at time intervals to the tumour size at the time of injection. Growth curves were compared: heat-inactivated with or without free 131I had no anti-tumour effect. Unlabelled HN-injected tumours had a slightly slower growth rate than untreated tumours (p < 0.02) and growth rate of 131I-HN-injected tumours was much lower (p < 0.00002). A pronounced inhibitory effect with intralesional 131I-labelled HN injection resulted from a combination of a) blockage of HA, a proliferation facilitating factor, and b) local irradiation of tumoral tissue, while uptake in normal tissues was minimized.

  17. Therapeutic efficacy of intralesional 131I-labelled hyaluronectin in grafted human glioblastoma

    International Nuclear Information System (INIS)

    Girard, N.; Courel, M.N.; Vera, P.; Delpech, B.

    2000-01-01

    The grafted human glioblastoma cell CB109 was used as a model for intralesional therapy with 131I-labelled hyaluronectin glycoprotein (131I-HN). 131I-HN bound specifically to in situ hyaluronic acid (HA), a main component of the extracellular matrix which is involved in tumour invasion. Labelling experimental conditions were determined and, finally, 25 μCi/μgHN, 1 μg chloramine-T/μgHN and a 60-s stirring period provided a 131I-HN preparation with an optimal affinity for HA (64% compared to unlabelled HN). Following intratumoral injection, 131I-HN was retained with a limited diffusion outside the tumour. On day 4 the radioactivity concentrated in the tumour was still 25 times greater than that in the liver, spleen and kidneys combined. For therapeutic assays, 65 μCi 131I-HN was injected into the tumour, resulting in a delivery of 6.8 Gy over a 7-day period. Controls received unlabelled HN, heat-inactivated HN, a mixture of inactivated HN plus free 131I or no treatment (six animals per group). Tumour volumes were evaluated every second day from treatment day and the rate of tumour growth was expressed as a ratio of tumour size at time intervals to the tumour size at the time of injection. Growth curves were compared: heat-inactivated with or without free 131I had no anti-tumour effect. Unlabelled HN-injected tumours had a slightly slower growth rate than untreated tumours (p < 0.02) and growth rate of 131I-HN-injected tumours was much lower (p < 0.00002). A pronounced inhibitory effect with intralesional 131I-labelled HN injection resulted from a combination of a) blockage of HA, a proliferation facilitating factor, and b) local irradiation of tumoral tissue, while uptake in normal tissues was minimized

  18. Therapeutic Efficacy of Ginger, Cisplatin and Radiation on Chemically-Induced Cancer in Male Albino Rats

    International Nuclear Information System (INIS)

    El-Beih, N.M.; Galal, S.M.; Fahmy, N.M.; Abd El-Azime, M.G.

    2015-01-01

    This study aimed to investigate the in vivo effect of dietary supplementation with ginger to evaluate its therapeutic effect against lung and kidney cancer and in combination with cisplatin as chemotherapy and radiotherapy in male albino rats. 54 male albino rats were divided into nine groups of 6 animals each, all animals were allowed to food and water ad libitum . Group I was treated with 0.5 ml saline, orlly for 12 consecutive weeks serve as con - trol group Group II injected with N-nitrosodimethylamine (NDMA) and carbon tetrachloride (CCl 4 ); all groups were injected with NDMA + CCl 4 for 6 weeks. Group III were given ginger for 6 consecutive weeks (200 mg/kg, b.wt./day). Group IV animals received cisplatin, group V irradiated with 2 Gy, group VI treated with ginger then irradiated, group VII treated with ginger then injected with cisplatin, group VIII injected with cisplatin then irradiated and group IX treated with ginger and cisplatin then irradiated. Antioxidant status in both kidney and lung tissues were estimated by determining the activity of antioxidant enzyme superoxide dismutase (SOD); as well as the level of reduced glutathione (GSH), Malondialdehyde (MDA) and Nitric oxide (NO). In parallel to histopathological investigations of lung and kidney tissues. In addition, Tumor Necrosis Factor Alpha (TNF-α) level, advanced oxidative protein product (AOPP), urea, creatinine and uric acid. Remarkable disturbances were observed in the levels of all tested parameters in NDMA + CCl 4 group. On the other hand, rats injected with the cancer agents then treated with cisplatin+radiation showed moderate improvements in the studied parameters while, treatment with ginger + cisplatin + radiation ameliorated the levels of the disturbed bio

  19. Anti-tumour therapeutic efficacy of OX40L in murine tumour model.

    Science.gov (United States)

    Ali, Selman A; Ahmad, Murrium; Lynam, June; McLean, Cornelia S; Entwisle, Claire; Loudon, Peter; Choolun, Esther; McArdle, Stephanie E B; Li, Geng; Mian, Shahid; Rees, Robert C

    2004-09-09

    OX40 ligand (OX40L), a member of TNF superfamily, is a co-stimulatory molecule involved in T cell activation. Systemic administration of mOX40L fusion protein significantly inhibited the growth of experimental lung metastasis and subcutaneous (s.c.) established colon (CT26) and breast (4T1) carcinomas. Vaccination with OX40L was significantly enhanced by combination treatment with intra-tumour injection of a disabled infectious single cycle-herpes simplex virus (DISC-HSV) vector encoding murine granulocyte macrophage-colony stimulating factor (mGM-CSF). Tumour rejection in response to OX40L therapy required functional CD4+ and CD8+ T cells and correlated with splenocyte cytotoxic T lymphocytes (CTLs) activity against the AH-1 gp70 peptide of the tumour associated antigen expressed by CT26 cells. These results demonstrate the potential role of the OX40L in cancer immunotherapy.

  20. TC > 0.05 as a Pharmacokinetic Parameter of Paclitaxel for Therapeutic Efficacy and Toxicity in Cancer Patients.

    Science.gov (United States)

    Xin, D S; Zhou, L; Li, C Z; Zhang, S Q; Huang, H Q; Qiu, G D; Lin, L F; She, Y Q; Zheng, J T; Chen, C; Fang, L; Chen, Zhe-Sheng; Zhang, S Y

    2018-03-05

    Paclitaxel (PTX) has remarkable anti-tumor activity, but it causes severe toxicities. There is an urgent need to seek an appropriate pharmacokinetic parameter of PTX to improve treatment efficacy and reduce adverse effects. To evaluate the association of pharmacokinetic parameter TC>0.05 of paclitaxel (PTX) and its therapeutic efficacy and toxicity in patients with solid tumors. A total of 295 patients with ovarian cancer, esophageal cancer, breast cancer, and non-small cell lung cancer (NSCLC), who were admitted to the Tumor Hospital of Shantou University Medical College, China, were recruited for this study. Patients received 3 weeks of PTX chemotherapy. The plasma concentrations of PTX were examined using the MyPaclitaxelTM kit. The patients' PTX TC>0.05 (the time during which PTX plasma concentration exceed 0.05 μmol/L) were calculated based on pharmacokinetic analysis. The results showed that: (1) the concentrations of PTX in these 295 patients ranged from 0.0358-0.127 μmol/L; (2) the PTX TC> 0.05 ranged from 14 to 38 h with a median time of 27 h; (3) among all treatment cycles, there was a statistically significant difference in the PTX TC>0.05 between CR+PR and SD+PD; (4) with the increasing value of TC>0.05, level of leukopenia and leukopenic fever increased; (5) high PTX TC>0.05 led to the occurrence of neutropenia, neutropenic fever, severe anemia, and severe peripheral neurotoxicity. Taken together, our results indicated that the pharmacokinetic parameter PTX TC>0.05 was an effective measure of treatment efficacy and toxicity in patients with solid tumors. Maintaining PTX TC>0.05 at 26 to 30 h could improve its efficacy and reduce the incidence of leukopenia, neutropenia, anemia, and peripheral neurotoxicity in these patients. PTX TC>0.05 is a key pharmacokinetic parameter of PTX which should be monitored to optimize individual treatment in patients with solid tumors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

    Science.gov (United States)

    Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

    2009-05-01

    Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

  2. Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

    Science.gov (United States)

    Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

    2016-08-01

    Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

  3. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    International Nuclear Information System (INIS)

    Numata, Kazushi; Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu; Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu; Karasawa, Eii; Tanaka, Katsuaki

    2010-01-01

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  4. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.j [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu [Department of Internal Medicine, Naruto General Hospital, 167 Naruto, Sanbu, Chiba 289-1326 (Japan); Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Karasawa, Eii [Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashi Kaigan-cho, Atami, Shizuoka 413-0012 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan)

    2010-08-15

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  5. Enhancing Self-Efficacy and Performance: An Experimental Comparison of Psychological Techniques

    Science.gov (United States)

    Wright, Bradley James; O'Halloran, Paul Daniel; Stukas, Arthur Anthony

    2016-01-01

    Purpose: We assessed how 6 psychological performance enhancement techniques (PETs) differentially improved self-efficacy (SE) and skill performance. We also assessed whether vicarious experiences and verbal persuasion as posited sources of SE (Bandura, 1982) were supported and, further, if the effects of the 6 PETs remained after controlling for…

  6. Recombinant, catalytically inactive juvenile hormone esterase enhances efficacy of baculovirus insecticides

    NARCIS (Netherlands)

    Meer, van M.M.M.; Bonning, B.C.; Ward, V.K.; Vlak, J.M.; Hammock, B.D.

    2000-01-01

    The insecticidal efficacy of baculoviruses can be enhanced by engineering the viral genome to express proteins that disrupt the physiology of the host insect. Here we describe the development of a genetically engineered Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) which expresses

  7. Enhancing Teacher Efficacy and Pedagogical Practices amongst General and Special Education Teachers

    Science.gov (United States)

    Coleman, Michael

    2017-01-01

    The purpose of this action research project was to collect both qualitative and quantitative data to acquire information in teacher efficacy from the viewpoint of teachers themselves so that pedagogical practices could be enhanced to better serve the special needs student population. In this study, the relationship between teachers' perception of…

  8. Using Acetaminophen's Toxicity Mechanism to Enhance Cisplatin Efficacy in Hepatocarcinoma and Hepatoblastoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Alexander J. Neuwelt

    2009-10-01

    Conclusions: Our results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies.

  9. Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: Preliminary result.

    Science.gov (United States)

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Kogame, Michio; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. PVnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0-23.3), 11.0 months (95% CI, 3.5-17.6) and 3.6 months (95% CI: 1.2-6.0), respectively. The P-value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.

  10. Polymer Nanoparticles as Smart Carriers for the Enhanced Release of Therapeutic Agents to the CNS.

    Science.gov (United States)

    Gagliardi, Mariacristina; Borri, Claudia

    2017-01-01

    The brain is the most protected organ in the human body; its protective shield, relying on a complex system of cells, proteins and transporters, prevents potentially harmful substances from entering the brain from the bloodstream but, on the other hand, it also stops drugs administered via the systemic route. To improve the efficacy of pharmacological treatments, targeted drug delivery by means of polymer nanoparticles is a challenging but, at the same time, efficient strategy. Thanks to a highly multidisciplinary approach, several ways to overcome the brain protection have provided effective solutions to treat a large number of diseases. Important advances in polymer science, together with the development of novel techniques for nanocarrier preparation, and the discovery of novel targeting ligands and molecules, allow a fine-tuning of size, shape, chemicophysical properties and surface chemistry of functional particulate systems; it enables the improvement of the therapeutic performances for several drugs, also toward districts that are difficult to be treated, such as the brain. This review focuses on the great strides made from scientists and doctors in the development of polymer nano-sized drug delivery systems for brain diseases. Even though the optimal nanocarrier was not yet discovered, important advances were made to strive for safer, performant and successful systems, with the expectation to find soon better solutions to cure some still untreatable pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Characterization of liver metastases: the efficacy of biphasic magnetic resonance imaging with ferucarbotran-enhancement

    International Nuclear Information System (INIS)

    Hong, H.S.; Byun, J.H.; Won, H.J.; Kim, K.W.; Lee, S.S.; Lee, M.G.; Yun, S.C.

    2010-01-01

    Aim: To retrospectively evaluate the efficacy of biphasic magnetic resonance imaging (MRI) of the liver with ferucarbotran-enhancement for the characterization of hepatic metastases. Materials and methods: Thirty-six patients underwent MRI of the liver with separate acquisition of double-contrast enhancement consisting of gadolinium and ferucarbotran. A total of 106 focal hepatic lesions (51 metastases, 31 cysts, 23 haemangiomas, and one eosinophilic abscess) were included. Two sets of MRI were analysed: (1) ferucarbotran set: ferucarbotran-enhanced T1-weighted (T1W) dynamic imaging combined with ferucarbotran-enhanced T2*-weighted (T2*W) delayed imaging and (2) double set: gadolinium-enhanced T1W dynamic imaging combined with ferucarbotran-enhanced T2*W delayed imaging. The diagnostic accuracy of the two sets was evaluated using alternative free-response receiver operating characteristic curve analysis. Sensitivity and specificity were compared using the McNemar test. The enhancement pattern of focal hepatic lesions was analysed on gadolinium and ferucarbotran-enhanced T1W dynamic imaging. Results: There was no significant difference in the accuracy of characterizing hepatic metastases between the two sets. Sensitivity and specificity were not significantly different between the sets (p > 0.05). Peripheral rim enhancement was exhibited in 57% of metastatic lesions on ferucarbotran-enhanced T1W dynamic imaging. The majority (96%) of hepatic haemangiomas demonstrated typical peripheral nodular enhancement with progression on ferucarbotran-enhanced T1W dynamic imaging and were easily differentiated from metastases. Conclusion: Biphasic MRI of the liver with ferucarbotran-enhancement alone provided comparable diagnostic efficacy to double-contrast MRI for the characterization of hepatic metastases.

  12. Evaluation of the safety and efficacy of therapeutic bandage contact lenses on post-cataract surgery patients.

    Science.gov (United States)

    Shi, Dan-Na; Song, Hang; Ding, Tong; Qiu, Wei-Qiang; Wang, Wei

    2018-01-01

    To evaluate the safety of therapeutic bandage contact lens for post-cataract surgery patients and to illustrate its efficacy on post-operative comfort and tear-film stability. A total of 40 participants were recruited and randomly divided into two groups. Group one was instructed to wear bandage contact lenses for a week and use antibiotic eye drops for a month since the first day after surgery. Group two received sub-conjunctival injection of tobramycin and was asked to wear eye pads on the first day after surgery and then were instructed to use antibiotic eye drops as the first group did. Ocular surface disease index (OSDI) questionnaire, slit-lamp microscope examination of tear break-up time (TBUT), corneal fluorescein score (CFS), tear meniscus height (TMH) together with anterior segment optical coherence tomography (AS-OCT) and corneal topography were evaluated preoperatively and postoperatively. The subjective feeling ( P =0.004), TBUT ( P <0.001) and TMH ( P =0.02) post-surgery had improved in patients who used bandage contact lenses compared with those who did not at 1wk post-surgery. Until three month postoperatively, the comfort degree ( P =0.004) and TMH ( P =0.01) of group two were still worse than group one. Moreover, TBUT ( P <0.001) and CFS ( P =0.004) of the group with eye pads got worse than the results before, whereas the group with bandage contact lenses recovered to normal. None of these patients had infections or other complications. Wearing therapeutic bandage contact lens after cataract surgery, compared with traditional eye-pads, is a safe method to improve tear-film stability and reduce post-operative discomfort without hindering corneal incision recovery.

  13. Evaluation of the safety and efficacy of therapeutic bandage contact lenses on post-cataract surgery patients

    Directory of Open Access Journals (Sweden)

    Dan-Na Shi

    2018-02-01

    Full Text Available AIM: To evaluate the safety of therapeutic bandage contact lens for post-cataract surgery patients and to illustrate its efficacy on post-operative comfort and tear-film stability. METHODS: A total of 40 participants were recruited and randomly divided into two groups. Group one was instructed to wear bandage contact lenses for a week and use antibiotic eye drops for a month since the first day after surgery. Group two received sub-conjunctival injection of tobramycin and was asked to wear eye pads on the first day after surgery and then were instructed to use antibiotic eye drops as the first group did. Ocular surface disease index (OSDI questionnaire, slit-lamp microscope examination of tear break-up time (TBUT, corneal fluorescein score (CFS, tear meniscus height (TMH together with anterior segment optical coherence tomography (AS-OCT and corneal topography were evaluated preoperatively and postoperatively. RESULTS: The subjective feeling (P=0.004, TBUT (P<0.001 and TMH (P=0.02 post-surgery had improved in patients who used bandage contact lenses compared with those who did not at 1wk post-surgery. Until three month postoperatively, the comfort degree (P=0.004 and TMH (P=0.01 of group two were still worse than group one. Moreover, TBUT (P<0.001 and CFS (P=0.004 of the group with eye pads got worse than the results before, whereas the group with bandage contact lenses recovered to normal. None of these patients had infections or other complications. CONCLUSION: Wearing therapeutic bandage contact lens after cataract surgery, compared with traditional eye-pads, is a safe method to improve tear-film stability and reduce post-operative discomfort without hindering corneal incision recovery.

  14. Therapeutic efficacy of bipolar radiofrequency thermotherapy for patients with chronic prostatitis: a retrospective analysis of 26 cases.

    Science.gov (United States)

    Lim, Ju Young; Shim, Seung Bum; Yoo, Dong Hoon; Park, Young Woong; Kim, Jong Yeon; Noh, Joon Hwa

    2012-07-01

    Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 years old and diagnosed with CP (National Institutes of Health [NIH]-category III) was performed. Twenty patients were diagnosed with inflammatory CP (NIH-category IIIa) and the rest with noninflammatory CP (NIH-category IIIb). We used the Tempro system at an intraprostatic temperature of 55℃ for 50 minutes with a medium heating rate. All patients also completed the NIH-Chronic Prostatitis Symptom Index (CPSI) before and after treatment. In the patients diagnosed with CP, the mean serum prostate-specific antigen (PSA) level was 0.9±0.3 ng/ml, the prostate volume was 27.1±5.5 g, and the average score for all 3 domains on the NIH-CPSI significantly decreased. The total scores decreased from 19.8±7.1 to 11.1±7.0, the pain domain decreased from 8.6±3.1 to 4.8±3.1, the voiding symptom domain decreased from 5.1±1.8 to 2.9±1.8, and the effect on the quality of life decreased from 6.1±2.2 to 3.4±2.2 (pthermotherapy for patients with CP intractable to conventional medication can provide significant improvement in the NIH-CPSI. Large, randomized controlled trials will also be required to confirm the efficacy of this therapy.

  15. Enhancing the efficacy of AREDS antioxidants in light-induced retinal degeneration.

    Science.gov (United States)

    Wong, Paul; Markey, M; Rapp, C M; Darrow, R M; Ziesel, A; Organisciak, D T

    2017-01-01

    week of supplemental AREDS plus carnosic acid resulted in higher levels of rod and cone cell proteins, and higher levels of retinal DNA than for AREDS alone. Rhodopsin regeneration was unaffected by the rosemary treatment. Retinal gene array analysis showed reduced expression of medium- wavelength opsin 1 and arrestin C in the high-light reared rats versus the low-light rats. The transition of rats from low cyclic light to a high cyclic light environment resulted in the differential expression of 280 gene markers, enriched for genes related to inflammation, apoptosis, cytokine, innate immune response, and receptors. Rosemary, zinc oxide plus rosemary, and AREDS plus rosemary suppressed 131, 241, and 266 of these genes (respectively) in high-light versus low-light animals and induced a small subset of changes in gene expression that were independent of light rearing conditions. Long-term environmental light intensity is a major determinant of retinal gene and protein expression, and of visual cell survival following acute photooxidative insult. Rats preconditioned by high-light rearing exhibit lower levels of cone opsin mRNA and protein, and lower mCAR protein, than low-light reared animals, but greater retention of retinal DNA and proteins following photooxidative damage. Rosemary enhanced the protective efficacy of AREDS and led to the greatest effect on the retinal genome in animals reared in high environmental light. Chronic administration of rosemary antioxidants may be a useful adjunct to the therapeutic benefit of AREDS in slowing disease progression in AMD.

  16. Maximizing the Therapeutic Efficacy of Imatinib Mesylate-Loaded Niosomes on Human Colon Adenocarcinoma Using Box-Behnken Design.

    Science.gov (United States)

    Kassem, Mohammed A; El-Sawy, Hossam S; Abd-Allah, Fathy I; Abdelghany, Tamer M; El-Say, Khalid M

    2017-01-01

    This research purposed to formulate an optimized imatinib mesylate (IM)-loaded niosomes to improve its chemotherapeutic efficacy. The influence of 3 formulation factors on niosomal vesicular size (Y 1 ), zeta potential (Y 2 ), entrapment capacity percentage (Y 3 ), the percentage of initial drug release after 2 h (Y 4 ), and the percentage of cumulative drug release after 24 h (Y 5 ) were studied and optimized using Box-Behnken design. Optimum desirability was specified and the optimized formula was prepared, stability tested, morphologically examined, checked for vesicular bilayer formation and evaluated for its in vitro cytotoxicity on 3 different cancer cell lines namely MCF-7, HCT-116, and HepG-2 in addition to 1 normal cell line to ensure its selectivity against cancer cells. The actual responses of the optimized IM formulation were 425.36 nm, -62.4 mV, 82.96%, 18.93%, and 89.45% for Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 , respectively. The optimized IM-loaded niosomes confirmed the spherical vesicular shape imaged by both light and electron microscopes and further proven by differential scanning calorimetry. Moreover, the optimized formula exhibited improved stability on storage at 4 ± 2°C and superior efficacy on MCF7, HCT-116, and HepG2 as IC 50 values were 6.7, 16.4, and 7.3 folds less than those of free drug, respectively. Interestingly, IC 50 of the optimized formula against normal cell line was ranged from 3 to 11 folds higher than in different cancer cells indicating a higher selectivity of the optimized formula to cancer cells. In conclusion, the incorporation of IM in niosomes enhanced its efficacy and selectivity toward cancer cells, presenting a promising tool to fight cancer using this approach. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  17. CpG Oligodeoxynucleotides Enhance the Efficacy of Adoptive Cell Transfer Using Tumor Infiltrating Lymphocytes by Modifying the Th1 Polarization and Local Infiltration of Th17 Cells

    Directory of Open Access Journals (Sweden)

    Lin Xu

    2010-01-01

    Full Text Available Adoptive cell transfer immunotherapy using tumor infiltrating lymphocytes (TILs was an important therapeutic strategy against tumors. But the efficacy remains limited and development of new strategies is urgent. Recent evidence suggested that CpG-ODNs might be a potent candidate for tumor immunotherapy. Here we firstly reported that CpG-ODNs could significantly enhance the antitumor efficacy of adoptively transferred TILs in vivo accompanied by enhanced activity capacity and proliferation of CD8+ T cells and CD8+ T cells, as well as a Th1 polarization immune response. Most importantly, we found that CpG-ODNs could significantly elevate the infiltration of Th17 cells in tumor mass, which contributed to anti-tumor efficacy of TILs in vivo. Our findings suggested that CpG ODNs could enhance the anti-tumor efficacy of adoptively transferred TILs through modifying Th1 polarization and local infiltration of Th17 cells, which might provide a clue for developing a new strategy for ACT based on TILs.

  18. Self-Efficacy for Coping with Cancer Enhances the Effect of Reiki Treatments During the Pre-Surgery Phase of Breast Cancer Patients.

    Science.gov (United States)

    Chirico, Andrea; D'Aiuto, Giuseppe; Penon, Antonella; Mallia, Luca; DE Laurentiis, Michelino; Lucidi, Fabio; Botti, Gerardo; Giordano, Antonio

    2017-07-01

    Self-efficacy for coping with cancer plays a critical role in influencing psychological cancer-related outcomes, some studies suggested its role in enhancing or reducing the effects of psychological interventions in cancer patients. Reiki has recently been included among the efficacious complementary therapeutic intervention for cancer patients. The present study evaluated the role of self-efficacy for coping with cancer as buffer of the Reiki treatment effects on cancer-related symptoms in a randomized controlled trial (intervention versus control group) of breast cancer patients (N=110) during the pre-surgery phase. Results showed that self-efficacy for coping with cancer can influence the effect of a Reiki treatment. Higher efficacious patients showed a more powerful effect of the Reiki intervention on both anxiety and mood than the low efficacious patients. From a practical perspective, the study provides insightful results for healthcare professionals. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  19. Enhanced antitumor efficacy of folate-linked liposomal doxorubicin with TGF-β type I receptor inhibitor

    International Nuclear Information System (INIS)

    Taniguchi, Yukimi; Kawano, Kumi; Minowa, Takuya; Shimojo, Yuki; Maitani, Yoshie; Sugino, Takashi

    2010-01-01

    Tumor cell targeting of drug carriers is a promising strategy and uses the attachment of various ligands to enhance the therapeutic potential of chemotherapy agents. Folic acid is a high-affinity ligand for folate receptor, which is a functional tumor-specific receptor. The transforming growth factor (TGF)-β type I receptor (TβR-I) inhibitor A-83-01 was expected to enhance the accumulation of nanocarriers in tumors by changing the microvascular environment. To enhance the therapeutic effect of folate-linked liposomal doxorubicin (F-SL), we co-administrated F-SL with A-83-01. Intraperitoneally injected A-83-01-induced alterations in the cancer-associated neovasculature were examined by magnetic resonance imaging (MRI) and histological analysis. The targeting efficacy of single intravenous injections of F-SL combined with A-83-01 was evaluated by measurement of the biodistribution and the antitumor effect in mice bearing murine lung carcinoma M109. A-83-01 temporarily changed the tumor vasculature around 3 h post injection. A-83-01 induced 1.7-fold higher drug accumulation of F-SL in the tumor than liposome alone at 24 h post injection. Moreover F-SL co-administrated with A-83-01 showed significantly greater antitumor activity than F-SL alone. This study shows that co-administration of TβR-I inhibitor will open a new strategy for the use of folate receptor (FR)-targeting nanocarriers for cancer treatment. (author)

  20. Targeting Polo-Like Kinase 1 Enhances Radiation Efficacy for Head-and-Neck Squamous Cell Carcinoma

    International Nuclear Information System (INIS)

    Gerster, Kate; Shi Wei; Ng, Benjamin; Yue Shijun; Ito, Emma; Waldron, John; Gilbert, Ralph; Liu Feifei

    2010-01-01

    Purpose: To investigate the efficacy of targeting polo-like kinase 1 (Plk1) combined with ionizing radiotherapy (RT) for head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: Polo-like kinase 1 messenger ribonucleic acid (mRNA) was targeted by small interfering RNA (siRNA) transfection into the FaDu HNSCC cell line; reduction was confirmed using quantitative real-time polymerase chain reaction. The cellular effects were assessed using [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium], clonogenic, flow cytometric, and caspase assays. In vivo efficacy of siPlk1 was evaluated using mouse xenograft models. Results: Small interfering Plk1 significantly decreased Plk1 mRNA expression, while also increasing cyclin B1 and p21(Waf1/CIP1) mRNA levels after 24 h. This depletion resulted in a time-dependent increase in FaDu cytotoxicity, which was enhanced by the addition of RT. Flow cytometric and caspase assays demonstrated progressive apoptosis, DNA double-strand breaks (γ-H2AX), G2/M arrest, and activation of caspases 3 and 7. Implantation of siPlk1-treated FaDu cells in severe combined immunodeficient mice delayed tumor formation, and systemic administration of siPlk1 inhibited tumor growth enhanced by RT. Conclusions: These data demonstrate the suitability of Plk1 as a potential therapeutic target for HNSCC, because Plk1 depletion resulted in significant cytotoxicity in vitro and abrogated tumor-forming potential in vivo. The effects of Plk1 depletion were enhanced with the addition of RT, indicating that Plk1 represents an important potential radiation sensitizer for HNSCC.

  1. Enhancement of Radiotherapeutic Efficacy by Paclitaxel-Loaded ph-Sensitive Block Copolymer Micelles

    International Nuclear Information System (INIS)

    Jinhyang, C.; Jaesook, P.; Dong-Hoon, J.

    2012-01-01

    Radiotherapy (RT) is a major modality for cancer treatment, but its efficacy is often compromised by the resistance caused by tumor-specific microenvironment including acidosis and hypoxia. For an effective RT, concurrent administration of radiosensitizer with RT has been emphasized. However, most anticancer agents enhancing radiotherapeutic efficacy have obstacles such as poor solubility and severe toxicity. Paclitaxel (PTX), a well-known radiosensitizer, is insoluble in water and needs toxic solvent like Cremophor EL. Nano materials in drug delivery systems have been utilized for improving the drawbacks of anti-cancer drugs. Solubilization, tumor accumulation, and toxicity attenuation of drug by nano materials are suitable for enhancement of radiotherapeutic efficacy. In this study, PTX was incorporated into ph-sensitive block copolymer micelle (psm-PTX), polyethylene glycol-graft-poly(β-amino ester), and pre clinically evaluated for its effect on RT. The size of psm-PTX was 125. 4.4±nm at ph 7.4. psm-PTX released PTX rapidly in the acidic condition (ph 6.5), while it was reasonably stable in the physiologic condition (ph 7.4). The clonogenic assay showed that psm-PTX greatly sensitized human non-small-cell lung cancer A549 cells to radiation. In the xenograft tumor model, the combination of psm-PTX and radiation significantly delayed the tumor growth. These results demonstrated the feasibility of psm-PTX to enhance the chemo radiotherapeutic efficacy.

  2. The enhancement of students' mathematical self-efficacy through teaching with metacognitive scaffolding approach

    Science.gov (United States)

    Prabawanto, S.

    2018-05-01

    This research aims to investigate the enhancement of students’ mathematical self- efficacy through teaching with metacognitive scaffolding approach. This research used a quasi- experimental design with pre-post respon control. The subjects were pre-service elementary school teachers in a state university in Bandung. In this study, there were two groups: experimental and control groups. The experimental group consists of 60 students who acquire teaching mathematics under metacognitive approach, while the control group consists of 58 students who acquire teaching mathematics under direct approach. Students were classified into three categories based on the mathematical prior ability, namely high, middle, and low. Data collection instruments consist of mathematical self-efficacy instruments. By using mean difference test, two conclusions of the research: (1) there is a significant difference in the enhancement of mathematical self-efficacy between the students who attended the course under metacognitive scaffolding approach and students who attended the course under direct approach, and (2) there is no significant interaction effect of teaching approaches and ability level based on the mathematical prior ability toward enhancement of students’ mathematical self-efficacy.

  3. Therapeutic Efficacy of Orally Delivered Doxorubicin Nanoparticles in Rat Tongue Cancer Induced by 4-Nitroquinoline 1-Oxide

    Directory of Open Access Journals (Sweden)

    Monir Moradzadeh Khiavi

    2015-06-01

    Full Text Available Purpose: Oral cancer is one of the most significant cancers in the world, and squamous cell carcinoma makes up about 94% of oral malignancies. The aim of the present study was to compare the efficacy of doxorubicin plus methotrexate - loaded nanoparticles on tongue squamous cell carcinoma induced by 4NQO and compare it with the commercial doxorubicin and methotrexate delivered orally on seventy SD male rats. Methods: 70 rats were divided into five groups. During the study, the animals were weighed by a digital scale once a week. Number of mortalities was recorded in the data collection forms. At the end of the treatment, biopsy samples were taken from rat tongues in order to evaluate the severity of dysplasia and the extent of cell proliferation. The results were analyzed using ANOVA, descriptive statistics and chi-square test. Results: No statistically significant difference was found in the mean weight of five groups (p>0.05. No significant relationship was found between groups and mortality rate (P = 0. 39. In addition, there was a significant relationship between groups and the degree of dysplasia (P <0.001. The statistical analysis showed a significant relationship between groups and the rate of cell proliferation (p <0.001. Conclusion: The results of the present study showed that the use of doxorubicin plus methotrexate - loaded nanoparticles orally had more therapeutic effects than commercial doxorubicin plus methotrexate.

  4. [Therapeutic efficacy and general tolerability of 4-carbomethoxythiazolidine chlorohydrate in a double-blind crossover experiment on chronic obstructive bronchopneumopathy].

    Science.gov (United States)

    Iaia, E

    1990-01-01

    The Authors describe a test performed on 20 hospitalized patients aged between 22 and 80, suffering from obstruent chronic broncho-pneumopathy. The test has been performed according to a double-blind pattern; each patient has been treated according to the 10-day long randomized scheme with one of the two drugs N-acetyl-L-cysteine, 4-carbomethoxythiazolidine. After a 7-day wash-out the patient has been treated with the other drug for a further period of 10 days. All patients have been administered both products at a dosage of 200 mg. three times a day. Every day following values have been registered: arterial pressure, body temperature; subjective and objective symptomatology relieves: cough, cephalea, asthenia, sibiluses, rhoncuses, rales, inspiratory and expiratory dyspnea. Furthermore before and after the treatment the quantity and the quality of the expectorate in order is evaluate the biologic tolerance of the examined drugs, before and after each treatment the following haematochemical and urinary tests have been performed: VES, azotemia, glycemia, SGOT, SGPT, LDH, alkaline phospatase, total and direct bilirubinaemia, prothrombinic activity, complete chemical analysis of urines. As shown in Tab. I-IX, a global analysis of the results proves that 4-carbomethoxythiazolidine is a very well-tolerated drug without any negative side-effect. As far as its therapeutic efficacy is concerned we can say that the mucolitic activity of 4-carbomethoxythiazolidine is the some of that of N-acetyl-L-cysteine.

  5. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2015-10-01

    REPORTABLE OUTCOMES: None OTHER ACHIEVEMENTS: No other achievements to report. REFERENCES: 1. Wolfl M, Kuball J, Ho WY, Nguyen H, Manley TJ...Valiante NM, Chen L, Lee C, Gumperz JE, Phillips JH, Lanier LL , Bigge JC, Parekh RB, Parham P. The inter-locus recombinant HLA-B*4601 has high

  6. Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

    Science.gov (United States)

    2016-06-01

    breast cancer subtypes, potentially including antigens preferentially expressed by breast cancer stem cells. We will identify both MHC-I- and MHC...two of them were previously identified as targets of T cells in chronic lymphocytic leukemia ( CLL ) patients. This analysis demonstrated that both...IFN- release CDCA7L protein [CDA7L] (422-430) HLA-A*03, HLA-C*03, HLA-C*12 chronic lymphocytic leukemia ( CLL ) 7 + CLLs (23%) Table 4

  7. Does Maternal HIV Disclosure Self-Efficacy Enhance Parent-Child Relationships and Child Adjustment?

    Science.gov (United States)

    Armistead, Lisa; Goodrum, Nada; Schulte, Marya; Marelich, William; LeCroix, Rebecca; Murphy, Debra A

    2018-02-09

    Nondisclosure of maternal HIV status to young children can negatively impact child functioning; however, many mothers do not disclose due to lack of self-efficacy for the disclosure process. This study examines demographic variations in disclosure self-efficacy, regardless of intention to disclose, and assesses the relationship between self-efficacy and child adjustment via the parent-child relationship among a sample of HIV+ mothers and their healthy children (N = 181 pairs). Mothers completed demographic and self-efficacy measures; children completed measures assessing the parent-child relationship and child adjustment (i.e., worry, self-concept, depression). Across demographics, few mothers reported confidence in disclosure. Results from covariance structural modeling showed mothers endorsing higher self-efficacy had children who reported better relationship quality, and, in turn, reported fewer adjustment difficulties; higher levels of disclosure self-efficacy also directly predicted fewer adjustment problems. Findings offer support for interventions aimed at providing mothers with skills to enhance confidence for disclosing their HIV status.

  8. MIS416 Enhances Therapeutic Functions of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Against Experimental Colitis by Modulating Systemic Immune Milieu

    Directory of Open Access Journals (Sweden)

    Byung-Chul Lee

    2018-05-01

    Full Text Available Human adult stem cells, including umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs, have recently been considered a promising alternative treatment for inflammatory bowel disease (IBD due to their unique immunomodulatory properties and ability to promote tissue regeneration. However, despite many years of research and pre-clinical studies, results from clinical trials using these cells have been diverse and conflicting. This discrepancy is caused by several factors, such as poor engraftment, low survival rate, and donor-dependent variation of the cells. Enhancement of consistency and efficacy of MSCs remains a challenge for the feasibility of cell-based therapy. In this study, we investigated whether administration of MIS416, a novel microparticle that activates NOD2 and TLR9 signaling, could enhance the therapeutic efficacy of hUCB-MSCs against Crohn’s disease, using dextran sulfate sodium (DSS-induced colitis model. Colitis was experimentally induced in mice by using 3% DSS, and mice were administered a retro-orbital injection of MIS416 and subsequent intraperitoneal injection of hUCB-MSCs. Mice were examined grossly, and blood, spleen, and colon tissues were subsequently collected for further ex vivo analyses. To explore the effects of MIS416 on the therapeutic process, hUCB-MSCs and primary isolated immune cells were cultured with MIS416, and in vitro assays were performed. Compared to the single administration of hUCB-MSCs, co-administration with MIS416 improved the therapeutic efficiency of the stem cells by significantly alleviating the symptoms of IBD. Interestingly, MIS416 did not exert any direct effect on the immunomodulatory capacity of hUCB-MSCs. Instead, systemically injected MIS416 altered the immune milieu in the colon which caused hUCB-MSCs to be more readily recruited toward the lesion site and to suppress inflammation more efficiently. In addition, considerable numbers of regulatory immune cells were stimulated

  9. A combination of complexation and self-nanoemulsifying drug delivery system for enhancing oral bioavailability and anticancer efficacy of curcumin.

    Science.gov (United States)

    Shukla, Mahendra; Jaiswal, Swati; Sharma, Abhisheak; Srivastava, Pradeep Kumar; Arya, Abhishek; Dwivedi, Anil Kumar; Lal, Jawahar

    2017-05-01

    Curcumin, the golden spice from Indian saffron, has shown chemoprotective action against many types of cancer including breast cancer. However, poor oral bioavailability is the major hurdle in its clinical application. In the recent years, self-nanoemulsifying drug delivery system (SNEDDS) has emerged as a promising tool to improve the oral absorption and enhancing the bioavailability of poorly water-soluble drugs. In this context, complexation with lipid carriers like phospholipid has also shown the tremendous potential to improve the solubility and therapeutic efficacy of certain drugs with poor oral bioavailability. In the present investigation, a systematic combination of both the approaches is utilized to prepare the phospholipid complex of curcumin and facilitate its incorporation into SNEDDS. The combined use of both the approaches has been explored for the first time to enhance the oral bioavailability and in turn increase the anticancer activity of curcumin. As evident from the pharmacokinetic studies and in situ single pass intestinal perfusion studies in Sprague-Dawley rats, the optimized SNEDDS of curcumin-phospholipid complex has shown enhanced oral absorption and bioavailability of curcumin. The cytotoxicity study in metastatic breast carcinoma cell line has shown the enhancement of cytotoxic action by 38.7%. The primary tumor growth reduction by 58.9% as compared with the control group in 4T1 tumor-bearing BALB/c mice further supported the theory of enhancement of anticancer activity of curcumin in SNEDDS. The developed formulation can be a potential and safe carrier for the oral delivery of curcumin.

  10. Protective and therapeutic efficacy of Mycobacterium smegmatis expressing HBHA-hIL12 fusion protein against Mycobacterium tuberculosis in mice.

    Directory of Open Access Journals (Sweden)

    Shanmin Zhao

    Full Text Available Tuberculosis (TB remains a major worldwide health problem. The only vaccine against TB, Mycobacterium bovis Bacille Calmette-Guerin (BCG, has demonstrated relatively low efficacy and does not provide satisfactory protection against the disease. More efficient vaccines and improved therapies are urgently needed to decrease the worldwide spread and burden of TB, and use of a viable, metabolizing mycobacteria vaccine may be a promising strategy against the disease. Here, we constructed a recombinant Mycobacterium smegmatis (rMS strain expressing a fusion protein of heparin-binding hemagglutinin (HBHA and human interleukin 12 (hIL-12. Immune responses induced by the rMS in mice and protection against Mycobacterium tuberculosis (MTB were investigated. Administration of this novel rMS enhanced Th1-type cellular responses (IFN-γ and IL-2 in mice and reduced bacterial burden in lungs as well as that achieved by BCG vaccination. Meanwhile, the bacteria load in M. tuberculosis infected mice treated with the rMS vaccine also was significantly reduced. In conclusion, the rMS strain expressing the HBHA and human IL-12 fusion protein enhanced immunogencity by improving the Th1-type response against TB, and the protective effect was equivalent to that of the conventional BCG vaccine in mice. Furthermore, it could decrease bacterial load and alleviate histopathological damage in lungs of M. tuberculosis infected mice.

  11. Defining New Therapeutics Using a More Immunocompetent Mouse Model of Antibody-Enhanced Dengue Virus Infection.

    Science.gov (United States)

    Pinto, Amelia K; Brien, James D; Lam, Chia-Ying Kao; Johnson, Syd; Chiang, Cindy; Hiscott, John; Sarathy, Vanessa V; Barrett, Alan D; Shresta, Sujan; Diamond, Michael S

    2015-09-15

    With over 3.5 billion people at risk and approximately 390 million human infections per year, dengue virus (DENV) disease strains health care resources worldwide. Previously, we and others established models for DENV pathogenesis in mice that completely lack subunits of the receptors (Ifnar and Ifngr) for type I and type II interferon (IFN) signaling; however, the utility of these models is limited by the pleotropic effect of these cytokines on innate and adaptive immune system development and function. Here, we demonstrate that the specific deletion of Ifnar expression on subsets of murine myeloid cells (LysM Cre(+) Ifnar(flox/flox) [denoted as Ifnar(f/f) herein]) resulted in enhanced DENV replication in vivo. The administration of subneutralizing amounts of cross-reactive anti-DENV monoclonal antibodies to LysM Cre(+) Ifnar(f/f) mice prior to infection with DENV serotype 2 or 3 resulted in antibody-dependent enhancement (ADE) of infection with many of the characteristics associated with severe DENV disease in humans, including plasma leakage, hypercytokinemia, liver injury, hemoconcentration, and thrombocytopenia. Notably, the pathogenesis of severe DENV-2 or DENV-3 infection in LysM Cre(+) Ifnar(f/f) mice was blocked by pre- or postexposure administration of a bispecific dual-affinity retargeting molecule (DART) or an optimized RIG-I receptor agonist that stimulates innate immune responses. Our findings establish a more immunocompetent animal model of ADE of infection with multiple DENV serotypes in which disease is inhibited by treatment with broad-spectrum antibody derivatives or innate immune stimulatory agents. Although dengue virus (DENV) infects hundreds of millions of people annually and results in morbidity and mortality on a global scale, there are no approved antiviral treatments or vaccines. Part of the difficulty in evaluating therapeutic candidates is the lack of small animal models that are permissive to DENV and recapitulate the clinical features

  12. Folate decorated dual drug loaded nanoparticle: role of curcumin in enhancing therapeutic potential of nutlin-3a by reversing multidrug resistance.

    Directory of Open Access Journals (Sweden)

    Manasi Das

    Full Text Available Retinoblastoma is the most common intraocular tumor in children. Malfunctioning of many signaling pathways regulating cell survival or apoptosis, make the disease more vulnerable. Notably, resistance to chemotherapy mediated by MRP-1, lung-resistance protein (LRP is the most challenging aspect to treat this disease. Presently, much attention has been given to the recently developed anticancer drug nutlin-3a because of its non-genotoxic nature and potency to activate tumor suppressor protein p53. However, being a substrate of multidrug resistance protein MRP1 and Pgp its application has become limited. Currently, research has step towards reversing Multi drug resistance (MDR by using curcumin, however its clinical relevance is restricted by plasma instability and poor bioavailability. In the present investigation we tried to encapsulate nutlin-3a and curcumin in PLGA nanoparticle (NPs surface functionalized with folate to enhance therapeutic potential of nutlin-3a by modulating MDR. We document that curcumin can inhibit the expression of MRP-1 and LRP gene/protein in a concentration dependent manner in Y79 cells. In vitro cellular cytotoxicity, cell cycle analysis and apoptosis studies were done to compare the effectiveness of native drugs (single or combined and single or dual drug loaded nanoparticles (unconjugated/folate conjugated. The result demonstrated an augmented therapeutic efficacy of targeted dual drug loaded NPs (Fol-Nut-Cur-NPs over other formulation. Enhanced expression or down regulation of proapoptotic/antiapoptotic proteins respectively and down-regulation of bcl2 and NFκB gene/protein by Fol-Nut-Cur-NPs substantiate the above findings. This is the first investigation exploring the role of curcumin as MDR modulator to enhance the therapeutic potentiality of nutlin-3a, which may opens new direction for targeting cancer with multidrug resistance phenotype.

  13. Comparison of the therapeutic efficacy of intravenous dimenhydrinate and intravenous piracetam in patients with vertigo: a randomised clinical trial.

    Science.gov (United States)

    Doğan, Nurettin Özgür; Avcu, Nazire; Yaka, Elif; Yılmaz, Serkan; Pekdemir, Murat

    2015-07-01

    The present study aimed to compare the therapeutic efficacy of dimenhydrinate and piracetam in patients with vertigo. A blinded, parallel group, superiority, randomised clinical trial was carried out on patients who presented to the emergency department (ED) with vertigo. Healthy adult patients presenting to the ED with undifferentiated vertigo were included in the study. The efficacy of intravenous dimenhydrinate (100 mg) and intravenous piracetam (2000 mg) for reducing the intensity of vertigo was compared in two randomised treatment groups using a 10-point numeric rating scale (NRS). The determination of NRS scores was performed at presentation and at the 30th minute of presentation, after the study drug was implemented, both in immobile and ambulatory positions. The primary outcome variable was reduction in vertigo intensity documented on the NRS at the 30th minute after medication administration, analysed by intention to treat. A total of 94 patients were included in the randomisation (n=47 in both groups). The baseline NRS scores were 7.55±2.00 in the dimenhydrinate group and 8.19±1.79 in the piracetam group. The changes from baseline for dimenhydrinate and piracetam were 2.92±3.11 and 3.75±3.40 (difference -0.83 (95% CI -2.23 to 0.57)) in the immobile position and were 2.04±3.07 and 2.72±2.91 (difference -0.68 (95% CI -2.03 to 0.67)) in the ambulatory position. Rescue medication need was similar in both treatment groups (p=0.330), and only one adverse reaction was reported. We found no evidence of a difference between dimenhydrinate and piracetam in relieving the symptoms of vertigo. Clinical Trials Registration ID: NCT01890538. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  14. Polymeric Nanoparticles Containing Taxanes Enhance Chemoradiotherapeutic Efficacy in Non-small Cell Lung Cancer

    International Nuclear Information System (INIS)

    Jung, Joohee; Park, Sung-Jin; Chung, Hye Kyung; Kang, Hye-Won; Lee, Sa-Won; Seo, Min Hyo; Park, Heon Joo; Song, Si Yeol; Jeong, Seong-Yun; Choi, Eun Kyung

    2012-01-01

    Purpose: To reduce the side effects and improve the efficacy of chemoradiation therapy, taxanes were incorporated into polymeric nanoparticles (PNP), and their synergic effect on radiation therapy in non-small cell lung cancer was evaluated. Methods and Materials: The properties of PNP-taxanes were characterized by transmission electron microscopy and dynamic light scattering. The chemoradiotherapeutic efficacy of PNP-taxanes was determined by clonogenic assay, cellular morphology, and flow cytometry in A549 cells. In mice bearing A549-derived tumors, the tumor growth delay was examined after the treatment of PNP-taxanes and/or ionizing radiation (IR). Results: The PNP-taxanes were found to be approximately 45 nm in average diameter and to have high solubility in water. They showed the properties of active internalization into cells and preserved the anticancer effect of free taxanes. The survival fraction of A549 cells by clonogenic assay was significantly reduced in the group receiving combined treatment of PNP-taxanes and IR. In addition, in vivo radiotherapeutic efficacy was markedly enhanced by the intravenous injection of PNP-taxanes into the xenograft mice. Conclusions: We have demonstrated the feasibility of PNP-taxanes to enhance the efficacy of chemoradiation therapy. These results suggest PNP-taxanes can hold an invaluable and promising position in treating human cancers as a novel and effective chemoradiation therapy agent.

  15. Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

    OpenAIRE

    Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

    2009-01-01

    Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of ...

  16. Enhancing Cross-Cultural Training Efficacy on Expatriate Adjustment through Emotional Intelligence and Social Capital

    OpenAIRE

    Susanto, Ely; Rostiani, Rokhima

    2012-01-01

    Cross cultural training is widely believed to make a positive contribution to expatriate adjustment. In practice, however, it is very costly and sometimes ineffective for expatriates. Therefore, there is a growing importance placed on increasing the cost effectiveness or enhancing the efficacy of crosscultural training by functioning individual expatriate’s social capital and emotional intelligence as moderating variables towards expatriate’s adjustment and performance. To do so we blend idea...

  17. Wee1 inhibition by MK-1775 leads to tumor inhibition and enhances efficacy of gemcitabine in human sarcomas.

    Directory of Open Access Journals (Sweden)

    Jenny M Kreahling

    Full Text Available Sarcomas are rare and heterogeneous mesenchymal tumors affecting both pediatric and adult populations with more than 70 recognized histologies. Doxorubicin and ifosfamide have been the main course of therapy for treatment of sarcomas; however, the response rate to these therapies is about 10-20% in metastatic setting. Toxicity with the drug combination is high, response rates remain low, and improvement in overall survival, especially in the metastatic disease, remains negligible and new agents are needed. Wee1 is a critical component of the G2/M cell cycle checkpoint control and mediates cell cycle arrest by regulating the phosphorylation of CDC2. Inhibition of Wee1 by MK1775 has been reported to enhance the cytotoxic effect of DNA damaging agents in different types of carcinomas. In this study we investigated the therapeutic efficacy of MK1775 in various sarcoma cell lines, patient-derived tumor explants ex vivo and in vivo both alone and in combination with gemcitabine, which is frequently used in the treatment of sarcomas. Our data demonstrate that MK1775 treatment as a single agent at clinically relevant concentrations leads to unscheduled entry into mitosis and initiation of apoptotic cell death in all sarcomas tested. Additionally, MK1775 significantly enhances the cytotoxic effect of gemcitabine in sarcoma cells lines with different p53 mutational status. In patient-derived bone and soft tissue sarcoma samples we showed that MK1775 alone and in combination with gemcitabine causes significant apoptotic cell death. Magnetic resonance imaging (MRI and histopathologic studies showed that MK1775 induces significant cell death and terminal differentiation in a patient-derived xenograft mouse model of osteosarcoma in vivo. Our results together with the high safety profile of MK1775 strongly suggest that this drug can be used as a potential therapeutic agent in the treatment of both adult as well as pediatric sarcoma patients.

  18. A Chitosan—Based Liposome Formulation Enhances the In Vitro Wound Healing Efficacy of Substance P Neuropeptide

    Directory of Open Access Journals (Sweden)

    Tamara Mengoni

    2017-12-01

    Full Text Available Currently, there is considerable interest in developing innovative biodegradable nanoformulations for controlled administration of therapeutic proteins and peptides. Substance P (SP is a neuropeptide of 11 amino acids that belongs to the tachykinins family and it plays an important role in wound healing. However, SP is easily degradable in vivo and has a very short half-life, so the use of chitosan-based nanocarriers could enhance its pharmaceutical properties. In light of the above, the aim of this work was to produce and characterize chitosan-coated liposomes loaded with SP (SP-CH-LP as novel biomaterials with potential application in mucosal wound healing. The loaded system’s biophysical properties were characterized by dynamic light scattering with non-invasive back scattering (DLS-NIBS, mixed mode measurements and phase analysis light scattering (M3-PALS and high performance liquid chromatography with ultraviolet/visible light detection (HPLC-UV/VIS. Then, the efficacy of the obtained nanoformulations was examined via proof-of-principle experiments using in vitro cell assays. These assays showed an increment on cell motility and proliferation after treatment with free and encapsulated neuropeptides. Additionally, the effect of SP on wound healing was enhanced by the entrapment on CH-LP. Overall, the amenability of chitosan-based nanomaterials to encapsulate peptides and proteins constitutes a promising approach towards potential novel therapies to treat difficult wounds.

  19. Multi-targeted therapy for leprosy: insilico strategy to overcome multi drug resistance and to improve therapeutic efficacy.

    Science.gov (United States)

    Anusuya, Shanmugam; Natarajan, Jeyakumar

    2012-12-01

    Leprosy remains a major public health problem, since single and multi-drug resistance has been reported worldwide over the last two decades. In the present study, we report the novel multi-targeted therapy for leprosy to overcome multi drug resistance and to improve therapeutic efficacy. If multiple enzymes of an essential metabolic pathway of a bacterium were targeted, then the therapy would become more effective and can prevent the occurrence of drug resistance. The MurC, MurD, MurE and MurF enzymes of peptidoglycan biosynthetic pathway were selected for multi targeted therapy. The conserved or class specific active site residues important for function or stability were predicted using evolutionary trace analysis and site directed mutagenesis studies. Ten such residues which were present in at least any three of the four Mur enzymes (MurC, MurD, MurE and MurF) were identified. Among the ten residues G125, K126, T127 and G293 (numbered based on their position in MurC) were found to be conserved in all the four Mur enzymes of the entire bacterial kingdom. In addition K143, T144, T166, G168, H234 and Y329 (numbered based on their position in MurE) were significant in binding substrates and/co-factors needed for the functional events in any three of the Mur enzymes. These are the probable residues for designing newer anti-leprosy drugs in an attempt to reduce drug resistance. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Pinocembrin ex vivo preconditioning improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats.

    Science.gov (United States)

    Ahmed, Lamiaa A; Rizk, Sherine M; El-Maraghy, Shohda A

    2017-08-15

    Pulmonary hypertension is still not curable and the available current therapies can only alleviate symptoms without hindering the progression of disease. The present study was directed to investigate the possible modulatory effect of pinocembrin on endothelial progenitor cells transplanted in monocrotaline-induced pulmonary hypertension in rats. Pulmonary hypertension was induced by a single subcutaneous injection of monocrotaline (60mg/kg). Endothelial progenitor cells were in vitro preconditioned with pinocembrin (25mg/L) for 30min before being i.v. injected into rats 2weeks after monocrotaline administration. Four weeks after monocrotaline administration, blood pressure, electrocardiography and right ventricular systolic pressure were recorded. Rats were sacrificed and serum was separated for determination of endothelin-1 and asymmetric dimethylarginine levels. Right ventricles and lungs were isolated for estimation of tumor necrosis factor-alpha and transforming growth factor-beta contents as well as caspase-3 activity. Moreover, protein expression of matrix metalloproteinase-9 and endothelial nitric oxide synthase in addition to myocardial connexin-43 was assessed. Finally, histological analysis of pulmonary arteries, cardiomyocyte cross-sectional area and right ventricular hypertrophy was performed and cryosections were done for estimation of cell homing. Preconditioning with pinocembrin provided a significant improvement in endothelial progenitor cells' effect towards reducing monocrotaline-induced elevation of inflammatory, fibrogenic and apoptotic markers. Furthermore, preconditioned cells induced a significant amelioration of endothelial markers and cell homing and prevented monocrotaline-induced changes in right ventricular function and histological analysis compared with native cells alone. In conclusion, pinocembrin significantly improves the therapeutic efficacy of endothelial progenitor cells in monocrotaline-induced pulmonary hypertension in rats

  1. The use of cell-sheet technique eliminates arrhythmogenicity of skeletal myoblast-based therapy to the heart with enhanced therapeutic effects.

    Science.gov (United States)

    Narita, Takuya; Shintani, Yasunori; Ikebe, Chiho; Kaneko, Masahiro; Harada, Narumi; Tshuma, Nomathamsanqa; Takahashi, Kunihiko; Campbell, Niall G; Coppen, Steven R; Yashiro, Kenta; Sawa, Yoshiki; Suzuki, Ken

    2013-09-20

    Clinical application of skeletal myoblast transplantation has been curtailed due to arrhythmogenicity and inconsistent therapeutic benefits observed in previous studies. However, these issues may be solved by the use of a new cell-delivery mode. It is now possible to generate "cell-sheets" using temperature-responsive dishes without artificial scaffolds. This study aimed to validate the safety and efficacy of epicardial placement of myoblast-sheets (myoblast-sheet therapy) in treating heart failure. After coronary artery ligation in rats, the same numbers of syngeneic myoblasts were transplanted by intramyocardial injection or cell-sheet placement. Continuous radio-telemetry monitoring detected increased ventricular arrhythmias, including ventricular tachycardia, after intramyocardial injection compared to the sham-control, while these were abolished in myoblast-sheet therapy. This effect was conjunct with avoidance of islet-like cell-cluster formation that disrupts electrical conduction, and with prevention of increased arrhythmogenic substrates due to exaggerated inflammation. Persistent ectopic donor cells were found in the lung only after intramyocardial injection, strengthening the improved safety of myoblast-sheet therapy. In addition, myoblast-sheet therapy enhanced cardiac function, corresponding to a 9.2-fold increase in donor cell survival, compared to intramyocardial injection. Both methods achieved reduced infarct size, decreased fibrosis, attenuated cardiomyocyte hypertrophy, and increased neovascular formation, in association with myocardial upregulation of a group of relevant molecules. The pattern of these beneficial changes was similar between two methods, but the degree was more substantial after myoblast-sheet therapy. The cell-sheet technique enhanced safety and therapeutic efficacy of myoblast-based therapy, compared to the current method, thereby paving the way for clinical application. Copyright © 2012 Elsevier Ireland Ltd. All rights

  2. Efficacy of gadolinium enhanced MR imaging for the diagnosis of Legg-Calve-Perthes disease

    International Nuclear Information System (INIS)

    Kim, Jee Eun; Kim, Hyung Sik; Kim, Ji Hye

    2008-01-01

    The purpose of this study was to evaluate the efficacy of gadolinium enhanced MR imaging for making the diagnosis of Legg-Calve-Perthes (LCP) disease. We studied the gadolinium enhanced MR images of 14 hips in 12 children who had the diagnosis of LCP disease. We retrospectively analyzed the extent of necrosis, the epiphyseal revascularization pathways and the metaphyseal changes. The absence of enhancement on gadolinium enhanced MRI was noted in all cases of LCP disease. Diffuse absence of enhancement was observed in 9 femoral epiphyses. Two of them showed normal bone marrow signal intensity on the T1 and T1-weighted images. Focal absence of enhancement was observed in 5 femoral epiphyses. Enhanced MRI showed better epiphyseal revascularization in the lateral column (five cases), in the lateral and medial columns (four cases) and in the transphyseal pathway (three cases). Metaphyseal change was observed in two cases. Gadolinium enhanced MRI allows detection of LCP disease and an accurate analysis of the different revascularization patterns, and this helpful for predicting the prognosis

  3. Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

    International Nuclear Information System (INIS)

    Postiglione, Ilaria; Chiaviello, Angela; Palumbo, Giuseppe

    2011-01-01

    Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors

  4. H-Ferritin Enriches the Curcumin Uptake and Improves the Therapeutic Efficacy in Triple Negative Breast Cancer Cells.

    Science.gov (United States)

    Pandolfi, Laura; Bellini, Michela; Vanna, Renzo; Morasso, Carlo; Zago, Andrea; Carcano, Sofia; Avvakumova, Svetlana; Bertolini, Jessica Armida; Rizzuto, Maria Antonietta; Colombo, Miriam; Prosperi, Davide

    2017-10-09

    Triple negative breast cancer (TNBC) is a highly aggressive, invasive, and metastatic tumor. Although it is reported to be sensitive to cytotoxic chemotherapeutics, frequent relapse and chemoresistance often result in treatment failure. In this study, we developed a biomimetic nanodrug consisting of a self-assembling variant (HFn) of human apoferritin loaded with curcumin. HFn nanocage improved the solubility, chemical stability, and bioavailability of curcumin, allowing us to reliably carry out several experiments in the attempt to establish the potential of this molecule as a therapeutic agent and elucidate the mechanism of action in TNBC. HFn biopolymer was designed to bind selectively to the TfR1 receptor overexpressed in TNBC cells. HFn-curcumin (CFn) proved to be more effective in viability assays compared to the drug alone using MDA-MB-468 and MDA-MB-231 cell lines, representative of basal and claudin-low TNBC subtypes, respectively. Cellular uptake of CFn was demonstrated by flow cytometry and label-free confocal Raman imaging. CFn could act as a chemosensitizer enhancing the cytotoxic effect of doxorubicin by interfering with the activity of multidrug resistance transporters. In addition, CFn exhibited different cell cycle effects on these two TNBC cell lines, blocking MDA-MB-231 in G0/G1 phase, whereas MDA-MB-468 accumulated in G2/M phase. CFn was able to inhibit the Akt phosphorylation, suggesting that the effect on the proliferation and cell cycle involved the alteration of PI3K/Akt pathway.

  5. Adverse events and therapeutic efficacy associated with TACE for hepatocellular carcinoma with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension

    International Nuclear Information System (INIS)

    Araki, Takuji; Okada, Taiki; Kimura, Kazufumi; Sawada, Eiichi; Sano, Katushiro; Araki, Tsutomu

    2012-01-01

    The aim of this study was to evaluate the short-term adverse events and therapeutic efficacy of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with a miriplatin-lipiodol suspension in comparison with a cisplatin-lipiodol suspension. Of patients who underwent TACE for unresectable HCCs in 2009 and 2010, twenty-nine and twenty-seven patients underwent TACE using cisplatin-lipiodol suspension (C-LS) and miriplatin-lipiodol suspension (M-LS), respectively. Adverse events of fever, pain, nausea, anorexia, elevation of aspartate aminotransferase (AST), total bilirubin, creatinine and a decrease in platelet count were evaluated by the National Cancer Institute Common Toxicity Criteria Ver.4. to compare the C-LS and M-LS groups. The short-term therapeutic efficacy of both groups was evaluated by the treatment effect (TE) on the CT images three months after TACE according to the General Rules for the Clinical and Pathological Study of Primary Liver Cancer (the 5th edition, Revised Version). With regard to the adverse events, the M-LS group had significantly less fever and anorexia than the C-LS group. No critical adverse events were observed in either group. The therapeutic efficacy was not significantly different between the groups. TACE with M-LS had fewer adverse events than TACE with C-LS, but neither TACE led to any critical adverse events. The short-term therapeutic efficacy of TACE with M-LS was equivalent to that of TACE with C-LS. (author)

  6. High intensity focused ultrasound treatment of adenomyosis: The relationship between the features of magnetic resonance imaging on T2 weighted images and the therapeutic efficacy

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Chunmei [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China); Setzen, Raymond [Department of Obstetrics and Gynecology, Chris Hani Baragwanath Academic Hospital, Johannesburg (South Africa); Liu, Zhongqiong; Liu, Yunchang [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China); Xie, Bin [Department of Ultrasound, Huanggang Central Hospital, Huanggang City, Hubei 438000 (China); Aili, Aixingzi, E-mail: 1819483078@qq.com [Shanghai First Maternity and Infant Health Hospital, Shanghai (China); Zhang, Lian, E-mail: lianwzhang@yahoo.com [State Key Laboratory of Ultrasound Engineering in Medicine Co-founded by Chongqing and the Ministry of Science and Technology, Chongqing Key Laboratory of Ultrasound in Medicine and Engineering, Chongqing Haifu Hospital, College of Biomedical Engineering, Chongqing Medical University, Chongqing (China)

    2017-04-15

    Objectives: To investigate the relationship between the features of magnetic resonance imaging (MRI) on T2 weighted images (T2WI) and the therapeutic efficacy of high intensity focused ultrasound (HIFU) on adenomyosis. Materials and methods: From January 2011 to November 2015, four hundred and twenty-eight patients with symptomatic adenomyosis were treated with HIFU. Based on the signal intensity and the number of hyperintense foci in the adenomyotic lesions on T2WI, the patients were classified into groups. The day after HIFU ablation patients underwent contrast-enhanced MRI and a comparison was made of non-perfused volume (NPV) ratio, energy efficiency factor (EEF), treatment time, sonication time, and adverse effects. Results: No significant difference in terms of HIFU treatment settings and results was observed between the group of patients with hypointense adenomyotic lesions and the group with isointense adenomyotic lesions (P > 0.05). However, the sonication time and EEF were significantly higher in the group with multiple hyperintense foci compared to the group with few hyperintense foci. The NPV ratio achieved in the lesions with multiple hyperintenese foci was significantly lower than that in the lesions with few hyperintense foci (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. Conclusions: Based on our results, the response of the adenomyotic lesions to HIFU treatment is not related to the signal intensity of adenomyotic lesions on T2WI. However, the number of the high signal intensity foci in the adenomyotic lesions on T2WI can be considered as a predictive factor to help select patients for HIFU treatment.

  7. High intensity focused ultrasound treatment of adenomyosis: The relationship between the features of magnetic resonance imaging on T2 weighted images and the therapeutic efficacy

    International Nuclear Information System (INIS)

    Gong, Chunmei; Setzen, Raymond; Liu, Zhongqiong; Liu, Yunchang; Xie, Bin; Aili, Aixingzi; Zhang, Lian

    2017-01-01

    Objectives: To investigate the relationship between the features of magnetic resonance imaging (MRI) on T2 weighted images (T2WI) and the therapeutic efficacy of high intensity focused ultrasound (HIFU) on adenomyosis. Materials and methods: From January 2011 to November 2015, four hundred and twenty-eight patients with symptomatic adenomyosis were treated with HIFU. Based on the signal intensity and the number of hyperintense foci in the adenomyotic lesions on T2WI, the patients were classified into groups. The day after HIFU ablation patients underwent contrast-enhanced MRI and a comparison was made of non-perfused volume (NPV) ratio, energy efficiency factor (EEF), treatment time, sonication time, and adverse effects. Results: No significant difference in terms of HIFU treatment settings and results was observed between the group of patients with hypointense adenomyotic lesions and the group with isointense adenomyotic lesions (P > 0.05). However, the sonication time and EEF were significantly higher in the group with multiple hyperintense foci compared to the group with few hyperintense foci. The NPV ratio achieved in the lesions with multiple hyperintenese foci was significantly lower than that in the lesions with few hyperintense foci (P < 0.05). No significant difference was observed in the rate of adverse effects between the two groups. Conclusions: Based on our results, the response of the adenomyotic lesions to HIFU treatment is not related to the signal intensity of adenomyotic lesions on T2WI. However, the number of the high signal intensity foci in the adenomyotic lesions on T2WI can be considered as a predictive factor to help select patients for HIFU treatment.

  8. Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use.

    Science.gov (United States)

    Altaie, Ala; Baboolal, Thomas G; Wall, Owen; Jones, Elena; McGonagle, Dennis

    2018-03-01

    Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid-derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury. SF-MSCs were obtained during knee arthroscopic procedures (N = 7). Colony forming unit-fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions. PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca ++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium. This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  9. Manipulation of factors affecting phytate hydrolysis in enhancing phytase efficacy in poultry: A review

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    Noraini*, S.

    2017-06-01

    Full Text Available Phosphorus in phytate is largely unavailable to chickens unless they are provided with dietary phytase. Phytase was shown to increase phytate degradation in the crop and proventriculus-gizzard and very little phytate degradation occurred in the duodenum-jejunum or ileum. These previous investigations were conducted on chickens fed corn based diet but not with wheat based diet. Increase in digesta passage or mean retention time (MRT along the gastrointestinal tract could enhance phytase efficacy as the prolonged reaction time between substrates and phytase may further facilitate phytate dephosphorylation. Dietary fat and fibre supplementation have been shown to influence intestinal MRT in chickens therefore it is expected that inclusion of both dietary fat and fibre could be manipulated to further improve phytase efficacy in broiler chickens. This paper provides a brief review of in vitro phytate hydrolysis, phytate hydrolysis in the gastrointestinal tract of broilers and factors that affect phytate hydrolysis that can be manipulated to enhance the efficacy of phytase in poultry diets.

  10. Biotechnological Approaches to Enhance Halotolerance and Photosynthetic Efficacy in the Cyanobacterium, Fremyella diplosiphon

    Science.gov (United States)

    Tabatabai, Ben

    Growing concerns over dwindling energy supplies linked to nonrenewable fossil fuels have driven profound interest in biofuels as a clean and sustainable alternative. Cyanobacteria are a promising source of third-generation biofuel due to their fast generation time and high net biomass conversion. In this study, the effect of salinity stress on Fremyella diplosiphon, a model organism for studying photosynthetic pathways, was investigated and nanobiotechnological approaches undertaken to enhance its halotolerance and photosynthetic efficacy. Heat-induced mutagenesis resulted in a mutant strain that could survive in 20 g L-1 sodium chloride (NaCl) with no loss in pigmentation. To further enhance F. diplosiphon halotolerance, expression plasmids harboring the hlyB and mdh genes were overexpressed in the wild type resulting in two transformants that thrived in 35 g L-1 NaCl, the average salinity of sea water. In addition, no significant reduction in photosynthetic efficacy was detected in the halotolerant strains relative to the wild type. Total lipid content and fatty acid methyl ester composition of wild type and halotolerant strains were assessed for their potential as a production-scale biofuel agent. Methyl palmitate, the methyl ester of hexodeconoate (C16:0), was found to be most abundant in the wild type and transformants accounting for 60-70% of total FAMEs produced. Efforts to enhance the photosynthetic efficiency of the strains revealed that gold nanoparticle-derived surface plasmon resonance augmented culture growth and pigment accumulation. Cell-nanoparticles interactions were visualized using scanning and transmission electron microscopy. Our findings address two key challenges that cyanobacterial biofuel agents need to overcome: enhanced halotolerance and photosynthetic efficacy to minimize freshwater input and artificial light supply. These innovations have paved the way for an efficient cyanobacterial cultivation system for large-scale production of

  11. Therapeutic efficacy of atorvastatin in treatment of non-alcoholic fatty liver disease in patients with type Ⅱ diabetes mellitus

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    FENG Mengdie

    2013-07-01

    Full Text Available ObjectiveTo observe the therapeutic efficacy of atorvastatin in the treatment of non-alcoholic fatty liver disease (NAFLD in patients with type Ⅱ diabetes mellitus. MethodsA total of 118 patients with type Ⅱ diabetes mellitus complicated by NAFLD, who visited the outpatient department of internal medicine or were hospitalized in our hospital from January 2010 to March 2012, were divided randomly into treatment group (n=61 and control group (n=57. Both groups received liver protection therapy and blood glucose control, and atorvastatin (20 mg/d was administered as an addition in the treatment group. The clinical symptoms, body mass index (BMI, blood levels of total cholesterol (TC, triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C, alanine aminotransferase (ALT, and aspartate aminotransferase (AST, and liver B-mode ultrasound findings were evaluated before and after 6 months of treatment. The enumeration data were analysed by chi-square test, the indices before and after treatment were compared by t-test. ResultsAfter 6 months of treatment, the treatment group had a significantly decreased clinical symptom score (t=21.07, P=0.0000, significantly decreased blood levels of TC ((6.80±1.20 vs (5.24±0.67 mmol/L, t=8.87, P=0000, LDL-C ((4.38±0.75 vs (3.45±0.68 mmol/L, t=7.17, P=0.0000, TG ((2.14±0.56 vs (1.69±0.34 mmol/L, t=5.36, P=0.0000, ALT ((61±11 vs (46±9 U/L, t=8.24, P=0.0000, and AST ((53±14 vs (41±12 U/L, t=5.08, P=0.0000, and increased blood HDL-C level (t=1.95, P>0.05, but there was no significant change in BMI (t=1.84, P=0.0683. No significant changes in these indices were found in the control group (P>0.05. Both groups showed changes in liver density as measured by B-mode ultrasound, but there was no significant difference between them (P>0.05. No adverse events occurred in either group. ConclusionAtorvastatin can markedly relieve clinical symptoms and lower

  12. Prevalence of Schistosoma mansoni infection and the therapeutic efficacy of praziquantel among school children in Manna District, Jimma Zone, southwest Ethiopia

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    Mitiku Bajiro

    2016-10-01

    Full Text Available Abstract Background Intestinal schistosomiasis is one of the neglected tropical parasitic diseases caused by Schistosoma mansoni. Currently, the control measures for the disease are mainly based on mass drug administration (MDA with praziquantel (PZQ targeting the school-age children. In Ethiopia, the potential foci for schistosomiasis and therapeutic efficacy of PZQ among school-age children remain poorly explored. Therefore, we determined both the prevalence and intensity of S. mansoni infection and the therapeutic efficacy of PZQ among school children in the Manna District (new foci for S. mansoni, Jimma Zone, southwest Ethiopia. Methods A cross-sectional study was conducted among the school children aged between 6 and 18 years in three primary schools in Manna district from March to April 2014. For diagnosis of S. mansoni, a single stool sample was obtained from each child and processed using single Kato Katz and examined under light microscopy. A questionnaire was used to collect demographic information of the school children participated in the study. School children excreting eggs of S. mansoni were administered with 40 mg/kg of PZQ and re-examined after three weeks post-treatment. The therapeutic efficacy of PZQ against S. mansoni was evaluated by means of cure rate and egg reduction rate. Results The overall prevalence of S. mansoni among the school children in the three primary schools in Manna District was 24.0 %. Higher prevalence was recorded for males 25.6 % (61/238 than for females 22.5 % (59/262. Majority (27.5 % of infection intensity was light with mean faecal egg count (FEC of 202 eggs per gram (EPG. The therapeutic efficacy of PZQ at a dose of 40 mg/kg was highly efficient (cure rate of 99.1 % and egg reduction rate of 99.9 % among the school children in the three primary schools in Manna District. Conclusions The school children in the three primary schools of Manna District, Jimma Zone were at moderate risk of the

  13. Enhancing adult therapeutic interpersonal relationships in the acute health care setting: an integrative review

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    Kornhaber R

    2016-10-01

    Full Text Available Rachel Kornhaber,1 Kenneth Walsh,1,2 Jed Duff,1,3 Kim Walker1,3 1School of Health Sciences, Faculty of Health, University of Tasmania, Alexandria, NSW, 2Tasmanian Health Services – Southern Region, Hobart, TAS, 3St Vincent’s Private Hospital, Sydney, NSW, Australia Abstract: Therapeutic interpersonal relationships are the primary component of all health care interactions that facilitate the development of positive clinician–patient experiences. Therapeutic interpersonal relationships have the capacity to transform and enrich the patients’ experiences. Consequently, with an increasing necessity to focus on patient-centered care, it is imperative for health care professionals to therapeutically engage with patients to improve health-related outcomes. Studies were identified through an electronic search, using the PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases of peer-reviewed research, limited to the English language with search terms developed to reflect therapeutic interpersonal relationships between health care professionals and patients in the acute care setting. This study found that therapeutic listening, responding to patient emotions and unmet needs, and patient centeredness were key characteristics of strategies for improving therapeutic interpersonal relationships. Keywords: health, acute care, therapeutic interpersonal relationships, relational care integrative review 

  14. Enhancing the hermeneutic single-case efficacy design: Bridging the research-practice gap.

    Science.gov (United States)

    Wall, Jessie M; Kwee, Janelle L; Hu, Monica; McDonald, Marvin J

    2017-09-01

    Systematic case study designs are emerging as alternative paradigm strategies for psychotherapy and social science research. Through enhanced sensitivity to context, these designs examine idiographic profiles of causal processes. We specifically advocate the use of the hermeneutic single-case efficacy design (HSCED). HSCED has recently been used to investigate the efficacy of an existing therapy with a new population (Observed and Experiential Integration for athlete performance barriers) and an emerging therapy (Lifespan Integration Therapy). We describe innovations in HSCED that were implemented for these studies. These developments include (a) integrating psychotherapists as case developers, (b) incorporating multiple cases in one investigation, and (c) tailoring the repertoire of assessment tools. These extensions strategically incorporated principles of contextual paradigms in HSCED, thus complementing single-case designs that neglect idiographic contexts. We discuss recommendations for using HSCED in practice-based research, highlighting its potential as a bridge to address the research-practice gap.

  15. Targeting estrogen/estrogen receptor alpha enhances Bacillus Calmette-Guérin efficacy in bladder cancer.

    Science.gov (United States)

    Shang, Zhiqun; Li, Yanjun; Hsu, Iawen; Zhang, Minghao; Tian, Jing; Wen, Simeng; Han, Ruifa; Messing, Edward M; Chang, Chawnshang; Niu, Yuanjie; Yeh, Shuyuan

    2016-05-10

    Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette-Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.

  16. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease.

    Science.gov (United States)

    Larson, Janet L; Covey, Margaret K; Kapella, Mary C; Alex, Charles G; McAuley, Edward

    2014-01-01

    People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. IN THIS RANDOMIZED CONTROLLED TRIAL, SUBJECTS WERE ASSIGNED TO: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR), health education with upper body resistance training (ED-UBR), or health education with gentle chair exercises (ED-Chair). Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Differences were observed in light physical activity (LPA) after 4 months of training, time by group interaction effect (P=0.045). The SE-UBR group increased time spent in LPA by +20.68±29.30 minutes/day and the other groups decreased time spent in LPA by -22.43±47.88 minutes/day and -25.73±51.76 minutes/day. Changes in LPA were not sustained at 12-month follow-up. There were no significant changes in moderate-to-vigorous physical activity, sedentary time, or functional performance. Subjects spent most of their waking hours sedentary: 72%±9% for SE-UBR, 68%±10% for ED-UBR, and 74%±9% for ED-Chair. The self-efficacy enhancing intervention produced a modest short-term increase in LPA. Further work is needed to increase the magnitude and duration of effect, possibly by targeting LPA.

  17. Enhancing Cross-Cultural Training Efficacy on Expatriate Adjustment through Emotional Intelligence and Social Capital

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    Ely Susanto

    2012-05-01

    Full Text Available Cross cultural training is widely believed to make a positive contribution to expatriate adjustment. In practice, however, it is very costly and sometimes ineffective for expatriates. Therefore, there is a growing importance placed on increasing the cost effectiveness or enhancing the efficacy of crosscultural training by functioning individual expatriate’s social capital and emotional intelligence as moderating variables towards expatriate’s adjustment and performance. To do so we blend ideas drawn from social capital theory and emotional intelligence to develop the structure that underlies the logic of this paper. Thus, this paper uses social capital and emotional intelligence theories to enrich extant literature on expatriate adjustment

  18. Mannosylated thiolated polyethylenimine nanoparticles for the enhanced efficacy of antimonial drug against Leishmaniasis.

    Science.gov (United States)

    Sarwar, Hafiz S; Ashraf, Sehreen; Akhtar, Sohail; Sohail, Muhammad F; Hussain, Syed Z; Rafay, Muhammad; Yasinzai, Masoom; Hussain, Irshad; Shahnaz, Gul

    2018-01-01

    Our aim was to inhibit trypanothione reductase (TR) and P-gp efflux pump of Leishmania by the use of thiolated polymers. Thus, increasing the intracellular accumulation and therapeutic effectiveness of antimonial compounds. Mannosylated thiolated chitosan and mannosylated thiolated chitosan-polyethyleneimine graft were synthesized and characterized. Meglumine antimoniate-loaded nanoparticles were prepared and evaluated for TR and P-gp efflux pump inhibition, biocompatibility, macrophage uptake and antileishmanial potential. Thiomers inhibited TR with Ki 2.021. The macrophage uptake was 33.7- and 18.9-fold higher with mannosylated thiolated chitosan-polyethyleneimine graft and mannosylated thiolated chitosan nanoparticles, respectively, as compared with the glucantime. Moreover, the in vitro antileishmanial activity showed 14.41- and 7.4-fold improved IC 50 for M-TCS-g-PEI and M-TCS, respectively as compared with glucantime. These results encouraged the concept that TR and P-gp inhibition by the use of thiomers improves the therapeutic efficacy of antimonial drugs.

  19. Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection

    Science.gov (United States)

    Niska, Jared A.; Shahbazian, Jonathan H.; Ramos, Romela Irene; Francis, Kevin P.; Bernthal, Nicholas M.

    2013-01-01

    Treatment of prosthetic joint infections often involves a two-stage exchange, with implant removal and antibiotic spacer placement followed by systemic antibiotic therapy and delayed reimplantation. However, if antibiotic therapy can be improved, one-stage exchange or implant retention may be more feasible, thereby decreasing morbidity and preserving function. In this study, a mouse model of prosthetic joint infection was used in which Staphylococcus aureus was inoculated into a knee joint containing a surgically placed metallic implant extending from the femur. This model was used to evaluate whether combination therapy of vancomycin plus rifampin has increased efficacy compared with vancomycin alone against these infections. On postoperative day 7, vancomycin with or without rifampin was administered for 6 weeks with implant retention. In vivo bioluminescence imaging, ex vivo CFU enumeration, X-ray imaging, and histologic analysis were carried out. We found that there was a marked therapeutic benefit when vancomycin was combined with rifampin compared with vancomycin alone. Taken together, our results suggest that the mouse model used could serve as a valuable in vivo preclinical model system to evaluate and compare efficacies of antibiotics and combinatory therapy for prosthetic joint infections before more extensive studies are carried out in human subjects. PMID:23917317

  20. Therapeutic efficacy of ranitidine bismuth citrate with clarithromycin for seven days in the eradication of Helicobacter pylori in Brazilian peptic ulcer patients

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    Jaime Natan Eisig

    Full Text Available CONTEXT: The curative treatment of peptic ulcer is made available nowadays through the eradication of the bacterium Helicobacter pylori, which is associated with it, but the best therapeutic regimen is yet to be determined. OBJECTIVE: To assess the efficacy of a therapeutic regimen with 400 mg ranitidine bismuth citrate associated with 500 mg clarithromycin given twice a day for seven days in a cohort of Brazilian patients with peptic ulcer. TYPE OF STUDY: Cross-sectional study. SETTING: Tertiary-care hospital. PATIENTS: One hundred and twenty nine outpatients, with active or healed peptic ulcers infected by Helicobacter pylori, diagnosed via endoscopy with confirmation via the urease test and histological examination, who had never undergone a regimen for the eradication of the bacterium. PROCEDURE: Administration of 400 mg ranitidine-bismuth and 500 mg clarithromycin twice a day, for seven days. MAIN MEASUREMENTS: Efficacy of the treatment, with a check on the cure done via another endoscopy eight weeks after drug administration. The eradication of the bacterium was determined via the urease test and histological examination. Patients who were negative for both were considered to be cured. RESULTS: Eight patients failed to complete the study. The eradication rate according to intention to treat was 81% (104/129 and per protocol was 86% (104/121. CONCLUSION: The bismuth ranitidine compound associated with clarithromycin used for one week was shown to be a simple, effective and well-tolerated therapeutic regimen for the eradication of Helicobacter pylori.

  1. HIV enhancing activity of semen impairs the antiviral efficacy of microbicides

    Science.gov (United States)

    Zirafi, Onofrio; Kim, Kyeong-Ae; Roan, Nadia R.; Kluge, Silvia F.; Müller, Janis A.; Jiang, Shibo; Mayer, Benjamin; Greene, Warner C.; Kirchhoff, Frank; Münch, Jan

    2015-01-01

    Topically applied microbicides potently inhibit HIV in vitro but have largely failed to exert protective effects in clinical trials. One possible reason for this discrepancy is that the preclinical testing of microbicides does not faithfully reflect the conditions of HIV sexual transmission. Here, we report that candidate microbicides that target HIV components show greatly reduced antiviral efficacy in the presence of semen, the main vector for HIV transmission. This diminished antiviral activity was dependent on the ability of amyloid fibrils in semen to enhance the infectivity of HIV. Thus, the anti-HIV efficacy of microbicides determined in the absence of semen greatly underestimated the drug concentrations needed to block semen-exposed virus. One notable exception was Maraviroc. This HIV entry inhibitor targets the host cell CCR5 coreceptor and was highly active against both untreated and semen-exposed HIV. These data help explain why microbicides have failed to protect against HIV in clinical trials and suggest that antiviral compounds targeting host factors hold promise for further development. These findings also suggest that the in vitro efficacy of candidate microbicides should be determined in the presence of semen to identify the best candidates for the prevention of HIV sexual transmission. PMID:25391483

  2. Enhancement of cell-based therapeutic angiogenesis using a novel type of injectable scaffolds of hydroxyapatite-polymer nanocomposite microspheres.

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    Yohei Mima

    Full Text Available BACKGROUND: Clinical trials demonstrate the effectiveness of cell-based therapeutic angiogenesis in patients with severe ischemic diseases; however, their success remains limited. Maintaining transplanted cells in place are expected to augment the cell-based therapeutic angiogenesis. We have reported that nano-hydroxyapatite (HAp coating on medical devices shows marked cell adhesiveness. Using this nanotechnology, HAp-coated poly(l-lactic acid (PLLA microspheres, named nano-scaffold (NS, were generated as a non-biological, biodegradable and injectable cell scaffold. We investigate the effectiveness of NS on cell-based therapeutic angiogenesis. METHODS AND RESULTS: Bone marrow mononuclear cells (BMNC and NS or control PLLA microspheres (LA were intramuscularly co-implanted into mice ischemic hindlimbs. When BMNC derived from enhanced green fluorescent protein (EGFP-transgenic mice were injected into ischemic muscle, the muscle GFP level in NS+BMNC group was approximate fivefold higher than that in BMNC or LA+BMNC groups seven days after operation. Kaplan-Meier analysis demonstrated that NS+BMNC markedly prevented hindlimb necrosis (P<0.05 vs. BMNC or LA+BMNC. NS+BMNC revealed much higher induction of angiogenesis in ischemic tissues and collateral blood flow confirmed by three-dimensional computed tomography angiography than those of BMNC or LA+BMNC groups. NS-enhanced therapeutic angiogenesis and arteriogenesis showed good correlations with increased intramuscular levels of vascular endothelial growth factor and fibroblast growth factor-2. NS co-implantation also prevented apoptotic cell death of transplanted cells, resulting in prolonged cell retention. CONCLUSION: A novel and feasible injectable cell scaffold potentiates cell-based therapeutic angiogenesis, which could be extremely useful for the treatment of severe ischemic disorders.

  3. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  4. Methotrexate loaded polyether-copolyester dendrimers for the treatment of gliomas: enhanced efficacy and intratumoral transport capability.

    Science.gov (United States)

    Dhanikula, Renu Singh; Argaw, Anteneh; Bouchard, Jean-Francois; Hildgen, Patrice

    2008-01-01

    Therapeutic benefit in glial tumors is often limited due to low permeability of delivery systems across the blood-brain barrier (BBB), drug resistance, and poor penetration into the tumor tissue. In an attempt to overcome these hurdles, polyether-copolyester (PEPE) dendrimers were evaluated as drug carriers for the treatment of gliomas. Dendrimers were conjugated to d-glucosamine as the ligand for enhancing BBB permeability and tumor targeting. The efficacy of methotrexate (MTX)-loaded dendrimers was established against U87 MG and U 343 MGa cells. Permeability of rhodamine-labeled dendrimers and MTX-loaded dendrimers across the in vitro BBB model and their distribution into avascular human glioma tumor spheroids was also studied. Glucosylated dendrimers were found to be endocytosed in significantly higher amounts than nonglucosylated dendrimers by both the cell lines. IC 50 of MTX after loading in dendrimers was lower than that of the free MTX, suggesting that loading MTX in PEPE dendrimers increased its potency. Similar higher activity of MTX-loaded glucosylated and nonglucosylated dendrimers was found in the reduction of tumor spheroid size. These MTX-loaded dendrimers were able to kill even MTX-resistant cells highlighting their ability to overcome MTX resistance. In addition, the amount of MTX-transported across BBB was three to five times more after loading in the dendrimers. Glucosylation further increased the cumulative permeation of dendrimers across BBB and hence increased the amount of MTX available across it. Glucosylated dendrimers distributed through out the avascular tumor spheroids within 6 h, while nonglucosylated dendrimers could do so in 12 h. The results show that glucosamine can be used as an effective ligand not only for targeting glial tumors but also for enhanced permeability across BBB. Thus, glucosylated PEPE dendrimers can serve as potential delivery system for the treatment of gliomas.

  5. Quantum dots as enhancers of the efficacy of bacterial lethal photosensitization

    International Nuclear Information System (INIS)

    Narband, N; Parkin, I P; Mubarak, M; Nair, S P; Wilson, M; Ready, D; Green, M A; Beeby, A

    2008-01-01

    Because of the increasing resistance of bacteria to antibiotics there is considerable interest in light-activated antimicrobial agents (LAAAs) as alternatives to antibiotics for treating localized infections. The purpose of this study was to determine whether CdSe/ZnS quantum dots (QD) could enhance the antibacterial activity of the LAAA, toluidine blue O (TBO). Suspensions of Staphylococcus aureus and Streptococcus pyogenes were exposed to white light (3600 lux) and TBO (absorbance maximum = 630 nm) in the presence and absence of 25 nm diameter QD (emission maximum = 627 nm). When the TBO:QD ratio was 2667:1, killing of Staph. aureus was enhanced by 1.72log 10 units. In the case of Strep. pyogenes, an enhanced kill of 1.55log 10 units was achieved using TBO and QD in the ratio 267:1. Singlet oxygen and fluorescence measurements showed that QD suppress the formation of singlet oxygen from TBO and that QD fluorescence is significantly quenched in the presence of TBO (70-90%). Enhanced killing appears to be attributable to a non-Foerster resonance energy transfer mechanism, whereby the QD converts part of the incident light to the absorption maximum for TBO; hence more light energy is harvested, resulting in increased concentrations of bactericidal radicals. QD may, therefore, be useful in improving the efficacy of antimicrobial photodynamic therapy.

  6. TH-302 in Combination with Radiotherapy Enhances the Therapeutic Outcome and Is Associated with Pretreatment [18F]HX4 Hypoxia PET Imaging.

    Science.gov (United States)

    Peeters, Sarah G J A; Zegers, Catharina M L; Biemans, Rianne; Lieuwes, Natasja G; van Stiphout, Ruud G P M; Yaromina, Ala; Sun, Jessica D; Hart, Charles P; Windhorst, Albert D; van Elmpt, Wouter; Dubois, Ludwig J; Lambin, Philippe

    2015-07-01

    Conventional anticancer treatments are often impaired by the presence of hypoxia. TH-302 selectively targets hypoxic tumor regions, where it is converted into a cytotoxic agent. This study assessed the efficacy of the combination treatment of TH-302 and radiotherapy in two preclinical tumor models. The effect of oxygen modification on the combination treatment was evaluated and the effect of TH-302 on the hypoxic fraction (HF) was monitored using [(18)F]HX4-PET imaging and pimonidazole IHC stainings. Rhabdomyosarcoma R1 and H460 NSCLC tumor-bearing animals were treated with TH-302 and radiotherapy (8 Gy, single dose). The tumor oxygenation status was altered by exposing animals to carbogen (95% oxygen) and nicotinamide, 21% or 7% oxygen breathing during the course of the treatment. Tumor growth and treatment toxicity were monitored until the tumor reached four times its start volume (T4×SV). Both tumor models showed a growth delay after TH-302 treatment, which further increased when combined with radiotherapy (enhancement ratio rhabdomyosarcoma 1.23; H460 1.49). TH-302 decreases the HF in both models, consistent with its hypoxia-targeting mechanism of action. Treatment efficacy was dependent on tumor oxygenation; increasing the tumor oxygen status abolished the effect of TH-302, whereas enhancing the HF enlarged TH-302's therapeutic effect. An association was observed in rhabdomyosarcoma tumors between the pretreatment HF as measured by [(18)F]HX4-PET imaging and the T4×SV. The combination of TH-302 and radiotherapy is promising and warrants clinical testing, preferably guided by the companion biomarker [(18)F]HX4 hypoxia PET imaging for patient selection. ©2015 American Association for Cancer Research.

  7. 78 FR 77471 - Prospective Grant of Exclusive License for: Convection Enhanced Delivery of a Therapeutic Agent...

    Science.gov (United States)

    2013-12-23

    ...; nationalized), U.S. Patent Application 7,371,225, European Patent Application 03756863.1, Australian Patent 2003299140, to Medicenna Therapeutics, Inc. having a principle place of business in 1075 West Georgia St... date of this published notice, NIH receives written evidence and argument that establishes that the...

  8. Therapeutic efficacy and toxicity of a single and double application of boron neutron capture therapy (BNCT) in a hamster cheek pouch oral precancer model

    International Nuclear Information System (INIS)

    Monti Hughes, A; Pozzi, E C C; Thorp, S; Garabalino, M A; Farias, R O; Gonzalez, S J; Heber, E M; Itoiz, M E; Aromando, R F; Molinari, A J; Miller, M; Nigg, D W; Curotto, P; Trivillin, V A; Schwint, A E

    2012-01-01

    Tumor development from tissue with potentially malignant disorders (PMD) gives rise to second primary tumors. We previously demonstrated the partial inhibitory effect on tumor development of Boron Neutron Capture Therapy (BNCT) mediated by the boron compounds BPA (boronophenylalanine) and decahydrodecaborate (GB-10) in a hamster pouch oral precancer model. Seeking to optimize BNCT, the aim of the present study was to contribute to the knowledge of BNCT radiobiology for oral precancer and assess new BNCT protocols in terms of inhibition of tumor development and radiotoxicity. Groups of cancerized hamsters were locally exposed to single or double applications (2 weeks apart) of BPA-BNCT or (GB-10 + BPA)-BNCT at a total dose of 8Gy to tissue with PMD; to a single application of BPA-BNCT at 6Gy and to a double application (4 weeks apart) of BPA-BNCT or (BPA + GB-10)-BNCT at a total dose of 10Gy. Cancerized, sham-irradiated hamsters served as controls. Clinical status, tumor development from tissue with PMD and mucositis were followed for 8 months. The marked therapeutic efficacy of single applications of BNCT at 6 and 8Gy were associated to severe radiotoxicity. Dose fractionation into 2 applications reduced mucositis but also reduced therapeutic efficacy, depending on dose and interval between applications. A double application (4 weeks apart) of (GB-10 + BPA)-BNCT at a total dose of 10Gy rendered the best therapeutic advantage, i.e. 63% - 100% inhibition of tumor development with only slight mucositis in 67% of cases. The data reported herein show that issues such as dose levels and dose fractionation, interval between applications, and choice of boron compounds are pivotal to therapeutic advantage and must be tailored for a particular pathology and anatomic site. The present study determined treatment conditions that would contribute to optimize BNCT for precancer and that would warrant cautious assessment in a clinical scenario (author)

  9. Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model.

    Directory of Open Access Journals (Sweden)

    Yuya Yoshimoto

    Full Text Available PURPOSE: There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL activity. METHODS AND MATERIALS: C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD was defined as the time (in days for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. RESULTS: In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days and prolonged median survival time (MST to 59 days (versus 28 days in the non-irradiated group. CD8(+ cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days. Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days, while anti-FR4 and anti-GITR antibodies did not affect efficacy. CONCLUSIONS: Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4

  10. Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model

    Science.gov (United States)

    Yoshimoto, Yuya; Suzuki, Yoshiyuki; Mimura, Kousaku; Ando, Ken; Oike, Takahiro; Sato, Hiro; Okonogi, Noriyuki; Maruyama, Takanori; Izawa, Shinichiro; Noda, Shin-ei; Fujii, Hideki; Kono, Koji; Nakano, Takashi

    2014-01-01

    Purpose There is growing evidence that tumor-specific immune responses play an important role in anti-cancer therapy, including radiotherapy. Using mouse tumor models we demonstrate that irradiation-induced anti-tumor immunity is essential for the therapeutic efficacy of irradiation and can be augmented by modulation of cytotoxic T lymphocyte (CTL) activity. Methods and Materials C57BL/6 mice, syngeneic EL4 lymphoma cells, and Lewis lung carcinoma (LL/C) cells were used. Cells were injected into the right femurs of mice. Ten days after inoculation, tumors were treated with 30 Gy of local X-ray irradiation and their growth was subsequently measured. The effect of irradiation on tumor growth delay (TGD) was defined as the time (in days) for tumors to grow to 500 mm3 in the treated group minus that of the untreated group. Cytokine production and serum antibodies were measured by ELISA and flow cytometry. Results In the EL4 tumor model, tumors were locally controlled by X-ray irradiation and re-introduced EL4 cells were completely rejected. Mouse EL4-specific systemic immunity was confirmed by splenocyte cytokine production and detection of tumor-specific IgG1 antibodies. In the LL/C tumor model, X-ray irradiation also significantly delayed tumor growth (TGD: 15.4 days) and prolonged median survival time (MST) to 59 days (versus 28 days in the non-irradiated group). CD8(+) cell depletion using an anti-CD8 antibody significantly decreased the therapeutic efficacy of irradiation (TGD, 8.7 days; MST, 49 days). Next, we examined whether T cell modulation affected the efficacy of radiotherapy. An anti-CTLA-4 antibody significantly increased the anti-tumor activity of radiotherapy (TGD was prolonged from 13.1 to 19.5 days), while anti-FR4 and anti-GITR antibodies did not affect efficacy. Conclusions Our results indicate that tumor-specific immune responses play an important role in the therapeutic efficacy of irradiation. Immunomodulation, including CTLA-4 blockade, may be a

  11. Chloroquine enhances the efficacy of cisplatin by suppressing autophagy in human adrenocortical carcinoma treatment

    Directory of Open Access Journals (Sweden)

    Qin L

    2016-03-01

    Full Text Available Liang Qin,1,* Tianyuan Xu,1,* Leilei Xia,1 Xianjin Wang,1 Xiang Zhang,1 Xiaohua Zhang,1 Zhaowei Zhu,1 Shan Zhong,1 Chuandong Wang,2 Zhoujun Shen1 1Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: It has been demonstrated that chloroquine (CQ enhances the efficacy of chemotherapy. However, little is known about whether CQ could enhance the efficacy of cisplatin (DDP in the treatment of adrenocortical carcinoma (ACC. In this study, we explore the efficacy and mechanism by which CQ affects DDP sensitivity in human ACC in vitro and in vivo.Methods: The autophagic gene Beclin-1 expression was detected by immunohistochemistry, and the protein levels were analyzed using immunoblotting assays of ACC tissues and normal adrenal cortex tissues. The ACC SW13 cells were treated with DDP and/or CQ. The cell viability assay was performed using the MTT method. Qualitative autophagy detection was performed by monodansylcadaverine staining of autophagic vacuoles. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to count cell apoptosis by flow cytometry. The autophagy-related protein (Beclin-1, LC3, and p62 and apoptosis relative protein (Bax and Bcl-2 levels were evaluated with Western blot analysis. Furthermore, a murine model of nude BALB/c mice bearing SW13 cell xenografts was established to evaluate the efficacy of concomitant therapy.Results: The expression of the autophagic gene Beclin-1 was significantly downregulated in ACC tissues compared to normal adrenal cortex tissues. The Beclin-1 protein level in ACC tissues was lower than that in normal adrenal cortex tissues (P<0.05. In vitro concomitant therapy (DDP and CQ was more

  12. Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

    Directory of Open Access Journals (Sweden)

    Sun DQ

    2014-07-01

    Full Text Available Deqing Sun,1,2 Xinbing Wei,1 Xia Xue,2 Zengjun Fang,3 Manru Ren,1 Haiyan Lou,1 Xiumei Zhang11Department of Pharmacology, School of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Pharmacy, 3Department of Clinical Pharmacology, Second Hospital of Shandong University, Jinan, People’s Republic of ChinaBackground: Acetylpuerarin (AP, because of its lower water solubility, shows poor absorption that hinders its therapeutic application. Thus, the aim of this study was to prepare nanoemulsions for AP, enhance its oral bioavailability, and thus improve the therapeutic effect.Methods: The nanoemulsions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS were prepared by high-pressure homogenization and characterized in terms of particle size, drug loading, morphology, and in vitro drug release. A lipid digestion model was used to predict in vivo drug solubilization in the gastrointestinal environment. The pharmacokinetics of AP formulations were performed in rats; meanwhile, a chylomicron flow-blocking rat model was used to evaluate the lymphatic drug transport. Moreover, the therapeutic effects of AP nanoemulsions on the model of focal cerebral ischemia-reperfusion for brain injury were also assessed.Results: The nanoemulsions with a droplet size of 150 nm were well stabilized by TPGS and showed a high loading capacity for AP. In the digestion model, the distribution of AP in aqueous phase/pellet phase was about 90%/10% for nanoemulsions and 5%/95% for oil solution, indicating that the drug encapsulated in nanoemulsions would present in solubilized form after transportation into the gastrointestinal tract, whereas drug precipitation would occur as the oil solution was orally administered. The area under the curve value of AP nanoemulsions was 5.76±0.56 µg·hour·mL-1, or was about 2.6 and 1.7 times as great as that of suspension and oil solution, respectively, indicating enhanced drug

  13. Therapeutic response assessment of percutaneous radiofrequency ablation for hepatocellular carcinoma: Utility of contrast-enhanced agent detection imaging

    International Nuclear Information System (INIS)

    Kim, Chan Kyo; Choi, Dongil; Lim, Hyo K.; Kim, Seung Hoon; Lee, Won Jae; Kim, Min Ju; Lee, Ji Yeon; Jeon, Yong Hwan; Lee, Jongmee; Lee, Soon Jin; Lim, Jae Hoon

    2005-01-01

    Purpose: To assess the utility of contrast-enhanced agent detection imaging (ADI) in the assessment of the therapeutic response to percutaneous radiofrequency (RF) ablation in patients with hepatocellular carcinoma (HCC). Materials and methods: Ninety patients with a total of 97 nodular HCCs (mean, 2.1 ± 1.3 cm; range, 1.0-5.0 cm) treated with percutaneous RF ablation under the ultrasound guidance were evaluated with contrast-enhanced ADI after receiving an intravenous bolus injection of a microbubble contrast agent (SH U 508A). We obtained serial contrast-enhanced ADI images during the time period from 15 to 90 s after the initiation of the bolus contrast injection. All of the patients underwent a follow-up four-phase helical CT at 1 month after RF ablation, which was then repeated at 2-4 month intervals during a period of at least 12 months. The results of the contrast-enhanced ADI were compared with those of the follow-up CT in terms of the presence or absence of residual unablated tumor and local tumor progression in the treated lesions. Results: On contrast-enhanced ADI, technical success was obtained in 94 (97%) of the 97 HCCs, while residual unablated tumors were found in three HCCs (3%). Two of the three tumors that were suspicious (was not proven) for incomplete ablation were subjected to additional RF ablation. The remaining one enhancing lesion that was suspicious of a residual tumor on contrast-enhanced ADI was revealed to be reactive hyperemia at the 1-month follow-up CT. Therefore; the diagnostic concordance between the contrast-enhanced ADI and 1-month follow-up CT was 99%. Of the 94 ablated HCCs without residual tumors on both the contrast-enhanced ADI and 1-month follow-up CT after the initial RF ablation, five (5%) had CT findings of local tumor progression at a subsequent follow-up CT. Conclusion: Despite its limitations in predicting local tumor progression in the treated tumors, contrast-enhanced ADI is potentially useful for evaluating the

  14. Male emotional intimacy: how therapeutic men's groups can enhance couples therapy.

    Science.gov (United States)

    Garfield, Robert

    2010-03-01

    Men's difficulty with emotional intimacy is a problem that therapists regularly encounter in working with heterosexual couples in therapy. The first part of this article describes historical and cultural factors that contribute to this dilemma in men's marriages and same-sex friendships. Therapeutic men's groups can provide a corrective experience for men, helping them to develop emotional intimacy skills while augmenting their work in couples therapy. A model for such groups is presented, including guidelines for referral, screening, and collaboration with other therapists. Our therapeutic approach encourages relationship-based learning through direct emotional expression and supportive feedback. We emphasize the development of friendship skills, core attributes of friendship (connection, communication, commitment, and cooperation) that contribute to emotional intimacy in men's relationships. Case examples are included to illustrate how this model works in clinical practice, as well as specific suggestions for further study that could lead to a more evidence-based practice.

  15. Preliminary comparison of the therapeutic efficacy of accelerated relative to conventional fractionation radiotherapy by treatment of spontaneous canine malignancies

    International Nuclear Information System (INIS)

    Denman, David L.; Levin, Rebecca; Buncher, C. Ralph; Aron, Bernard S.

    1996-01-01

    Purpose/Objective: This study's ultimate goals involve development of an accelerated fractionation (AF) regimen with an integrated final concomitant boost (CB) and examination of factors prognostic of the CB's therapeutic efficacy which could be measured during the initial AF portion to determine for which patients CB should be used. These endpoints can be accurately determined quickly by evaluating the treatment (tx) of spontaneous canine veterinary patient tumors. Because surviving tumor clonogen growth rate increases after radiotherapy (RT) begins, this accelerated repopulation (AR) should be reduced by AF. Furthermore, CB using a small field encompassing only the tumor bed, given as a second daily tx during the last week of RT, should further reduce AR. The initial portion of this project which is nearing completion was designed to determine if incidentally treated normal tissues could tolerate the AF regimen and project whether addition of the tumor bed CB would also be tolerated. Materials and Methods: Currently 20 canine patients with biopsy proven localized tumors have received canine AF radiotherapy given as 3.2Gy/fraction(fx) administered 5 days a week (Mon-Fri) to a total of 15 fxs (48Gy) within 18 elapsed days. RT is given with a 60 Co teletherapy unit. Their tumor response, control, survival, and acute normal tissue responses are being directly compared to results we previously obtained from canines receiving a nearly equivalent dose/fx and total dose conventional fractionation (CF) regimen which was given alone or with adjuvant hyperthermia (HT). In that study the canines were stratified by tumor histology and anatomic site and randomly assigned to receive canine CF (3.5Gy/fx, 3 fxs/week [Mon-Wed-Fri] to 14 fxs (49Gy) in an elapsed time of approx. 30 days) either alone or followed weekly by local HT (44 deg. +/- 2 deg. C) for 30 minutes (5 HT fxs). As is currently done, these CF+/-HT patients were followed up to 3 years to quantitate the magnitudes

  16. Natural Product-Derived Treatments for Attention-Deficit/Hyperactivity Disorder: Safety, Efficacy, and Therapeutic Potential of Combination Therapy

    Science.gov (United States)

    Ahn, James; Ahn, Hyung Seok; Cheong, Jae Hoon; dela Peña, Ike

    2016-01-01

    Typical treatment plans for attention-deficit/hyperactivity disorder (ADHD) utilize nonpharmacological (behavioral/psychosocial) and/or pharmacological interventions. Limited accessibility to behavioral therapies and concerns over adverse effects of pharmacological treatments prompted research for alternative ADHD therapies such as natural product-derived treatments and nutritional supplements. In this study, we reviewed the herbal preparations and nutritional supplements evaluated in clinical studies as potential ADHD treatments and discussed their performance with regard to safety and efficacy in clinical trials. We also discussed some evidence suggesting that adjunct treatment of these agents (with another botanical agent or pharmacological ADHD treatments) may be a promising approach to treat ADHD. The analysis indicated mixed findings with regard to efficacy of natural product-derived ADHD interventions. Nevertheless, these treatments were considered as a “safer” approach than conventional ADHD medications. More comprehensive and appropriately controlled clinical studies are required to fully ascertain efficacy and safety of natural product-derived ADHD treatments. Studies that replicate encouraging findings on the efficacy of combining botanical agents and nutritional supplements with other natural product-derived therapies and widely used ADHD medications are also warranted. In conclusion, the risk-benefit balance of natural product-derived ADHD treatments should be carefully monitored when used as standalone treatment or when combined with other conventional ADHD treatments. PMID:26966583

  17. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity

    International Nuclear Information System (INIS)

    Mullins, Dana; Proulx, Denise; Saoudi, A.; Ng, Cheng E.

    2005-01-01

    Purpose: Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. Methods: We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 AM or 3 HALO [hours after light onset]), late rest period (3 PM or 9 HALO), early active period (9 PM or 15 HALO), and late active period (3 AM or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Results: Treatment with either TPT or XR at 3 AM demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 PM, in particular, showed increased toxicity without any enhanced efficacy. Conclusions: Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial

  18. Chronomodulation of topotecan or X-radiation treatment increases treatment efficacy without enhancing acute toxicity.

    Science.gov (United States)

    Mullins, Dana; Proulx, Denise; Saoudi, A; Ng, Cheng E

    2005-05-01

    Topotecan (TPT), a camptothecin analog, is currently used to treat human ovarian and small-cell lung cancer and is in clinical trials for other tumor sites. However, it is unknown whether chronomodulation of TPT treatment is beneficial. We examined the effects of administering TPT or X-radiation (XR) alone at different times of the day or night. We treated mice bearing human colorectal tumor xenografts at four different times representing the early rest period (9 am or 3 HALO [hours after light onset]), late rest period (3 pm or 9 HALO), early active period (9 pm or 15 HALO), and late active period (3 am or 21 HALO) of the mice. We gave either TPT (12 mg/kg, injected i.p.) or XR (4 Gy, directed to the tumor) twice weekly on Days 0, 4, 7, 10 within 2 weeks. Treatment with either TPT or XR at 3 am demonstrated the greatest efficacy (measured by a tumor regrowth assay) without significantly increasing acute toxicity (assessed by a decrease in leukocyte counts or body weight). Conversely, treatment at 3 pm, in particular, showed increased toxicity without any enhanced efficacy. Our study provided the first evidence that chronomodulation of TPT treatments, consistent with the findings of other camptothecin analogs, is potentially clinically beneficial. Additionally, our findings suggest that chronomodulation of fractionated XR treatments is also potentially clinically beneficial.

  19. Enhancing the efficacy of computerized feedback interventions for college alcohol misuse: An exploratory randomized trial.

    Science.gov (United States)

    Miller, Mary Beth; Leavens, Eleanor L; Meier, Ellen; Lombardi, Nathaniel; Leffingwell, Thad R

    2016-02-01

    Personalized feedback interventions (PFIs) have been associated with decreased alcohol consumption and related problems among college students; however, the necessary and sufficient components responsible for efficacy remain unclear. The present study investigated the relative efficacy of 3 computerized PFIs with differing content, the content-specific mechanisms of change within PFIs, and the moderating roles of comparison orientation and baseline risk in intervention outcomes. College students (N = 212) reporting alcohol use in a typical week completed an assessment prior to randomization (norms PFI, enhanced PFI, choice PFI, assessment only) and 1 month postintervention. Participants who received a PFI reported greater decreases in alcohol use, peak blood alcohol concentration (BAC), related problems, and perceptions of typical students' drinking than those in the control group. Neither tendency to compare oneself with others nor baseline risk moderated outcomes. PFIs influenced weekly alcohol use indirectly through changes in descriptive normative perceptions and alcohol-related consequences indirectly through changes in peak BAC. Computerized PFIs are more effective than assessment alone in decreasing alcohol use and related problems among college students. Normative comparisons may be sufficient to elicit behavior change, and inclusion of select additional components may not yield significant improvements in outcomes. However, the consistent benefit of including feedback on physical and monetary costs of drinking and moderation strategies, although nonsignificant, may warrant the negligible increase in time and money required to provide such information electronically. Computerized PFIs seem to be an ideal first step to the prevention and treatment of college alcohol misuse. (c) 2016 APA, all rights reserved).

  20. An Analysis of a Novel, Short-Term Therapeutic Psychoeducational Program for Children and Adolescents with Chronic Neurological Illness and Their Parents; Feasibility and Efficacy.

    Science.gov (United States)

    Joo, Bonglim; Lee, Young-Mock; Kim, Heung Dong; Eom, Soyong

    2017-01-01

    The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children ( n = 8) and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale) at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

  1. Self-efficacy enhancing intervention increases light physical activity in people with chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Larson JL

    2014-10-01

    Full Text Available Janet L Larson,1,2 Margaret K Covey,2 Mary C Kapella,2 Charles G Alex,3,4 Edward McAuley,5 1Division of Acute, Critical and Long-Term Care Programs, School of Nursing, University of Michigan, Ann Arbor, MI, 2Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago, Chicago, IL, 3Division of Pulmonary and Critical Care Medicine, Edward Hines Jr VA Hospital, Hines, IL, 4Advocate Christ Medical Center, Oaklawn, IL, 5Department of Kinesiology and Community Health, College of Applied Health Sciences, University of Illinois Urbana-Champagne, Urbana, IL, USA Background: People with chronic obstructive pulmonary disease lead sedentary lives and could benefit from increasing their physical activity. The purpose of this study was to determine if an exercise-specific self-efficacy enhancing intervention could increase physical activity and functional performance when delivered in the context of 4 months of upper body resistance training with a 12-month follow-up. Methods: In this randomized controlled trial, subjects were assigned to: exercise-specific self-efficacy enhancing intervention with upper body resistance training (SE-UBR, health education with upper body resistance training (ED-UBR, or health education with gentle chair exercises (ED-Chair. Physical activity was measured with an accelerometer and functional performance was measured with the Functional Performance Inventory. Forty-nine people with moderate to severe chronic obstructive pulmonary disease completed 4 months of training and provided valid accelerometry data, and 34 also provided accelerometry data at 12 months of follow-up. The self-efficacy enhancing intervention emphasized meeting physical activity guidelines and increasing moderate-to-vigorous physical activity. Results: Differences were observed in light physical activity (LPA after 4 months of training, time by group interaction effect (P=0.045. The SE-UBR group increased time spent in

  2. Cyclooxygenase-2 inhibitor enhances the efficacy of a breast cancer vaccine: role of IDO.

    Science.gov (United States)

    Basu, Gargi D; Tinder, Teresa L; Bradley, Judy M; Tu, Tony; Hattrup, Christine L; Pockaj, Barbara A; Mukherjee, Pinku

    2006-08-15

    We report that administration of celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, in combination with a dendritic cell-based cancer vaccine significantly augments vaccine efficacy in reducing primary tumor burden, preventing metastasis, and increasing survival. This combination treatment was tested in MMTV-PyV MT mice that develop spontaneous mammary gland tumors with metastasis to the lungs and bone marrow. Improved vaccine potency was associated with an increase in tumor-specific CTLs. Enhanced CTL activity was attributed to a significant decrease in levels of tumor-associated IDO, a negative regulator of T cell activity. We present data suggesting that inhibiting COX-2 activity in vivo regulates IDO expression within the tumor microenvironment; this is further corroborated in the MDA-MB-231 human breast cancer cell line. Thus, a novel mechanism of COX-2-induced immunosuppression via regulation of IDO has emerged that may have implications in designing future cancer vaccines.

  3. Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Kenji Ikemura

    2017-12-01

    Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

  4. Local vibration enhanced the efficacy of passive exercise on mitigating bone loss in hindlimb unloading rats

    Science.gov (United States)

    Huang, Yunfei; Luan, Huiqin; Sun, Lianwen; Bi, Jingfang; Wang, Ying; Fan, Yubo

    2017-08-01

    Spaceflight induced bone loss is seriously affecting astronauts. Mechanical stimulation from exercise has been shown to restrain bone resorption as well as improve bone formation. Current exercise countermeasures in space cannot prevent it completely. Active exercise may convert to passive exercise in some ways because of the loss of gravity stimulus and inertia of exercise equipment. The aim of this study was to compare the efficacy of passive exercise or/and local vibration on counteracting the deterioration of the musculoskeletal system, including bone, muscle and tendons in tail-suspended rats. We hypothesized that local vibration could enhance the efficacy of passive exercise on countering bone loss. 40 Sprague Dawley rats were randomly distributed into five groups (n = 8, each): tail-suspension (TS), TS+35 Hz vibration (TSV), TS + passive exercise (TSP), TS + passive exercise coupled with 35 Hz vibration (TSPV) and control (CON). Passive exercise or/and local vibration was performed for 21 days. On day 0 and 21, bone mineral density (BMD) was observed by dual energy X-ray absorptiometry (DXA), and trabecular microstructure was evaluated by microcomputer tomography (μCT) analysis in vivo. Mechanical properties of tibia and tendon were determined by a mechanical testing system. Soleus and bone ash weight was tested by an electronic balance. Results showed that the passive exercise could not prevent the decrease of trabecular BMD, microstructure and bone ash weight induced by TS, whereas vibration and passive exercise coupled with local vibration (PV) could. Biomechanical properties of the tibia and tendon in TSPV group significantly increased compared with TS group. In summary, PV in this study was the best method in preventing weightlessness-induced bone loss. Consistent with our hypothesis, local vibration partly enhanced the effect of passive exercise. Furthermore, this study will be useful in improving countermeasure for astronauts, but also for the

  5. Superselective Particle Embolization Enhances Efficacy of Radiofrequency Ablation: Effects of Particle Size and Sequence of Action

    International Nuclear Information System (INIS)

    Tanaka, Toshihiro; Isfort, Peter; Braunschweig, Till; Westphal, Saskia; Woitok, Anna; Penzkofer, Tobias; Bruners, Philipp; Kichikawa, Kimihiko; Schmitz-Rode, Thomas; Mahnken, Andreas H.

    2013-01-01

    Purpose. To evaluate the effects of particle size and course of action of superselective bland transcatheter arterial embolization (TAE) on the efficacy of radiofrequency ablation (RFA). Methods. Twenty pigs were divided into five groups: group 1a, 40-μm bland TAE before RFA; group 1b, 40-μm bland TAE after RFA; group 2a, 250-μm bland TAE before RFA; group 2b, 250-μm bland TAE after RFA and group 3, RFA alone. A total of 40 treatments were performed with a combined CT and angiography system. The sizes of the treated zones were measured from contrast-enhanced CTs on days 1 and 28. Animals were humanely killed, and the treated zones were examined pathologically. Results. There were no complications during procedures and follow-up. The short-axis diameter of the ablation zone in group 1a (mean ± standard deviation, 3.19 ± 0.39 cm) was significantly larger than in group 1b (2.44 ± 0.52 cm; P = 0.021), group 2a (2.51 ± 0.32 cm; P = 0.048), group 2b (2.19 ± 0.44 cm; P = 0.02), and group 3 (1.91 ± 0.55 cm; P 3 ). At histology, 40-μm microspheres were observed to occlude smaller and more distal arteries than 250-μm microspheres. Conclusion. Bland TAE is more effective before RFA than postablation embolization. The use of very small 40-μm microspheres enhances the efficacy of RFA more than the use of larger particles.

  6. Therapeutic efficacy and microSPECT/CT imaging of {sup 188}Re-DXR-liposome in a C26 murine colon carcinoma solid tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-J.; Chang, C.-H.; Yu, C.-Y.; Chang, T.-J.; Chen, L.-C. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, M.-H. [National Health Research Institutes, Miaoli, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Ting Gann [National Health Research Institutes, Miaoli, Taiwan (China)], E-mail: gann.ting@msa.hinet.net

    2010-01-15

    Nanocarriers can selectively target cancer sites and carry payloads, thereby improving diagnostic and therapeutic effectiveness and reducing toxicity. The objective of this study was to investigate the therapeutic efficacy of a new co-delivery radiochemotherapeutics of {sup 188}Re-N,N-bis (2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA)-labeled pegylated liposomal doxorubicin (DXR) ({sup 188}Re-DXR-liposome) in a C26 murine colon carcinoma solid tumor model. To evaluate the targeting and localization of {sup 188}Re-DXR-liposome in C26 murine tumor-bearing mice, biodistribution, microSPECT/CT imaging and pharmacokinetic studies were performed. The antitumor effect of {sup 188}Re-DXR-liposome was assessed by tumor growth inhibition, survival ratio and histopathological hematoxylin-eosin staining. The tumor target and localization of the nanoliposome delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome were demonstrated in the biodistribution, pharmacokinetics and in vivo nuclear imaging studies. In the study on therapeutic efficacy, the tumor-bearing mice treated with bimodality radiochemotherapeutics of {sup 188}Re-DXR-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI=0.048; 74 days) than those treated with radiotherapeutics of {sup 188}Re-liposome (MGI=0.134; 60 days) and chemotherapeutics of Lipo-Dox (MGI=0.413; 38 days). The synergistic tumor regression effect was observed with the combination index (CI) exceeding 1 (CI=1.145) for co-delivery radiochemotherapeutics of {sup 188}Re-DXR-liposome. Two (25%) of the mice treated with radiochemotherapeutics were completely cured after 120 days. The therapeutic efficacy of radiotherapeutics of {sup 188}Re-liposome and the synergistic effect of the combination radiochemotherapeutics of {sup 188}Re-DXR-liposome have been demonstrated in a C26 murine solid tumor animal model, which pointed to the potential benefit and promise of the co-delivery of

  7. Combination therapy of potential gene to enhance oral cancer therapeutic effect

    Science.gov (United States)

    Yeh, Chia-Hsien; Hsu, Yih-Chih

    2015-03-01

    The epidermal growth factor receptor (EGFR) over-regulation related to uncontrolled cell division and promotes progression in tumor. Over-expression of human epidermal growth factor receptor (EGFR) has been detected in oral cancer cells. EGFR-targeting agents are potential therapeutic modalities for treating oral cancer based on our in vitro study. Liposome nanotechnology is used to encapsulate siRNA and were modified with target ligand to receptors on the surface of tumor cells. We used EGFR siRNA to treat oral cancer in vitro.

  8. TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice

    Science.gov (United States)

    Welford, Abigail F.; Biziato, Daniela; Coffelt, Seth B.; Nucera, Silvia; Fisher, Matthew; Pucci, Ferdinando; Di Serio, Clelia; Naldini, Luigi; De Palma, Michele; Tozer, Gillian M.; Lewis, Claire E.

    2011-01-01

    Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies. PMID:21490397

  9. Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

    Science.gov (United States)

    2014-01-01

    The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

  10. Silencing of Foxp3 enhances the antitumor efficacy of GM-CSF genetically modified tumor cell vaccine against B16 melanoma

    Directory of Open Access Journals (Sweden)

    Miguel A

    2017-01-01

    Full Text Available Antonio Miguel,1 Luis Sendra,1 Verónica Noé,2 Carles J Ciudad,2 Francisco Dasí,3,4 David Hervas,5 María José Herrero,1,6 Salvador F Aliño17 1Department of Pharmacology, Faculty of Medicine, University of Valencia, 2Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, University of Barcelona, 3Research University Hospital of Valencia, INCLIVA Health Research Institute, 4Department of Physiology, Faculty of Medicine, University of Valencia Foundation, 5Biostatistics Unit, 6Pharmacogenetics Unit, Instituto de Investigación Sanitaria La Fe (IIS La Fe, 7Clinical Pharmacology Unit, ACM Hospital Universitario y Politécnico La Fe, Valencia, Spain Abstract: The antitumor response after therapeutic vaccination has a limited effect and seems to be related to the presence of T regulatory cells (Treg, which express the immunoregulatory molecules CTLA4 and Foxp3. The blockage of CTLA4 using antibodies has shown an effective antitumor response conducing to the approval of the human anti-CTLA4 antibody ipilimumab by the US Food and Drug Administration. On the other hand, Foxp3 is crucial for Treg development. For this reason, it is an attractive target for cancer treatment. This study aims to evaluate whether combining therapeutic vaccination with CTLA4 or Foxp3 gene silencing enhances the antitumor response. First, the “in vitro” cell entrance and gene silencing efficacy of two tools, 2'-O-methyl phosphorotioate-modified oligonucleotides (2'-OMe-PS-ASOs and polypurine reverse Hoogsteen hairpins (PPRHs, were evaluated in EL4 cells and cultured primary lymphocytes. Following B16 tumor transplant, C57BL6 mice were vaccinated with irradiated B16 tumor cells engineered to produce granulocyte-macrophage colony-stimulating factor (GM-CSF and were intraperitoneally treated with CTLA4 and Foxp3 2'-OMe-PS-ASO before and after vaccination. Tumor growth, mice survival, and CTLA4 and Foxp3 expression in blood cells were measured. The following

  11. The impact of enhancing perceived self-efficacy in torture survivors.

    Science.gov (United States)

    Morina, Naser; Bryant, Richard A; Doolan, Emma L; Martin-Sölch, Chantal; Plichta, Michael M; Pfaltz, Monique C; Schnyder, Ulrich; Schick, Matthis; Nickerson, Angela

    2018-01-01

    Perceived self-efficacy (SE) is an important factor underlying psychological well-being. Refugees suffer many experiences that can compromise SE. This study tested the impact of enhancing perceived SE on coping with trauma reminders and distress tolerance in tortured refugees. Torture survivors (N = 40) were administered a positive SE induction in which they retrieved mastery-related autobiographical memories, or a non-SE (NSE) induction, and then viewed trauma-related images. Participants rated their distress following presentation of each image. Participants then completed a frustration-inducing mirror-tracing task to index distress tolerance. Participants in the SE condition reported less distress and negative affect, and improved coping in relation to viewing the trauma-related images than those in the NSE condition. The SE induction also led to greater persistence with the mirror-tracing task than the NSE induction. These findings provide initial evidence that promoting SE in tortured refugees can assist with managing distress from trauma reminders, and promoting greater distress tolerance. Enhancing perceived SE in tortured refugees may increase their capacity to tolerate distress during therapy, and may be a useful means to improve treatment response. © 2017 Wiley Periodicals, Inc.

  12. Novel Curcumin Diclofenac Conjugate Enhanced Curcumin Bioavailability and Efficacy in Streptococcal Cell Wall-induced Arthritis.

    Science.gov (United States)

    Jain, S K; Gill, M S; Pawar, H S; Suresh, Sarasija

    2014-09-01

    Curcumin-diclofenac conjugate as been synthesized by esterification of phenolic group of curcumin with the acid moiety of diclofenac, and characterized by mass spectrometry, NMR, FTIR, DSC, thermogravimetric analysis and X-ray diffraction analysis. The relative solubility of curcumin-diclofenac conjugate, curcumin and diclofenac; stability of curcumin-diclofenac conjugate in intestinal extract; permeability study of curcumin-diclofenac conjugate using the everted rat intestinal sac method; stability of curcumin-diclofenac conjugate in gastrointestinal fluids and in vitro efficacy have been evaluated. In vivo bioavailability of curcumin-diclofenac conjugate and curcumin in Sprague-Dawley rats, and antiarthritic activity of curcumin-diclofenac conjugate, curcumin and diclofenac in modified streptococcal cell wall-induced arthritis model in Balb/c mice to mimic rheumatoid arthritis in humans have also been studied. In all of the above studies, curcumin-diclofenac conjugate exhibited enhanced stability as compared to curcumin; its activity was twice that of diclofenac in inhibiting thermal protein denaturation taken as a measure of in vitro antiinflammatory activity; it enhanced the bioavailability of curcumin by more than five folds, and significantly (Parthritis in streptococcal cell wall-induced arthritis model as compared to both diclofenac and curcumin.

  13. Motivation Enhancement Therapy with pregnant substance-abusing women: does baseline motivation moderate efficacy?

    Science.gov (United States)

    Ondersma, Steven J; Winhusen, Theresa; Erickson, Sarah J; Stine, Susan M; Wang, Yun

    2009-04-01

    Some evidence suggests that motivational approaches are less efficacious--or even counter-productive--with persons who are relatively motivated at baseline. The present study was conducted to examine whether disordinal moderation by baseline motivation could partially explain negative findings in a previous study [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173]. Analyses also focused on the relative utility of the University of Rhode Island Change Assessment (URICA) scale, vs. a single goal question as potential moderators of Motivation Enhancement Therapy (MET). Participants were 200 pregnant women presenting for substance abuse treatment at one of four sites. Women were randomly assigned to either a three-session MET condition or treatment as usual (TAU). Generalized Estimating Equations (GEE) revealed no significant moderation effects on drug use at post-treatment. At follow-up, contrary to expectations, participants who had not set a clear quit goal at baseline were less likely to be drug-free if randomized to MET (OR=0.48); participants who did set a clear quit goal were more likely to be drug-free if randomized to MET (OR=2.53). No moderating effects were identified via the URICA. Disordinal moderation of MET efficacy by baseline motivation may have contributed somewhat to the negative results of the [Winhusen, T., Kropp, F., Babcock, D., Hague, D., Erickson, S.J., Renz, C., Rau, L., Lewis, D., Leimberger, J., Somoza, E., 2008. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J. Subst. Abuse Treat. 35, 161-173] study, but in the opposite direction expected. A simple question regarding intent to quit may be useful in identifying persons who may differentially respond to motivational

  14. Loss of CHD1 causes DNA repair defects and enhances prostate cancer therapeutic responsiveness

    DEFF Research Database (Denmark)

    Kari, Vijayalakshmi; Mansour, Wael Yassin; Raul, Sanjay Kumar

    2016-01-01

    The CHD1 gene, encoding the chromo-domain helicase DNA-binding protein-1, is one of the most frequently deleted genes in prostate cancer. Here, we examined the role of CHD1 in DNA double-strand break (DSB) repair in prostate cancer cells. We show that CHD1 is required for the recruitment of Ct......-homologous end joining. Together, we provide evidence for a previously unknown role of CHD1 in DNA DSB repair via HR and show that CHD1 depletion sensitizes cells to PARP inhibitors, which has potential therapeutic relevance. Our findings suggest that CHD1 deletion, like BRCA1/2 mutation in ovarian cancer, may...... serve as a marker for prostate cancer patient stratification and the utilization of targeted therapies such as PARP inhibitors, which specifically target tumors with HR defects....

  15. Curcumin-Loaded Blood-Stable Polymeric Micelles for Enhancing Therapeutic Effect on Erythroleukemia.

    Science.gov (United States)

    Gong, Feirong; Chen, Dan; Teng, Xin; Ge, Junhua; Ning, Xianfeng; Shen, Ya-Ling; Li, Jian; Wang, Shanfeng

    2017-08-07

    Curcumin has high potential in suppressing many types of cancer and overcoming multidrug resistance in a multifaceted manner by targeting diverse molecular targets. However, the rather low systemic bioavailability resulted from its poor solubility in water and fast metabolism/excretion in vivo has hampered its applications in cancer therapy. To increase the aqueous solubility of curcumin while retaining the stability in blood circulation, here we report curcumin-loaded copolymer micelles with excellent in vitro and in vivo stability and antitumor efficacy. The two copolymers used for comparison were methoxy-poly(ethylene glycol)-block-poly(ε-caprolactone) (mPEG-PCL) and N-(tert-butoxycarbonyl)-l-phenylalanine end-capped mPEG-PCL (mPEG-PCL-Phe(Boc)). In vitro cytotoxicity evaluation against human pancreatic SW1990 cell line showed that the delivery of curcumin in mPEG-PCL-Phe(Boc) micelles to cancer cells was efficient and dosage-dependent. The pharmacokinetics in ICR mice indicated that intravenous (i.v.) administration of curcumin/mPEG-PCL-Phe(Boc) micelles could retain curcumin in plasma much better than curcumin/mPEG-PCL micelles. Biodistribution results in Sprague-Dawley rats also showed higher uptake and slower elimination of curcumin into liver, lung, kidney, and brain, and lower uptake into heart and spleen of mPEG-PCL-Phe(Boc) micelles, as compared with mPEG-PCL micelles. Further in vivo efficacy evaluation in multidrug-resistant human erythroleukemia K562/ADR xenograft model revealed that i.v. administration of curcumin-loaded mPEG-PCL-Phe(Boc) micelles significantly delayed tumor growth, which was attributed to the improved stability of curcumin in the bloodstream and increased systemic bioavailability. The mPEG-PCL-Phe(Boc) micellar system is promising in overcoming the key challenge of curcumin's to promote its applications in cancer therapy.

  16. Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

    International Nuclear Information System (INIS)

    Siemann, Dietmar W.; Rojiani, Amyn M.

    2002-01-01

    Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

  17. The Development of a Cultural-Based Educational Program to Enhance Breast Self-Examination (BSE Self-Efficacy

    Directory of Open Access Journals (Sweden)

    Juanita Juanita

    2012-08-01

    Full Text Available Purpose: To develop the educational program which is appropriate with Islamic culture in order to enhance BSE self-efficacy of nursing students and thus promote BSE practice. Method: This study is a development research study which is consisting of three phases including: 1 reviewing several existing BSE educational programs; 2 program design based on SCT and Islamic culture; and 3 program validation by three experts. Result: Based on previous studies, the most appropriate theory to enhance self-efficacy was Social Cognitive Theory (SCT because this theory provides several strategies to increase the self-efficacy. Further, the program that used Islamic culture was more appropriate to increase BSE practice among Muslim women. As a result, the newly developed program was developed used SCT and Islamic culture. This program was comprised of four sessions including: 1 exploring Islamic mandate on prevention and individual responsibility in health promotion, and culture-related beliefs toward BSE, 2 health education by conducting lecturing session and watching a video about BSE procedures, 3 BSE training activities including BSE demonstration and return demonstration, 4 follow-up by conducting a meeting. Conclusion: The cultural-based educational program for enhancing BSE self-efficacy and promoting BSE is a program using multifaceted methods. It designed based on a review of the literature from previous studies and were supported by research findings on experimental studies in other population. Keywords: Cultural, Educational program development, Breast self-examination, Self-efficacy.

  18. Addition of DHA synergistically enhances the efficacy of regorafenib for kidney cancer therapy

    Science.gov (United States)

    Kim, Jeffrey; Ulu, Arzu; Wan, Debin; Yang, Jun; Hammock, Bruce D; Weiss, Robert H.

    2016-01-01

    Kidney cancer is the 6th most common cancer in the US and its incidence is increasing. The treatment of this malignancy took a major step forward with the recent introduction of targeted therapeutics such as the kinase inhibitors. Unfortunately, kinase inhibition is associated with the onset of resistance after 1–2 years of treatment. Regorafenib, like many multi-kinase inhibitors, was designed to block the activities of several key kinase pathways involved in oncogenesis (Ras/Raf/MEK/ERK) and tumor angiogenesis (VEGF-receptors), and we have recently shown that it also possesses soluble epoxide hydrolase (sEH) inhibitory activity which may be contributing to its salutary effects in patients. Since sEH inhibition results in increases in the DHA-derived epoxydocosapentaenoic acids (EDPs) which we have previously described to possess anti-cancer properties, we asked whether the addition of DHA to a therapeutic regimen in the presence of regorafenib would enhance its beneficial effects in vivo. We now show that the combination of regorafenib and DHA results in a synergistic effect upon tumor invasiveness as well as p-VEGFR attenuation. In addition, this combination showed a reduction in tumor weights, greater than each agent alone, in a mouse xenograft model of human RCC, yielding the expected oxylipin profiles; this data was supported in several RCC cell lines which showed similar results in vitro. Since DHA is the predominant component of fish oil, our data suggest that this non-toxic dietary supplement could be administered with regorafenib during therapy for advanced RCC and could be the basis of a clinical trial. PMID:26921392

  19. In vivo testing of the therapeutic efficacy of chloroquine on falciparum malaria infections in Chirundu, Mashonaland West, Zimbabwe.

    Science.gov (United States)

    Barduagni, P; Schwartz, U; Nyamayaro, W; Chauke, T L

    1998-10-01

    To detect the level of the in vivo chloroquine efficacy in falciparum malaria infections, in order to assess the need for change in the management and treatment of uncomplicated malaria. Prospective descriptive study. Chirundu Rural Clinic, Mashonaland West Province. 63 patients confirmed by a positive blood slide for P. falciparum who attended Chirundu clinic, who were eligible for the study and, who also agreed to participate. Frequency of treatment success, early treatment failure and late treatment failure in uncomplicated patients treated with chloroquine. Out of 63 cases enrolled and completely followed up, chloroquine treatment was effective in 54 cases (85.7%) and was not effective in nine cases (14.3%). All treatment failures were successfully treated with sulphadoxine + pyrimethamine (Fansidar) or quinine following the approved guidelines. Chloroquine remains highly effective in the treatment of malaria due to P. falciparum in the Zambezi Valley of Hurungwe district and therefore, has to remain the first line drug. Likewise, guidelines for the use of sulphadoxine + pyrimethamine (Fansidar) or quinine as second line drugs, are adequate to the local situation. Health workers directly supervised the patients when they were swallowing the tablets during the whole course, and this without doubt, indirectly increased the efficacy of chloroquine. It is vital to confirm the malaria diagnosis on the spot appointing microscopists or distributing a limited stock of Parasight-F test.

  20. Therapeutic potential of using the vascular disrupting agent OXi4503 to enhance mild temperature thermoradiation

    DEFF Research Database (Denmark)

    Horsman, Michael R

    2015-01-01

    period (simultaneous treatment) or at 1 or 4 h prior to starting the heating (sequential treatments). Response was the percentage of mice showing local tumour control at 90 days or skin moist desquamation between days 11-23. From the radiation dose response curves the dose producing tumour control (TCD......(50)) or moist desquamation (MDD50) in 50% of mice was calculated. RESULTS: The TCD(50) and MDD50 values for radiation alone were 54 Gy and 29 Gy, respectively. Simultaneously heating the tissues enhanced radiation response, the respective TCD(50) and MDD50 values being significantly (chi-square test......, p sequential treatment in both tissues. OXi4503 enhanced the radiation response of tumour and skin. Combined with radiation and heat, the only effect was in tumours where OXi4503 prevented the decrease in sensitisation...

  1. Enhancing Self-Efficacy and Performance: An Experimental Comparison of Psychological Techniques.

    Science.gov (United States)

    Wright, Bradley James; O'Halloran, Paul Daniel; Stukas, Arthur Anthony

    2016-01-01

    We assessed how 6 psychological performance enhancement techniques (PETs) differentially improved self-efficacy (SE) and skill performance. We also assessed whether vicarious experiences and verbal persuasion as posited sources of SE (Bandura, 1982 ) were supported and, further, if the effects of the 6 PETs remained after controlling for achievement motivation traits and self-esteem. A within-subject design assessed each individual across 2 trials for 3 disparate PETs. A between-groups design assessed differences between PETs paired against each other for 3 similar novel tasks. Participants (N = 96) performed 2 trials of 10 attempts at each of the tasks (kick, throw, golf putt) in a counterbalanced sequence using their nondominant limb. Participants completed the Sport Orientation Questionnaire, Rosenberg Self-Esteem Scale, and General Self-Efficacy Scale and were randomly allocated to either the modeling or imagery, goal-setting or instructional self-statement, or knowledge-of-results or motivational feedback conditions aligned with each task. An instructional self-statement improved performance better than imagery, modeling, goal setting, and motivational and knowledge-of-results augmented feedback. Motivational auditory feedback most improved SE. Increased SE change scores were related to increased performance difference scores on all tasks after controlling for age, sex, achievement motivation, and self-esteem. Some sources of SE may be more influential than others on both SE and performance improvements. We provide partial support for the sources of SE proposed by Bandura's social-cognitive theory with verbal persuasion but not vicarious experiences improving SE.

  2. The Effectiveness of Group Motivational Interviewing Sessions on Enhancing of Addicted Women’s Self-Esteem and Self Efficacy

    Directory of Open Access Journals (Sweden)

    Samireh Dehghani F

    2013-07-01

    Full Text Available Objective: The aim of present research was to study of the effectiveness of motivational interviewing on enhancing of self-esteem and self-efficacy in addicted women who were under therapy. Method: The research method was semi experimental research design namely: pretest-posttest with witness group. The population consisted of all addicted women who were referred to Ayandeh Roshan recovery addiction camp of Isfahan city during summer in 1391. By available sampling, 30 women selected and divided randomly to two experimental and witness groups (N= 15, per group. Experimental group received eight sessions of 90 minutes based on group counseling sessions following motivational interviewing style. For gathering data, Cooper Smith’s self-esteem and general self-efficacy questionnaires administered among two groups. Results: The results indicated the effectiveness of motivational interviewing. Conclusion: It can be concluded that motivational interviewing has had enhancing effect on self-esteem and self-efficacy among experimental group.

  3. Inspiring Instructional Change in Elementary School Science: The Relationship Between Enhanced Self-efficacy and Teacher Practices

    Science.gov (United States)

    Sandholtz, Judith Haymore; Ringstaff, Cathy

    2014-10-01

    This longitudinal study examined the extent to which teachers' participation in a 3-year professional development program enhanced their self-efficacy and prompted changes in science instruction in the early elementary grades. The study used a mixed-methods design, and included 39 teachers who taught in kindergarten, first grade, or second grade classrooms in rural school districts. Data sources, administered pre-program and at the end of each year, included a self-efficacy assessment and teacher survey. Interviews and classroom observations provided corroborating data about teachers' beliefs and science instruction. Results showed significant increases in teachers' overall self-efficacy in teaching science, personal efficacy, and outcome expectancy efficacy during the 3 years. Gains in self-efficacy were correlated with changes in reported instructional practices, particularly student participation activities. However, changes in self-efficacy tended not to be correlated with changes in instructional time. Contextual factors beyond teachers' direct control, such as curricular and testing requirements in mathematics and language arts influenced time allotted to science instruction.

  4. Enhancing self-efficacy improves episodic future thinking and social-decision making in combat veterans with posttraumatic stress disorder.

    Science.gov (United States)

    Brown, Adam D; Kouri, Nicole A; Rahman, Nadia; Joscelyne, Amy; Bryant, Richard A; Marmar, Charles R

    2016-08-30

    Posttraumatic Stress Disorder (PTSD) is associated with maladaptive changes in self-identity, including impoverished perceived self-efficacy. This study examined if enhancing perceptions of self-efficacy in combat veterans with and without symptoms of PTSD promotes cognitive strategies associated with positive mental health outcomes. Prior to completing a future thinking and social problem-solving task, sixty-two OEF/OIF veterans with and without symptoms of PTSD were randomized to either a high self-efficacy (HSE) induction in which they were asked to recall three autobiographical memories demonstrating self-efficacy or a control condition in which they recalled any three autobiographical events. An interaction between HSE and PTSD revealed that individuals with symptoms of PTSD in the HSE condition generated future events with more self-efficacious statements than those with PTSD in the control condition, whereas those without PTSD did not differ in self-efficacy content across the conditions. In addition, individuals in the HSE condition exhibited better social problem solving than those in the control condition. Increasing perceptions of self-efficacy may promote future thinking and problem solving in ways that are relevant to overcoming trauma and adversity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Does computerized working memory training with game elements enhance motivation and training efficacy in children with ADHD?

    NARCIS (Netherlands)

    Prins, P.J.M.; Dovis, S.; Ponsioen, A.; ten Brink, E.; van der Oord, S.

    2011-01-01

    This study examined the benefits of adding game elements to standard computerized working memory (WM) training. Specifically, it examined whether game elements would enhance motivation and training performance of children with ADHD, and whether it would improve training efficacy. A total of 51

  6. Efficacy of Information and Communication Technology in Enhancing Learning Outcomes of Students with Hearing Impairment in Ibadan

    Science.gov (United States)

    Egaga, Patrick I.; Aderibigbe, S. Akinwumi

    2015-01-01

    The study aimed at examining the efficacy of Information and Communication Technology (ICT) in enhancing learning outcomes of students with hearing impairment in Ibadan. The study adopted a pretest, post-test, control group quasi-experimental research design. Purposive sampling techniques was used for the selection of thirty participants…

  7. The future of drug discovery: enabling technologies for enhancing lead characterization and profiling therapeutic potential.

    Science.gov (United States)

    Janero, David R

    2014-08-01

    Technology often serves as a handmaiden and catalyst of invention. The discovery of safe, effective medications depends critically upon experimental approaches capable of providing high-impact information on the biological effects of drug candidates early in the discovery pipeline. This information can enable reliable lead identification, pharmacological compound differentiation and successful translation of research output into clinically useful therapeutics. The shallow preclinical profiling of candidate compounds promulgates a minimalistic understanding of their biological effects and undermines the level of value creation necessary for finding quality leads worth moving forward within the development pipeline with efficiency and prognostic reliability sufficient to help remediate the current pharma-industry productivity drought. Three specific technologies discussed herein, in addition to experimental areas intimately associated with contemporary drug discovery, appear to hold particular promise for strengthening the preclinical valuation of drug candidates by deepening lead characterization. These are: i) hydrogen-deuterium exchange mass spectrometry for characterizing structural and ligand-interaction dynamics of disease-relevant proteins; ii) activity-based chemoproteomics for profiling the functional diversity of mammalian proteomes; and iii) nuclease-mediated precision gene editing for developing more translatable cellular and in vivo models of human diseases. When applied in an informed manner congruent with the clinical understanding of disease processes, technologies such as these that span levels of biological organization can serve as valuable enablers of drug discovery and potentially contribute to reducing the current, unacceptably high rates of compound clinical failure.

  8. Ultrasound enhanced release of therapeutics from drug-releasing implants based on titania nanotube arrays.

    Science.gov (United States)

    Aw, Moom Sinn; Losic, Dusan

    2013-02-25

    A non-invasive and external stimulus-driven local drug delivery system (DDS) based on titania nanotube (TNT) arrays loaded with drug encapsulated polymeric micelles as drug carriers and ultrasound generator is described. Ultrasound waves (USW) generated by a pulsating sonication probe (Sonotrode) in phosphate buffered saline (PBS) at pH 7.2 as the medium for transmitting pressure waves, were used to release drug-loaded nano-carriers from the TNT arrays. It was demonstrated that a very rapid release in pulsatile mode can be achieved, controlled by several parameters on the ultrasonic generator. This includes pulse length, time, amplitude and power intensity. By optimization of these parameters, an immediate drug-micelles release of 100% that spans a desirable time of 5-50 min was achieved. It was shown that stimulated release can be generated and reproduced at any time throughout the TNT-Ti implant life, suggesting considerable potential of this approach as a feasible and tunable ultrasound-mediated drug delivery system in situ via drug-releasing implants. It is expected that this concept can be translated from an in vitro to in vivo regime for therapeutic applications using drug-releasing implants in orthopedic and coronary stents. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  9. Triads in Equine-Assisted Social Work Enhance Therapeutic Relationships with Self-Harming Adolescents.

    Science.gov (United States)

    Carlsson, Catharina

    2017-01-01

    Despite an increasing number of studies, there is still a lack of knowledge about the unique features that underlie the process in equine assisted social work (EASW). This study aimed to reveal, through qualitative methods, the dyads within the triad that become stronger during the process of EASW, as well as the effect of the participation of the horse on the relationship between the counselor and client. Data were collected through in-depth interviews with nine female self-harming clients aged 15-21 years and eight staff members. The interviews, together with video-recorded human-horse interactions with three staff members and four clients were analyzed, resulting in additional issues answered by these three staff members and four clients in a second interview. Critical dialogues between patterns and fragmentations in the narratives and video-recordings, as well as a dialogue with the participants while they were viewing videos of their own EASW sessions, led to the conclusion that adding a horse qualitatively changes therapeutic relationships in EASW. The different triads consist of different liaisons between actors in the triad, giving rise to unique combinations. The quality of the relationships depends on both the staff and the clients' attachment orientations. Further research is needed to investigate how the degree of emotional connection to the horse affects the impact that horses have on triads in EASW.

  10. Enhance Therapeutic Effect Compared with Single Transplantation in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Dandan Wang

    2012-01-01

    Full Text Available The clinical trial of allogenic mesenchymal stem cells (MSCs transplantation for refractory SLE patients has shown significant safety and efficacy profiles. However, the optimum frequency of the MSCs transplantation (MSCT is unknown. This study was undertaken to observe whether double transplantations of MSCs is superior to single transplantation. Fifty-eight refractory SLE patients were enrolled in this study, in which 30 were randomly given single MSCT, and the other 28 were given double MSCT. Patients were followed up for rates of survival, disease remission, and relapse, as well as transplantation-related adverse events. SLE disease activity index (SLEDAI and serologic features were evaluated. Our results showed that no remarkable differences between single and double allogenic MSCT were found in terms of disease remission and relapse, amelioration of disease activity, and serum indexes in an SLE clinical trial with more than one year followup. This study demonstrated that single MSCs transplantation at the dose of one million MSCs per kilogram of body weight was sufficient to induce disease remission for refractory SLE patients.

  11. Beyond the Therapeutic Hour: An Exploratory Pilot Study of Using Technology to Enhance Alliance and Engagement within Face-to-Face Psychotherapy

    Science.gov (United States)

    Richards, Penelope; Simpson, Susan

    2015-01-01

    In this paper we introduce and investigate the capacity for a novel, technologically advanced system (goACT) to enhance face-to-face psychotherapy. Specifically, we explore the capacity for goACT to enhance therapeutic alliance (TA) and engagement, and reduce distress. Using a mixed-methods, multiple-baseline design we present the first study to…

  12. A double-blind randomized controlled pilot trial examining the safety and efficacy of therapeutic touch in premature infants.

    Science.gov (United States)

    Whitley, Julie Anne; Rich, Bonnie L

    2008-12-01

    To explore the hypothesis that nontouch therapy such as therapeutic touch (TT) reduces stress to a clinically important degree and is safe to use in preterm infants. A pilot randomized, double-blind, controlled trial. Two groups of 10 infants were enrolled and randomly assigned to treatment or nontreatment groups. Gestational age was less than 29 weeks. Demographic descriptions of the 2 groups were statistically similar. The observer and staff were blinded to assignment; the TT practitioner was blinded to observed measurements. Each infant received either TT or no therapeutic touch (NTT) for 5 minutes on 3 consecutive days at the same time of day, behind a curtain. Heart period variability (HPV) was measured 5 minutes before, during, and after the treatment phase. Examination of the parameters of oxygen saturation and episodes of apnea demonstrated no increase in adverse events in TT group compared with NTT group. Repeated-measures multivariate analysis of variance on HPV revealed differences in the interaction of group assignment with low-frequency, high-frequency, and low-to-high- frequency ratio interaction (F2,143 = 8.076, P = .000) and for group, day, and low-frequency, high-frequency, and low-to-high-frequency ratio (F2,288 = 3.146, P = .015), and in the posttreatment time period (F1,16 = 6.259, P = .024), reflective of greater parasympathetic activity in TT group. In this pilot trial, HPV showed an increase for the TT group compared with the NTT group. The study reveals no adverse effects of TT in preterm infants.

  13. Therapeutic Efficacy of an ω-3-Fatty Acid-Containing 17-β Estradiol Nano-Delivery System against Experimental Atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Dipti Deshpande

    Full Text Available Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel ω-3-fatty acid-rich, 17-β-estradiol (17-βE-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs with the 17-βE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/- mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-βE and/or ω-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-βE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-βE-loaded, CREKA-peptide-modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease.

  14. Enhanced therapeutic effect of multiple injections of HSV-TK + GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model

    International Nuclear Information System (INIS)

    Vlachaki, Maria T.; Chhikara, Madhu; Aguilar, Laura; Zhu Xiaohong; Chiu, Kam J.; Woo, Shiao; Teh, Bin S.; Thompson, Timothy C.; Butler, E. Brian; Aguilar-Cordova, Estuardo

    2001-01-01

    Purpose: Standard therapies for breast cancer lack tumor specificity and have significant risk for recurrence and toxicities. Herpes simplex virus-thymidine kinase (HSV-tk) gene therapy combined with radiation therapy (XRT) may be effective because of complementary mechanisms and distinct toxicity profiles. HSV-tk gene therapy followed by systemic administration of ganciclovir (GCV) enhances radiation-induced DNA damage by generating high local concentrations of phosphorylated nucleotide analogs that increase radiation-induced DNA breaks and interfere with DNA repair mechanisms. In addition, radiation-induced membrane damage enhances the 'bystander effect' by facilitating transfer of nucleotide analogs to neighboring nontransduced cells and by promoting local and systemic immune responses. This study assesses the effect of single and multiple courses of HSV-tk gene therapy in combination with ionizing radiation in a mouse mammary cancer model. Methods and Materials: Mouse mammary TM40D tumors transplanted s.c. in syngeneic immunocompetent BALB-c mice were treated with either adenoviral-mediated HSV-tk gene therapy or local radiation or the combination of gene and radiation therapy. A vector consisting of a replication-deficient (E1-deleted) adenovirus type 5 was injected intratumorally to administer the HSV-tk gene, and GCV was initiated 24 h later for a total of 6 days. Radiation was given as a single dose of 5 Gy 48 h after the HSV-tk injection. A metastatic model was developed by tail vein injection of TM40D cells on the same day that the s.c. tumors were established. Systemic antitumor effect was evaluated by counting the number of lung nodules after treating only the primary tumors with gene therapy, radiation, or the combination of gene and radiation therapy. To assess the therapeutic efficacy of multiple courses of this combinatorial approach, one, two, and three courses of HSV-tk + GCV gene therapy, in combination with radiation, were compared to HSV-tk or

  15. Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer.

    Science.gov (United States)

    Šišić, Ibrahim; Pojskić, Belma; Mekić Abazović, Alma; Kovčin, Vladimir

    2015-08-01

    To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus), leucovorin (folfox) between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC). A total of 63 patients were treated for mCRC in the period January 2009 - January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients) and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 - January 2006 (second group, 33 patients). The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D), 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS), progression free survival, hematological and non-hematological toxicity . Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy. Copyright© by the Medical Assotiation of Zenica-Doboj Canton.

  16. Therapeutic efficacy and toxicity of bolus application of chemotherapy protocol in the treatment of metastatic colorectal cancer

    Directory of Open Access Journals (Sweden)

    Ibrahim Šišić

    2015-08-01

    Full Text Available Aim To compare efficacy and toxicity of bolus application of chemotherapy protocol, oxaliplatin, fluorouracil (bolus, leucovorin (folfox between two groups of patients in the therapy of metastatic colorectal carcinoma (mCRC. Methods A total of 63 patients were treated for mCRC in the period January 2009 – January 2010 at the Department of Oncology of the Cantonal Hospital Zenica, Bosnia and Herzegovina (first group, 30 patients and at the Department of Oncology of the Clinical Hospital Centre Bežanijska kosa in Belgrade, Serbia, in the period January 2005 – January 2006 (second group, 33 patients. The patients were treated according the same protocol, i.v. bolus infusion, but in different day intervals (D, 1, 8, 15/28 days or D1-D5/28 days, respectively. In all patients the following factors were analyzed: tumor response, overall survival (OS, progression free survival, hematological and non-hematological toxicity. Results Colon was the primary localization in almost two thirds of patients. There was no statistically significant difference between the groups according to the age, hematological and non-hematological toxicity, as well as in achieved OS. Progression free survival expressed in months was in average 5 months though with a large range between minimal and maximal survival time. Conclusion Both groups have shown equivalent efficacy to applied chemotherapy protocols. Overall survival in the two groups matched data from the literature. Further research should confirm success of the combination of chemotherapy protocols and their combination with the biological therapy.

  17. An Analysis of a Novel, Short-Term Therapeutic Psychoeducational Program for Children and Adolescents with Chronic Neurological Illness and Their Parents; Feasibility and Efficacy

    Directory of Open Access Journals (Sweden)

    Bonglim Joo

    2017-05-01

    Full Text Available The purpose of this intervention was to develop a therapeutic psycho-educational program that improves quality of life in children and adolescents who are experiencing chronic neurological illness, including epilepsy, and their parents, and to analyze the intervention's feasibility and efficacy and participants' satisfaction. Participants were eight children (n = 8 and adolescents and their parents; participating children were experiencing chronic neurological illness with psychological comorbidity; children with intellectual impairment were excluded (IQ < 80. The program was carried out weekly for four sessions. In each of the 4 weeks, children's session content addressed self, emotion, coping skills, and finishing up, respectively; and parents' session content targeted family dynamic and emotional intervention, coping skills, childcare and education, and finishing up, respectively. Clinical psychologists administered psychological assessments (viz., Child Behavior Checklist, Pediatric Quality of Life Inventory, Parenting Stress Index, Beck Depression Inventory, Children's Depression Inventory, and Revised Children's Manifest Anxiety Scale at pre- and post-intervention, and administered satisfaction surveys following the intervention. Participants' opinions about the program's necessity, contents, and process, and participants' overall program satisfaction were analyzed. Parents and children reported high levels of satisfaction with the program. Externalizing behavioral problems, anxiety/depression, and emotional functioning from quality of life showed improvement after the intervention. Although not statistically significant, total child stress trended downward from pre- to post-intervention. A four-session structured therapeutic psycho-educational program for children and adolescents with chronic neurological illness and their parents was successfully implemented, showing good compliance and high satisfaction and efficacy.

  18. Development and Evaluation of Naproxen Sodium Gel Using Piper cubeba for Enhanced Transdermal Drug Delivery and Therapeutic Facilitation.

    Science.gov (United States)

    Patwardhan, Sunetra; Patil, Manohar; Sockalingam, Anbazhagan

    2017-01-01

    The absorption of drug through skin avoids many side effects of oral route like gastric irritation, nausea, systemic toxicity etc and thus improves patient compliance. Naproxen sodium (NPRS) is one of the potent NSAID agents. The present study was aimed to develop and evaluate the gel formulation containing NPRS for transdermal drug delivery reducing the side effects and improving patient compliance. The patents on topical delivery of NSAIDS (US 9012402 B1, US 9072659 B2, US 20150258196 A1) and patents indicating use of herbal penetration enhancers (US 20100273746A1, WO 2005009510 A2, US 6004969 A) helped in selecting the drug, excipients. Current protocol employs various extracts of Piper cubeba fruit to evaluate its role in absorption of NPRS. Various batches containing 1% NPRS and varying concentrations of synthetic permeation enhancers or the extracts were formulated in carbopol gel. Gel was evaluated for parameters like organoleptic parameters, pH, viscosity and spreadability. An ex-vivo percutaneous absorption of NPRS from gel was investigated and compared with best performing synthetic enhancer, transcutol P (TP). The batch containing 2% n-hexane extract (NHE) of Piper cubeba showed higher permeation than TP and Chloroform (CE), Methanolic (ME) and aqueous (AE) extracts as well. It showed improved % cumulative release (85.09%) and flux (278.61μg/cm2.h), as compared to TP and other extracts. Histopathology indicated the formulation safer as compared to that with synthetic enhancer. It suggests P. cubeba as effective and safer tool for transdermal delivery and acts as therapeutic facilitator for naproxen. GC-MS analysis indicates lignans & terpenes in NHE to which this permeation enhancement activity may be attributed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

    Science.gov (United States)

    Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

    2012-01-01

    Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

  20. Nanomedicine for therapeutic drug therapy: Approaches to increase the efficacy of drug therapy with nanoemulsion delivery and reduce the toxicity of quantum dots

    Science.gov (United States)

    Kambalapally, Swetha Reddy

    The advancement of nanotechnology has paved the way for novel nanoscale materials for use in a wide range of applications. The use of these nanomaterials in biomedicine facilitates the improvement of existing technologies for disease prevention and treatment through diagnostics, tumor detection, drug delivery, medical imaging and vaccine development. Nanotechnology delivery systems for therapeutic uses includes the formulation of nanoparticles in emulsions. These novel delivery systems can improve drug efficacy by their ability to enhance bioavailability, minimize drug side effects, decrease drug toxicity, provide targeted site delivery and increase circulation of the drug in the blood. Additionally, these delivery systems also improve the drug stability and encapsulation efficiency. In the Introduction, this thesis will describe a novel technique for the preparation of nanoemulsions which was utilized in drug delivery and diagnostic applications. This novel Phase Inversion Temperature (PIT) method is a solvent and polymer-free and low energy requiring emulsification method, typically utilizing oils stabilized by nonionic surfactants to prepare water in oil (W/O) emulsions. The correlation between the particle size, zeta potential and the emulsion stability is described. The use of this nanoemulsion delivery system for pharmaceuticals and nutraceuticals by utilizing in vitro systems was investigated. Using the PIT method, a self assembling nanoemulsion (SANE) of gamma Tocotrienols (gammaT3), a component of Vitamin E family has been demonstrated to reduce cholesterol accumulation in HepG-2 cells. The nanoemulsion is stable and the particle size is around 20 nm with a polydispersity index (PDI) of 0.065. The effect of the nano gammaT3 on the metabolism of cholesterol, HMG-CoA activity and Apo-B levels were evaluated in an in vitro system utilizing HepG2 cells. A new class of nanoparticles, Quantum dots (QDs) has shown immense potential as novel nanomaterials used as

  1. Magnetic targeting as a strategy to enhance therapeutic effects of mesenchymal stromal cells.

    Science.gov (United States)

    Silva, Luisa H A; Cruz, Fernanda F; Morales, Marcelo M; Weiss, Daniel J; Rocco, Patricia R M

    2017-03-09

    Mesenchymal stromal cells (MSCs) have been extensively investigated in the field of regenerative medicine. It is known that the success of MSC-based therapies depends primarily on effective cell delivery to the target site where they will secrete vesicles and soluble factors with immunomodulatory and potentially reparative properties. However, some lesions are located in sites that are difficult to access, such as the heart, spinal cord, and joints. Additionally, low MSC retention at target sites makes cell therapy short-lasting and, therefore, less effective. In this context, the magnetic targeting technique has emerged as a new strategy to aid delivery, increase retention, and enhance the effects of MSCs. This approach uses magnetic nanoparticles to magnetize MSCs and static magnetic fields to guide them in vivo, thus promoting more focused, effective, and lasting retention of MSCs at the target site. In the present review, we discuss the magnetic targeting technique, its principles, and the materials most commonly used; we also discuss its potential for MSC enhancement, and safety concerns that should be addressed before it can be applied in clinical practice.

  2. Internships enhancing entrepreneurial intent and self-efficacy: Investigating tertiary-level entrepreneurship education programmes

    Directory of Open Access Journals (Sweden)

    Melodi Botha

    2016-09-01

    Full Text Available Background: Entrepreneurship education interventions are deemed effective when they enhance interns’ entrepreneurial intent (EI and entrepreneurial self-efficacy (ESE. Notwithstanding the emergence of internship as an experiential learning approach in entrepreneurship education, evidence about their potential to foster EI and ESE lacks systemisation. Aim: The aim of this study was to determine whether internships enhance EI and ESE. Furthermore, to what extent South African tertiary institutions include internships in their entrepreneurship and management curricula and the obstacles to such inclusion. Setting: South Africa has made a concerted effort to insert an entrepreneurship component across tertiary curricula. The evolution of this entrepreneurship component to experiential learning approaches is, however, unclear. Methods: A qualitative research approach was followed. Firstly, it reviewed empirical evidence for the positive relationship between internships and EI and ESE. Secondly, it conducted a survey of entrepreneurship and business management programmes at all 23 South African tertiary institutions and content analysed the retrieved information to determine whether such programmes include internships. Finally, 10 experts were interviewed to unveil the constraints inhibiting the inclusion of internships in tertiary curricula. Results: The results revealed empirical support for the positive influence of internships on both EI and ESE. Significant lack of inclusion of internships in tertiary curricula in South Africa emerged, owing mainly to administrative issues, curriculum re-design challenges, and lack of mentoring capacity. Conclusion: Tertiary-level entrepreneurship education programmes should include an internship component. The paper suggested that tertiary institutions pilot-test the inclusion of internships with a small number of students and a selected cohort of small business owners.

  3. Enhanced protective efficacy of a chimeric form of the schistosomiasis vaccine antigen Sm-TSP-2.

    Directory of Open Access Journals (Sweden)

    Mark S Pearson

    Full Text Available The large extracellular loop of the Schistosoma mansoni tetraspanin, Sm-TSP-2, when fused to a thioredoxin partner and formulated with Freund's adjuvants, has been shown to be an efficacious vaccine against murine schistosomiasis. Moreover, Sm-TSP-2 is uniquely recognised by IgG(1 and IgG(3 from putatively resistant individuals resident in S. mansoni endemic areas in Brazil. In the present study, we expressed Sm-TSP-2 at high yield and in soluble form in E. coli without the need for a solubility enhancing fusion partner. We also expressed in E. coli a chimera called Sm-TSP-2/5B, which consisted of Sm-TSP-2 fused to the immunogenic 5B region of the hookworm aspartic protease and vaccine antigen, Na-APR-1. Sm-TSP-2 formulated with alum/CpG showed significant reductions in adult worm and liver egg burdens in two separate murine schistosomiasis challenge studies. Sm-TSP-2/5B afforded significantly greater protection than Sm-TSP-2 alone when both antigens were formulated with alum/CpG. The enhanced protection obtained with the chimeric fusion protein was associated with increased production of anti-Sm-TSP-2 antibodies and IL-4, IL-10 and IFN-γ from spleen cells of vaccinated animals. Sera from 666 individuals from Brazil who were infected with S. mansoni were screened for potentially deleterious IgE responses to Sm-TSP-2. Anti-Sm-TSP-2 IgE to this protein was not detected (also shown previously for Na-APR-1, suggesting that the chimeric antigen Sm-TSP-2/5B could be used to safely and effectively vaccinate people in areas where schistosomes and hookworms are endemic.

  4. The efficacy of fat suppressed and gadolinium enhanced dynamic MR imaging in pancreatic adenocarcinomas

    International Nuclear Information System (INIS)

    Gabata, Toshifumi

    1994-01-01

    The efficacy of both fat suppressed T1-weighted imaging (T1WI) and dynamic gadolinium-enhanced MR imaging (dynamic MRI) was compared with conventional MR sequences and dynamic CT in 22 patients with histologically proven pancreatic adenocarcinoma (PAC). In the control group of 30 patients without pancreatic disease, the pancreas was shown as a markedly higher signal intensity on fat suppressed T1WI than on conventional MR sequences. The signal noise ratio (SNR) of the normal pancreas and the contrast noise ratio (CNR) between the normal pancreas and muscle were significantly higher on fat suppressed T1WI than the other MR sequences. In the group of PAC patients without chronic pancreatitis (n=14), CNR between the tumor and the normal pancreas significantly differed among imaging techniques, including fat suppressed T1WI, dynamic MRI, and the other conventional MR sequences. In the group of PAC with chronic pancreatitis (n=8), CNR between the tumor and the associated chronic pancreatitis was remarkably diminished on both fat suppressed T1WI and conventional T1WI; however, it was significantly higher on dynamic MRI than the other pulse sequences. The early phase of dynamic MRI clearly identified the tumors in the group of PAC. The capability of conventional T1WI and dynamic CT to demonstrate peripancreatic tumor extension was significantly higher than that of fat suppressed T1WI. In conclusion, fat suppressed T1WI and dynamic MRI were useful in detecting pancreatic carcinoma. (N.K.)

  5. Assessing delivery and quantifying efficacy of small interfering ribonucleic acid therapeutics in the skin using a dual-axis confocal microscope

    Science.gov (United States)

    Ra, Hyejun; Gonzalez-Gonzalez, Emilio; Smith, Bryan R.; Gambhir, Sanjiv S.; Kino, Gordon S.; Solgaard, Olav; Kaspar, Roger L.; Contag, Christopher H.

    2010-05-01

    Transgenic reporter mice and advances in imaging instrumentation are enabling real-time visualization of cellular mechanisms in living subjects and accelerating the development of novel therapies. Innovative confocal microscope designs are improving their utility for microscopic imaging of fluorescent reporters in living animals. We develop dual-axis confocal (DAC) microscopes for such in vivo studies and create mouse models where fluorescent proteins are expressed in the skin for the purpose of advancing skin therapeutics and transdermal delivery tools. Three-dimensional image volumes, through the different skin compartments of the epidermis and dermis, can be acquired in several seconds with the DAC microscope in living mice, and are comparable to histologic analyses of reporter protein expression patterns in skin sections. Intravital imaging with the DAC microscope further enables visualization of green fluorescent protein (GFP) reporter gene expression in the skin over time, and quantification of transdermal delivery of small interfering RNA (siRNA) and therapeutic efficacy. Visualization of transdermal delivery of nucleic acids will play an important role in the development of innovative strategies for treating skin pathologies.

  6. Focus on the therapeutic efficacy of 3BNC117 against HIV-1: In vitro studies, in vivo studies, clinical trials and challenges.

    Science.gov (United States)

    Liu, Zhi-Jun; Bai, Jing; Liu, Feng-Li; Zhang, Xiang-Yang; Wang, Jing-Zhang

    2017-11-01

    3BNC117, which was discovered in 2011, is a broadly neutralizing antibody (bNAb) and specifically neutralizes the human immunodeficiency virus type-1 (HIV-1) by targeting the CD4-binding site. This is the first comprehensive review that focuses on the role of 3BNC117 in the prevention of HIV-1 and acquired immune deficiency syndrome (AIDS). Briefly, 3BNC117 neutralizes many HIV/SHIV strains in vitro, blocks HIV-1 acquisition in animal models via a pre-exposure prophylaxis, alleviates HIV-1-associated viremia via a post-exposure therapeutic effect, prevents the establishment of latent HIV-1 reservoirs, and induces both humoral and cellular anti-HIV immune responses in vivo. The outcomes of Phase I and Phase IIa clinical trials in 2015 and 2016 showed the safety, tolerability, and therapeutic efficacy of 3BNC117 in HIV-1-infected human individuals. Nevertheless, anti-3BNC117 antibodies and HIV-1 strains resistant to 3BNC117 pose clinical challenges to immunotherapy with 3BNC117, so potential strategies for optimizing the potency of 3BNC117 are suggested here. Predictably, HIV-1 prevention and AIDS treatment will benefit from combinational immunotherapies with 3BNC117 and other pharmaceuticals (bNAbs, antiretroviral medicines, viral inducers, etc.) in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

    Science.gov (United States)

    Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

    2017-01-01

    Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

  8. Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Antonio Lobasso

    2017-09-01

    Full Text Available BackgroundThyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc. Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4 malabsorption in patients with Hashimoto’s thyroiditis (HT and SSc.Case reportHere, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure.ConclusionA recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

  9. Radioimmunotherapy targeting the extra domain B of fibronectin in C6 rat gliomas: a preliminary study about the therapeutic efficacy of iodine-131-labeled SIP(L19)

    International Nuclear Information System (INIS)

    Spaeth, Nicolas; Wyss, Matthias T.; Pahnke, Jens; Biollaz, Gregoire; Trachsel, Eveline; Drandarov, Konstantin; Treyer, Valerie; Weber, Bruno; Neri, Dario; Buck, Alfred

    2006-01-01

    Despite aggressive treatment protocols, patients suffering from glioblastoma multiforme still experience poor outcome. Therefore, new adjuvant therapeutic options such as radioimmunotherapy (RIT) have been studied and have resulted in significant survival benefit. In this study, we assessed the efficacy of a novel radioimmunotherapeutic approach targeting the extra domain B (EDB) of fibronectin, a marker of angiogenesis, in glioma-bearing rats. Methods: C6 gliomas were induced intracerebrally in Wistar rats. Ten to 11 days later, 220-360 MBq of iodine-131-labeled anti-EDB SIP(L19) ('small immunoprotein') was administered intravenously into nine animals, yielding a radiation dose of 13-21 Gy. Another nine rats served as controls. Then the following parameters were compared: median survival time, tumor size and histology. Results: Histological examination of the tumors revealed typical glioblastoma characteristics. Eleven of 18 rats developed a tumor size bigger than 150 mm 3 . When these animals were used for survival analysis, median survival did significantly differ between groups [22 days (therapy; n=7) vs. 16 days (control; n=4); P 131 I-SIP(L19)-RIT showed promising potential in treating C6 gliomas, warranting further studies. However, larger trials with preferentially higher doses are needed to confirm this finding and, potentially, to further increase the efficacy of this treatment

  10. Comparison of Therapeutic Efficacies of Norethisterone, Tranexamic Acid and Levonorgestrel-Releasing Intrauterine System for the Treatment of Heavy Menstrual Bleeding: A Randomized Controlled Study.

    Science.gov (United States)

    Kiseli, Mine; Kayikcioglu, Fulya; Evliyaoglu, Ozlem; Haberal, Ali

    2016-01-01

    Our aim was to compare the therapeutic efficacies of norethisterone acid (NETA), tranexamic acid and levonorgestrel-releasing intrauterine system (LNG-IUS) in treating idiopathic heavy menstrual bleeding (HMB). Women with heavy uterine bleeding were randomized to receive NETA, tranexamic acid or LNG-IUS for 6 months. The primary outcome was a decrease in menstrual bleeding as assessed by pictorial blood loss assessment charts and hematological parameters analyzed at the 1st, 3rd and 6th months. Health-related quality of life (QOL) variables were also recorded and analyzed. Twenty-eight patients were enrolled in each treatment group, but the results of only 62 were evaluated. NETA, tranexamic acid, and LNG-IUS reduced menstrual blood loss (MBL) by 53.1, 60.8, and 85.8%, respectively, at the 6th month. LNG-IUS was more effective than NETA and tranexamic acid in decreasing MBL. LNG-IUS was also more efficient than tranexamic acid in correcting anemia related to menorrhagia. Satisfaction rates were comparable among the NETA (70%), tranexamic acid (63%) and LNG-IUS (77%) groups. QOL in physical aspects increased significantly in the tranexamic acid and LNG-IUS groups. The positive effect of LNG-IUS on QOL parameters, as well as its high efficacy, makes it a first-line option for HMB. © 2016 S. Karger AG, Basel.

  11. Application in the STRATHE trial of a score system to compare the efficacy and the tolerability of different therapeutic strategies in the management of hypertension

    Directory of Open Access Journals (Sweden)

    Bernard Waeber

    2008-02-01

    Full Text Available Bernard Waeber1, Jean-Jacques Mourad21Division de Physiopathologie Clinique, Centre Hospitalier Universitaire Vaudois et Université de Lausanne, Lausanne, Switzerland; 2Hôpital Avicienne, Bobigny, FranceAbstract: A score system integrating the evolution of efficacy and tolerability over time was applied to a subpopulation of the STRATHE trial, a trial performed according to a parallel group design, with a double-blind, random allocation to either a fixed-dose combination strategy (perindopril/indapamide 2 mg/0.625 mg, with the possibility to increase the dose to 3 mg/0.935 mg, and 4 mg/1.250 mg if needed, n = 118, a sequential monotherapy approach (atenolol 50 mg, followed by losartan 50 mg and amlodipine 5 mg if needed, n = 108, or a stepped-care strategy (valsartan 40 mg, followed by valsartan 80 mg and valsartan 80 mg+ hydrochlorothiazide 12.5 mg if needed, n = 103. The aim was to lower blood pressure below 140/90 mmHg within a 9-month period. The treatment could be adjusted after 3 and 6 months. Only patients in whom the study protocol was strictly applied were included in this analysis. At completion of the trial the total score averaged 13.1 ± 70.5 (mean ± SD using the fixed-dose combination strategy, compared with –7.2 ± 81.0 using the sequential monotherapy approach and –17.5 ± 76.4 using the stepped-care strategy. In conclusion, the use of a score system allows the comparison of antihypertensive therapeutic strategies, taking into account at the same time efficacy and tolerability. In the STRATHE trial the best results were observed with the fixed-dose combination containing low doses of an angiotensin enzyme converting inhibitor (perindopril and a diuretic (indapamide.Keywords: antihypertensive therapy, tolerability, antihypertensive efficacy, fixed-dose combination, sequential monotherapy, stepped-care treatment

  12. Therapeutic response assessment of high intensity focused ultrasound therapy for uterine fibroid: Utility of contrast-enhanced ultrasonography

    International Nuclear Information System (INIS)

    Zhou Xiaodong; Ren Xiaolong; Zhang Jun; He Guangbin; Zheng Minjuan; Tian Xue; Li Li; Zhu Ting; Zhang Min; Wang Lei; Luo Wen

    2007-01-01

    Purpose: To assess the utility of contrast-enhanced ultrasonography (ceUS) in the assessment of the therapeutic response to high intensity focused ultrasound (HIFU) ablation in patients with uterine fibroid. Materials and methods: Sixty-four patients with a total of 64 uterine fibroids (mean: 5.3 ± 1.2 cm; range: 3.2-8.9 cm) treated with HIFU ablation under the ultrasound guidance were evaluated with ceUS after receiving an intravenous bolus injection of a microbubble contrast agent (SonoVue) within 1 week after intervention. We obtained serial ceUS images during the time period from beginning to 5 min after the initiation of the bolus contrast injection. All of the patients underwent a contrast enhanced MRI (ceMRI) and ultrasound guided needle puncture biopsy within 1 week after HIFU ablation. And as a follow-up, all of the patients underwent US at 1, 3, 6 and 12 months after HIFU treatment. The volume change was observed and compared to pre- and post-HIFU ablation. The results of the ceUS were compared with those of the ceMRI in terms of the presence or absence of residual unablated tumor and pathologic change in the treated lesions. Results: On ceUS, diagnostic accuracy was 100%, while residual unablated tumors were found in three uterine fibroids (4.7%) and failed treatment was found in eight uterine fibroids (12.5%). All the 11 fibroids were subjected to additional HIFU ablation. Of the 58 ablated fibroids without residual tumors on both the ceUS and ceMRI after the HIFU ablation, the volumes of all the fibroids decreased in different degrees during the 1 year follow-up USs. And histologic examinations confirmed findings of necrotic and viable tumor tissue, respectively. Conclusion: CEUS is potentially useful for evaluating the early therapeutic effect of percutaneous HIFU ablation for uterine fibroids

  13. The significance of the host inflammatory response on the therapeutic efficacy of cell therapies utilising human adult stem cells

    International Nuclear Information System (INIS)

    Navarro, Melba; Pu, Fanrong; Hunt, John A.

    2012-01-01

    Controlling the fate of implanted hMSCs is one of the major drawbacks to be overcome to realize tissue engineering strategies. In particular, the effect of the inflammatory environment on hMSCs behaviour is poorly understood. Studying and mimicking the inflammatory process in vitro is a very complex and challenging task that involves multiple variables. This research addressed the questions using in vitro co-cultures of primary derived hMSCs together with human peripheral blood mononucleated cells (PBMCs); the latter are key agents in the inflammatory process. This work explored the in vitro phenotypic changes of hMSCs in co-culture direct contact with monocytes and lymphocytes isolated from blood using both basal and osteogenic medium. Our findings indicated that hMSCs maintained their undifferentiated phenotype and pluripotency despite the contact with PBMCs. Moreover, hMSCs demonstrated increased proliferation and were able to differentiate specifically down the osteogenic lineage pathway. Providing significant crucial evidence to support the hypothesis that inflammation and host defence mechanisms could be utilised rather than avoided and combated to provide for the successful therapeutic application of stem cell therapies.

  14. Therapeutic Efficacy of Topically Applied Antioxidant Medicinal Plant Extracts in a Mouse Model of Experimental Dry Eye.

    Science.gov (United States)

    Choi, Won; Lee, Jee Bum; Cui, Lian; Li, Ying; Li, Zhengri; Choi, Ji Suk; Lee, Hyo Seok; Yoon, Kyung Chul

    2016-01-01

    Purpose. To investigate the therapeutic effects of topical administration of antioxidant medicinal plant extracts in a mouse model of experimental dry eye (EDE). Methods. Eye drops containing balanced salt solution (BSS) or 0.001%, 0.01%, and 0.1% extracts were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after desiccating stress. In addition, we evaluated the levels of interleukin- (IL-) 1β, tumor necrosis factor- (TNF-) α, IL-6, interferon- (IFN-) γ, and IFN-γ associated chemokines, percentage of CD4+C-X-C chemokine receptor type 3 positive (CXCR3+) T cells, goblet cell density, number of 4-hydroxy-2-nonenal (4-HNE) positive cells, and extracellular reactive oxygen species (ROS) production. Results. Compared to the EDE and BSS control groups, the mice treated with topical application of the 0.1% extract showed significant improvements in all clinical parameters, IL-1β, IL-6, TNF-α, and IFN-γ levels, percentage of CD4+CXCR3+ T cells, goblet cell density, number of 4-HNE-positive cells, and extracellular ROS production (P model mice.

  15. Therapeutic efficacy of the combination of doxorubicin-loaded liposomes with inertial cavitation generated by confocal ultrasound in AT2 Dunning rat tumour model.

    Science.gov (United States)

    Mestas, Jean-Louis; Fowler, R Andrew; Evjen, Tove J; Somaglino, Lucie; Moussatov, Alexei; Ngo, Jacqueline; Chesnais, Sabrina; Røgnvaldsson, Sibylla; Fossheim, Sigrid L; Nilssen, Esben A; Lafon, Cyril

    2014-09-01

    The combination of liposomal doxorubicin (DXR) and confocal ultrasound (US) was investigated for the enhancement of drug delivery in a rat tumour model. The liposomes, based on the unsaturated phospholipid dierucoylphosphocholine, were designed to be stable during blood circulation in order to maximize accumulation in tumour tissue and to release drug content upon US stimulation. A confocal US setup was developed for delivering inertial cavitation to tumours in a well-controlled and reproducible manner. In vitro studies confirm drug release from liposomes as a function of inertial cavitation dose, while in vivo pharmacokinetic studies show long blood circulation times and peak tumour accumulation at 24-48 h post intravenous administration. Animals injected 6 mg kg(-1) liposomal DXR exposed to US treatment 48 h after administration show significant tumour growth delay compared to control groups. A liposomal DXR dose of 3 mg kg(-1), however, did not induce any significant therapeutic response. This study demonstrates that inertial cavitation can be generated in such a fashion as to disrupt drug carrying liposomes which have accumulated in the tumour, and thereby increase therapeutic effect with a minimum direct effect on the tissue. Such an approach is an important step towards a therapeutic application of cavitation-induced drug delivery and reduced chemotherapy toxicity.

  16. Assessment of Safety and Functional Efficacy of Stem Cell-Based Therapeutic Approaches Using Retinal Degenerative Animal Models

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2017-01-01

    Full Text Available Dysfunction and death of retinal pigment epithelium (RPE and or photoreceptors can lead to irreversible vision loss. The eye represents an ideal microenvironment for stem cell-based therapy. It is considered an “immune privileged” site, and the number of cells needed for therapy is relatively low for the area of focused vision (macula. Further, surgical placement of stem cell-derived grafts (RPE, retinal progenitors, and photoreceptor precursors into the vitreous cavity or subretinal space has been well established. For preclinical tests, assessments of stem cell-derived graft survival and functionality are conducted in animal models by various noninvasive approaches and imaging modalities. In vivo experiments conducted in animal models based on replacing photoreceptors and/or RPE cells have shown survival and functionality of the transplanted cells, rescue of the host retina, and improvement of visual function. Based on the positive results obtained from these animal experiments, human clinical trials are being initiated. Despite such progress in stem cell research, ethical, regulatory, safety, and technical difficulties still remain a challenge for the transformation of this technique into a standard clinical approach. In this review, the current status of preclinical safety and efficacy studies for retinal cell replacement therapies conducted in animal models will be discussed.

  17. Safety and therapeutic efficacy of artesunate suppositories for treatment of malaria in children in Papua New Guinea.

    Science.gov (United States)

    Karunajeewa, Harin A; Kemiki, Adedayo; Alpers, Michael P; Lorry, Kerry; Batty, Kevin T; Ilett, Kenneth F; Davis, Timothy M

    2003-03-01

    Although suppositories of artemisinin derivatives may be a valuable option for treatment of malaria in children when circumstances prevent oral and parenteral therapy, few confirmatory data have been published. We assessed the safety and efficacy of rectal artesunate in 47 children ages 5 to 10 years with uncomplicated malaria acquired in a hyperendemic area of Papua New Guinea. Thirty were symptomatic and had Plasmodium falciparum parasitemia >2000/microl (Group 1), 12 had and either a parasitemia suppositories were well-tolerated. After 24 h only one child (from Group 1) had persistent parasitemia, and only one (from Group 3) had not defervesced. These two children received intramuscular quinine and recovered uneventfully. Three Group 2 children redeveloped fever and tachycardia at 24 h, but each responded to simple supportive measures and remained aparasitemic. Intrarectal artesunate is safe, effective initial treatment for uncomplicated malaria in children. A transient fever spike can sometimes occur after parasite clearance. We recommend that children with uncomplicated malaria receive two doses of > or =10 mg/kg rectal artesunate within the first 24 h.

  18. Therapeutic efficacy of interleukin-2 activated killer cells against adriamycin resistant mouse B16-BL6 melanoma.

    Science.gov (United States)

    Gautam, S C; Chikkala, N F; Lewis, I; Grabowski, D R; Finke, J H; Ganapathi, R

    1992-01-01

    Development of multidrug-resistance (MDR) remains a major cause of failure in the treatment of cancer with chemotherapeutic agents. In our efforts to explore alternative treatment regimens for multidrug-resistant tumors we have examined the sensitivity of MDR tumor cell lines to lymphokine activated killer (LAK) cells. Adriamycin (ADM) resistant B16-BL6 melanoma, L1210 and P388 leukemic cell lines were tested for sensitivity to lysis by LAK cells in vitro. While ADM-resistant B16-BL6 and L1210 sublines were found to exhibit at least 2-fold greater susceptibility to lysis by LAK cells, sensitivity of ADM-resistant P388 cell was similar to that of parental cells. Since ADM-resistant B16-BL6 cells were efficiently lysed by LAK cells in vitro, the efficacy of therapy with LAK cells against the ADM-resistant B16-BL6 subline in vivo was evaluated. Compared to mice bearing parental B16-BL6 tumor cells, the adoptive transfer of LAK cells and rIL2 significantly reduced formation of experimental metastases (P less than 0.009) and extended median survival time (P less than 0.001) of mice bearing ADM-resistant B16-BL6 tumor cells. Results suggest that immunotherapy with LAK cells and rIL2 may be a useful modality in the treatment of cancers with the MDR phenotype.

  19. Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2013-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

  20. Therapeutic efficacy of guided tissue regeneration and connective tissue autotransplants with periosteum in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2008-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practice as an ethiological factor of periodontal diseases, and symptoms of the disease have caused the development of various surgical procedures and techniques of the reconstruction of periodontal defects. The aim of this study was to verify efficacy of surgical procedures that include connective tissue autotransplants with periosteum and guided tissue regeneration for the treatment of gingival recession. Methods. The study included 20 teet with gingival recession, Müller class II and III. Ten teeth with gingival recession were treated with resorptive membrane and coronary guided surgical flap (GTR group. On the contralateral side 10 teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (TVT group. We measured the degree of epithelial attachment (DEA, width of subgingival curettage (WGC and vertical deepness of recession (VDR. For statistical significance we used Student's ttest. Results. The study revealed statistical significance in reducing VDR by both used treatments. Root deepness in GTR and TVT group was 63.5%, and 90%, respectively. With both surgical techniques we achieved coronary dislocation of the epithelial attachment, larger zone of gingival curettage, and better oral hygiene. Conclusion. Current surgical techniques are effective in the regeneration of deep periodontal spaces and the treatment of gingival recession. Significantly better results were achieved with the used coronary guided surgical flap than with guided tissue regeneration.

  1. Therapeutic efficacy and toxicity of {sup 225}Ac-labelled vs. {sup 213}Bi-labelled tumour-homing peptides in a preclinical mouse model of peritoneal carcinomatosis

    Energy Technology Data Exchange (ETDEWEB)

    Essler, Markus; Gaertner, Florian C.; Blechert, Birgit; Senekowitsch-Schmidtke, Reingard; Seidl, Christof [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Neff, Frauke [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-04-15

    Targeted delivery of alpha-particle-emitting radionuclides is a promising novel option in cancer therapy. We generated stable conjugates of the vascular tumour-homing peptide F3 both with {sup 225}Ac and {sup 213}Bi that specifically bind to nucleolin on the surface of proliferating tumour cells. The aim of our study was to determine the therapeutic efficacy of {sup 225}Ac-DOTA-F3 in comparison with that of {sup 213}Bi-DTPA-F3. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were determined via clonogenic assays. The therapeutic efficacy of both constructs was assayed by repeated treatment of mice bearing intraperitoneal MDA-MB-435 xenograft tumours. Therapy was monitored by bioluminescence imaging. Nephrotoxic effects were analysed by histology. ID{sub 50} values of {sup 213}Bi-DTPA-F3 and {sup 225}Ac-DOTA-F3 were 53 kBq/ml and 67 Bq/ml, respectively. The median survival of control mice treated with phosphate-buffered saline was 60 days after intraperitoneal inoculation of 1 x 10{sup 7} MDA-MB-435 cells. Therapy with 6 x 1.85 kBq of {sup 225}Ac-DOTA-F3 or 6 x 1.85 MBq of {sup 213}Bi-DTPA-F3 prolonged median survival to 95 days and 97 days, respectively. While F3 labelled with short-lived {sup 213}Bi (t{sub 1/2} 46 min) reduced the tumour mass at early time-points up to 30 days after treatment, the antitumour effect of {sup 225}Ac-DOTA-F3 (t{sub 1/2} 10 days) increased at later time-points. The difference in the fraction of necrotic cells after treatment with {sup 225}Ac-DOTA-F3 (43%) and with {sup 213}Bi-DTPA-F3 (36%) was not significant. Though histological analysis of kidney samples revealed acute tubular necrosis and tubular oedema in 10-30% of animals after treatment with {sup 225}Ac-DOTA-F3 or {sup 213}Bi-DTPA-F3, protein casts were negligible (2%), indicating only minor damage to the kidney. Therapy with both {sup 225}Ac-DOTA-F3 and {sup 213}Bi-DTPA-F3 increased survival of mice with peritoneal carcinomatosis. Mild renal toxicity of both

  2. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

    2011-01-15

    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  3. Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations.

    Science.gov (United States)

    Barua, Neil U; Gill, Steven S; Love, Seth

    2014-03-01

    Convection-enhanced delivery (CED) describes a direct method of drug delivery to the brain through intraparenchymal microcatheters. By establishing a pressure gradient at the tip of the infusion catheter in order to exploit bulk flow through the interstitial spaces of the brain, CED offers a number of advantages over conventional drug delivery methods-bypass of the blood-brain barrier, targeted distribution through large brain volumes and minimization of systemic side effects. Despite showing early promise, CED is yet to fulfill its potential as a mainstream strategy for the treatment of neurological disease. Substantial research effort has been dedicated to optimize the technology for CED and identify the parameters, which govern successful drug distribution. It seems likely that successful clinical translation of CED will depend on suitable catheter technology being used in combination with drugs with optimal physicochemical characteristics, and on neuropathological analysis in appropriate preclinical models. In this review, we consider the factors most likely to influence the success or failure of CED, and review its application to the treatment of high-grade glioma, Parkinson's disease (PD) and Alzheimer's disease (AD). © 2013 International Society of Neuropathology.

  4. The efficacy of a brief motivational enhancement education program on CPAP adherence in OSA: a randomized controlled trial.

    Science.gov (United States)

    Lai, Agnes Y K; Fong, Daniel Y T; Lam, Jamie C M; Weaver, Terri E; Ip, Mary S M

    2014-09-01

    Poor adherence to CPAP treatment in OSA adversely affects the effectiveness of this therapy. This randomized controlled trial (RCT) examined the efficacy of a brief motivational enhancement education program in improving adherence to CPAP treatment in subjects with OSA. Subjects with newly diagnosed OSA were recruited into this RCT. The control group received usual advice on the importance of CPAP therapy and its care. The intervention group received usual care plus a brief motivational enhancement education program directed at enhancing the subjects' knowledge, motivation, and self-efficacy to use CPAP through the use of a 25-min video, a 20-min patient-centered interview, and a 10-min telephone follow-up. Self-reported daytime sleepiness adherence-related cognitions and quality of life were assessed at 1 month and 3 months. CPAP usage data were downloaded at the completion of this 3-month study. One hundred subjects with OSA (mean ± SD, age 52 ± 10 years; Epworth Sleepiness Scales [ESS], 9 ± 5; median [interquartile range] apnea-hypopnea index, 29 [20, 53] events/h) prescribed CPAP treatment were recruited. The intervention group had better CPAP use (higher daily CPAP usage by 2 h/d [Cohen d = 1.33, P motivational enhancement education in addition to usual care were more likely to show better adherence to CPAP treatment, with greater improvements in treatment self-efficacy and daytime sleepiness. ClinicalTrials.gov; No.: NCT01173406; URL: www.clinicaltrials.gov.

  5. Neferine augments therapeutic efficacy of cisplatin through ROS- mediated non-canonical autophagy in human lung adenocarcinoma (A549 cells).

    Science.gov (United States)

    Kalai Selvi, Sivalingam; Vinoth, Amirthalingam; Varadharajan, Thiyagarajan; Weng, Ching Feng; Vijaya Padma, Viswanadha

    2017-05-01

    Combination of dietary components with chemotherapy drugs is an emerging new strategy for cancer therapy to increase antitumor responses. Neferine, major bisbenzylisoquinoline alkaloid isolated from the seed embryo of Nelumbo nucifera (Lotus). In the present study, we investigated the efficacy of the combinatorial regimen of neferine and cisplatin compared to cisplatin high dose in human lung adenocarcinoma (A549) cells. Co-treatment with neferine enhanced cisplatin-induced autophagy in A549 cells was accompanied by Acidic vesicular accumulation (AVO), enhanced generation of reactive oxygen species (ROS) and depletion of intracellular glutathione (GSH), down regulation of PI3K/AKT/mTOR pathway, conversion of LC3B-I to LC3B-II. This enhanced autophagy developed via a non-canonical mechanism that did not require Beclin-1, PI3KCIII. In conclusion, these results suggest that neferine enhances cisplatin -induced autophagic cancer cell death through downregulation of PI3K/Akt/mTOR signaling pro-survival pathway and ROS- mediated Beclin-1 and PI3K CIII independent autophagy in human lung adenocarcinoma (A549 cells). Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Therapeutic efficacy of human hepatocyte transplantation in a SCID/uPA mouse model with inducible liver disease.

    Directory of Open Access Journals (Sweden)

    Donna N Douglas

    2010-02-01

    Full Text Available Severe Combined Immune Deficient (SCID/Urokinase-type Plasminogen Activator (uPA mice undergo liver failure and are useful hosts for the propagation of transplanted human hepatocytes (HH which must compete with recipient-derived hepatocytes for replacement of the diseased liver parenchyma. While partial replacement by HH has proven useful for studies with Hepatitis C virus, complete replacement of SCID/uPA mouse liver by HH has never been achieved and limits the broader application of these mice for other areas of biomedical research. The herpes simplex virus type-1 thymidine kinase (HSVtk/ganciclovir (GCV system is a powerful tool for cell-specific ablation in transgenic animals. The aim of this study was to selectively eliminate murine-derived parenchymal liver cells from humanized SCID/uPA mouse liver in order to achieve mice with completely humanized liver parenchyma. Thus, we reproduced the HSVtk (vTK/GCV system of hepatic failure in SCID/uPA mice.In vitro experiments demonstrated efficient killing of vTK expressing hepatoma cells after GCV treatment. For in vivo experiments, expression of vTK was targeted to the livers of FVB/N and SCID/uPA mice. Hepatic sensitivity to GCV was first established in FVB/N mice since these mice do not undergo liver failure inherent to SCID/uPA mice. Hepatic vTK expression was found to be an integral component of GCV-induced pathologic and biochemical alterations and caused death due to liver dysfunction in vTK transgenic FVB/N and non-transplanted SCID/uPA mice. In SCID/uPA mice with humanized liver, vTK/GCV caused death despite extensive replacement of the mouse liver parenchyma with HH (ranging from 32-87%. Surprisingly, vTK/GCV-dependent apoptosis and mitochondrial aberrations were also localized to bystander vTK-negative HH.Extensive replacement of mouse liver parenchyma by HH does not provide a secure therapeutic advantage against vTK/GCV-induced cytotoxicity targeted to residual mouse hepatocytes

  7. Ibrutinib enhances chimeric antigen receptor T-cell engraftment and efficacy in leukemia.

    Science.gov (United States)

    Fraietta, Joseph A; Beckwith, Kyle A; Patel, Prachi R; Ruella, Marco; Zheng, Zhaohui; Barrett, David M; Lacey, Simon F; Melenhorst, Jan Joseph; McGettigan, Shannon E; Cook, Danielle R; Zhang, Changfeng; Xu, Jun; Do, Priscilla; Hulitt, Jessica; Kudchodkar, Sagar B; Cogdill, Alexandria P; Gill, Saar; Porter, David L; Woyach, Jennifer A; Long, Meixiao; Johnson, Amy J; Maddocks, Kami; Muthusamy, Natarajan; Levine, Bruce L; June, Carl H; Byrd, John C; Maus, Marcela V

    2016-03-03

    Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is highly promising but requires robust T-cell expansion and engraftment. A T-cell defect in chronic lymphocytic leukemia (CLL) due to disease and/or therapy impairs ex vivo expansion and response to CAR T cells. To evaluate the effect of ibrutinib treatment on the T-cell compartment in CLL as it relates to CAR T-cell generation, we examined the phenotype and function of T cells in a cohort of CLL patients during their course of treatment with ibrutinib. We found that ≥5 cycles of ibrutinib therapy improved the expansion of CD19-directed CAR T cells (CTL019), in association with decreased expression of the immunosuppressive molecule programmed cell death 1 on T cells and of CD200 on B-CLL cells. In support of these findings, we observed that 3 CLL patients who had been treated with ibrutinib for ≥1 year at the time of T-cell collection had improved ex vivo and in vivo CTL019 expansion, which correlated positively together and with clinical response. Lastly, we show that ibrutinib exposure does not impair CAR T-cell function in vitro but does improve CAR T-cell engraftment, tumor clearance, and survival in human xenograft models of resistant acute lymphocytic leukemia and CLL when administered concurrently. Our collective findings indicate that ibrutinib enhances CAR T-cell function and suggest that clinical trials with combination therapy are warranted. Our studies demonstrate that improved T-cell function may also contribute to the efficacy of ibrutinib in CLL. These trials were registered at www.clinicaltrials.gov as #NCT01747486, #NCT01105247, and #NCT01217749. © 2016 by The American Society of Hematology.

  8. The efficacy of downhill running as a method to enhance running economy in trained distance runners.

    Science.gov (United States)

    Shaw, Andrew J; Ingham, Stephen A; Folland, Jonathan P

    2018-06-01

    Running downhill, in comparison to running on the flat, appears to involve an exaggerated stretch-shortening cycle (SSC) due to greater impact loads and higher vertical velocity on landing, whilst also incurring a lower metabolic cost. Therefore, downhill running could facilitate higher volumes of training at higher speeds whilst performing an exaggerated SSC, potentially inducing favourable adaptations in running mechanics and running economy (RE). This investigation assessed the efficacy of a supplementary 8-week programme of downhill running as a means of enhancing RE in well-trained distance runners. Nineteen athletes completed supplementary downhill (-5% gradient; n = 10) or flat (n = 9) run training twice a week for 8 weeks within their habitual training. Participants trained at a standardised intensity based on the velocity of lactate turnpoint (vLTP), with training volume increased incrementally between weeks. Changes in energy cost of running (E C ) and vLTP were assessed on both flat and downhill gradients, in addition to maximal oxygen uptake (⩒O 2max). No changes in E C were observed during flat running following downhill (1.22 ± 0.09 vs 1.20 ± 0.07 Kcal kg -1  km -1 , P = .41) or flat run training (1.21 ± 0.13 vs 1.19 ± 0.12 Kcal kg -1  km -1 ). Moreover, no changes in E C during downhill running were observed in either condition (P > .23). vLTP increased following both downhill (16.5 ± 0.7 vs 16.9 ± 0.6 km h -1 , P = .05) and flat run training (16.9 ± 0.7 vs 17.2 ± 1.0 km h -1 , P = .05), though no differences in responses were observed between groups (P = .53). Therefore, a short programme of supplementary downhill run training does not appear to enhance RE in already well-trained individuals.

  9. Protection Motivation and Self-Efficacy: A Model of Health Enhancement.

    Science.gov (United States)

    Stanley, Melinda A.

    Protection motivation theory proposes that a perceived threat to health activates cognitive appraisals of the severity of the threatened event, the probability of its occurrence, and the efficacy of a coping response; a recent reformulation of the theory incorporates self-efficacy expectancy as a fourth mediating cognitive process. To test the…

  10. Comparison of Efficacy and Safety of Different Therapeutic Regimens as 
Second-line Treatment for Small Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Zhihua LI

    2015-05-01

    Full Text Available Background and objective Small-cell lung cancer (SCLC is an aggressive disease for which the mainstay of treatment is cytotoxic chemotherapy. Despite good initial responses most patients will relapse or progress after the first-line therapy. The evidence of a benefit from second-line chemotherapy is limited in patients with relapsed/advanced SCLC. Some drugs are recommended by guidelines, but more regimens are formulated based on experience in clinical. So we conducted this retrospective study in order to compare the efficacy and safety of different second-line treatment regimens. Methods We totally analyzed 309 patients received second-line treatment in our retrospective study. 157 patients received best supportive care (BSC, and the rest 152 patients received second-line chemotherapy. The Kaplan-Meier method survival curves and Log-rank test were used to analysis the differences among different groups. The endpoints were objective response rate (ORR, disease control rate (DCR, progression-free survival (PFS, and overall survival (OS. Results Patients administered second-line chemotherapy lived significantly longer, with a total OS from first-line therapy of 11.5 mo compared to 6.0 mo in patients with best supportive care alone (P<0.001, and the ORR, DCR, PFS and OS of the former (including the sensitive disease and resistance/refractory disease patients were obviously better than that of the latter. The ORR and DCR of the patients who received second-line chemotherapy is 39.5% and 59.2%, respectively. The median PFS and OS from second-line chemotherapy were 3.3 mo and 5.3 mo. The patients who received second-line chemotherapy were divided by types of second-line regimens. The sensitive disease patients were from group A (VP-16-based rechallenge and group B1 (CPT-11-based regimen. The ORR of the two groups were 48.6% and 35.3%, and the DCR were 68.6% and 58.8%, respectively. There was no statistically significant difference (P=0.264; P=0

  11. Phospholipase A2 activation as a therapeutic approach for cognitive enhancement in early-stage Alzheimer disease.

    Science.gov (United States)

    Schaeffer, Evelin L; Forlenza, Orestes V; Gattaz, Wagner F

    2009-01-01

    Alzheimer disease (AD) is the leading cause of dementia in the elderly and has no known cure. Evidence suggests that reduced activity of specific subtypes of intracellular phospholipases A2 (cPLA2 and iPLA2) is an early event in AD and may contribute to memory impairment and neuropathology in the disease. The objective of this study was to review the literature focusing on the therapeutic role of PLA2 stimulation by cognitive training and positive modulators, or of supplementation with arachidonic acid (PLA2 product) in facilitating memory function and synaptic transmission and plasticity in either research animals or human subjects. MEDLINE database was searched (no date restrictions) for published articles using the keywords Alzheimer disease (mild, moderate, severe), mild cognitive impairment, healthy elderly, rats, mice, phospholipase A(2), phospholipid metabolism, phosphatidylcholine, arachidonic acid, cognitive training, learning, memory, long-term potentiation, protein kinases, dietary lipid compounds, cell proliferation, neurogenesis, and neuritogenesis. Reference lists of the identified articles were checked to select additional studies of interest. Overall, the data suggest that PLA2 activation is induced in the healthy brain during learning and memory. Furthermore, learning seems to regulate endogenous neurogenesis, which has been observed in AD brains. Finally, PLA2 appears to be implicated in homeostatic processes related to neurite outgrowth and differentiation in both neurodevelopmental processes and response to neuronal injury. The use of positive modulators of PLA2 (especially of cPLA2 and iPLA2) or supplementation with dietary lipid compounds (e.g., arachidonic acid) in combination with cognitive training could be a valuable therapeutic strategy for cognitive enhancement in early-stage AD.

  12. Enhanced efficacy of combined {sup 213}Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    Energy Technology Data Exchange (ETDEWEB)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Gilbertz, Klaus-Peter [German Armed Forces, Institute of Radiobiology, Munich (Germany); Baumgart, Anja [Technische Universitaet Muenchen, III. Medical Department, Munich (Germany); Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K. [Helmholtz Zentrum Muenchen, Institute of Pathology, Neuherberg (Germany); Bruchertseifer, Frank; Morgenstern, Alfred [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2012-12-15

    Targeted therapy with {alpha}-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the {alpha}-emitter {sup 213}Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined {sup 213}Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with {sup 213}Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined {sup 213}Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either {sup 213}Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with {sup 213}Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 {mu}g) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with {sup 213}Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either {sup 213}Bi-DTPA-F3 or paclitaxel alone. Combined treatment with {sup 213}Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  13. Enhanced efficacy of combined 213Bi-DTPA-F3 and paclitaxel therapy of peritoneal carcinomatosis is mediated by enhanced induction of apoptosis and G2/M phase arrest

    International Nuclear Information System (INIS)

    Vallon, Mario; Seidl, Christof; Blechert, Birgit; Li, Zhoulei; Gaertner, Florian C.; Senekowitsch-Schmidtke, Reingard; Essler, Markus; Gilbertz, Klaus-Peter; Baumgart, Anja; Aichler, Michaela; Feuchtinger, Annette; Walch, Axel K.; Bruchertseifer, Frank; Morgenstern, Alfred

    2012-01-01

    Targeted therapy with α-particle emitting radionuclides is a promising new option in cancer therapy. Stable conjugates of the vascular tumour-homing peptide F3 with the α-emitter 213 Bi specifically target tumour cells. The aim of our study was to determine efficacy of combined 213 Bi-diethylenetriaminepentaacetic acid (DTPA)-F3 and paclitaxel treatment compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel both in vitro and in vivo. Cytotoxicity of treatment with 213 Bi-DTPA-F3 and paclitaxel, alone or in combination, was assayed towards OVCAR-3 cells using the alamarBlue assay, the clonogenic assay and flow cytometric analyses of the mode of cell death and cell cycle arrest. Therapeutic efficacy of the different treatment options was assayed after repeated treatment of mice bearing intraperitoneal OVCAR-3 xenograft tumours. Therapy monitoring was performed by bioluminescence imaging and histopathologic analysis. Treatment of OVCAR-3 cells in vitro with combined 213 Bi-DTPA-F3 and paclitaxel resulted in enhanced cytotoxicity, induction of apoptosis and G2/M phase arrest compared to treatment with either 213 Bi-DTPA-F3 or paclitaxel. Accordingly, i.p. xenograft OVCAR-3 tumours showed the best response following repeated (six times) combined therapy with 213 Bi-DTPA-F3 (1.85 MBq) and paclitaxel (120 μg) as demonstrated by bioluminescence imaging and histopathologic investigation of tumour spread on the mesentery of the small and large intestine. Moreover, mean survival of xenograft mice that received combined therapy with 213 Bi-DTPA-F3 and paclitaxel was significantly superior to mice treated with either 213 Bi-DTPA-F3 or paclitaxel alone. Combined treatment with 213 Bi-DTPA-F3 and paclitaxel significantly increased mean survival of mice with peritoneal carcinomatosis of ovarian origin, thus favouring future therapeutic application. (orig.)

  14. Gold nanorod-mediated hyperthermia enhances the efficacy of HPMA copolymer-90Y conjugates in treatment of prostate tumors

    International Nuclear Information System (INIS)

    Buckway, Brandon; Frazier, Nick; Gormley, Adam J.; Ray, Abhijit; Ghandehari, Hamidreza

    2014-01-01

    Introduction: The treatment of prostate cancer using a radiotherapeutic 90 Y labeled N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer can be enhanced with localized tumor hyperthermia. An 111 In labeled HPMA copolymer system for single photon emission computerized tomography (SPECT) was developed to observe the biodistribution changes associated with hyperthermia. Efficacy studies were conducted in prostate tumor bearing mice using the 90 Y HPMA copolymer with hyperthermia. Methods: HPMA copolymers containing 1, 4, 7, 10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) were synthesized by reversible addition-fragmentation transfer (RAFT) copolymerization and subsequently labeled with either 111 In for imaging or 90 Y for efficacy studies. Radiolabel stability was characterized in vitro with mouse serum. Imaging and efficacy studies were conducted in DU145 prostate tumor bearing mice. Imaging was performed using single photon emission computerized tomography (SPECT). Localized mild tumor hyperthermia was achieved by plasmonic photothermal therapy using gold nanorods. Results: HPMA copolymer-DOTA conjugates demonstrated efficient labeling and stability for both radionuclides. Imaging analysis showed a marked increase of radiolabeled copolymer within the hyperthermia treated prostate tumors, with no significant accumulation in non-targeted tissues. The greatest reduction in tumor growth was observed in the hyperthermia treated tumors with 90 Y HPMA copolymer conjugates. Histological analysis confirmed treatment efficacy and safety. Conclusion: HPMA copolymer-DOTA conjugates radiolabeled with both the imaging and treatment radioisotopes, when combined with hyperthermia can serve as an image guided approach for efficacious treatment of prostate tumors

  15. A comparison of targeting of neuroblastoma with mIBG and anti L1-CAM antibody mAb chCE7: therapeutic efficacy in a neuroblastoma xenograft model and imaging of neuroblastoma patients

    NARCIS (Netherlands)

    Hoefnagel, C. A.; Rutgers, M.; Buitenhuis, C. K.; Smets, L. A.; de Kraker, J.; Meli, M.; Carrel, F.; Amstutz, H.; Schubiger, P. A.; Novak-Hofer, I.

    2001-01-01

    Iodine-131 labelled anti L1-CAM antibody mAb chCE7 was compared with the effective neuroblastoma-seeking agent 131I-labelled metaiodobenzylguanidine (MIBG) with regard to (a) its therapeutic efficacy in treating nude mice with neuroblastoma xenografts and (b) its tumour targeting ability in

  16. Evaluation of pulmonary hypertension and surgical therapeutic efficacy using first-pass radionuclide pulmonary perfusion imaging in patients with pulmonary hypertension of valvular heart disease

    International Nuclear Information System (INIS)

    Wang Xuemei; Shi Rongfang; Fang Wei; Wang Daoyu; Zhou Baogui; Wang Qi; Pan Shiwei

    2004-01-01

    Objective: To evaluate pulmonary hypertension (PH) and surgical therapeutic efficacy using first-pass radionuclide pulmonary perfusion imaging (FPPPI) and pulmonary perfusion imaging (PPI) in patients with PH of valvular heart disease. Methods: One hundred and sixteen patients with valvular disease were included in the study. Swan-Ganz catheterization, echocardiography, FPPPI and PPI were performed on all patients before surgery. The patients were divided into four groups. Results: 1) Correlation coefficients were 0.856, 0.503 and 0.572 (P<0.01) between lung equilibrium time (LET) by FPPPI, superior lung/low lung ratio (S/L) by PPI , systolic pulmonary arterial pressure (SPAP) from echocardiography and SPAP from the catheter manometer. 2)The sensitivity, specificity and accuracy of PAP using FPPPI measuring were 94.7%, 68.3% and 85.3%, respectively. The sensitivity, specificity and accuracy of PAP using PPI measuring were 78.8%, 52.8% and 70.7%, respectively. The sensitivity, specificity and accuracy of PAP using FPPPI plus PPI measuring were 96.4%, 72.7% and 89.7%, respectively. 3)LET by FPPPI before surgery and 5-14 d after surgery were (27.71 ± 10.85) and (20.96 ± 6.25) s, respectively (P<0.001). SPL by PPI were 1.43 ± 0.41 and 1.30 ± 0.35, respectively (P<0.001). 4) Complete improvement rates of LET in the PAP slightly risen group, moderately risen group and weightily risen group were 47.6%, 34.5% and 1/4, respectively; part improvement rates of LET for corresponding groups were 40.5%, 62.1% and 3/4, respectively (P<0.001). Complete improvement rates of SPL were 31.0%, 34.5% and 0/4, respectively; part improvement rates of SPL were 35.7%, 55.2% and 3/4, respectively (P<0.05). Complete improvement rates of LET + SPL were 57.1%, 58.6% and 1/4; part improvement rates of LET+SPL were 38.1%, 41.4% and 3/4, respectively (P<0.01). Conclusions: 1)FPPPI is better than PPI and echocardiography for evaluating PH in valvular heart disease. 2)Combined FPPPI and PPI can

  17. Therapeutic efficacy of milbemycin oxime/praziquantel oral formulation (Milbemax® against Thelazia callipaeda in naturally infested dogs and cats

    Directory of Open Access Journals (Sweden)

    Motta Bruna

    2012-05-01

    Full Text Available Abstract Background Over the last few decades, canine and feline thelaziosis caused by Thelazia callipaeda eye worms has gained the attention of the veterinary community due to the spread of this ocular infestation in geographical areas previously regarded as non endemic. The therapeutic efficacy of milbemycin oxime/praziquantel tablets (Milbemax® against T. callipaeda was tested in naturally infested dogs and cats. Methods From January 2009 to July 2011 a placebo controlled and randomized field study was conducted in T. callipaeda endemic areas of Switzerland (CH and Italy (ITA involving client-owned animals. Dogs (n = 56 and cats (n = 31 were physically examined at enrolment Day 0 (D0 and twice afterwards (D7 and D14. Infested animals were orally treated with Milbemax® or with placebo tablets on D0 and, if an animal was found still infested with T. callipaeda, also on D7. On D14 nematodes were flushed from the conjunctiva, identified and counted. Results Out of 56 dogs, 43 were included in the statistical analysis, whereas 13 were excluded because the products under investigation were not administered with food, as required by the label. On D7 and D14, 72.7% and 90.9% of treated dogs were eye worm free, whereas in the placebo group 95.2% and 76.2% still harbored nematodes, resulting in a mean percentage worm count reduction for the Milbemax® group of 86.1% and 96.8%, respectively. Both results were significantly higher (p = 0.0001 than the placebo group. Out of the 31 cats included in the study at D7 and D14, 53.3% and 73.3% treated with Milbemax® were free of T. callipaeda, while 81.3% and 73.3 in the placebo group were still harbouring eye worms, resulting in a mean percentage worm count reduction for the treated group of 62.2% and 80.0%, respectively. Both results were significantly higher (p = 0.0106 and p = 0.0043 than the placebo group. Conclusions The commercial formulation of milbemycin oxime at the minimal dose

  18. Characterization of the pharmacokinetics, brain distribution, and therapeutic efficacy of the adenosine A1 receptor partial agonist 2'-deoxy-N6-cyclopentyladenosine in sarin-poisoned rats

    International Nuclear Information System (INIS)

    Bueters, Tjerk J.H.; IJzerman, Ad P.; Helden, Herman P.M. van; Danhof, Meindert

    2003-01-01

    Characterization of the pharmacokinetics, brain distribution, and therapeutic efficacy of the adenosine A 1 receptor partial agonist 2'-deoxy-N 6 -cyclopentyladenosine in sarin-poisoned rats. Bueters, T.J.H., IJzerman, A.P., Van Helden, H.P.M., and Danhof, M. (2003). The objective of the present study was to determine (1) the influence of sarin poisoning (144 μg/kg sc) on the pharmacokinetics and brain distribution of the adenosine A 1 receptor partial agonist 2'-deoxy-N 6 -cyclopentyladenosine (2'dCPA), and (2) the effect of 2'dCPA (20 mg/kg iv) on the central acetylcholine (ACh) release and protection against sarin toxicity. A five-compartment model successfully described the pharmacokinetic profile of 2'dCPA in blood and brain microdialysate. A covariate analysis revealed that the volume of distribution of 2'dCPA in blood was different in sarin-poisoned rats, 177 ± 7 versus 148 ± 8 ml in control rats. However, the transport of 2'dCPA from blood to the brain was unaffected as reflected by the values of the intercompartmental transport clearances, 0.21 ± 0.02 and 0.21 ± 0.04 μl/min in control and sarin-poisoned rats, respectively. Also the area-under-curve (AUC) ratios of brain microdialysate and blood were identical with values of 0.02 ± 0.001 and 0.02 ± 0.002, respectively, demonstrating the restricted transport of 2'dCPA into the brain in both treatment groups. Treatment of sarin-poisoned rats by 2'dCPA did not adequately prevent the accumulation of ACh in the central nervous system. 2'dCPA delayed the emergence of concomitant symptoms compared to untreated rats, but eventually only 29% of the animals survived 24 h. In conclusion, the pharmacokinetic profile of 2'dCPA in blood was slightly changed by sarin, but not the distribution of 2'dCPA into the brain. The therapeutic efficacy of 2'dCPA against sarin was limited, presumably due to insufficient quantities of 2'dCPA reaching the brain

  19. Enhanced antitumor efficacy and reduced systemic toxicity of sulfatide-containing nanoliposomal doxorubicin in a xenograft model of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Jia Lin

    Full Text Available Sulfatide is a glycosphingolipid known to interact with several extracellular matrix proteins, such as tenascin-C which is overexpressed in many types of cancer including that of the colon. In view of the limited success of chemotherapy in colorectal cancer and high toxicity of doxorubicin (DOX, a sulfatide-containing liposome (SCL encapsulation approach was taken to overcome these barriers. This study assessed the in vitro cytotoxicity, biodistribution, therapeutic efficacy and systemic toxicity in vivo of sulfatide-containing liposomal doxorubicin (SCL-DOX using human colonic adenocarcinoma HT-29 xenograft as the experimental model. In vitro, SCL-DOX was shown to be delivered into the nuclei and displayed prolonged retention compared with the free DOX. The use of this nanodrug delivery system to deliver DOX for treatment of tumor-bearing mice produced a much improved therapeutic efficacy in terms of tumor growth suppression and extended survival in contrast to the free drug. Furthermore, treatment of tumor-bearing mice with SCL-DOX resulted in a lower DOX uptake in the principal sites of toxicity of the free drug, namely the heart and skin, as well as reduced myelosuppression and diminished cardiotoxicity. Such natural lipid-guided nanodrug delivery systems may represent a new strategy for the development of effective anticancer chemotherapeutics targeting the tumor microenvironment for both primary tumor and micrometastases.

  20. Comparative evaluation of therapeutic efficacy of sulfadiazine-trimethoprim, oxytetracycline, enrofloxacin and florfenicol on Staphylococcus aureus-induced arthritis in broilers.

    Science.gov (United States)

    Mosleh, N; Shomali, T; Namazi, F; Marzban, M; Mohammadi, M; Boroojeni, A Motamedi

    2016-04-01

    Staphylococcus aureus is an important human and veterinary pathogen that causes economic loss in the poultry industry. This study aimed to compare therapeutic efficacy of 4 commonly used antibiotics in poultry on S. aureus-induced arthritis in broilers. Sixty broilers, 8 weeks of age, were assigned at random into 7 groups as follows: (1) negative control (n = 5); (2) vehicle control (n = 5); (3) sulfadiazine-trimethoprim, 250 ml/1000 l drinking water (n = 10); (4) oxytetracycline 20%, 1 mg/l drinking water (n = 10); (5) florfenicol 10%, 1/1000 v/v in drinking water (n = 10); (6) enrofloxacin 10%, 1/1000 v/v in drinking water (n = 10) and (7) positive control (n = 10). Birds in group 2 were injected with 1 ml of sterile TSB medium into the right tibiotarsal joint on d 0 while other birds (except group 1) were challenged with 1 ml of 1.2 × 10(10) CFU/ml suspension of S. aureus bacteria. Antibiotic therapy was started from d 4 post challenge and continued for 5 d. At the end, birds were weighed and clinical severity of arthritis was determined. After blood collection, birds were slaughtered and tibiotarsal and hip joints were evaluated grossly. The content of inflammatory exudates of tibiotarsal joint and the degree of femoral head necrosis were recorded. Mucin clot test and histopathological evaluation were performed on right tibiotarsal joint. Serum interleukin 6 was also assayed. Sulfadiazine-trimethoprim had higher therapeutic efficiency with regard to most of the assayed criteria, whereas none of the antibiotics significantly affected femoral head necrosis and body weight. These data will help clinicians to have better antibiotic choice in field conditions.

  1. Therapeutic Efficacy of Fenugreek Extract or/and Choline with Docosahexaenoic Acid in Attenuating Learning and Memory Deficits in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Anjaneyulu K

    2018-04-01

    Full Text Available Background: Studies have demonstrated that estradiol influences cognitive functions. Phytoestrogens and many other estrogen-like compounds in plants have beneficial effects on cognitive performance in postmenopausal women. However, there is no evident report of fenugreek and choline-Docosahexaenoic Acid (DHA on cognition in ovariectomized rats. Aim and Objectives: The present study was aimed to evaluate the therapeutic efficacy of fenugreek extract or/and choline- DHA in attenuating ovariectomy-induced memory impairment, brain antioxidant status and hippocampal neural cell deficits in the rat model. Material and Methods: Female Wistar 9-10 months old rats were grouped (n=12/group as - (1 Normal Control (NC, (2 Ovariectomized (OVX, (3 OVX+FG (hydroalcoholic seed extract of fenugreek, (4 OVX+C-DHA,(5 OVX+FG+C-DHA and (6 OVX+Estradiol. Groups 2- 6 were bilaterally OVX. FG, C-DHA was supplemented orally for 30 days, 14 days after ovariectomy. Assessment of learning and memory was performed by passive avoidance test. Oxidative stress and antioxidant markers were assessed by standard methods. Nissl stained hippocampal sections were analyzed to determine alterations in neural cell numbers in CA1, CA3 and dentate gyrus. Results: Supplementation of FG or/and choline with DHA to OVX rats, caused significant improvement in learning and memory as well as decreased neural cell deficits compared to the same in OVX rats. Further, significantly reduced levels of brain Malondialdehyde (MDA and increased levels of Glutathione (GSH were observed. Conclusion: Therapeutic supplementation of FG with choline-DHA significantly attenuates ovariectomy-induced neurocognitive deficits in rats.

  2. The Jak2 Inhibitor, G6, Alleviates Jak2-V617F–Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow

    Directory of Open Access Journals (Sweden)

    Annet Kirabo

    2011-11-01

    Full Text Available We recently developed a Janus kinase 2 (Jak2 small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F– mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F–mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F–mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6. In the liver, G6 eliminated Jak2-V617F–driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the spleno-megaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho–signal transducer and activator of transcription 5 (STAT5. It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67% on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F–mediated myeloproliferative neoplasia.

  3. A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT

    Directory of Open Access Journals (Sweden)

    Lorf Thomas

    2010-04-01

    Full Text Available Abstract Background Immunosuppression with calcineurin inhibitors (CNI increases the risk of renal dysfunction after orthotopic liver transplantation (OLT. Controlled trials have shown improvement of renal function in patients that received delayed and/or reduced-dose CNI after OLT. Delaying immunosuppression with CNI in combination with induction therapy does not increase the risk of acute rejection but reduces the incidence of acute renal dysfunction. Based on this clinical data this study protocol was designed to assess the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation. Methods/Design A prospective therapeutic exploratory, non-placebo controlled, two stage monocenter trial in a total of 29 liver transplant patients was designed to assess the safety and efficacy of de-novo CNI-free immunosuppression with basiliximab, mycophenolate sodium, prednisolone and everolimus. The primary endpoint is the rate of steroid resistant rejections. Secondary endpoints are the incidence of acute rejection, kidney function (assessed by incidence and duration of renal replacement therapy, incidence of chronic renal failure, and measurement glomerular filtration rate, liver allograft function (assessed by measurement of AST, ALT, total bilirubin, AP, GGT, treatment failure, (i. e., re-introduction of CNI, incidence of adverse events, and mortality up to one year after OLT. Discussion This prospective, two-stage, single-group pilot study represents an intermediate element of the research chain. If the data of the phase II study corroborates safety of de-novo CNI-free immunosuppressive regimen this should be confirmed in a randomized, prospective, controlled double-blinded clinical trial. The exploratory data from this trial may then also facilitate the design (e. g. sample size calculation of this phase III trial. Trial registration number NCT00890253 (clinicaltrials.gov

  4. Providing Sources of Self-Efficacy Through Technology Enhanced Post-Stroke Rehabilitation in the Home.

    Science.gov (United States)

    Parker, Jack; Mawson, Susan

    2017-01-01

    This research explores the impact of receiving feedback through a Personalised Self-Managed Rehabilitation System (PSMrS) for home-based post-stroke rehabilitation on the users' self-efficacy; more specifically, mastery experiences and the interpretation of biomechanical data. Embedded within a realistic evaluation methodological approach, exploring the promotion of self-efficacy from the utilisation of computer-based technology to facilitate post-stroke upper-limb rehabilitation in the home included; semi-structured interviews, quantitative user data (activity and usage), observations and field notes. Data revealed that self-efficacy was linked with obtaining positive knowledge of results feedback. Encouragingly, this also transferred to functional activities such as, confidence to carry out kitchen tasks and bathroom personal activities. Findings suggest the PSMrS was able to provide key sources of self-efficacy by providing feedback which translated key biomechanical data to the users. Users could interpret and understand their performance, gain a sense of mastery and build their confidence which in some instances led to increased confidence to carry out functional activities. However, outcome expectations and socio-structural factors impacted on the self-efficacy associated with the use of the system. Increasing the understanding of how these factors promote or inhibit self-management and self-efficacy is therefore crucial to the successful adoption of technology solutions and promotion of self-efficacy.

  5. Efficacy of liver parenchymal enhancement and liver volume to standard liver volume ratio on Gd-EOB-DTPA-enhanced MRI for estimation of liver function

    Energy Technology Data Exchange (ETDEWEB)

    Yoneyama, Tomohide; Fukukura, Yoshihiko; Kamimura, Kiyohisa; Takumi, Koji; Umanodan, Aya; Nakajo, Masayuki [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Radiology, Kagoshima City (Japan); Ueno, Shinichi [Kagoshima University Graduate School of Medical and Dental Sciences, Department of Surgical Oncology and Digestive Surgery, Kagoshima City (Japan)

    2014-04-15

    We aimed to develop and assess the efficacy of a liver function index that combines liver enhancement and liver volume to standard liver volume (LV/SLV) ratio on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI. In all, 111 patients underwent a Gd-EOB-DTPA-enhanced MRI, including T1 mapping, before and 20 min after Gd-EOB-DTPA administration. We calculated the following Gd-EOB-DTPA-enhanced MRI-based liver function indices: relative enhancement of the liver, corrected enhancement of the liver-to-spleen ratio, LSC{sub N}20, increase rate of the liver-to-muscle ratio, reduction rate of T1 relaxation time of the liver, ΔR1 of the liver and K{sub Hep}; the indices were multiplied by the LV/SLV ratio. We calculated the correlations between an indocyanine green (ICG) clearance and the Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio, by using Pearson correlation analysis. There were significant correlations between all Gd-EOB-DTPA-enhanced MRI-based liver function indices and ICG clearance (r = -0.354 to -0.574, P < 0.001). All Gd-EOB-DTPA-enhanced MRI-based liver function indices multiplied by the LV/SLV ratio (r = -0.394 to -0.700, P < 0.001) were more strongly correlated with the ICG clearance than those without multiplication by the LV/SLV ratio. Gd-EOB-DTPA-enhanced MRI-based liver function indices that combine liver enhancement and the LV/SLV ratio may more reliably estimate liver function. (orig.)

  6. Automated digital image analysis of islet cell mass using Nikon's inverted eclipse Ti microscope and software to improve engraftment may help to advance the therapeutic efficacy and accessibility of islet transplantation across centers.

    Science.gov (United States)

    Gmyr, Valery; Bonner, Caroline; Lukowiak, Bruno; Pawlowski, Valerie; Dellaleau, Nathalie; Belaich, Sandrine; Aluka, Isanga; Moermann, Ericka; Thevenet, Julien; Ezzouaoui, Rimed; Queniat, Gurvan; Pattou, Francois; Kerr-Conte, Julie

    2015-01-01

    Reliable assessment of islet viability, mass, and purity must be met prior to transplanting an islet preparation into patients with type 1 diabetes. The standard method for quantifying human islet preparations is by direct microscopic analysis of dithizone-stained islet samples, but this technique may be susceptible to inter-/intraobserver variability, which may induce false positive/negative islet counts. Here we describe a simple, reliable, automated digital image analysis (ADIA) technique for accurately quantifying islets into total islet number, islet equivalent number (IEQ), and islet purity before islet transplantation. Islets were isolated and purified from n = 42 human pancreata according to the automated method of Ricordi et al. For each preparation, three islet samples were stained with dithizone and expressed as IEQ number. Islets were analyzed manually by microscopy or automatically quantified using Nikon's inverted Eclipse Ti microscope with built-in NIS-Elements Advanced Research (AR) software. The AIDA method significantly enhanced the number of islet preparations eligible for engraftment compared to the standard manual method (p image analysis utilizing the Nikon Instruments software is an unbiased, simple, and reliable teaching tool to comprehensively assess the individual size of each islet cell preparation prior to transplantation. Implementation of this technology to improve engraftment may help to advance the therapeutic efficacy and accessibility of islet transplantation across centers.

  7. Short-Term Therapeutic Efficacy of the Isobar TTL Dynamic Internal Fixation System for the Treatment of Lumbar Degenerative Disc Diseases.

    Science.gov (United States)

    Qian, Jiale; Bao, Zhaohua; Li, Xuefeng; Zou, Jun; Yang, Huilin

    2016-07-01

    At present, posterior interbody fusion surgery with pedicle internal fixation is the gold standard for the treatment of lumbar degenerative disc diseases. However, an increasing number of studies have shown that because fused lumbar vertebrae lose their physiological activity, the compensatory range of motion (ROM) of the adjacent levels increases. To address this issue, dynamic internal fixation systems have been developed. Our goal was to investigate the short-term therapeutic efficacy of the Isobar TTL dynamic internal fixation system for the treatment of lumbar degenerative disc diseases and its effect on the ROM of the surgical segments. Retrospective Evaluation. Tertiary hospital setting in China. Twenty-four lumbar degenerative disc disease patients who underwent posterior lumbar decompression and single-segment Isobar TTL dynamic internal fixation at our hospital between January 2013 and July 2014 were retrospectively analyzed. The preoperative and one month, 3 month, and 12 month postoperative visual analog scale (VAS) pain scores, Japanese Orthopedic Association (JOA) scores, and Oswestry Disability Index (ODI) scores were observed and recorded to assess the clinical therapeutic effect; the lumbar ROM was measured preoperatively and at the last follow-up to evaluate the preservation of functional movement in the dynamically stabilized segment. All patients underwent the operation successfully without complications during hospitalization and were followed for 12 to 27 months, with an average of 18 months. The patients' preoperative and one month, 3 month, and 12 month postoperative VAS scores were 6.42 ± 0.72, 1.71 ± 0.86, 1.38 ± 0.65, and 1.37 ± 0.58, respectively, and their JOA scores were 9.54 ± 1.89, 21.21 ± 1.98, 22.50 ± 1.47, and 23.46 ± 1.32, respectively. The preoperative ODI score was 42.04 ± 2.63; the one month, 3 month, and 12 month postoperative ODI scores were 22.79 ± 1.61, 18.63 ± 1.61, and 15.08 ± 1.21, respectively. These

  8. Enhanced antitumor efficacy and counterfeited cardiotoxicity of combinatorial oral therapy using Doxorubicin- and Coenzyme Q10-liquid crystalline nanoparticles in comparison with intravenous Adriamycin

    DEFF Research Database (Denmark)

    Swarnakar, Nitin K; Thanki, Kaushik; Jain, Sanyog

    2014-01-01

    and strong synergism for combination at 1:10 dose ratio owing to higher cellular uptake, nuclear colocalization, higher apoptotic index and 8-OHdG levels. The prophylactic antitumor efficacy of the CoQ10-LCNPs was also established using tumor induction and progression studies. Finally, therapeutic antitumor......, with Dox-induced-cardiotoxicity was completely counterfeited in combination. In nutshell, LCNPs pose great potential in improving the therapeutic efficacy of drugs by oral route of administration. FROM THE CLINICAL EDITOR: This study describes the use of liquid crystalline nanoparticles containing coenzyme...

  9. Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells

    Science.gov (United States)

    Ju, Jingfang

    2018-01-01

    Background Resistance to 5-Fluorouracil (5-FU) based chemotherapy is the major reason for failure of treating patients with advanced colorectal cancer. Materials and methods In this study, we developed a novel miR-129 mimic with potent efficacy in eliminating resistant colon cancer stem cells both in vitro and in vivo. We integrated 5-FU into miR-129 by replacing Uracil (U) to generate 5-FU-miR-129 mimics (Mimic-1). Results Mimic-1 is a strong therapeutic candidate with a number of unique features. Mimic-1 can be delivered to cancer cells without any transfection reagents (e.g. lipids, viral vector, nanoparticles). Mimic-1 is more potent at inhibiting cell proliferation and inducing cell cycle arrest at G1 phase than native miR-129 and the other mimics tested, while retaining target specificity. Mimic-1 prevents colon cancer metastasis in vivo without toxicity. Conclusion This represents a significant advancement in the development of a nontoxic and highly potent miRNA based cancer therapeutics and establishes a foundation for further developing Mimic-1 as a novel anti-cancer therapeutic for treating colorectal cancer. PMID:29507661

  10. Neural induction with neurogenin 1 enhances the therapeutic potential of mesenchymal stem cells in an amyotrophic lateral sclerosis mouse model.

    Science.gov (United States)

    Chan-Il, Choi; Young-Don, Lee; Heejaung, Kim; Kim, Seung Hyun; Suh-Kim, Haeyoung; Kim, Sung-Soo

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is characterized by progressive dysfunction and degeneration of motor neurons in the central nervous system (CNS). In the absence of effective drug treatments for ALS, stem cell treatment has emerged as a candidate therapy for this disease. To date, however, there is no consensus protocol that stipulates stem cell types, transplantation timing, or frequency. Using an ALS mouse model carrying a high copy number of a mutant human superoxide dismutase-1 (SOD1)(G93A) transgene, we investigated the effect of neural induction on the innate therapeutic potential of mesenchymal stem cells (MSCs) in relation to preclinical transplantation parameters. In our study, the expression of monocyte chemoattractant protein-1 (MCP-1) was elevated in the ALS mouse spinal cord. Neural induction of MSCs with neurogenin 1 (Ngn1) upregulated the expression level of the MCP-1 receptor, CCR2, and enhanced the migration activity toward MCP-1 in vitro. Ngn1-expressing MSCs (MSCs-Ngn1) showed a corresponding increase in tropism to the CNS after systemic transplantation in ALS mice. Notably, MSCs-Ngn1 delayed disease onset if transplanted during preonset ages,whereas unprocessed MSCs failed to do so. If transplanted near the onset ages, a single treatment with MSCs-Ngn1 was sufficient to enhance motor functions during the symptomatic period (15–17 weeks), whereas unprocessed MSCs required repeated transplantation to achieve similar levels of motor function improvement. Our data indicate that systemically transplanted MSCs-Ngn1 can migrate to the CNS and exert beneficial effects on host neural cells for an extended period of time through paracrine functions, suggesting a potential benefit of neural induction of transplanted MSCs in long-term treatment of ALS.

  11. Combining vascular and cellular targeting regimens enhances the efficacy of photodynamic therapy

    International Nuclear Information System (INIS)

    Chen Bin; Pogue, Brian W.; Hoopes, P. Jack; Hasan, Tayyaba

    2005-01-01

    Purpose: Photodynamic therapy (PDT) can be designed to target either tumor vasculature or tumor cells by varying the drug-light interval. Photodynamic therapy treatments with different drug-light intervals can be combined to increase tumor response by targeting both tumor vasculature and tumor cells. The sequence of photosensitizer and light delivery can influence the effect of combined treatments. Methods and materials: The R3327-MatLyLu rat prostate tumor model was used in this study. Photosensitizer verteporfin distribution was quantified by fluorescence microscopy. Tumor blood flow changes were monitored by laser-Doppler system and tumor hypoxia was quantified by the immunohistochemical staining for the hypoxic marker EF5. The therapeutic effects of PDT treatments were evaluated by the histologic examination and tumor regrowth assay. Results: Fluorescence microscopic studies indicated that tumor localization of verteporfin changed from predominantly within the tumor vasculature at 15 min after injection, to being throughout the tumor parenchyma at 3 h after injection. Light treatment (50 J/cm 2 ) at 15 min after verteporfin injection (0.25 mg/kg, i.v.) induced significant tumor vascular damage, as manifested by tumor blood flow reduction and increase in the tumor hypoxic fraction. In contrast, the vascular effect observed after the same light dose (50 J/cm 2 ) delivered 3 h after administration of verteporfin (1 mg/kg, i.v.) was an initial acute decrease in blood flow, followed by recovery to the level of control. The EF5 staining revealed no significant increase in hypoxic fraction at 1 h after PDT using 3 h drug-light interval. The combination of 3-h interval PDT and 15-min interval PDT was more effective in inhibiting tumor growth than each individual PDT treatment. However, it was found that the combined treatment with the sequence of 3-h interval PDT before 15-min interval PDT led to a superior antitumor effect than the other combinative PDT treatments

  12. Vaccination efficacy with marrow mesenchymal stem cell against cancer was enhanced under simulated microgravity

    International Nuclear Information System (INIS)

    Li, Jing; Chen, Jun; Li, Xiuyu; Qian, Yanfang

    2017-01-01

    Stem cell vaccination can induce consistent and strong anti-tumor immunity against cancer in mice model. The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine MSCs. Based on this conception, we first compared their tumor vaccines intervention effects of adult MSCs and MSCs under simulated microgravity (MSC/SMG). In this study, BALB/c mice were vaccinated with MSCs or MSC/SMG, compared with mice vaccinated with phosphate buffered saline (PBS) as negative controls. We then subcutaneously implanted the A549 human lung cancer cell line into vaccinated mice and monitored tumor growth potential in vivo. The smaller tumor size and less tumor weight were observed in mice vaccinated with MSCs or MSC/SMG, compared with that of the Control group. Particularly, it was much more significant in the group of MSC/SMG than that group of the MSCs. Vaccination with SMG treated MSCs inhibited proliferation and promoted apoptosis of tumor tissue. SMG/MSC vaccination induced bothTh1-mediated cytokine response; CD8-dependent cytotoxic response which reduced the proportion of Treg cells. Furthermore, SMG/MSC vaccination significantly increased MHC1 and HSPs proteins expression. In conclusion, we demonstrated the SMG could improve tumor-suppressive activity of MSC. The enhanced anti-tumor immune response of MSCs/SMG was strongly associated with the higher expression of MHC class I molecule on DCs, and the abundance of HSPs in the SMG treated MSCs may make antigens in the MSC more cross-presentable to the host DCs for generating protective antitumor activity. This study gains an insight into the mechanism of MSCs anti-tumor efficacy and gives a new strategy for cancer therapies in the future. - Highlights: • Vaccination with SMG

  13. Efficacy and safety of penile girth enhancement by autologous fat injection for patients with thin penises.

    Science.gov (United States)

    Kang, Dong Hyuk; Chung, Jae Hoon; Kim, Yong Jin; Lee, Haeng Nam; Cho, Seung Hoon; Chang, Taek Hee; Lee, Seung Wook

    2012-08-01

    This study aimed to investigate the efficacy and safety of autologous fat injection (AFI) for penile girth enhancement (PGE) in patients with thin penises. This study investigated 52 patients with a small penile circumference who underwent AFI for PGE and were followed up for more than 6 months. The patients whose proximal one third (G1) and distal one third of their penis (G2) had a mean thickness of 7.4 cm or less were selected as subjects. After fat suction using a liposuction device, fat was evenly injected into the superficial, middle, and deep layers of the Colles' fascia. Patient age and operative time were analyzed. The G1, G2, flaccid (L1), stretched length (L2), and five-item version of the International Index of Erectile Function-5 (IIEF-5) before and 6 months after the surgery were compared. Postoperative complications were surveyed. The patient mean age was 42.15 years (range, 22-56) years, and the operative time was 44.44 min (range, 37-49 min). The injected fat volume was 38.54 ml (range, 25-49 ml). Preoperatively, G1 was 7.01±0.39 cm, and G2 was 7.06±0.37 cm. Postoperatively, G1 was 9.29±0.82 cm (P<0.001), and G2 was 9.34±0.86 (P<0.001) cm 6 months after the surgery. The difference between L1 and L2 before and after the surgery was not significant. The IIEF-5 was 19.10±3.22 before the surgery and 19.90±3.05 after the surgery (P=0.001). The only complication was nodular fat observed in one case (1.92%). The use of AFI for PGE in men with thin penises was effective and safe without major complications. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.

  14. Stimulated phase-shift acoustic nanodroplets enhance vancomycin efficacy against methicillin-resistant Staphylococcus aureus biofilms

    Directory of Open Access Journals (Sweden)

    Guo H

    2017-06-01

    Full Text Available Hao Guo,1 Ziming Wang,1 Quanyin Du,1 Pan Li,2 Zhigang Wang,2 Aimin Wang1 1Department of Orthopedics, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China Purpose: Bacterial biofilms on the surface of prostheses are becoming a rising concern in managing prosthetic joint infections. The inherent resistant features of biofilms render traditional antimicrobial therapy unproductive and revision surgery outcomes uncertain. This situation has prompted the exploration of novel antimicrobial strategies. The synergy of ultrasound microbubbles and vancomycin has been proposed as an efficient alternative for biofilm eradication. The purpose of this study was to evaluate the anti-biofilm effect of stimulated phase-shift acoustic nanodroplets (NDs combined with vancomycin.Materials and methods: We fabricated lipid phase-shift NDs with a core of liquid perfluoropentane. A new phase change mode for NDs incorporating an initial unfocused low-intensity pulsed ultrasound for 5 minutes and a subsequent incubation at 37°C into a 24-hour duration was developed. Methicillin-resistant Staphylococcus aureus (MRSA biofilms were incubated with vancomycin and NDs under the hybrid stimulation. Biofilm morphology following treatment was determined using confocal laser scanning microscopy and scanning electron microscopy. Resazurin assay was used to quantify bactericidal efficacy against MRSA biofilm bacteria.Results: NDs treated sequentially with ultrasound and heating at 37°C achieved gradual and substantial ND vaporization and cavitation in a successive process. NDs after stimulation were capable of generating stronger destruction on biofilm structure which was best characterized by residual circular arc margins and more dead bacteria. Furthermore, NDs

  15. CT spectral imaging for monitoring the therapeutic efficacy of VEGF receptor kinase inhibitor AG-013736 in rabbit VX2 liver tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Yan, Xiaopeng; Chai, Yaru; Chen, Yan; Gao, Jianbo; Pan, Yuanwei; Li, Shuai; Guo, Hua; Zhou, Yue [The First Affiliated Hospital of Zhengzhou University, The Department of Radiology, Zhengzhou, Henan Province (China)

    2017-03-15

    The aim of this study was to evaluate the value of computed tomography (CT) spectral imaging in assessing the therapeutic efficacy of a vascular endothelial growth factor (VEGF) receptor inhibitor AG-013736 in rabbit VX2 liver tumours. Twenty-three VX2 liver tumour-bearing rabbits were scanned with CT in spectral imaging mode during the arterial phase (AP) and portal phase (PP). The iodine concentrations(ICs)of tumours normalized to aorta (nICs) at different time points (baseline, 2, 4, 7, 10, and 14 days after treatment) were compared within the treated group (n = 17) as well as between the control (n = 6) and treated groups. Correlations between the tumour size, necrotic fraction (NF), microvessel density (MVD), and nICs were analysed. The change of nICs relative to baseline in the treated group was lower compared to the control group. A greater decrease in the nIC of a tumour at 2 days was positively correlated with a smaller increase in tumour size at 14 days (P < 0.05 for both). The tumour nIC values in AP and PP had correlations with MVD (r = 0.71 and 0.52) and NF (r = -0.54 and -0.51) (P < 0.05 for all). CT spectral imaging allows for the evaluation and early prediction of tumour response to AG-013736. (orig.)

  16. Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy.

    Science.gov (United States)

    Watanabe, Satoru; Chan, Kitti Wing-Ki; Dow, Geoffrey; Ooi, Eng Eong; Low, Jenny G; Vasudevan, Subhash G

    2016-03-01

    Although the antiviral drug celgosivir, an α-glucosidase I inhibitor, is highly protective when given twice daily to AG129 mice infected with dengue virus, a similar regimen of twice daily dosing did not significantly reduce serum viral loads in patients in a recent clinical trial. This failure presumably might reflect the initiation of treatment when patients were already viremic. To better mimic the clinical setting, we used viruses isolated from patients to develop new mouse models of DENV1 and DENV2 infection and employed the models to test the twice daily treatment, begun either on the day of infection or on the third day post-infection, when the mice had peak of viremia. We found that, although the treatment started on day 0 was effective on viral load reduction, it provided no benefit when begun on day 3, indicating that in vivo antiviral efficacy becomes less prominent once viremia reaches the peak level. To determine if the therapeutic regimen in humans could be improved, we tested regimen of four-times daily treatment and found that the treatment significantly reduced viremia, suggesting that a similar regimen may be effective in a human clinical trial. A new clinical trial to investigate an altered dosing regimen has been approved (NCT02569827). Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Physical Therapists in Primary Care Are Interested in High Quality Evidence Regarding Efficacy of Therapeutic Ultrasound for Knee Osteoarthritis: A Provincial Survey

    Directory of Open Access Journals (Sweden)

    Norma J. MacIntyre

    2013-01-01

    Full Text Available Recent high-level evidence favours therapeutic ultrasound (US for reducing pain in people with knee osteoarthritis (OA. It is unknown how current practice patterns align with current evidence regarding US efficacy and whether physical therapists perceive a need for further high-level evidence. We conducted a descriptive electronic survey to characterize the beliefs and use of US among physical therapists in Ontario treating people with nonsurgical knee OA. Most of the 123 respondents (81% reported at least some use of US with 45% using it often or sometimes. The main goal for using US was to reduce pain in the surrounding soft tissue (n=66 and/or the knee joint (n=43. Almost half (46% endorsed the belief that US is likely to be beneficial for clients with nonsurgical knee OA. Most respondents (85% expressed interest in the results of a randomized controlled trial evaluating the effectiveness of US on pain and physical function. Patterns of use reflect the respondents’ belief that US is likely to be beneficial for knee OA pain.

  18. Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model.

    Science.gov (United States)

    Mukherjee, Pinku; Tinder, Teresa L; Basu, Gargi D; Pathangey, Latha B; Chen, Lieping; Gendler, Sandra J

    2004-01-01

    To study immunology in breast tumors, we have utilized a mammary gland adenocarcinoma model in which mice develop spontaneous tumors of the mammary gland which are initiated at puberty and express a human tumor antigen, MUC1. MUC1 (CD227) is over-expressed in 90% of human breast cancers and its glycosylation status and pattern of expression in cancer cells is altered. Humoral and cellular responses to MUC1 have been reported in breast cancer patients and therefore, MUC1 is being evaluated as a target for immune intervention. This mouse model of spontaneous breast cancer allows the evaluation of anti-MUC1 immune responses at all stages of the disease. In this report, we review the model as it pertains to a) the development of the tumor, b) MUC1 expression, and the native immune responses against MUC1 as tumors progress, and c) the immune suppressive microenvironment within the developing tumor. Finally, we report our latest findings describing the therapeutic efficacy of adoptively transferred MUC1-specific cytotoxic T lymphocytes (MUC1-CTL) in these mice and discuss ways to increase their effectiveness by agonistic monoclonal antibody against CD137 T cell costimulatory molecule.

  19. Evaluation of therapeutically induced hypertension in patients with delayed cerebral vasospasm by xenon-enhanced computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Touho, Hajime; Karasawa, Jun; Ohnishi, Hideyuki; Shishido, Hisashi; Yamada, Keisuke; Shibamoto, Keiji [Osaka Neurological Inst., Toyonaka (Japan)

    1992-08-01

    Serial cerebral blood flow (CBF) measurement were made with stable xenon-enhanced computed tomography in 20 patients with angiographically confirmed reputerd intracranial aneurysms, before and during induced hypertension with continuous infusion of dopamine. All patients showed angiogaphic vasospasm during their course. Twelve patients without symptomatic vasospasm (Group 1) had the lowest hemispheric CBF on the craniotomy side of 31.6[+-]6.8 ml/100 gm/min on days 4-9 (control value, 40.1[+-]2.0 ml/100 gm/min), while the other eight patients with symptomatic vasopsasm (Group 2) had the lowest hemispheric CBF on the craniotomy side of 25.0[+-]7.6 ml/100 gm/min on days 10-14. The critical hemispheric CBF inducing neurological deficits was about 20 ml/ 100 gm/min in Group 2. Dysautoregulation was usually present in Groups 1 and 2, but therapeutically induced hypertension could reverse the delayed neurological deficits, it begun early at the stage of delayed vasospasm. (author).

  20. Therapeutic-Ultrasound-Triggered Shape Memory of a Melamine-Enhanced Poly(vinyl alcohol) Physical Hydrogel.

    Science.gov (United States)

    Li, Guo; Yan, Qiang; Xia, Hesheng; Zhao, Yue

    2015-06-10

    Therapeutic-ultrasound-triggered shape memory was demonstrated for the first time with a melamine-enhanced poly(vinyl alcohol) (PVA) physical hydrogel. The addition of a small amount of melamine (up to 1.5 wt %) in PVA results in a strong hydrogel due to the multiple H-bonding between the two constituents. A temporary shape of the hydrogel can be obtained by deformation of the hydrogel (∼65 wt % water) at room temperature, followed by fixation of the deformation by freezing/thawing the hydrogel under strain, which induces crystallization of PVA. We show that the ultrasound delivered by a commercially available device designed for the patient's pain relief could trigger the shape recovery process as a result of ultrasound-induced local heating in the hydrogel that melts the crystallized PVA cross-linking. This hydrogel is thus interesting for potential applications because it combines many desirable properties, being mechanically strong, biocompatible, and self-healable and displaying the shape memory capability triggered by a physiological stimulus.

  1. Benzimidazoles Promote Anti-TNF Mediated Induction of Regulatory Macrophages and Enhance Therapeutic Efficacy in a Murine Model

    NARCIS (Netherlands)

    Wildenberg, Manon E.; Levin, Alon D.; Ceroni, Alessandro; Guo, Zhen; Koelink, Pim J.; Hakvoort, Theodorus B. M.; Westera, Liset; Bloemendaal, Felicia M.; Brandse, Johannan F.; Simmons, Alison; D'Haens, Geert R.; Ebner, Daniel; van den Brink, Gijs R.

    2017-01-01

    Background and Aims: Regulatory macrophages play a critical role in tissue repair, and we have previously shown that anti-tumour necrosis factor [TNF] antibodies induce these macrophages in vitro and in vivo in IBD patients. The induction of regulatory macrophages can be potentiated using the

  2. Ultrasound-induced cavitation enhances the delivery and therapeutic efficacy of an oncolytic virus in an in vitro model.

    Science.gov (United States)

    Bazan-Peregrino, Miriam; Arvanitis, Costas D; Rifai, Bassel; Seymour, Leonard W; Coussios, Constantin-C

    2012-01-30

    We investigated whether ultrasound-induced cavitation at 0.5 MHz could improve the extravasation and distribution of a potent breast cancer-selective oncolytic adenovirus, AdEHE2F-Luc, to tumour regions that are remote from blood vessels. We developed a novel tumour-mimicking model consisting of a gel matrix containing human breast cancer cells traversed by a fluid channel simulating a tumour blood vessel, through which the virus and microbubbles could be made to flow. Ultrasonic pressures were chosen to maximize either broadband emissions, associated with inertial cavitation, or ultraharmonic emissions, associated with stable cavitation, while varying duty cycle to keep the total acoustic energy delivered constant for comparison across exposures. None of the exposure conditions tested affected cell viability in the absence of the adenovirus. When AdEHE2F-Luc was delivered via the vessel, inertial cavitation increased transgene expression in tumour cells by up to 200 times. This increase was not observed in the absence of Coxsackie and Adenovirus Receptor cell expression, discounting sonoporation as the mechanism of action. In the presence of inertial cavitation, AdEHE2F-Luc distribution was greatly improved in the matrix surrounding the vessel, particularly in the direction of the ultrasound beam; this enabled AdEHE2F-Luc to kill up to 80% of cancer cells within the ultrasound focal volume in the gel 24 hours after delivery, compared to 0% in the absence of cavitation. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Enhancement of Self Efficacy of Vocational School Students in Buffer Solution Topics through Guided Inquiry Learning

    Science.gov (United States)

    M, Ardiany; W, Wahyu; A, Supriatna

    2017-09-01

    The more students who feel less confident in learning, so doing things that are less responsible, such as brawl, drunkenness and others. So researchers need to do research related to student self efficacy in learning, in order to reduce unwanted things. This study aims to determine the effect of guided inquiry learning on improving self-efficacy of learners in the buffer solution topics. The method used is the mixed method which is the two group pretest postest design. The subjects of the study are 60 students of class XI AK in one of the SMKN in Bandung, consisting of 30 experimental class students and 30 control class students. The instruments used in this study mix method consist of self-efficacy questionnaire of pretest and posttest learners, interview guides, and observation sheet. Data analysis using t test with significant α = 0,05. Based on the result of inquiry of guided inquiry study, there is a significant improvement in self efficacy aspect of students in the topic of buffer solution. Data of pretest and posttest interview, observation, questionnaire showed significant result, that is improvement of experimental class with conventionally guided inquiry learning. The mean of self-efficacy of student learning there is significant difference of experiment class than control class equal to 0,047. There is a significant relationship between guided inquiry learning with self efficacy and guided inquiry learning. Each correlation value is 0.737. The learning process with guided inquiry is fun and challenging so that students can expose their ideas and opinions without being forced. From the results of questionnaires students showed an attitude of interest, sincerity and a good response of learning. While the results of questionnaires teachers showed that guided inquiry learning can make students learn actively, increased self-efficacy.

  4. Long-term exposure to estrogen enhances chemotherapeutic efficacy potentially through epigenetic mechanism in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chang

    Full Text Available Chemotherapy is the most common clinical option for treatment of breast cancer. However, the efficacy of chemotherapy depends on the age of breast cancer patients. Breast tissues are estrogen responsive and the levels of ovarian estrogen vary among the breast cancer patients primarily between pre- and post-menopausal age. Whether this age-dependent variation in estrogen levels influences the chemotherapeutic efficacy in breast cancer patients is not known. Therefore, the objective of this study was to evaluate the effects of natural estrogen 17 beta-estradiol (E2 on the efficacy of chemotherapeutic drugs in breast cancer cells. Estrogen responsive MCF-7 and T47D breast cancer cells were long-term exposed to 100 pg/ml estrogen, and using these cells the efficacy of chemotherapeutic drugs doxorubicin and cisplatin were determined. The result of cell viability and cell cycle analysis revealed increased sensitivities of doxorubicin and cisplatin in estrogen-exposed MCF-7 and T47D cells as compared to their respective control cells. Gene expression analysis of cell cycle, anti-apoptosis, DNA repair, and drug transporter genes further confirmed the increased efficacy of chemotherapeutic drugs in estrogen-exposed cells at molecular level. To further understand the role of epigenetic mechanism in enhanced chemotherapeutic efficacy by estrogen, cells were pre-treated with epigenetic drugs, 5-aza-2-deoxycytidine and Trichostatin A prior to doxorubicin and cisplatin treatments. The 5-aza-2 deoxycytidine pre-treatment significantly decreased the estrogen-induced efficacy of doxorubicin and cisplatin, suggesting the role of estrogen-induced hypermethylation in enhanced sensitivity of these drugs in estrogen-exposed cells. In summary, the results of this study revealed that sensitivity to chemotherapy depends on the levels of estrogen in breast cancer cells. Findings of this study will have clinical implications in selecting the chemotherapy strategies for

  5. Communicative social capital and collective efficacy as determinants of access to health-enhancing resources in residential communities.

    Science.gov (United States)

    Matsaganis, Matthew D; Wilkin, Holley A

    2015-04-01

    This article contributes to the burgeoning literature on the social determinants of health disparities. The authors investigate how communication resources and collective efficacy, independently and in combination, shape residents' access to health enhancing resources (including healthcare services, sources of healthier food options, and public recreation spaces) in their communities. Using random digit dial telephone survey data from 833 residents of South Los Angeles communities the authors show that communicative social capital-that is, an information and problem-solving resource that accrues to residents as they become more integrated into their local communication network of neighbors, community organizations, and local media-plays a significant role in access to health resources. This relationship is complicated by individuals' health insurance and health status, as communicative social capital magnifies the sense of absence of resources for those who are in worse health and lack insurance. Communicative social capital builds collective efficacy, which is positively related to access to health-enhancing resources, but it also mediates the negative relationship between communicative social capital and access to health resources. Residents with richer stores of communicative social capital and collective efficacy report better access to health resources. The authors conclude with a discussion of implications of these findings and suggestions for future research.

  6. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    International Nuclear Information System (INIS)

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression

  7. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  8. Efficacy of therapeutic nuclear medicine

    International Nuclear Information System (INIS)

    Hoefnagel, C.A.

    1998-01-01

    The following topics are discussed: (i) 131 I therapy of thyrotoxicosis; (ii) 131 I therapy of differentiated thyroid carcinoma; (iii) 32 P therapy of myeloproliferative disease; (iv) 131 MIBG therapy of neural crest tumors; (v) radiolabelled peptides in neuroendocrine tumors; (vi) radioimmunotherapy; (vii) palliative bone therapy of painful skeletal metastases; (viii) radiosynoviorthesis; (ix) alternative approaches; (x) side effects and long-term effects

  9. Enhancing Self-Efficacy in Elementary Science Teaching With Professional Learning Communities

    Science.gov (United States)

    Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

    2013-11-01

    Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in personal self-efficacy and outcome expectancy among teachers engaged in PLCs that featured Demonstration Laboratories, Lesson Study, and annual Summer Institutes. Significant changes favoring the experimental group were found on all quantitative measures of self-efficacy. Structured clinical interviews revealed that observed changes were largely attributable to a wide range of direct (mastery) and vicarious experiences, as well as emotional reinforcement and social persuasion.

  10. How Setting Goals Enhances Learners’ Self-Efficacy Beliefs in Listening Comprehension

    Directory of Open Access Journals (Sweden)

    Liliana Ballesteros Muñoz

    2014-04-01

    Full Text Available This article outlines a study that explores the relationship between SMART goal setting (Specific, Measurable, Attainable, Relevant, and Time-based and learning English in Colombia concerning a foreign language learners’ self-efficacy beliefs in listening. The participants were seventh and ninth grade students of two schools in Bogotá, Colombia. The results revealed that self-efficacy was highly positive when related to goal setting as students were able to set SMART goals to improve their listening comprehension and learners showed improvement in self-efficacy beliefs and felt more motivated while completing listening tasks related to songs. Furthermore this study shows that goal setting training can be incorporated successfully into the English as a foreign language classroom.

  11. The small-molecule TNF-alpha modulator, UTL-5g, reduces side effects induced by cisplatin and enhances the therapeutic effect of cisplatin in vivo.

    Science.gov (United States)

    Shaw, JiaJiu; Chen, Ben; Huang, Wen-Hsin; Lee, An-Rong; Media, Joseph; Valeriote, Frederick A

    2011-01-01

    We investigated a small-molecule modulator of tumor necrosis factor alpha (TNF-alpha), UTL-5g (also referred to as GBL-5g), as a potential chemoprotective agent against cisplatin-induced side effects including nephrotoxicity, hepatotoxicity and hematotoxicity. Pretreatment of UTL-5g i.p. in BDF1 mice reduced the levels of blood urea nitrogen (BUN) and creatinine induced by cisplatin treatment. The levels of both aspartate transaminase (AST) and alanine transaminase (ALT) in these animals were also reduced by UTL-5g. Pretreatment of UTL-5g did not significantly affect the number of white blood cells (WBC) under current experimental conditions, yet it markedly increased blood platelet counts by more than threefold. Therapeutic assessment in SCID mice inoculated with human HCT-15 tumor cells showed that UTL-5g did not attenuate the anti-tumor effect of cisplatin but increased the therapeutic efficacy of cisplatin. The LD50 of UTL-5g was determined to be > 2,000 mg/kg by an acute toxicity study. In summary, our studies showed that 1) UTL-5g significantly reduces nephrotoxicity and hepatotoxicity induced by cisplatin in mice, presumably by lowering the levels of TNF-alpha, 2) UTL-5g markedly increased blood platelet counts in mice and 3) UTL-5g treatment increased the therapeutic efficacy of cisplatin against HCT-15 cells inoculated in SCID mice.

  12. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study.

    Science.gov (United States)

    Vaughan-Williams, Charles H; Raman, Jaishree; Raswiswi, Eric; Immelman, Etienne; Reichel, Holger; Gate, Kelly; Knight, Steve

    2012-12-28

    Zulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

  13. Assessment of the therapeutic efficacy of artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in northern KwaZulu-Natal: an observational cohort study

    Directory of Open Access Journals (Sweden)

    Vaughan-Williams Charles H

    2012-12-01

    suggests lumefantrine resistance has yet to emerge in KwaZulu-Natal. In addition, data from this investigation implies the possible re-emergence of chloroquine-sensitive parasites. Results from this study must be viewed with caution, given the extremely small sample size. A larger study is needed to accurately determine therapeutic efficacy of artemether-lumefantrine and resistance marker prevalence. The high proportion of rapid diagnostic test false-positive results requires further investigation.

  14. Quantitative pre-clinical screening of therapeutics for joint diseases using contrast enhanced micro-computed tomography.

    Science.gov (United States)

    Willett, N J; Thote, T; Hart, M; Moran, S; Guldberg, R E; Kamath, R V

    2016-09-01

    The development of effective therapies for cartilage protection has been limited by a lack of efficient quantitative cartilage imaging modalities in pre-clinical in vivo models. Our objectives were two-fold: first, to validate a new contrast-enhanced 3D imaging analysis technique, equilibrium partitioning of an ionic contrast agent-micro computed tomography (EPIC-μCT), in a rat medial meniscal transection (MMT) osteoarthritis (OA) model; and second, to quantitatively assess the sensitivity of EPIC-μCT to detect the effects of matrix metalloproteinase inhibitor (MMPi) therapy on cartilage degeneration. Rats underwent MMT surgery and tissues were harvested at 1, 2, and 3 weeks post-surgery or rats received an MMPi or vehicle treatment and tissues harvested 3 weeks post-surgery. Parameters of disease progression were evaluated using histopathology and EPIC-μCT. Correlations and power analyses were performed to compare the techniques. EPIC-μCT was shown to provide simultaneous 3D quantification of multiple parameters, including cartilage degeneration and osteophyte formation. In MMT animals treated with MMPi, OA progression was attenuated, as measured by 3D parameters such as lesion volume and osteophyte size. A post-hoc power analysis showed that 3D parameters for EPIC-μCT were more sensitive than 2D parameters requiring fewer animals to detect a therapeutic effect of MMPi. 2D parameters were comparable between EPIC-μCT and histopathology. This study demonstrated that EPIC-μCT has high sensitivity to provide 3D structural and compositional measurements of cartilage and bone in the joint. EPIC-μCT can be used in combination with histology to provide a comprehensive analysis to screen new potential therapies. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  15. Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats.

    Science.gov (United States)

    Tang, Wei-Ping; Akahoshi, Tomohiko; Piao, Jing-Shu; Narahara, Sayoko; Murata, Masaharu; Kawano, Takahito; Hamano, Nobuhito; Ikeda, Tetsuo; Hashizume, Makoto

    2016-08-01

    Clinical studies suggest that splenectomy improves liver function in cirrhotic patients, but the influence of splenectomy on stem cell transplantation is poorly understood. This study investigated the effect of splenectomy on stem cell infusion and elucidated its mechanism. Rat adipose tissue-derived mesenchymal stem cells were infused into cirrhosis rats with or without splenectomy, followed by the assessment of the in vivo distribution of stem cells and pathological changes. Stromal cell-derived factor-1 and hepatocyte growth factor expression were also investigated in splenectomized cirrhosis patients and rats. Splenectomy, prior to cell infusion, improved liver function and suppressed fibrosis progression more efficiently than cell infusion alone in the experimental cirrhosis model. Stromal cell-derived factor-1 and hepatocyte growth factor levels after splenectomy were increased in patients and rats. These upregulated cytokines significantly facilitated stem cell motility, migration and proliferation in vitro. C-X-C chemokine receptor type 4 neutralization weakened the promotion of cell migration by these cytokines. The infused cells integrated into liver fibrosis septa and participated in regeneration more efficiently in splenectomized rats. Direct coculture with stem cells led to inhibition of hepatic stellate cell proliferation. In addition, hepatocyte growth factor induced hepatic stellate cell apoptosis via the c-jun N-terminal kinase-p53 pathway. Splenectomy prior to cell infusion enhanced the therapeutic effect of stem cells on cirrhosis, which involved upregulation of stromal cell-derived factor-1 and hepatocyte growth factor after splenectomy. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Perceptual Training Methods Compared: The Relative Efficacy of Different Approaches to Enhancing Sport-Specific Anticipation

    Science.gov (United States)

    Abernethy, Bruce; Schorer, Jorg; Jackson, Robin C.; Hagemann, Norbert

    2012-01-01

    The comparative efficacy of different perceptual training approaches for the improvement of anticipation was examined using a goalkeeping task from European handball that required the rapid prediction of shot direction. Novice participants (N = 60) were assigned equally to four different training groups and two different control groups (a placebo…

  17. Enhancing Entrepreneurship: The Role of Goal Orientation and Self-Efficacy

    Science.gov (United States)

    Culbertson, Satoris S.; Smith, Michael R.; Leiva, Pedro I.

    2011-01-01

    Entrepreneurship has become increasingly important in the workplace. Research suggests motivational traits are important in pursuing entrepreneurial activities. Yet, the extent to which factors influencing entrepreneurial versus managerial goals differ remains unclear. This study assessed the influence of goal orientation and self-efficacy in…

  18. Enhancing Self-Efficacy in Elementary Science Teaching with Professional Learning Communities

    Science.gov (United States)

    Mintzes, Joel J.; Marcum, Bev; Messerschmidt-Yates, Christl; Mark, Andrew

    2013-01-01

    Emerging from Bandura's Social Learning Theory, this study of in-service elementary school teachers examined the effects of sustained Professional Learning Communities (PLCs) on self-efficacy in science teaching. Based on mixed research methods, and a non-equivalent control group experimental design, the investigation explored changes in…

  19. Enhanced efficacy of imipenem-colistin combination therapy against multiple-drug-resistant Enterobacter cloacae: in vitro activity and a Galleria mellonella model

    Directory of Open Access Journals (Sweden)

    Haifei Yang

    2018-02-01

    Conclusion: This is the first report demonstrating the efficacy of antimicrobial agents in the G. mellonella larvae model of infections caused by E. cloacae. Our study suggested that imipenem-colistin combination was highly active against E. cloacae both in vitro and in the simple invertebrate model, and provided preliminary in vivo evidence that such combination might be useful therapeutically.

  20. Eficacia terapéutica de la acupuntura en pacientes con sacrolumbalgia Acupuncture therapeutic efficacy in patients with lower back pain

    Directory of Open Access Journals (Sweden)

    Soini González Gámez

    2011-03-01

    Full Text Available Se realizó un ensayo clinicoterapéutico de fase II en 100 pacientes con sacrolumbalgia aguda, que acudieron al Servicio de Medicina Natural y Tradicional del Centro Médico Psicopedagógico "América Labadí Arce" de Santiago de Cuba, desde julio del 2009 hasta igual mes del 2010, a fin de evaluar la eficacia del tratamiento acupuntural en ellos, para lo cual fueron conformados 2 grupos de estudio (A y B de 50 integrantes cada uno: los primeros recibieron los efectos de la medicina natural y los segundos de la convencional. Se obtuvo que los tratados con acupuntura mejoraron en menor tiempo y con menos reacciones adversas en comparación con los consumidores de fármacos, de donde se infiere que la técnica milenaria china resultó eficaz para aliviar el dolor lumbar en quienes se aplicó.A phase II clinical therapeutical trial on 100 patients with acute lower back pain who attended the Natural and Traditional Medicine Service at ¨América Labadí¨ Psychopedagogical Medical Center from Santiago de Cuba was carried out from July, 2009 to July, 2010 in order to assess the efficacy of the acupunctural treatment on them. To achieve this goal, two study groups (A and B composed of 50 members each were created: the first ones received the natural medicine effects and the second ones received the conventional medicine effects. The results were as follows: those treated with acupuncture improved their physical condition in a short period of time and had less side effects compared to the patients who used drugs, in which case it can be inferred that Chinese millenary technique was effective to relieve lumbar pain on whom it was applied.

  1. Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Jiang Li

    2017-01-01

    Full Text Available No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A (BTXA injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic foot after stroke to optimize this treatment in these patients. Eligible patients (n = 104 were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses (200 U or 400 U and two concentrations (50 U/mL or 100 U/mL. The following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment: spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden's graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4–7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

  2. Systematic review of clinical trials assessing the therapeutic efficacy of visceral leishmaniasis treatments: A first step to assess the feasibility of establishing an individual patient data sharing platform.

    Directory of Open Access Journals (Sweden)

    Jacob T Bush

    2017-09-01

    Full Text Available There are an estimated 200,000 to 400,000 cases of visceral leishmaniasis (VL annually. A variety of factors are taken into account when considering the best therapeutic options to cure a patient and reduce the risk of resistance, including geographical area, malnourishment and HIV coinfection. Pooled analyses combine data from many studies to answer specific scientific questions that cannot be answered with individual studies alone. However, the heterogeneity of study design, data collection, and analysis often makes direct comparison difficult. Individual Participant Data (IPD files can be standardised and analysed, allowing detailed analysis of this merged larger pool, but only a small fraction of systematic reviews and meta-analyses currently employ pooled analysis of IPD. We conducted a systematic literature review to identify published studies and studies reported in clinical trial registries to assess the feasibility of developing a VL data sharing platform to facilitate an IPD-based analysis of clinical trial data. Studies conducted between 1983 to 2015 that reported treatment outcome were eligible.From the 2,271 documents screened, 145 published VL clinical trials were identified, with data from 26,986 patients. Methodologies varied for diagnosis and treatment outcomes, but overall the volume of data potentially available on different drugs and dose regimens identified hundreds or possibly thousands of patients per arm suitable for IPD pooled meta-analyses.A VL data sharing platform would provide an opportunity to maximise scientific use of available data to enable assessment of treatment efficacy, contribute to evidence-based clinical management and guide optimal prospective data collection.

  3. Induction of spontaneous hyaline cartilage regeneration using a double-network gel: efficacy of a novel therapeutic strategy for an articular cartilage defect.

    Science.gov (United States)

    Kitamura, Nobuto; Yasuda, Kazunori; Ogawa, Munehiro; Arakaki, Kazunobu; Kai, Shuken; Onodera, Shin; Kurokawa, Takayuki; Gong, Jian Ping

    2011-06-01

    A double-network (DN) gel, which was composed of poly-(2-acrylamido-2-methylpropanesulfonic acid) and poly-(N,N'-dimetyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. To establish the efficacy of a therapeutic strategy for an articular cartilage defect using a DN gel. Controlled laboratory study. A 4.3-mm-diameter osteochondral defect was created in rabbit trochlea. A DN gel plug was implanted into the defect of the right knee so that a defect 2 mm in depth remained after surgery. An untreated defect of the left knee provided control data. The osteochondral defects created were examined by histological and immunohistochemical evaluations, surface assessment using confocal laser scanning microscopy, and real-time polymerase chain reaction (PCR) analysis at 4 and 12 weeks. Samples were quantitatively evaluated with 2 scoring systems reported by Wayne et al and O'Driscoll et al. The DN gel-implanted defect was filled with a sufficient volume of the hyaline cartilage tissue rich in proteoglycan and type 2 collagen. Quantitative evaluation using the grading scales revealed a significantly higher score in the DN gel-implanted defects compared with the untreated control at each period (P cartilage at 12 weeks (P = .0106), while there was no statistical difference between the DN gel-implanted and normal knees. This study using the mature rabbit femoral trochlea osteochondral defect model demonstrated that DN gel implantation is an effective treatment to induce cartilage regeneration in vivo without any cultured cells or mammalian-derived scaffolds. This study has prompted us to develop a potential innovative strategy to repair cartilage lesions in the field of joint surgery.

  4. Increased Loading, Efficacy and Sustained Release of Silibinin, a Poorly Soluble Drug Using Hydrophobically-Modified Chitosan Nanoparticles for Enhanced Delivery of Anticancer Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Cha Yee Kuen

    2017-11-01

    Full Text Available Conventional delivery of anticancer drugs is less effective due to pharmacological drawbacks such as lack of aqueous solubility and poor cellular accumulation. This study reports the increased drug loading, therapeutic delivery, and cellular accumulation of silibinin (SLB, a poorly water-soluble phenolic compound using a hydrophobically-modified chitosan nanoparticle (pCNP system. In this study, chitosan nanoparticles were hydrophobically-modified to confer a palmitoyl group as confirmed by 2,4,6-Trinitrobenzenesulfonic acid (TNBS assay. Physicochemical features of the nanoparticles were studied using the TNBS assay, and Attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR analyses. The FTIR profile and electron microscopy correlated the successful formation of pCNP and pCNP-SLB as nano-sized particles, while Dynamic Light Scattering (DLS and Field Emission-Scanning Electron Microscopy (FESEM results exhibited an expansion in size between pCNP and pCNP-SLB to accommodate the drug within its particle core. To evaluate the cytotoxicity of the nanoparticles, a Methylthiazolyldiphenyl-tetrazolium bromide (MTT cytotoxicity assay was subsequently performed using the A549 lung cancer cell line. Cytotoxicity assays exhibited an enhanced efficacy of SLB when delivered by CNP and pCNP. Interestingly, controlled release delivery of SLB was achieved using the pCNP-SLB system, conferring higher cytotoxic effects and lower IC50 values in 72-h treatments compared to CNP-SLB, which was attributed to the hydrophobic modification of the CNP system.

  5. Genetic incorporation of the protein transduction domain of Tat into Ad5 fiber enhances gene transfer efficacy

    Directory of Open Access Journals (Sweden)

    Siegal Gene P

    2007-10-01

    Full Text Available Abstract Background Human adenovirus serotype 5 (Ad5 has been widely explored as a gene delivery vector for a variety of diseases. Many target cells, however, express low levels of Ad5 native receptor, the Coxsackie-Adenovirus Receptor (CAR, and thus are resistant to Ad5 infection. The Protein Transduction Domain of the HIV Tat protein, namely PTDtat, has been shown to mediate protein transduction in a wide range of cells. We hypothesize that re-targeting Ad5 vector via the PTDtat motif would improve the efficacy of Ad5-mediated gene delivery. Results In this study, we genetically incorporated the PTDtat motif into the knob domain of Ad5 fiber, and rescued the resultant viral vector, Ad5.PTDtat. Our data showed the modification did not interfere with Ad5 binding to its native receptor CAR, suggesting Ad5 infection via the CAR pathway is retained. In addition, we found that Ad5.PTDtat exhibited enhanced gene transfer efficacy in all of the cell lines that we have tested, which included both low-CAR and high-CAR decorated cells. Competitive inhibition assays suggested the enhanced infectivity of Ad5.PTDtat was mediated by binding of the positively charged PTDtat peptide to the negatively charged epitopes on the cells' surface. Furthermore, we investigated in vivo gene delivery efficacy of Ad5.PTDtat using subcutaneous tumor models established with U118MG glioma cells, and found that Ad5.PTDtat exhibited enhanced gene transfer efficacy compared to unmodified Ad5 vector as analyzed by a non-invasive fluorescence imaging technique. Conclusion Genetic incorporation of the PTDtat motif into Ad5 fiber allowed Ad5 vectors to infect cells via an alternative PTDtat targeting motif while retaining the native CAR-mediated infection pathway. The enhanced infectivity was demonstrated in both cultured cells and in in vivo tumor models. Taken together, our study identifies a novel tropism expanded Ad5 vector that may be useful for clinical gene therapy

  6. Enhancing Diversity in Undergraduate Science: Self-Efficacy Drives Performance Gains with Active Learning.

    Science.gov (United States)

    Ballen, Cissy J; Wieman, Carl; Salehi, Shima; Searle, Jeremy B; Zamudio, Kelly R

    2017-01-01

    Efforts to retain underrepresented minority (URM) students in science, technology, engineering, and mathematics (STEM) have shown only limited success in higher education, due in part to a persistent achievement gap between students from historically underrepresented and well-represented backgrounds. To test the hypothesis that active learning disproportionately benefits URM students, we quantified the effects of traditional versus active learning on student academic performance, science self-efficacy, and sense of social belonging in a large (more than 250 students) introductory STEM course. A transition to active learning closed the gap in learning gains between non-URM and URM students and led to an increase in science self-efficacy for all students. Sense of social belonging also increased significantly with active learning, but only for non-URM students. Through structural equation modeling, we demonstrate that, for URM students, the increase in self-efficacy mediated the positive effect of active-learning pedagogy on two metrics of student performance. Our results add to a growing body of research that supports varied and inclusive teaching as one pathway to a diversified STEM workforce. © 2017 C. J. Ballen et al. CBE—Life Sciences Education © 2017 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  7. Enhancing Study Motivation and Efficacy among First-year Students Using Minute Papers in the Interdisciplinary Subject of Yakugaku Nyumon.

    Science.gov (United States)

    Yamaki, Kouya; Ikeda, Koji; Ueda, Kumiko; Habu, Yasushi; Nakayama, Yoshiaki; Takeda, Norihiko; Moriwaki, Kensuke; Wada, Akimori; Koyama, Junko; Kodama, Noriko; Kitagawa, Shuji

    2017-01-01

    Active learning in higher education is important for learning efficacy and motivation. Accordingly, lectures that integrate strategies toward active learning, such as minute papers, debates, and collaborative learning, have become widely adopted. Minute papers facilitate communication among both teachers and students, and can be used as a tool for reviewing lectures. In the present study, we examined the effect of using minute papers on learning efficacy and motivation. To enhance the curriculum of the interdisciplinary course Yakugaku Nyumon, which consists of an omnibus lecture series and problem-based learning, minute papers with exercises were provided to applicants. In a follow-up questionnaire, students who used minute papers (S-USE) responded that they had a better understanding of the relationships, ranging from basic to clinical subject matter, than students who did not use such papers (S-NON). Using the Attention, Relevance, Confidence, and Satisfaction (ARCS) model questionnaire to measure study motivation, S-USE scored higher for some questionnaires than S-NON. This finding indicates that minute papers promoted learning motivation among students taking the Yakugaku Nyumon course. In regular examinations, the average score of S-USE was also statistically higher than that of S-NON. These results demonstrate that minute papers possibly encouraged students to actively review the lectures, thereby increasing both learning efficacy and motivation. This study shows that through promoting active, self-learning, minute papers are suitable for improving curricular strategies in subjects that rely on passive learning methods.

  8. Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe rate at Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

    Energy Technology Data Exchange (ETDEWEB)

    Takan, Gokhan; Guldu, Ozge Kozgus; Medine, Emin Ilker [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2017-06-01

    Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe rate at Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe rate at Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe rate at Au) nanoparticles and radiolabeled with {sup 131}I to combine magnetic targeted drug delivery and radiotherapy. Fe rate at Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe rate at Au nanoparticles (Fe rate at Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe rate at Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

  9. Radioiodination of cyclin dependent kinase inhibitor Olomoucine loaded Fe rate at Au nanoparticle and evaluation of the therapeutic efficacy on cancerous cells

    International Nuclear Information System (INIS)

    Takan, Gokhan; Guldu, Ozge Kozgus; Medine, Emin Ilker

    2017-01-01

    Magnetic nanoparticles have promising biomedical applications such as drug delivery, novel therapeutics and diagnostic imaging. Magnetic drug delivery combination works on the delivery of magnetic nanoparticles loaded with drug to the target tissue by means of an external magnetic field. Gold coated iron oxide (Fe rate at Au) nanoparticles can provide useful surface chemistry and biological reactivity. Covalent conjugation to the Fe rate at Au nanoparticles through cleavable linkages can be used to deliver drugs to tumor cells, then the drug can be released by an external. In this paper, purine based cyclin dependent kinases (CDKs) inhibitor Olomoucine (Olo) [2-(Hydroxyethylamino)-6-benzylamino-9-methylpurine] was loaded on gold coated iron oxide (Fe rate at Au) nanoparticles and radiolabeled with "1"3"1I to combine magnetic targeted drug delivery and radiotherapy. Fe rate at Au nanoparticles were synthesized by microemulsion method. The characterization of nanoparticles was examined by TEM, VSM and XRD. Amine activation was utilized by cysteamine hydrochloride and then CDI was used for conjugation of Olomoucine. Antiproliferative effect and cytotoxicity of Olomoucine loaded Fe rate at Au nanoparticles (Fe rate at Au-Olo) were investigated on MCF7 and A549 cell lines. Proliferation rate was decreased while uptake of Fe rate at Au-Olo on both cell lines was high in comparison with Olomoucine. Also, enhanced incorporation ratio was observed under external magnetic field.

  10. Therapeutic approaches for celiac disease

    Science.gov (United States)

    Plugis, Nicholas M.; Khosla, Chaitan

    2015-01-01

    Celiac disease is a common, lifelong autoimmune disorder for which dietary control is the only accepted form of therapy. A strict gluten-free diet is burdensome to patients and can be limited in efficacy, indicating there is an unmet need for novel therapeutic approaches to supplement or supplant dietary therapy. Many molecular events required for disease pathogenesis have been recently characterized and inspire most current and emerging drug-discovery efforts. Genome-wide association studies (GWAS) confirm the importance of human leukocyte antigen genes in our pathogenic model and identify a number of new risk loci in this complex disease. Here, we review the status of both emerging and potential therapeutic strategies in the context of disease pathophysiology. We conclude with a discussion of how genes identified during GWAS and follow-up studies that enhance susceptibility may offer insight into developing novel therapies. PMID:26060114

  11. Topical methotrexate pretreatment enhances the therapeutic effect of topical 5-aminolevulinic acid-mediated photodynamic therapy on hamster buccal pouch precancers

    OpenAIRE

    Deng-Fu Yang; Jeng-Woei Lee; Hsin-Ming Chen; Yih-Chih Hsu

    2014-01-01

    Topical 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is effective for treatment of human oral precancerous lesions. This animal study aimed to assess whether topical methotrexate (MTX) pretreatment could enhance the therapeutic effect of topical ALA-PDT on hamster buccal pouch precancerous lesions. Methods: Twenty hamster buccal pouch precancerous lesions were treated with either topical ALA-PDT with topical MTX pretreatment (topical MTX-ALA-PDT group, n = 10) or topical A...

  12. Therapeutic Efficacy Comparison of 5 Major EGFR-TKIs in Advanced EGFR-positive Non-Small-cell Lung Cancer: A Network Meta-analysis Based on Head-to-Head Trials.

    Science.gov (United States)

    Zhang, Yaxiong; Zhang, Zhonghan; Huang, Xiaodan; Kang, Shiyang; Chen, Gang; Wu, Manli; Miao, Siyu; Huang, Yan; Zhao, Hongyun; Zhang, Li

    2017-09-01

    Five major first- and second-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), including erlotinib, gefitinib, icotinib, afatinib, and dacomitinib, are currently optional for patients with advanced non-small-cell lung cancer (NSCLC) who harbor EGFR mutations. However, there was no head-to-head-based network meta-analysis among all the TKIs in EGFR-mutated populations. Eligible literature was searched from an electronic database. Data of objective response rate, disease control rate, progression-free survival, and overall survival were extracted from enrolled studies. Multiple treatment comparisons based on Bayesian network integrated the efficacy of all included treatments. Six phase III randomized trials involving 1055 EGFR-mutated patients with advanced NSCLC were enrolled. Multiple treatment comparisons showed that 5 different EGFR-TKIs shared equivalent therapeutic efficacy in terms of all outcome measures. Rank probabilities indicated that dacomitinib and afatinib had potentially better efficacy compared with erlotinib, gefitinib, and icotinib in the EGFR-mutated patients. When compared with other agents, potential survival benefits (progression-free and overall survival) were observed in dacomitinib, whereas afatinib showed a better rank probability in overall response rate and disease control rate. Our study indicated a preferable therapeutic efficacy in the second-generation TKIs (dacomitinib and afatinib) when compared with the first-generation TKIs (erlotinib, gefitinib, and icotinib). Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Antigen-Sparing and Enhanced Efficacy of Multivalent Vaccines Adjuvanted with Immunopotentiators in Chickens

    Directory of Open Access Journals (Sweden)

    Peipei Wu

    2017-05-01

    Full Text Available We previously described that immunopotentiators, CVCVA5, increased the efficacy of H5 and H9 subtype avian influenza vaccines in chickens, ducks, and geese. In this study, we further investigated the effects of the CVCVA5 for improving the efficacy of other univalent or multivalent inactivated vaccines. The immune response administrated with half-dose of monovalent vaccine plus CVCVA5 were higher than those of one dose of monovalent vaccine without immunopotentiators as measured by levels of antibodies from serum, tears and bronchoalveolar lavage fluids, and cytokines of IFNγ and IL-4 from serum. Vaccines included the univalent vaccine of Newcastle Disease virus (ND, Egg Drop Syndrome virus (EDS, Infectious Bronchitis virus (IB, and Infectious Bursal Disease virus (IBD. The CVCVA5 also improved the immune response of both ND and IBD vaccines with less dosage. The sterile protective immunity was monitored with one- or a half-dose of adjuvanted ND vaccine or one dose of adjuvanted IBD vaccine, respectively. The improved immune efficacy was observed in a half-dose of adjuvanted bivalent vaccines compared to one dose of vaccines without CVCVA5 as measured by the antibody levels, including bivalent vaccine of ND-H9, ND-IB, and ND-IBD. The CVCVA5 also boosted the immune efficacy of the tetravalent vaccine (ND-IB-EDS-H9. A half-dose of adjuvanted commercial vaccine or 75% antigen-sparing adjuvanted vaccine elicited similar antibody levels to those of one dose non-adjuvanted commercial vaccines. The CVCVA5 improved the effect of a booster vaccination as measured by the antibody levels against H5 or H9 virus antigens, in which chickens primed with the adjuvanted ND-IB vaccines given a booster with H5–H9 bivalent vaccines without CVCVA5 using 5-day intervals. The inflammatory response may contribute to these additional effects by increasing the levels of IFNγ and IL-4 after the injection of the adjuvanted ND-IB vaccines. Results indicated that the

  14. Day treatment versus enhanced standard methadone services for opioid-dependent patients: a comparison of clinical efficacy and cost.

    Science.gov (United States)

    Avants, S K; Margolin, A; Sindelar, J L; Rounsaville, B J; Schottenfeld, R; Stine, S; Cooney, N L; Rosenheck, R A; Li, S H; Kosten, T R

    1999-01-01

    This study examined the differential efficacy and relative costs of two intensities of adjunctive psychosocial services--a day treatment program and enhanced standard care--for the treatment of opioid-dependent patients maintained on methadone hydrochloride. A 12-week randomized clinical trial with 6-month follow-up was conducted in a community-based methadone maintenance program. Of the 308 patients who met inclusion criteria, 291 began treatment (day treatment program: N=145; enhanced standard care: N=146), and 237 completed treatment (82% of those assigned to the day treatment program and 81% of those receiving enhanced standard care). Two hundred twenty of the patients participated in the 6-month follow-up (75% of those in the day treatment program and 73% of those in enhanced standard care provided a follow-up urine sample for screening). Both interventions were 12 weeks in duration, manual-guided, and provided by master's-level clinicians. The day treatment was an intensive, 25-hour-per-week program. The enhanced standard care was standard methadone maintenance plus a weekly skills training group and referral to on- and off-site services. Outcome measures included twice weekly urine toxicology screens, severity of addiction-related problems, prevalence of HIV risk behaviors, and program costs. Although the cost of the day treatment program was significantly higher, there was no significant difference in the two groups' use of either opiates or cocaine. Over the course of treatment, drug use, drug-related problems, and HIV risk behaviors decreased significantly for patients assigned to both treatment intensities. Improvements were maintained at follow-up. Providing an intensive day treatment program to unemployed, inner-city methadone patients was not cost-effective relative to a program of enhanced methadone maintenance services, which produced comparable outcomes at less than half the cost.

  15. Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial.

    Science.gov (United States)

    Choudhary, Sv; Bisati, S; Singh, Al; Koley, S

    2013-11-01

    To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris. This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams. In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each. Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud's dextrose agar with chloramphenicol and cycloheximide. Statistical analysis was done using students paired and unpaired t-tests from the data obtained. Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1(st) and 2(nd) week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2(nd) week

  16. Efficacy and safety of terbinafine hydrochloride 1% cream vs. sertaconazole nitrate 2% cream in tinea corporis and tinea cruris: A comparative therapeutic trial

    Directory of Open Access Journals (Sweden)

    S V Choudhary

    2013-01-01

    Full Text Available Context: To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris. Aims: This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams. Settings and Design: In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream and Group B (treatment with sertaconazole cream. A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each. Materials and Methods: Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud′s dextrose agar with chloramphenicol and cycloheximide. Statistical Analysis Used: Statistical analysis was done using students paired and unpaired t-tests from the data obtained. Results: Comparison between Group A and Group B for complete cure (clinical and mycological showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1 st and 2 nd week, statistically non

  17. Complete Biological Evaluation of Therapeutical Radiopharmaceuticals in Rodents, Laboratory Beagles and Veterinary Patients - Preclinical Distribution-, Kinetic-, Excretion-, Internal Dosimetry-, Radiotoxicological-, Radiation Safety- and Efficacy Data

    International Nuclear Information System (INIS)

    Balogh, L.; Domokos, M.; Polyak, A.; Thuroczy, J.; Janoki, G.

    2009-01-01

    The research and development of various novel therapeutical radiopharmaceuticals is a huge demand in many laboratories world-wide. Beside of multiple bone metastases pain-palliation and radiosynovectomy agents a number of specific radiopharmaceutical applicants mainly for oncological applications are in the pipeline. Numerous in vitro methods are available in the first line to test the radiolabelling efficiency, the possible radioactive and non-labelled impurities, the stability of the label at different conditions and mediums, and some specific characteristics of radiopharmaceutical applicants eg.: receptor binding assays, antigen-antibody assays. But, still before human clinical trials there are several questions to be solved in regards of toxicology, radiotoxicology, radiation safety and maybe most importantly the efficacy tasks. All these issues cannot be answered without animal tests. Several decades back animal tests in radiopharmacy meant only standard bioassays in a large number of healthy rodents. Later on pathological models eg.: human tumor xenografts in immunodeficient animals came-out and through them radiopharmaceutical tumor-uptake by the targets were available to evaluate in vivo as well. Xenografts are still popular and widely used models in the field but instead of wide-scaled bioassays nowadays repeated scintiscans or hybrid images (SPECT/CT, PET/CT) are more and more often used to answer kinetic-, excretion-, tumor uptake, internal dosimetry (Minimum Effective Dose, Maximum Tolerable Dose, critical organ doses, tumor doses) questions. Greater animals like laboratory Beagles are more closely in size, clinical and metabolic parameters to the human objects so playing a more perfect role of human medical doctor and especially veterinary patients. Easy to understand that many of the spontaneously occurring companion animal diseases are a good model of human pathological diseases. The need of a better diagnosis and treatment of that animals meets with

  18. Therapeutic efficacy of stereotactic radiotherapy with gamma knife on early-stage non-small-cell lung cancer and life quality of patients

    International Nuclear Information System (INIS)

    Ren Zhengting; Cui Di; Ren Ye; Dai Zhuojie; Su Xiaoming; Fan Jingjing; Shen Yulong; Ma Huizhen; Wang Zongye

    2012-01-01

    Objective: To evaluate the therapeutic efficacy of stereotactic body radiotherapy (SBRT) with gamma knife on stage Ⅰ-Ⅱ non-small-cell lung cancer (NSCLC)and the quality of life of the patients undergoing this therapy. Methods: Twenty NSCLC patients with the median age of 76, 10 at stage Ⅰ and 10 at stage Ⅱ who were unable or unwilling to undergo surgery were given SBRT with gamma knife at the doses of 3-6 Gy in 8-15 fractions,finished within 2 to 3 weeks. The prescription isodose line was 50%,the marginal dose was 39-56 Gy, the central dose was 78-112 Gy, and the total biologically effective dose was 51-83 Gy. The patients were observed after admission and followed up by chest CT 1, 3, 6, and 12 months after treatment until progressive disease or death. EORTC QLQ-LC43 questionnaire was used to investigate the changes in quality of life. Results: The 20 patients were followed up for 24 (12-46) months. At six months after the treatment,the overall response rate was 80%, and the complete response rate was 35%. The 1, 2 and 3-year local control rates were 100%, 95% and 95%, respectively. The 1, 2 and 3-year overall survival rates were 95%, 80% and 50% respectively; The 1, 2, and 3-year progression free survival rates were 85%, 64% and 33%, respectively. The failure rate was 20% and the rate of progress within the planning target volume was 5%. No acute toxicity at grade 3 and over occurred in any patient during the treatment. 15% of the patients developed grade 1-2 radiation pneumonia. Age, gender, pathologic index or not were weakly correlated with the overall survival. The emotional function was improved significantly after treatment (P<0.05), dyspnea and cough were improved at different degrees, however, not significantly. There were no significant changes in the physical function and symptoms, such as fatigue,lack of appetite, insomnia, etc. Conclusions: Significantly improving the motional function and maintaining the quality of life, SBRT with gamma knife

  19. Entomopathogenic fungus generated Nanoparticles for enhancement of efficacy in Culex quinquefasciatus and Anopheles stephensi

    Directory of Open Access Journals (Sweden)

    N. SONI, S. PRAKASH

    2012-05-01

    Full Text Available Objective: To evaluate to efficacy of silver and gold generated larvicide with the help of entomopathogenic fungus Chrysosporium tropicum against the Culex quinquefasciatus and Anopheles stephensi larvae. Methods: The silver and gold nanoparticles were quantified and observed by the Micro-scan reader and X-ray diffraction technique. The micrographs of silver and gold nanoparticles were obtained by the Transmission electron microscope and Scanning electron microscope. The larvicidal efficacy was then performed at six different log concentrations by the probit analysis. Results: The characterization study confirmed the spherical shaped and sized (20-50 and 2-15 nm of silver and gold nanoparticles. The all larval stages of Cx. quinquefasciatus were found more susceptible to the synthesized silver nanoparticles. Whereas, the larvae of An. stephensi were found more susceptible to larvicide synthesized with gold nanoparticles. Conclusions: The results suggested that the silver and gold nanoparticles generated by the entomopathogenic fungus C. tropicum is an environmentally safer and greener approach for mosquito control and new possibility in vector control strategy.

  20. Therapeutic efficacy of Traditional Chinese medicine, "Kuan-Sin-Yin", in patients undergoing chemotherapy for advanced colon cancer - A controlled trial.

    Science.gov (United States)

    Chien, Tsai-Ju; Liu, Chia-Yu; Lu, Ruey-Hwa; Kuo, Chin-Wei; Lin, Yang-Chao; Hsu, Chung-Hua

    2016-12-01

    Traditional Chinese Medicine (TCM) has been used increasingly as complementary medicine in cancer care. Kuan-Sin-Yin (KSY) is a TCM decoction containing seven herbs known to cause immunomodulation or anticancer activity, and which are associated with the TCM concept of Qi and energy supply. Kuan-Sin-Yin has cytostatic effects on cancer cells in animal models. The aim of this study is to evaluate the level of improvement in meridian energy and heart-rate variability (HRV) and to assess whether these observations are compatible with TCM theory. A non-randomized controlled trial was designed with monitoring of the meridian electro-conductivity and heart-rate variability (HRV) to compare the efficacy of Kuan-Sin-Yin in the control and experimental groups. 52 patients were enrolled in this study. We also measured cancer-related symptoms and quality of life as secondary outcomes. We found that colon cancer patients who received KSY as complementary therapy benefitted with enhancement of meridian energy (Yin meridian: 27.90:35.45μA; p=0.014; Yang meridian: 27.09:33.55μA; p=0.024) and increases in HRV activity (78.40:129.04ms; SDNN: p=0.001) and parasympathetic tone(HF:1644.80:3217.92 ms 2 ; p=0.003; RMMSD:99.76:164.52ms; p=0.002). Cancer-related symptoms decreased (ECOG>1:46.2:7.7%; p=0.0001), and quality of life (KSY group: PCS 35.46:42.12, p=0.0001; MCS: 44.50:47.55, p=0.209) was improved with statistical significance. The correlation of positive results reflected in meridian energy and HRV activity confirms the positive role of complementary medicine of Kuan-Sin-Yin in cancer care. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Wu, T; Little, TL; Bound, MJ

    2016-01-01

    to evaluate whether a proteinpreload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4)inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying,and lower postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODSTwenty-two patients with type 2 diabetes treated...... with metformin were studiedon four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) onboth the evening before and the morning of each study day. The latter dose wasfollowed after 60 min by a preload drink containing either 25 gwhey protein (WHEY)or control flavoring (CTRL), and after...... intact GLP-1 and GIP, slower gastric emptying, and lowerpostprandial glycemia (P vildagliptin to slow gastric emptying, increase plasma intactincretins, and reduce postprandial...

  2. Enhancing the efficacy of cytotoxic agents for cancer therapy using photochemical internalisation.

    Science.gov (United States)

    Martinez de Pinillos Bayona, Alejandra; Moore, Caroline M; Loizidou, Marilena; MacRobert, Alexander J; Woodhams, Josephine H

    2016-03-01

    Photochemical internalisation (PCI) is a technique for improving cellular delivery of certain bioactive agents which are prone to sequestration within endolysosomes. There is a wide range of agents suitable for PCI-based delivery including toxins, oligonucleotides, genes and immunoconjugates which demonstrates the versatility of this technique. The basic mechanism of PCI involves triggering release of the agent from endolysosomes within the target cells using a photosensitiser which is selectively retained with the endolysosomal membranes. Excitation of the photosensitiser by visible light leads to disruption of the membranes via photooxidative damage thereby releasing the agent into the cytosol. This treatment enables the drugs to reach their intended subcellular target more efficiently and improves their efficacy. In this review we summarise the applications of this technique with the main emphasis placed on cancer chemotherapy. © 2015 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

  3. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

    Directory of Open Access Journals (Sweden)

    Youngsoo Sohn

    2013-03-01

    Full Text Available Human α-galactosidase A (GLA has been used in enzymereplacement therapy for patients with Fabry disease. Weexpressed recombinant GLA from Chinese hamster ovary cellswith very high productivity. When compared to an approvedGLA (agalsidase beta, its size and charge were found to besmaller and more neutral. These differences resulted from thelack of terminal sialic acids playing essential roles in the serumhalf-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acidcontent, a combined reaction using galactosyltransferase,sialyltransferase, and their sugar substrates at the same timewas developed and optimized to reduce the incubation time.The product generated by this reaction had nearly the samesize, isoelectric points, and sialic acid content as agalsidasebeta. Furthermore, it had better in vivo efficacy to degrade theaccumulated globotriaosylceramide in target organs of Fabrymice compared to an unmodified version. [BMB Reports 2013;46(3: 157-162

  4. Enhancing memory self-efficacy during menopause through a group memory strategies program.

    Science.gov (United States)

    Unkenstein, Anne E; Bei, Bei; Bryant, Christina A

    2017-05-01

    Anxiety about memory during menopause can affect quality of life. We aimed to improve memory self-efficacy during menopause using a group memory strategies program. The program was run five times for a total of 32 peri- and postmenopausal women, age between 47 and 60 years, recruited from hospital menopause and gynecology clinics. The 4-week intervention consisted of weekly 2-hour sessions, and covered how memory works, memory changes related to ageing, health and lifestyle factors, and specific memory strategies. Memory contentment (CT), reported frequency of forgetting (FF), use of memory strategies, psychological distress, and attitude toward menopause were measured. A double-baseline design was applied, with outcomes measured on two baseline occasions (1-month prior [T1] and in the first session [T2]), immediately postintervention (T3), and 3-month postintervention (T4). To describe changes in each variable between time points paired sample t tests were conducted. Mixed-effects models comparing the means of random slopes from T2 to T3 with those from T1 to T2 were conducted for each variable to test for treatment effects. Examination of the naturalistic changes in outcome measures from T1 to T2 revealed no significant changes (all Ps > 0.05). CT, reported FF, and use of memory strategies improved significantly more from T2 to T3, than from T1 to T2 (all Ps attitude toward menopause nor psychological distress improved significantly more postintervention than during the double-baseline (all Ps > 0.05). Improvements in reported CT and FF were maintained after 3 months. The use of group interventions to improve memory self-efficacy during menopause warrants continued evaluation.

  5. Enhanced antimicrobial efficacy of thermal-reduced silver nanoparticles supported by titanium dioxide.

    Science.gov (United States)

    Chen, Yen-Chi; Yu, Kuo-Pin

    2017-06-01

    The antimicrobial efficacy of silver nanoparticles (AgNPs) is influenced by many factors, including the particle size, AgNP oxidation state and support materials. In this study, AgNPs are synthesized and supported by two types of TiO 2 powders (P25 and Merck TiO 2 ) using two heat-treatment temperatures (120 and 200°C). The formation of well-dispersed AgNPs with diameters ranging from 3.2 to 5.7nm was confirmed using transmission electron microscopy. X-ray photoelectron spectroscopy and X-ray diffraction indicated that the majority of the AgNPs were reduced from Ag + to Ag 0 at 200°C. The AgNP antimicrobial activity was determined by the zone of inhibition against three fungi, A. niger, P. spinulosum and S. chartarum, and two bacteria, E. coli (Gram-negative) and S. epidermidis (Gram-positive). The antimicrobial activity of metallic AgNPs was more pronounced than that of silver nitrate and some antimicrobial drugs. The AgNPs exhibited optimal antimicrobial efficacy when the AgNP dispersion on the surface of TiO 2 was in the region between 0.2 and 0.7μg-Ag/m 2 . The minimum (critical) AgNP concentrations needed to inhibit the growth of bacteria (E. coli) and fungi (A. niger) were 13.48 and 25.4μg/mL, respectively. The results indicate that AgNPs/TiO 2 nanocomposites are a promising disinfectant against both bacteria and fungi. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Enhanced efficacy and sensory properties of an anti-dandruff shampoo containing zinc pyrithione and climbazole.

    Science.gov (United States)

    Turner, G A; Matheson, J R; Li, G-Z; Fei, X-Q; Zhu, D; Baines, F L

    2013-02-01

    Dandruff is a common complaint and is suffered by as much as half of the population at some time post puberty. The condition is characterized by the presence of flakes on the scalp and in the hair, and is often accompanied by itch. The most common treatment for dandruff is the use of shampoo formulations that contain fungistatic agents such as zinc pyrithione (ZPT) and octopirox. Whilst most antidandruff shampoos are effective in resolving the symptoms of dandruff these shampoos can often result in hair condition that is less than acceptable to consumers which can lead to a tendency for them to revert to use of a non-antidandruff shampoo. This can result in a rapid return of dandruff symptoms. The aim of this investigation was to study the impact of using a combination of antidandruff actives and silicones on the resolution of dandruff and to deliver superior sensory properties to the hair. We have demonstrated that shampoo containing the dual active system of ZPT/Climbazole deposits both active agents onto a model skin surface (VitroSkin) and reduces Malassezia furfur regrowth in vitro. Clinical evaluation of the dual active shampoo demonstrated superior efficacy and retained superiority during a regression phase where all subjects reverted to using a non-antidandruff shampoo. We have also demonstrated that it is possible to deposit silicone materials from antidandruff shampoo uniformly over both virgin and damaged hair fibres that results in smoother hair fibres (as evidenced by reduced dry friction). This combination of antidandruff agents and conditioning silicones delivered from a shampoo provides subjects with superior antidandruff efficacy and desired end sensory benefits ensuring compliance and longer term dandruff removal. © 2012 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  7. Overcoming Barriers of Age to Enhance Efficacy of Cancer Immunotherapy: The Clout of the Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Mark Owyong

    2018-03-01

    Full Text Available There is a growing list of cancer immunotherapeutics approved for use in a population with an increasing number of aged individuals. Cancer immunotherapy (CIT mediates tumor destruction by activating anti-tumor immune responses that have been silenced through the oncogenic process. However, in an aging individual, immune deregulation is positively correlated with age. In this context, it is vital to examine the age-related changes in the tumor microenvironment (TME and specifically, those directly affecting critical players to ensure CIT efficacy. Effector T cells, regulatory T cells, myeloid-derived suppressor cells, tumor-associated macrophages, and tumor-associated neutrophils play important roles in promoting or inhibiting the inflammatory response, while cancer-associated fibroblasts are key mediators of the extracellular matrix (ECM. Immune checkpoint inhibitors function optimally in inflamed tumors heavily invaded by CD4 and CD8 T cells. However, immunosenescence curtails the effector T cell response within the TME and causes ECM deregulation, creating a biophysical barrier impeding both effective drug delivery and pro-inflammatory responses. The ability of the chimeric antigen receptor T (CAR-T cell to artificially induce an adaptive immune response can be modified to degrade essential components of the ECM and alleviate the age-related changes to the TME. This review will focus on the age-related alterations in ECM and immune-stroma interactions within the TME. We will discuss strategies to overcome the barriers of immunosenescence and matrix deregulation to ameliorate the efficacy of CIT in aged subjects.

  8. Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

    Science.gov (United States)

    Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

    2016-07-01

    The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Connected: Recommendations and Techniques in Order to Employ Internet Tools for the Enhancement of Online Therapeutic Relationships. Experiences from Italy.

    Science.gov (United States)

    Manfrida, Gianmarco; Albertini, Valentina; Eisenberg, Erica

    2017-01-01

    The article explores the different types of therapeutic relationship that can evolve both on- and offline, thanks to the use of tools, such as software and applications, which enable therapists and patients contact outside of the traditional setting. Given the premise that it is practically impossible today to maintain a relationship without the use of internet and telephones, it becomes necessary to question the ways in which the online space can become a useful extension of the therapeutic setting. The authors, starting from a consideration regarding the specificity of the online therapeutic relationship, analyze the best ways to use text and email messaging with patients. Furthermore, specific interactions via group chats are presented, for example, to coordinate a therapeutic team involving several professionals. Further, video chat settings are discussed through a clinical case presentation. Lastly, the therapist's management of social networks is debated, underscoring the importance for the therapists that his or her online identity be consistent with the offline image which patients are introduced to in the traditional setting of the therapy room.

  10. Encapsulation of the therapeutic microbe Akkermansia muciniphila in a double emulsion enhances survival in simulated gastric conditions

    NARCIS (Netherlands)

    Ark, van der Kees C.H.; Nugroho, Avis Dwi Wahyu; Berton-Carabin, Claire; Wang, Che; Belzer, Clara; Vos, de Willem M.; Schroen, Karin

    2017-01-01

    There is considerable attention for developing Akkermansia muciniphila as a new therapeutic microbe since it has shown to prevent diet-induced obesity and type 2 diabetes in mice. However, A. muciniphila is sensitive to gastric conditions such as low pH and oxygen. Therefore, we explored the

  11. Zinc supplementation induces apoptosis and enhances antitumor efficacy of docetaxel in non-small-cell lung cancer

    Directory of Open Access Journals (Sweden)

    Kocdor H

    2015-07-01

    Full Text Available Hilal Kocdor,1,2 Halil Ates,1 Suleyman Aydin,3 Ruksan Cehreli,1 Firat Soyarat,2 Pinar Kemanli,2 Duygu Harmanci,2 Hakan Cengiz,2 Mehmet Ali Kocdor4 1Institute of Oncology, Dokuz Eylul University, 2Department of Molecular Medicine, Institute of Health Sciences, Dokuz Eylul University, Izmir Turkey; 3Department of Biochemistry, Firat University School of Medicine, Elazig, 4Department of Surgery, School of Medicine, Dokuz Eylul University, Izmir, Turkey Background: Exposure to exogenous zinc results in increased apoptosis, growth inhibition, and altered oxidative stress in cancer cells. Previous studies also suggested that zinc sensitizes some cancer cells to cytotoxic agents depending on the p53 status. Therefore, zinc supplementation may show anticancer efficacy solely and may increase docetaxel-induced cytotoxicity in non-small-cell lung cancer cells.Methods: Here, we report the effects of several concentrations of zinc combined with docetaxel on p53-wild-type (A549 and p53-null (H1299 cells. We evaluated cellular viability, apoptosis, and cell cycle progression as well as oxidative stress parameters, including superoxide dismutase, glutathione peroxidase, and malondialdehyde levels.Results: Zinc reduced the viability of A549 cells and increased the apoptotic response in both cell lines in a dose-dependent manner. Zinc also amplified the docetaxel effects and reduced its inhibitory concentration 50 (IC50 values. The superoxide dismutase levels increased in all treatment groups; however, glutathione peroxidase was slightly increased in the combination treatments. Zinc also caused malondialdehyde elevations at 50 µM and 100 µM.Conclusion: Zinc has anticancer efficacy against non-small-cell lung cancer cells in the presence of functionally active p53 and enhances docetaxel efficacy in both p53-wild-type and p53-deficient cancer cells. Keywords: lung cancer, zinc, docetaxel, A549, H1299

  12. Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose

    Directory of Open Access Journals (Sweden)

    Torre-Iglesias PM

    2014-09-01

    Full Text Available Paloma Marina de la Torre-Iglesias,1,2 Juan José García-Rodriguez,3 Guillermo Torrado,4 Susana Torrado,1,2 Santiago Torrado-Santiago,1,5 Francisco Bolás-Fernández3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Complutense University, Madrid, Spain; 2Institute of Industrial Pharmacy, Complutense University, Madrid, Spain; 3Department of Parasitology, Faculty of Pharmacy, Complutense University, Madrid, Spain; 4Department of Pharmaceutical Technology, Faculty of Pharmacy, Alcala University, Alcala de Henares (Madrid, Spain; 5Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD, Madrid, Spain Background: Mebendazole (MBZ is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. Methods: In the present study we prepared redispersible microparticles (RDM containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC. We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis.Results: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s under the curve (AUC0

  13. Physical activity enhances long-term quality of life in older adults: efficacy, esteem, and affective influences.

    Science.gov (United States)

    Elavsky, Steriani; McAuley, Edward; Motl, Robert W; Konopack, James F; Marquez, David X; Hu, Liang; Jerome, Gerald J; Diener, Ed

    2005-10-01

    Physical activity has been effective in enhancing quality of life (QOL) of older adults over relatively short periods of time. However, little is known about the long-term effects of physical activity and even less about the possible mediators of this relationship. We examined the mediating effects of psychological variables on the relationship between physical activity and global QOL (satisfaction with life) in older adults over a 4-year period. Participants (N = 174, M age = 66.7 years) completed a battery of psychosocial measures at 1 and 5 years following enrollment in a 6-month randomized controlled exercise trial. Panel analysis conducted within a covariance modeling framework indicated that physical activity was related to self-efficacy, physical self-esteem, and positive affect at 1 year, and in turn, greater levels of self-efficacy and positive affect were associated with higher levels of QOL. Analyses indicated that changes in physical activity over the 4-year period were related to increases in physical self-esteem and positive affect, but only positive affect directly influenced improvements in QOL. The findings lend support to the position that physical activity effects on QOL are in part mediated by intermediate psychological outcomes and that physical activity can have long-term effects on well-being.

  14. Enhancement of surfactant efficacy during the cleanup of engine oil contaminated soil using salt and multi-walled carbon nanotubes.

    Science.gov (United States)

    Bonal, Niteesh Singh; Paramkusam, Bala Ramudu; Basudhar, Prabir Kumar

    2018-06-05

    The study aims to enhance the efficacy of surfactants using salt and multi-walled carbon nanotubes (MWCNT) for washing used engine oil (UEO) contaminated soil and compare the geotechnical properties of contaminated soil before and after washing (batch washing and soil washing). From batch washing of the contaminated soil the efficacy of the cleaning process is established. Contamination of soil with hydrocarbons present in UEO significantly affects its' engineering properties manifesting in no plasticity and low specific gravity; the corresponding optimum moisture content value is 6.42% while maximum dry density is 1.770 g/cc, which are considerably lower than those of the uncontaminated soil. The result also showed decrease in the values of cohesion intercept and increase in the friction angle values. The adopted soil washing technique resulted increase in specific gravity from 1.85 to 2.13 and cohesion from 0.443 to 1.04 kg/cm 2 and substantial decrease in the friction angle from 31.16° to 17.14° when washed with most efficient combination of SDS surfactant along with sodium meta-silicate (salt) and MWCNT. Effectiveness of the washing of contaminated soil by batch processing and soil washing techniques has been established qualitatively. The efficiency of surfactant treatment has been observed to be increased significantly by the addition of salt and MWCNT. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Enhancing predicted efficacy of tumor treating fields therapy of glioblastoma using targeted surgical craniectomy: A computer modeling study

    DEFF Research Database (Denmark)

    Korshoej, Anders Rosendal; Saturnino, Guilherme Bicalho; Rasmussen, Line Kirkegaard

    2016-01-01

    the potential of the intervention to improve the clinical efficacy of TTFields therapy of brain cancer. Methods: We used finite element analysis to calculate the electrical field distribution in realistic head models based on MRI data from two patients: One with left cortical/subcortical glioblastoma and one......Objective: The present work proposes a new clinical approach to TTFields therapy of glioblastoma. The approach combines targeted surgical skull removal (craniectomy) with TTFields therapy to enhance the induced electrical field in the underlying tumor tissue. Using computer simulations, we explore...... with deeply seated right thalamic anaplastic astrocytoma. Field strength was assessed in the tumor regions before and after virtual removal of bone areas of varying shape and size (10 to 100 mm) immediately above the tumor. Field strength was evaluated before and after tumor resection to assess realistic...

  16. Psychedelics and hypnosis: Commonalities and therapeutic implications.

    Science.gov (United States)

    Lemercier, Clément E; Terhune, Devin B

    2018-06-01

    Recent research on psychedelics and hypnosis demonstrates the value of both methods in the treatment of a range of psychopathologies with overlapping applications and neurophenomenological features. The potential of harnessing the power of suggestion to influence the phenomenological response to psychedelics toward more therapeutic action has remained unexplored in recent research and thereby warrants empirical attention. Here we aim to elucidate the phenomenological and neurophysiological similarities and dissimilarities between psychedelic states and hypnosis in order to revisit how contemporary knowledge may inform their conjunct usage in psychotherapy. We review recent advances in phenomenological and neurophysiological research on psychedelics and hypnosis, and we summarize early investigations on the coupling of psychedelics and hypnosis in scientific and therapeutic contexts. Results/outcomes: We highlight commonalities and differences between psychedelics and hypnosis that point to the potential efficacy of combining the two in psychotherapy. We propose multiple research paths for coupling these two phenomena at different stages in the preparation, acute phase and follow-up of psychedelic-assisted psychotherapy in order to prepare, guide and integrate the psychedelic experience with the aim of enhancing therapeutic outcomes. Harnessing the power of suggestion to modulate response to psychedelics could enhance their therapeutic efficacy by helping to increase the likelihood of positive responses, including mystical-type experiences.

  17. Nkx2.5 enhances the efficacy of mesenchymal stem cells transplantation in treatment heart failure in rats.

    Science.gov (United States)

    Deng, Bo; Wang, Jin Xin; Hu, Xing Xing; Duan, Peng; Wang, Lin; Li, Yang; Zhu, Qing Lei

    2017-08-01

    The aim of this study is to determine whether Nkx2.5 transfection of transplanted bone marrow mesenchymal stem cells (MSCs) improves the efficacy of treatment of adriamycin-induced heart failure in a rat model. Nkx2.5 was transfected in MSCs by lentiviral vector transduction. The expressions of Nkx2.5 and cardiac specific genes in MSCs and Nkx2.5 transfected mesenchymal stem cells (MSCs-Nkx2.5) were analyzed with quantitative real-time PCR and Western blot in vitro. Heart failure models of rats were induced by adriamycin and were then randomly divided into 3 groups: injected saline, MSCs or MSCs-Nkx2.5 via the femoral vein respectively. Four weeks after injection, the cardiac function, expressions of cardiac specific gene, fibrosis formation and collagen volume fraction in the myocardium as well as the expressions of GATA4 and MEF2 in rats were analyzed with echocardiography, immunohistochemistry, Masson staining, quantitative real-time PCR and Western blot, respectively. Nkx2.5 enhanced cardiac specific gene expressions including α-MHC, TNI, CKMB, connexin-43 in MSCs-Nkx2.5 in vitro. Both MSCs and MSCs-Nkx2.5 improved cardiac function, promoted the differentiation of transplanted MSCs into cardiomyocyte-like cells, decreased fibrosis formation and collagen volume fraction in the myocardium, as well as increased the expressions of GATA4 and MEF2 in adriamycin-induced rat heart failure models. Moreover, the effect was much more remarkable in MSCs-Nkx2.5 than in MSCs group. This study has found that Nkx2.5 enhances the efficacy of MSCs transplantation in treatment adriamycin-induced heart failure in rats. Nkx2.5 transfected to transplanted MSCs provides a potential effective approach to heart failure. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Synergistic effects of dendritic cell targeting and laser-microporation on enhancing epicutaneous skin vaccination efficacy.

    Science.gov (United States)

    Machado, Yoan; Duinkerken, Sanne; Hoepflinger, Veronika; Mayr, Melissa; Korotchenko, Evgeniia; Kurtaj, Almedina; Pablos, Isabel; Steiner, Markus; Stoecklinger, Angelika; Lübbers, Joyce; Schmid, Maximillian; Ritter, Uwe; Scheiblhofer, Sandra; Ablinger, Michael; Wally, Verena; Hochmann, Sarah; Raninger, Anna M; Strunk, Dirk; van Kooyk, Yvette; Thalhamer, Josef; Weiss, Richard

    2017-11-28

    Due to its unique immunological properties, the skin is an attractive target tissue for allergen-specific immunotherapy. In our current work, we combined a dendritic cell targeting approach with epicutaneous immunization using an ablative fractional laser to generate defined micropores in the upper layers of the skin. By coupling the major birch pollen allergen Bet v 1 to mannan from S. cerevisiae via mild periodate oxidation we generated hypoallergenic Bet-mannan neoglycoconjugates, which efficiently targeted CD14 + dendritic cells and Langerhans cells in human skin explants. Mannan conjugation resulted in sustained release from the skin and retention in secondary lymphoid organs, whereas unconjugated antigen showed fast renal clearance. In a mouse model, Bet-mannan neoglycoconjugates applied via laser-microporated skin synergistically elicited potent humoral and cellular immune responses, superior to intradermal injection. The induced antibody responses displayed IgE-blocking capacity, highlighting the therapeutic potential of the approach. Moreover, application via micropores, but not by intradermal injection, resulted in a mixed TH1/TH17-biased immune response. Our data clearly show that applying mannan-neoglycoconjugates to an organ rich in dendritic cells using laser-microporation is superior to intradermal injection. Due to their low IgE binding capacity and biodegradability, mannan neoglycoconjugates therefore represent an attractive formulation for allergen-specific epicutaneous immunotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Targeted Adenoviral Vector Demonstrates Enhanced Efficacy for In Vivo Gene Therapy of Uterine Leiomyoma.

    Science.gov (United States)

    Abdelaziz, Mohamed; Sherif, Lotfy; ElKhiary, Mostafa; Nair, Sanjeeta; Shalaby, Shahinaz; Mohamed, Sara; Eziba, Noura; El-Lakany, Mohamed; Curiel, David; Ismail, Nahed; Diamond, Michael P; Al-Hendy, Ayman

    2016-04-01

    Gene therapy is a potentially effective non-surgical approach for the treatment of uterine leiomyoma. We demonstrated that targeted adenovirus vector, Ad-SSTR-RGD-TK/GCV, was highly effective in selectively inducing apoptosis and inhibiting proliferation of human leiomyoma cells in vitro while sparing normal myometrial cells. An in-vivo study, to compare efficacy and safety of modified adenovirus vector Ad-SSTR-RGD-TK/GCV versus untargeted vector for treatment of leiomyoma. Female nude mice were implanted with rat leiomyoma c