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Sample records for potential therapy agent

  1. Rosemary (Rosmarinus officinalis L.) Extract as a Potential Complementary Agent in Anticancer Therapy.

    PubMed

    González-Vallinas, Margarita; Reglero, Guillermo; Ramírez de Molina, Ana

    2015-01-01

    Cancer remains an important cause of mortality nowadays and, therefore, new therapeutic approaches are still needed. Rosemary (Rosmarinus officinalis L.) has been reported to possess antitumor activities both in vitro and in animal studies. Some of these activities were attributed to its major components, such as carnosic acid, carnosol, ursolic acid, and rosmarinic acid. Initially, the antitumor effects of rosemary were attributed to its antioxidant activity. However, in recent years, a lack of correlation between antioxidant and antitumor effects exerted by rosemary was reported, and different molecular mechanisms were related to its tumor inhibitory properties. Moreover, supported by the U.S. Food and Drug Administration and the European Food and Safety Authority, specific compositions of rosemary extract were demonstrated to be safe for human health and used as antioxidant additive in foods, suggesting the potential easy application of this agent as a complementary approach in cancer therapy. In this review, we aim to summarize the reported anticancer effects of rosemary, the demonstrated molecular mechanisms related to these effects and the interactions between rosemary and currently used anticancer agents. The possibility of using rosemary extract as a complementary agent in cancer therapy in comparison with its isolated components is discussed.

  2. Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies?

    PubMed

    Angelini, Daniel J; Dorsey, Russell M; Willis, Kristen L; Hong, Charles; Moyer, Robert A; Oyler, Jonathan; Jensen, Neil S; Salem, Harry

    2013-01-01

    Chemical warfare agents (CWAs) as well as biological toxins present a significant inhalation injury risk to both deployed warfighters and civilian targets of terrorist attacks. Inhalation of many CWAs and biological toxins can induce severe pulmonary toxicity leading to the development of acute lung injury (ALI) as well as acute respiratory distress syndrome (ARDS). The therapeutic options currently used to treat these conditions are very limited and mortality rates remain high. Recent evidence suggests that human stem cells may provide significant therapeutic options for ALI and ARDS in the near future. The threat posed by CWAs and biological toxins for both civilian populations and military personnel is growing, thus understanding the mechanisms of toxicity and potential therapies is critical. This review will outline the pulmonary toxic effects of some of the most common CWAs and biological toxins as well as the potential role of stem cells in treating these types of toxic lung injuries.

  3. Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis.

    PubMed

    Zumla, Alimuddin; Rao, Martin; Dodoo, Ernest; Maeurer, Markus

    2016-06-15

    Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation.

  4. Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis.

    PubMed

    Zumla, Alimuddin; Rao, Martin; Dodoo, Ernest; Maeurer, Markus

    2016-01-01

    Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation. PMID:27301245

  5. Triterpenoids as potential agents for the chemoprevention and therapy of breast cancer

    PubMed Central

    Bishayee, Anupam; Ahmed, Shamima; Brankov, Nikoleta; Perloff, Marjorie

    2010-01-01

    Breast cancer remains a major cause of death in the United States as well as the rest of the world. In view of the limited treatment options for patients with advanced breast cancer, preventive and novel therapeutic approaches play an important role in combating this disease. The plant-derived triterpenoids, commonly used for medicinal purposes in many Asian countries, posses various pharmacological properties. A large number of triterpenoids are known to exhibit cytotoxicity against a variety of tumor cells as well as anticancer efficacy in preclinical animal models. Numerous triterpenoids have been synthesized by structural modification of natural compounds. Some of these analogs are considered to be the most potent antiinflammatory and anticarcinogenic triterpenoids known. This review examines the potential role of natural triterpenoids and their derivatives in the chemoprevention and treatment of mammary tumors. Both in vitro and in vivo effects of these agents and related molecular mechanisms are presented. Potential challenges and future directions involved in the advancement of these promising compounds in the prevention and therapy of human breast cancer are also identified. PMID:21196213

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

    PubMed

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

    2015-10-01

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

  7. Phthalocyanine derivatives possessing 2-(morpholin-4-yl)ethoxy groups as potential agents for photodynamic therapy.

    PubMed

    Kucinska, Malgorzata; Skupin-Mrugalska, Paulina; Szczolko, Wojciech; Sobotta, Lukasz; Sciepura, Mateusz; Tykarska, Ewa; Wierzchowski, Marcin; Teubert, Anna; Fedoruk-Wyszomirska, Agnieszka; Wyszko, Eliza; Gdaniec, Maria; Kaczmarek, Mariusz; Goslinski, Tomasz; Mielcarek, Jadwiga; Murias, Marek

    2015-03-12

    Three 2-(morpholin-4-yl)ethoxy substituted phthalocyanines were synthesized and characterized. Phthalocyanine derivatives revealed moderate to high quantum yields of singlet oxygen production depending on the solvent applied (e.g., in DMF ranging from 0.25 to 0.53). Their photosensitizing potential for photodynamic therapy was investigated in an in vitro model using cancer cell lines. Biological test results were found particularly encouraging for the zinc(II) phthalocyanine derivative possessing two 2-(morpholin-4-yl)ethoxy substituents in nonperipheral positions. Cells irradiated for 20 min at 2 mW/cm(2) revealed the lowest IC50 value at 0.25 μM for prostate cell line (PC3), whereas 1.47 μM was observed for human malignant melanoma (A375) cells. The cytotoxic activity in nonirradiated cells of novel phthalocyanine was found to be very low. Moreover, the cellular uptake, localization, cell cycle, apoptosis through an ELISA assay, and immunochemistry method were investigated in LNCaP cells. Our results showed that the tested photosensitizer possesses very interesting biological activity, depending on experimental conditions.

  8. Iron oxide nanoparticles functionalized with novel hydrophobic and hydrophilic porphyrins as potential agents for photodynamic therapy.

    PubMed

    Penon, Oriol; Marín, María J; Amabilino, David B; Russell, David A; Pérez-García, Lluïsa

    2016-01-15

    The preparation of novel porphyrin derivatives and their immobilization onto iron oxide nanoparticles to build up suitable nanotools for potential use in photodynamic therapy (PDT) has been explored. To achieve this purpose, a zinc porphyrin derivative, ZnPR-COOH, has been synthesized, characterized at the molecular level and immobilized onto previously synthesized iron oxide nanoparticles covered with oleylamine. The novel nanosystem (ZnPR-IONP) has been thoroughly characterized by a variety of techniques such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, X-ray photoloectron spectroscopy (XPS) and transmission electron microscopy (TEM). In order to probe the capability of the photosensitizer for PDT, the singlet oxygen production of both ZnPR-IONP and the free ligand ZnPR-COOH have been quantified by measuring the decay in absorption of the anthracene derivative 9,10-anthracenedipropionic acid (ADPA), showing an important increase on singlet oxygen production when the porphyrin is incorporated onto the IONP (ZnPR-IONP). On the other hand, the porphyrin derivative PR-TRIS3OH, incorporating several polar groups (TRIS), was synthesized and immobilized with the intention of obtaining water soluble nanosystems (PR-TRIS-IONP). When the singlet oxygen production ability was evaluated, the values obtained were similar to ZnPR-COOH/ZnPR-IONP, again much higher in the case of the nanoparticles PR-TRIS-IONP, with more than a twofold increase. The efficient singlet oxygen production of PR-TRIS-IONP together with their water solubility, points to the great promise that these new nanotools represent for PDT.

  9. Iron oxide nanoparticles functionalized with novel hydrophobic and hydrophilic porphyrins as potential agents for photodynamic therapy.

    PubMed

    Penon, Oriol; Marín, María J; Amabilino, David B; Russell, David A; Pérez-García, Lluïsa

    2016-01-15

    The preparation of novel porphyrin derivatives and their immobilization onto iron oxide nanoparticles to build up suitable nanotools for potential use in photodynamic therapy (PDT) has been explored. To achieve this purpose, a zinc porphyrin derivative, ZnPR-COOH, has been synthesized, characterized at the molecular level and immobilized onto previously synthesized iron oxide nanoparticles covered with oleylamine. The novel nanosystem (ZnPR-IONP) has been thoroughly characterized by a variety of techniques such as UV-Vis absorption spectroscopy, fluorescence spectroscopy, X-ray photoloectron spectroscopy (XPS) and transmission electron microscopy (TEM). In order to probe the capability of the photosensitizer for PDT, the singlet oxygen production of both ZnPR-IONP and the free ligand ZnPR-COOH have been quantified by measuring the decay in absorption of the anthracene derivative 9,10-anthracenedipropionic acid (ADPA), showing an important increase on singlet oxygen production when the porphyrin is incorporated onto the IONP (ZnPR-IONP). On the other hand, the porphyrin derivative PR-TRIS3OH, incorporating several polar groups (TRIS), was synthesized and immobilized with the intention of obtaining water soluble nanosystems (PR-TRIS-IONP). When the singlet oxygen production ability was evaluated, the values obtained were similar to ZnPR-COOH/ZnPR-IONP, again much higher in the case of the nanoparticles PR-TRIS-IONP, with more than a twofold increase. The efficient singlet oxygen production of PR-TRIS-IONP together with their water solubility, points to the great promise that these new nanotools represent for PDT. PMID:26454374

  10. Bacteriophage: Time to Re-Evaluate the Potential of Phage Therapy as a Promising Agent to Control Multidrug-Resistant Bacteria

    PubMed Central

    Sabouri Ghannad, Masoud; Mohammadi, Avid

    2012-01-01

    Nowadays the most difficult problem in treatment of bacterial infections is the appearance of resistant bacteria to the antimicrobial agents so that the attention is being drawn to other potential targets. In view of the positive findings of phage therapy, many advantages have been mentioned which utilizes phage therapy over chemotherapy and it seems to be a promising agent to replace the antibiotics. This review focuses on an understanding of phages for the treatment of bacterial infectious diseases as a new alternative treatment of infections caused by multiple antibiotic resistant bacteria. Therefore, utilizing bacteriophage may be accounted as an alternative therapy. It is appropriate time to re-evaluate the potential of phage therapy as an effective bactericidal and a promising agent to control multidrug-resistant bacteria. PMID:23494063

  11. Non-carrier-added 186, 188Re labeled 17a-ethynylestradiol : a potential breast cancer imaging and therapy agent

    SciTech Connect

    Fassbender, M. E.; Phillips, Dennis R.; Peterson, E. J.; Ott, K. C.; Arterburn, J. B.

    2001-01-01

    Receptor-targeted radiopharmaceuticals constitute potential agents for the diagnosis and therapy of cancer. Breast cancer is the most prevalent form of diagnosed cancer in women in the United States, and it accounts for the second highest number of cases of cancer fatalities (1). In Approximately two-thirds of the breast tumors, estrogen and progesterone steroid hormone receptors can be found. Such tumors can often be treated successfully with anti-estrogen hormone therapy (2). Hence, the ability to determine the estrogen receptor (ER) contend of the breast tumor is essential for making the most appropriate choice of treatment for the patient. Along with this diagnostic aspect, steroid-based radiopharmaceuticals with high specific activity offer an encouraging prospect for therapeutic applications: {sup 186,188}Re labeled steroids binding to receptors expressed by cancer cells appear to be potential agents for the irradiation of small to medium-sized tumors. {sup 186}Re has been regarded as an ideal radionuclide for radiotherapy due to its appropriate half-live of 90 h and {beta}-energy of 1.07 MeV. Moreover, the {gamma}-emission of 137 keV that allows in vivo imaging while in therapy is an additional bonus. {sup 188}Re is obtained from a {sup 188}W/{sup 188}Re radionuclide generator system, representing an advantage for availability at radiopharmacy laboratory by daily elution. In addition, {sup 188}Re emits high energy beta particles with an average energy of 769 keV, and the emission of the 155 keV allows simultaneous imaging for biodistribution evaluation in vivo. In order to avoid competitive saturation of the binding sites of the ligand receptor, Re labeled steroids with high specific activity are required, and the removal of all excess unlabeled ligands is mandatory. {sup 188}Re is eluted from a {sup 188}W/{sup 188}Re generator produced and provided by Oak Ridge National Laboratory (3). This paper outlines the solid phase-supported preparation of an n

  12. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

  13. Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Xiong, Hejian; Wei, Xing; Zhou, Dongfang; Qi, Yanxin; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

    2016-09-21

    Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT. PMID:27548011

  14. Amphiphilic Polycarbonates from Carborane-Installed Cyclic Carbonates as Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Xiong, Hejian; Wei, Xing; Zhou, Dongfang; Qi, Yanxin; Xie, Zhigang; Chen, Xuesi; Jing, Xiabin; Huang, Yubin

    2016-09-21

    Carboranes with rich boron content have showed significant applications in the field of boron neutron capture therapy. Biodegradable derivatives of carborane-conjugated polymers with well-defined structure and tunable loading of boron atoms are far less explored. Herein, a new family of amphiphilic carborane-conjugated polycarbonates was synthesized by ring-opening polymerization of a carborane-installed cyclic carbonate monomer. Catalyzed by TBD from a poly(ethylene glycol) macroinitiator, the polymerization proceeded to relatively high conversions (>65%), with low polydispersity in a certain range of molecular weight. The boron content was readily tuned by the feed ratio of the monomer and initiator. The resultant amphiphilic polycarbonates self-assembled in water into spherical nanoparticles of different sizes depending on the hydrophilic-to-hydrophobic ratio. It was demonstrated that larger nanoparticles (PN150) were more easily subjected to protein adsorption and captured by the liver, and smaller nanoparticles (PN50) were more likely to enter cancer cells and accumulate at the tumor site. PN50 with thermal neutron irradiation exhibited the highest therapeutic efficacy in vivo. The new synthetic method utilizing amphiphilic biodegradable boron-enriched polymers is useful for developing more-selective and -effective boron delivery systems for BNCT.

  15. Gadolinia nanofibers as a multimodal bioimaging and potential radiation therapy agent

    SciTech Connect

    Grishin, A. M. E-mail: grishin@inmatech.com; Jalalian, A.; Tsindlekht, M. I.

    2015-05-15

    Continuous bead-free C-type cubic gadolinium oxide (Gd{sub 2}O{sub 3}) nanofibers 20-30 μm long and 40-100 nm in diameter were sintered by sol-gel calcination assisted electrospinning technique. Dipole-dipole interaction of neighboring Gd{sup 3+} ions in nanofibers with large length-to-diameter aspect ratio results in some kind of superparamagnetic behavior: fibers are magnetized twice stronger than Gd{sub 2}O{sub 3} powder. Being compared with commercial Gd-DTPA/Magnevist{sup ®}, Gd{sub 2}O{sub 3} diethyleneglycol-coated (Gd{sub 2}O{sub 3}-DEG) fibers show high 1/T{sub 1} and 1/T{sub 2} proton relaxivities. Intense room temperature photoluminescence, high NMR relaxivity and high neutron scattering cross-section of {sup 157}Gd nucleus promise to integrate Gd{sub 2}O{sub 3} fibers for multimodal bioimaging and neutron capture therapy.

  16. Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.

    PubMed

    Clement, Omoshile O; Freeman, Clive M; Hartmann, Rolf W; Handratta, Venkatesh D; Vasaitis, Tadas S; Brodie, Angela M H; Njar, Vincent C O

    2003-06-01

    We report here a molecular modeling investigation of steroidal and nonsteroidal inhibitors of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17). Using the pharmacophore perception technique, we have generated common-feature pharmacophore model(s) to explain the putative binding requirements for two classes of human CYP17 inhibitors. Common chemical features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipHop program, are one to two hydrogen bond acceptors (HBAs) and three hydrophobic groups. For azole-steroidal ligands, the 3beta-OH group of ring A and the N-3 of the azole ring attached to ring D at C-17 act as hydrogen bond acceptors. A model that permits hydrogen bond interaction between the azole functionality on ring D and the enzyme is consistent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts with Fe(II) of heme. In general, pharmacophore models derived for steroid and nonsteroidal compounds bear striking similarities to all azole sites mapping the HBA functionality and to three hydrophobic features describing the hydrophobic interactions between the ligands and the enzyme. Using the pharmacophore model derived for azole-steroidal inhibitors as a 3D search query against several 3D multiconformational Catalyst formatted databases, we identified several steroidal compounds with potential inhibition of this enzyme. Biological testing of some of these compounds show low to high inhibitory potency against the human CYP17 enzyme. This shows the potential of our pharmacophore model in identifying new and potent CYP17 inhibitors. Further refinement of the model is in progress with a view to identifying and optimizing new leads. PMID:12773039

  17. Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy.

    PubMed

    Clement, Omoshile O; Freeman, Clive M; Hartmann, Rolf W; Handratta, Venkatesh D; Vasaitis, Tadas S; Brodie, Angela M H; Njar, Vincent C O

    2003-06-01

    We report here a molecular modeling investigation of steroidal and nonsteroidal inhibitors of human cytochrome P450 17alpha-hydroxylase-17,20-lyase (CYP17). Using the pharmacophore perception technique, we have generated common-feature pharmacophore model(s) to explain the putative binding requirements for two classes of human CYP17 inhibitors. Common chemical features in the steroid and nonsteroid human CYP17 enzyme inhibitors, as deduced by the Catalyst/HipHop program, are one to two hydrogen bond acceptors (HBAs) and three hydrophobic groups. For azole-steroidal ligands, the 3beta-OH group of ring A and the N-3 of the azole ring attached to ring D at C-17 act as hydrogen bond acceptors. A model that permits hydrogen bond interaction between the azole functionality on ring D and the enzyme is consistent with experimental deductions for type II CYP17 inhibitors where a sixth ligating atom interacts with Fe(II) of heme. In general, pharmacophore models derived for steroid and nonsteroidal compounds bear striking similarities to all azole sites mapping the HBA functionality and to three hydrophobic features describing the hydrophobic interactions between the ligands and the enzyme. Using the pharmacophore model derived for azole-steroidal inhibitors as a 3D search query against several 3D multiconformational Catalyst formatted databases, we identified several steroidal compounds with potential inhibition of this enzyme. Biological testing of some of these compounds show low to high inhibitory potency against the human CYP17 enzyme. This shows the potential of our pharmacophore model in identifying new and potent CYP17 inhibitors. Further refinement of the model is in progress with a view to identifying and optimizing new leads.

  18. Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

    PubMed

    Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

    2005-01-01

    milestone toward improving cancer diagnosis and tumor characterization. More importantly, this paper describes a new family of bifunctional agents that combine two modalities into a single cost-effective "see and treat" approach, namely, a single agent that can be used for contrast agent-enhanced MR imaging followed by targeted photodynamic therapy.

  19. HS-133, a novel fluorescent phosphatidylinositol 3-kinase inhibitor as a potential imaging and anticancer agent for targeted therapy

    PubMed Central

    Lee, Hyunseung; Son, Mi Kwon; Yun, Sun-Mi; Ahn, Sung-Hoon; Lee, Kyeong-Ryoon; Lee, Soyoung; Kim, Donghee; Hong, Sungwoo; Hong, Soon-Sun

    2014-01-01

    As PI3K/Akt signaling is frequently deregulated in a wide variety of human tumors, PI3K inhibitors are an emerging class of drugs for cancer treatment. The monitoring of the drug behavior and distribution in the biological system can play an important role for targeted therapy and provide information regarding the response or resistance to available therapies. In this study, therefore, we have developed a family of xanthine derivatives, serving as a dual function exhibiting fluorescence, as well as inhibiting PI3K. Among them, HS-133 showed anti-proliferative effects and was monitored for its subcellular localization by a fluorescence microscopy. HS-133 suppressed the PI3K/Akt pathway and induced cell cycle arrest at the G0/G1 phase. The induction of apoptosis by HS-133 was confirmed by the increases of the cleaved PARP, caspase-3, and caspase-8. Furthermore, HS-133 decreased the protein expression of HIF-1α and VEGF, as well inhibited the tube formation and migration of the human umbilical vein endothelial cells. In vivo imaging also showed that tumors were visualized fluorescent with HS-133, and its oral administration significantly inhibited the growth of tumor in SkBr3 mouse xenograft models. Thus, we suggest that HS-133 may be used as a fluorescent anticancer agent against human breast cancer. PMID:25338206

  20. Safranal as a novel anti-tubulin binding agent with potential use in cancer therapy: An in vitro study.

    PubMed

    Naghshineh, Ali; Dadras, Ali; Ghalandari, Behafarid; Riazi, Gholam Hossein; Modaresi, Seyed Mohamad Sadegh; Afrasiabi, Ali; Aslani, Mahsa Kiani

    2015-08-01

    Safranal, a component of saffron, indicates anti-tumor activities; however, the precise mechanism of this effect has remained elusive. In this study we investigated tubulin assembly and structure in the presence of safranal to open the new horizons about the potential of safranal as an anti-tumor agent via microtubule disfunction. Anti-microtubule activity of safranal was evaluated by turbidimetric method and transmission electron microscopy (TEM). Safranal (0.1-70μM) was incubated with tubulin (5μM) and tubulin structural changes was surveyed using fluorometry. Tubulin binding site with safranal was estimated by molecular docking. Microtubule polymerization decreased significantly in the presence of safranal, regardless of its concentration and the IC50 value was obtained 72.19μM. Safranal was situated between α and β tubulin closer to α-tubulin and hydrogen bond with Gly 142 and hydrophobic interactions played critical roles for safranal molecule stabilization in binding site. It seems that decline of tubulin assembly could result from tubulin structural changes through safranal bindings between alpha and beta tubulin with ΔG(0) of -5.63kcal/mol. Safranal can be taken into account as an anticancer agent; however, in vivo experiments are required to confirm this conclusion.

  1. Human Anti-Oxidation Protein A1M--A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy.

    PubMed

    Ahlstedt, Jonas; Tran, Thuy A; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

    2015-12-18

    Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α₁-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies.

  2. Human Anti-Oxidation Protein A1M—A Potential Kidney Protection Agent in Peptide Receptor Radionuclide Therapy

    PubMed Central

    Ahlstedt, Jonas; Tran, Thuy A.; Strand, Sven-Erik; Gram, Magnus; Åkerström, Bo

    2015-01-01

    Peptide receptor radionuclide therapy (PRRT) has been in clinical use for 15 years to treat metastatic neuroendocrine tumors. PRRT is limited by reabsorption and retention of the administered radiolabeled somatostatin analogues in the proximal tubule. Consequently, it is essential to develop and employ methods to protect the kidneys during PRRT. Today, infusion of positively charged amino acids is the standard method of kidney protection. Other methods, such as administration of amifostine, are still under evaluation and show promising results. α1-microglobulin (A1M) is a reductase and radical scavenging protein ubiquitously present in plasma and extravascular tissue. Human A1M has antioxidation properties and has been shown to prevent radiation-induced in vitro cell damage and protect non-irradiated surrounding cells. It has recently been shown in mice that exogenously infused A1M and the somatostatin analogue octreotide are co-localized in proximal tubules of the kidney after intravenous infusion. In this review we describe the current situation of kidney protection during PRRT, discuss the necessity and implications of more precise dosimetry and present A1M as a new, potential candidate for renal protection during PRRT and related targeted radionuclide therapies. PMID:26694383

  3. Strategies for the design and synthesis of boronated nucleic acid and protein components as potential delivery agents for neutron capture therapy

    SciTech Connect

    Wyzlic, I.M.; Tjarks, W.; Soloway, A.H.; Anisuzzaman, A.K.M.; Rong, Feng-Guang; Barth, R.F. )

    1994-03-30

    Strategies for the design and synthesis of boronated nucleosides, amino acids, and peptides as potential delivery agents for boron neutron capture therapy (BNCT) are described. For BNCT to be a useful treatment modality, there is a need to design and synthesize nontoxic boron compounds that selectively target tumor cells, accumulate in sufficient amounts (20-30 [mu]g [sup 10]B/g of tumor) and persist at therapeutic levels for a sufficient time prior to neutron irradiation. Boronated nucleosides, amino acids and peptides are such promising target compounds. Such structures may be selectively used by proliferating neoplastic cells compared with mitotically less active normal cells and therefore achieve the tissue differentials necessary for BNCT. The rationale for synthesis of boronated nucleic acid and protein components is discussed. Results of biological and clinical studies of some boronated nucleosides, nucleotides, amino acids and peptides are presented. Boronated nucleosides, amino acids and peptides can be considered as potential targeting agents for BNCT. 96 refs., 4 figs.

  4. Metal-based phthalocyanines as a potential photosensitizing agent in photodynamic therapy for the treatment of melanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maduray, Kaminee; Odhav, B.

    2014-03-01

    Photodynamic therapy (PDT) is an emerging medical treatment that uses photosensitizers (drug) which are activated by laser light for the generation of cytotoxic free radicals and singlet oxygen molecules that cause tumor cell death. In the recent years, there has been a focus on using and improving an industrial colorant termed phthalocyanines as a prospective photosensitizer because of its unique properties. This in vitro study investigated the photodynamic effect of indium (InPcCl) and iron (FePcCl) phthalocyanine chlorides on human skin cancer cells (melanoma). Experimentally, 2 x 104 cells/ml were seeded in 24-well tissue culture plates and allowed to attach overnight, after which cells were treated with different concentrations (2 μg/ml - 100 μg/ml) of InPcCl and FePcCl. After 2 h, cells were irradiated with constant light doses of 2.5 J/cm2, 4.5 J/cm2 and 8.5 J/cm2 delivered from a diode laser. Post-irradiated cells were incubated for 24 h before cell viability was measured using the MTT Assay. At 24 h after PDT, irradiation with a light dose of 2.5 J/cm2 for each photosensitizing concentration of InPcCl and FePcCl produced a significant decrease in cell viability, but when the treatment light dose was further increased to 4.5 J/cm2 and 8.5 J/cm2 the cell survival was less than 55% for photosensitizing concentrations of InPcCl and FePcCl from 4 μg/ml to 100 μg/ml. This PDT study concludes that low concentrations on InPcCl and FePcCl activated with low level light doses can be used for the effective in vitro killing of melanoma cancer cells.

  5. Evaluation of iron-chelating agents in cultured heart muscle cells. Identification of a potential drug for chelation therapy.

    PubMed

    Sciortino, C V; Byers, B R; Cox, P

    1980-12-01

    Primary cultures of neonatal rat cardiac muscle cells incorporated radioiron from both [55Fe]transferrin and 59FeCl3 (added simultaneously). To evaluate the effect of iron chelators on such uptake, deferri chelators were added 6 hr after addition of the radioiron sources. The microbial chelator agrobactin was significantly more effective than the drug defoxamine in reduction of 55Fe uptake from [55Fe]transferrin; both chelators halted 59Fe3+ uptake. Agrobactin may have potential in chelation therpay for iron-overload disease. Certain other microbial chelators lowered radioiron uptake from either [55Fe]transferrin of 59FeCl3. These chelators should be useful inhibitors for studies of animal cell iron uptake and intracellular iron flow.

  6. Bacteriocins as Potential Anticancer Agents

    PubMed Central

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies. PMID:26617524

  7. Bacteriocins as Potential Anticancer Agents.

    PubMed

    Kaur, Sumanpreet; Kaur, Sukhraj

    2015-01-01

    Cancer remains one of the leading causes of deaths worldwide, despite advances in its treatment and detection. The conventional chemotherapeutic agents used for the treatment of cancer have non-specific toxicity toward normal body cells that cause various side effects. Secondly, cancer cells are known to develop chemotherapy resistance in due course of treatment. Thus, the demand for novel anti-cancer agents is increasing day by day. Some of the experimental studies have reported the therapeutic potential of bacteriocins against various types of cancer cell lines. Bacteriocins are ribosomally-synthesized cationic peptides secreted by almost all groups of bacteria. Some bacteriocins have shown selective cytotoxicity toward cancer cells as compared to normal cells. This makes them promising candidates for further investigation and clinical trials. In this review article, we present the overview of the various cancer cell-specific cytotoxic bacteriocins, their mode of action and efficacies.

  8. Anti-Inflammatory Agents for Cancer Therapy

    PubMed Central

    Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen

    2010-01-01

    Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321

  9. Brucella as a potential agent of bioterrorism.

    PubMed

    Doganay, Gizem D; Doganay, Mehmet

    2013-04-01

    Perception on bioterrorism has changed after the deliberate release of anthrax by the postal system in the United States of America in 2001. Potential bioterrorism agents have been reclassified based on their dissemination, expected rate of mortality, availability, stability, and ability to lead a public panic. Brucella species can be easily cultured from infected animals and human materials. Also, it can be transferred, stored and disseminated easily. An intentional contamination of food with Brucella species could pose a threat with low mortality rate. Brucella spp. is highly infectious through aerosol route, making it an attractive pathogen to be used as a potential agent for biological warfare purposes. Recently, many studies have been concentrated on appropriate sampling of Brucella spp. from environment including finding ways for its early detection and development of new decontamination procedures such as new drugs and vaccines. There are many ongoing vaccine development studies; some of which recently received patents for detection and therapy of Brucella spp. However, there is still no available vaccine for humans. In this paper, recent developments and recent patents on brucellosis are reviewed and discussed.

  10. Therapeutic Potential of Spirooxindoles as Antiviral Agents.

    PubMed

    Ye, Na; Chen, Haiying; Wold, Eric A; Shi, Pei-Yong; Zhou, Jia

    2016-06-10

    Antiviral therapeutics with profiles of high potency, low resistance, panserotype, and low toxicity remain challenging, and obtaining such agents continues to be an active area of therapeutic development. Due to their unique three-dimensional structural features, spirooxindoles have been identified as privileged chemotypes for antiviral drug development. Among them, spiro-pyrazolopyridone oxindoles have been recently reported as potent inhibitors of dengue virus NS4B, leading to the discovery of an orally bioavailable preclinical candidate (R)-44 with excellent in vivo efficacy in a dengue viremia mouse model. This review highlights recent advances in the development of biologically active spirooxindoles for their antiviral potential, primarily focusing on the structure-activity relationships (SARs) and modes of action, as well as future directions to achieve more potent analogues toward a viable antiviral therapy. PMID:27627626

  11. Gadolinium as a Neutron Capture Therapy Agent

    NASA Astrophysics Data System (ADS)

    Shih, Jing-Luen Allen

    The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging and researchers around the world are once again making efforts to develop this therapeutic modality. Boron-10 is the agent receiving the most attention for neutron capture therapy but ^{157}Gd is a nuclide that also holds interesting properties of being a neutron capture therapy agent. The objective of this study is to evaluate ^{157}Gd as a neutron capture therapy agent. In this study it is determined that tumor concentrations of about 300 mug ^{157}Gd/g tumor can be achieved in brain tumors with some FDA approved MRI contrast agents such as Gd-DTPA and Gd-DOTA, and up to 628 mug ^{157 }Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations show that with only 250 ppm of ^{157}Gd in tumor, neutron capture therapy can deliver 2,000 cGy to a tumor of 2 cm diameter or larger with 5 times 10^{12} n/cm ^2 fluence at the tumor. Dose measurements which were made with films and TLD's in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 times 10^{12 } n/cm^2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on the films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose which will further enhance the therapeutic effects. A technique that combines brachytherapy with Gd neutron capture therapy has been evaluated. Monte Carlo calculations show that 5,000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm^3 with a 3-plane implant of a total of 9 Gd needles. The tumor to normal tissue advantage of this method is as good as ^{60} Co brachytherapy. Measurements of prompt gamma dose with films and TLD-700's in a lucite phantom verify the Monte Carlo evaluation. A technique which displays the Gd

  12. TRPV1 antagonists as potential antitussive agents.

    PubMed

    McLeod, Robbie L; Correll, Craig C; Jia, Yanlin; Anthes, John C

    2008-01-01

    Cough is an important defensive pulmonary reflex that removes irritants, fluids, or foreign materials from the airways. However, when cough is exceptionally intense or when it is chronic and/or nonproductive it may require pharmacologic suppression. For many patients, antitussive therapies consist of OTC products with inconsequential efficacies. On the other hand, the prescription antitussive market is dominated by older opioid drugs such as codeine. Unfortunately, "codeine-like" drugs suppress cough at equivalent doses that also often produce significant ancillary liabilities such as GI constipation, sedation, and respiratory depression. Thus, the discovery of a novel and effective antitussive drug with an improved side effect profile relative to codeine would fulfill an unmet clinical need in the treatment of cough. Afferent pulmonary nerves are endowed with a multitude of potential receptor targets, including TRPV1, that could act to attenuate cough. The evidence linking TRPV1 to cough is convincing. TRPV1 receptors are found on sensory respiratory nerves that are important in the generation of the cough reflex. Isolated pulmonary vagal afferent nerves are responsive to TRPV1 stimulation. In vivo, TRPV1 agonists such as capsaicin elicit cough when aerosolized and delivered to the lungs. Pertinent to the debate on the potential use of TRPV1 antagonist as antitussive agents are the observations that airway afferent nerves become hypersensitive in diseased and inflamed lungs. For example, the sensitivity of capsaicin-induced cough responses following upper respiratory tract infection and in airway inflammatory diseases such as asthma and COPD is increased relative to that of control responses. Indeed, we have demonstrated that TRPV1 antagonism can attenuate antigen-induced cough in the allergic guinea pig. However, it remains to be determined if the emerging pharmacologic profile of TRPV1 antagonists will translate into a novel human antitussive drug. Current

  13. Potential interactions between alternative therapies and warfarin.

    PubMed

    Heck, A M; DeWitt, B A; Lukes, A L

    2000-07-01

    Potential and documented interactions between alternative therapy agents and warfarin are discussed. An estimated one third of adults in the United States use alternative therapies, including herbs. A major safety concern is potential interactions of alternative medicine products with prescription medications. This issue is especially important with respect to drugs with narrow therapeutic indexes, such as warfarin. Herbal products that may potentially increase the risk of bleeding or potentiate the effects of warfarin therapy include angelica root, arnica flower, anise, asafoetida, bogbean, borage seed oil, bromelain, capsicum, celery, chamomile, clove, fenugreek, feverfew, garlic, ginger ginkgo, horse chestnut, licorice root, lovage root, meadowsweet, onion, parsley, passionflower herb, poplar, quassia, red clover, rue, sweet clover, turmeric, and willow bark. Products that have been associated with documented reports of potential interactions with warfarin include coenzyme Q10, danshen, devil's claw, dong quai, ginseng, green tea, papain, and vitamin E. Interpretation of the available information on herb-warfarin interactions is difficult because nearly all of it is based on in vitro data, animal studies, or individual case reports. More study is needed to confirm and assess the clinical significance of these potential interactions. There is evidence that a wide range of alternative therapy products have the potential to interact with warfarin. Pharmacists and other health care professionals should question all patients about use of alternative therapies and report documented interactions to FDA's MedWatch program. PMID:10902065

  14. Potential interactions between alternative therapies and warfarin.

    PubMed

    Heck, A M; DeWitt, B A; Lukes, A L

    2000-07-01

    Potential and documented interactions between alternative therapy agents and warfarin are discussed. An estimated one third of adults in the United States use alternative therapies, including herbs. A major safety concern is potential interactions of alternative medicine products with prescription medications. This issue is especially important with respect to drugs with narrow therapeutic indexes, such as warfarin. Herbal products that may potentially increase the risk of bleeding or potentiate the effects of warfarin therapy include angelica root, arnica flower, anise, asafoetida, bogbean, borage seed oil, bromelain, capsicum, celery, chamomile, clove, fenugreek, feverfew, garlic, ginger ginkgo, horse chestnut, licorice root, lovage root, meadowsweet, onion, parsley, passionflower herb, poplar, quassia, red clover, rue, sweet clover, turmeric, and willow bark. Products that have been associated with documented reports of potential interactions with warfarin include coenzyme Q10, danshen, devil's claw, dong quai, ginseng, green tea, papain, and vitamin E. Interpretation of the available information on herb-warfarin interactions is difficult because nearly all of it is based on in vitro data, animal studies, or individual case reports. More study is needed to confirm and assess the clinical significance of these potential interactions. There is evidence that a wide range of alternative therapy products have the potential to interact with warfarin. Pharmacists and other health care professionals should question all patients about use of alternative therapies and report documented interactions to FDA's MedWatch program.

  15. Quorum Quenching Agents: Resources for Antivirulence Therapy

    PubMed Central

    Tang, Kaihao; Zhang, Xiao-Hua

    2014-01-01

    The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy. PMID:24886865

  16. Quorum quenching agents: resources for antivirulence therapy.

    PubMed

    Tang, Kaihao; Zhang, Xiao-Hua

    2014-06-01

    The continuing emergence of antibiotic-resistant pathogens is a concern to human health and highlights the urgent need for the development of alternative therapeutic strategies. Quorum sensing (QS) regulates virulence in many bacterial pathogens, and thus, is a promising target for antivirulence therapy which may inhibit virulence instead of cell growth and division. This means that there is little selective pressure for the evolution of resistance. Many natural quorum quenching (QQ) agents have been identified. Moreover, it has been shown that many microorganisms are capable of producing small molecular QS inhibitors and/or macromolecular QQ enzymes, which could be regarded as a strategy for bacteria to gain benefits in competitive environments. More than 30 species of marine QQ bacteria have been identified thus far, but only a few of them have been intensively studied. Recent studies indicate that an enormous number of QQ microorganisms are undiscovered in the highly diverse marine environments, and these marine microorganism-derived QQ agents may be valuable resources for antivirulence therapy.

  17. Potential new agents for chronic lymphocytic leukemia treatment.

    PubMed

    Kiliańska, Zofia M; Rogalińska, Małgorzata

    2010-11-01

    Chronic lymphocytic leukemia (CLL) is the most frequent type of hematological cancer in the Western World. An accumulation of leukemic cells in peripheral blood of patients is a result of apoptosis disturbances as well as an increase in germinal centers CLL cell proliferation. The differences between CLL patients in the course and response to therapy reflects personal variability between patients in their genetic material. It was documented that many sufferers from CLL are over 60 years old, and because of many countries' population obsolescence this type of leukemia could become more frequent in the future. CLL remains incurable, and the therapy regimens available at present could induce even complete remissions, but finally a relapse of the disease. The etiology of this disease is still not known, but our understanding of the processes running in CLL cells has significantly increased. A number of new agents with potential of CLL cell elimination by apoptosis or autophagy were characterized. Some of them reflect potential in cell sensitization to standard therapy. The major challenge for the future is to develop targeted anti-cancer therapy and design the optimal personalized manner of CLL treatment. A special interest is focused on anti-cancer agents - natural substances of plant origin. This paper reviews chosen new anti-leukemic agents belonging to different drug-classes (new monoclonal antibodies or apoptosis-, BCR signaling- and cell cycle-related inhibitors, substances of plant origin) which are under intense investigation in preclinical studies and early clinical trials. PMID:21235440

  18. Gadolinium oxide nanoparticles as potential multimodal imaging and therapeutic agents.

    PubMed

    Kim, Tae Jeong; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

    2013-01-01

    Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

  19. Newer agents in antiplatelet therapy: a review

    PubMed Central

    Yeung, Jennifer; Holinstat, Michael

    2012-01-01

    Antiplatelet therapy remains the mainstay in preventing aberrant platelet activation in pathophysiological conditions such as myocardial infarction, ischemia, and stroke. Although there has been significant advancement in antiplatelet therapeutic approaches, aspirin still remains the gold standard treatment in the clinical setting. Limitations in safety, efficacy, and tolerability have precluded many of the antiplatelet inhibitors from use in patients. Unforeseen incidences of increased bleeding risk and recurrent arterial thrombosis observed in patients have hampered the development of superior next generation antiplatelet therapies. The pharmacokinetic and pharmacodynamic profiles have also limited the effectiveness of a number of antiplatelet inhibitors currently in use due to variability in metabolism, time to onset, and reversibility. A focused effort in the development of newer antiplatelet therapies to address some of these shortcomings has resulted in a significant number of potential antiplatelet drugs which target enzymes (phosphodiesterase, cyclooxygenase), receptors (purinergic, prostaglandins, protease-activated receptors, thromboxane), and glycoproteins (αIIbβ3, GPVI, vWF, GPIb) in the platelet. The validation and search for newer antiplatelet therapeutic approaches proven to be superior to aspirin is still ongoing and should yield a better pharmacodynamic profile with fewer untoward side-effects to what is currently in use today. PMID:22792011

  20. Potential molecular targets for Ewing's sarcoma therapy.

    PubMed

    Jully, Babu; Rajkumar, Thangarajan

    2012-10-01

    Ewing's sarcoma (ES) is a highly malignant tumor of children and young adults. Modern therapy for Ewing's sarcoma combines high-dose chemotherapy for systemic control of disease, with advanced surgical and/or radiation therapeutic approaches for local control. Despite optimal management, the cure rate for localized disease is only approximately 70%, whereas the cure rate for metastatic disease at presentation is less than 30%. Patients who experience long-term disease-free survival are at risk for significant side-effects of therapy, including infertility, limb dysfunction and an increased risk for second malignancies. The identification of new targets for innovative therapeutic approaches is, therefore, strongly needed for its treatment. Many new pharmaceutical agents have been tested in early phases of clinical trials in ES patients who have recurrent disease. While some agents led to partial response or stable disease, the percentages of drugs eliciting responses or causing an overall effect have been minimal. Furthermore, of the new pharmaceuticals being introduced to clinical practice, the most effective agents also have dose-limiting toxicities. Novel approaches are needed to minimize non-specific toxicity, both for patients with recurrence and at diagnosis. This report presents an overview of the potential molecular targets in ES and highlights the possibility that they may serve as therapeutic targets for the disease. Although additional investigations are required before most of these approaches can be assessed in the clinic, they provide a great deal of hope for patients with Ewing's sarcoma. PMID:23580819

  1. Turning on the Radio: Epigenetic Inhibitors as Potential Radiopriming Agents

    PubMed Central

    Oronsky, Bryan; Scicinski, Jan; Kim, Michelle M.; Cabrales, Pedro; Salacz, Michael E.; Carter, Corey A.; Oronsky, Neil; Lybeck, Harry; Lybeck, Michelle; Larson, Christopher; Reid, Tony R.; Oronsky, Arnold

    2016-01-01

    First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity. PMID:27384589

  2. Current therapy and the development of therapeutic options for the treatment of diseases due to bacterial agents of potential biowarfare and bioterrorism.

    PubMed

    Greenfield, Ronald A; Bronze, Michael S

    2004-02-01

    An important part of biodefense is the optimization of current therapy and the development of new therapeutic options for the treatment of the diseases most likely encountered in the form of biological weapons. Guidelines for the prevention and treatment of anthrax, plague, tularemia and botulinum toxin intoxication are reviewed. The strategies in development for the prevention of anthrax focus primarily on active and passive immunization against protective antigen, because of its central role as a toxin delivery module. Novel vaccine strategies for plague, tularemia and botulism are also reviewed.

  3. Potential anti-HIV agents from marine resources: an overview.

    PubMed

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-11-29

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy.

  4. Potential Anti-HIV Agents from Marine Resources: An Overview

    PubMed Central

    Vo, Thanh-Sang; Kim, Se-Kwon

    2010-01-01

    Human immunodeficiency virus (HIV) infection causes acquired immune deficiency syndrome (AIDS) and is a global public health issue. Anti-HIV therapy involving chemical drugs has improved the life quality of HIV/AIDS patients. However, emergence of HIV drug resistance, side effects and the necessity for long-term anti-HIV treatment are the main reasons for failure of anti-HIV therapy. Therefore, it is essential to isolate novel anti-HIV therapeutics from natural resources. Recently, a great deal of interest has been expressed regarding marine-derived anti-HIV agents such as phlorotannins, sulfated chitooligosaccharides, sulfated polysaccharides, lectins and bioactive peptides. This contribution presents an overview of anti-HIV therapeutics derived from marine resources and their potential application in HIV therapy. PMID:21339954

  5. Calcium channel as a potential anticancer agent.

    PubMed

    Kriazhev, L

    2009-11-01

    Anticancer treatment in modern clinical practices includes chemotherapy and radiation therapy with or without surgical interventions. Efficiency of both methods varies greatly depending on cancer types and stages. Besides, chemo- and radiotherapy are toxic and damaging that causes serious side effects. This fact prompts the search for alternative methods of antitumor therapy. It is well known that prolonged or high increase of intracellular calcium concentration inevitably leads to the cell death via apoptosis or necrosis. However, stimulation of cell calcium level by chemical agents is hardly achievable because cells have very sophisticated machinery for maintaining intracellular calcium in physiological ranges. This obstacle can be overridden, nevertheless. It was found that calcium channels in so called calcium cells in land snails are directly regulated by extracellular calcium concentration. The higher the concentration the higher the calcium intake is through the channels. Bearing in mind that extracellular/intracellular calcium concentration ratio in human beings is 10,000-12,000 fold the insertion of the channel into cancer cells would lead to fast and uncontrollable by the cells calcium intake and cell death. Proteins composing the channel may be extracted from plasma membrane of calcium cells and sequenced by mass-spectrometry or N-terminal sequencing. Either proteins or corresponding genes could be used for targeted delivery into cancer cells.

  6. Therapeutic potential of chalcones as cardiovascular agents.

    PubMed

    Mahapatra, Debarshi Kar; Bharti, Sanjay Kumar

    2016-03-01

    Cardiovascular diseases are the leading cause of death affecting 17.3 million people across the globe and are estimated to affect 23.3 million people by year 2030. In recent years, about 7.3 million people died due to coronary heart disease, 9.4 million deaths due to high blood pressure and 6.2 million due to stroke, where obesity and atherosclerotic progression remain the chief pathological factors. The search for newer and better cardiovascular agents is the foremost need to manage cardiac patient population across the world. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates to inhibit various cardiovascular, hematological and anti-obesity targets like angiotensin converting enzyme (ACE), cholesteryl ester transfer protein (CETP), diacylglycerol acyltransferase (DGAT), acyl-coenzyme A: cholesterol acyltransferase (ACAT), pancreatic lipase (PL), lipoprotein lipase (LPL), calcium (Ca(2+))/potassium (K(+)) channel, COX-1, TXA2 and TXB2. In this review, a comprehensive study of chalcones, their therapeutic targets, structure activity relationships (SARs), mechanisms of actions (MOAs) have been discussed. Chemically diverse chalcone scaffolds, their derivatives including structural manipulation of both aryl rings, replacement with heteroaryl scaffold(s) and hybridization through conjugation with other pharmacologically active scaffold have been highlighted. Chalcones which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-hypertensive, anti-anginal, anti-arrhythmic and cardioprotective agents. With the knowledge of these molecular targets, structural insights and SARs, this review may be helpful for (medicinal) chemists to design more potent, safe, selective and cost effective chalcone derivatives as potential cardiovascular agents. PMID:26876916

  7. Rodents as potential couriers for bioterrorism agents.

    PubMed

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control.

  8. Rodents as potential couriers for bioterrorism agents.

    PubMed

    Lõhmus, Mare; Janse, Ingmar; van de Goot, Frank; van Rotterdam, Bart J

    2013-09-01

    Many pathogens that can cause major public health, economic, and social damage are relatively easily accessible and could be used as biological weapons. Wildlife is a natural reservoir for many potential bioterrorism agents, and, as history has shown, eliminating a pathogen that has dispersed among wild fauna can be extremely challenging. Since a number of wild rodent species live close to humans, rodents constitute a vector for pathogens to circulate among wildlife, domestic animals, and humans. This article reviews the possible consequences of a deliberate spread of rodentborne pathogens. It is relatively easy to infect wild rodents with certain pathogens or to release infected rodents, and the action would be difficult to trace. Rodents can also function as reservoirs for diseases that have been spread during a bioterrorism attack and cause recurring disease outbreaks. As rats and mice are common in both urban and rural settlements, deliberately released rodentborne infections have the capacity to spread very rapidly. The majority of pathogens that are listed as potential agents of bioterrorism by the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases exploit rodents as vectors or reservoirs. In addition to zoonotic diseases, deliberately released rodentborne epizootics can have serious economic consequences for society, for example, in the area of international trade restrictions. The ability to rapidly detect introduced diseases and effectively communicate with the public in crisis situations enables a quick response and is essential for successful and cost-effective disease control. PMID:23971813

  9. Gold nanoparticles as novel agents for cancer therapy

    PubMed Central

    Jain, S; Hirst, D G; O'Sullivan, J M

    2012-01-01

    Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. This review introduces the field of nanotechnology with a focus on recent gold nanoparticle research which has led to early-phase clinical trials. In particular, the pre-clinical evidence for gold nanoparticles as sensitisers with ionising radiation in vitro and in vivo at kilovoltage and megavoltage energies is discussed. PMID:22010024

  10. Plants' Metabolites as Potential Antiobesity Agents

    PubMed Central

    Gooda Sahib, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Fawzi; Abdul Hamid, Azizah

    2012-01-01

    Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research. PMID:22666121

  11. Can nanotechnology potentiate photodynamic therapy?

    PubMed Central

    Huang, Ying-Ying; Sharma, Sulbha K.; Dai, Tianhong; Chung, Hoon; Yaroslavsky, Anastasia; Garcia-Diaz, Maria; Chang, Julie; Chiang, Long Y.

    2015-01-01

    Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill cancer cells and infectious microorganisms. Due to the tendency of most photosensitizers (PS) to be poorly soluble and to form nonphotoactive aggregates, drug-delivery vehicles have become of high importance. The nanotechnology revolution has provided many examples of nanoscale drug-delivery platforms that have been applied to PDT. These include liposomes, lipoplexes, nanoemulsions, micelles, polymer nanoparticles (degradable and nondegradable), and silica nanoparticles. In some cases (fullerenes and quantum dots), the actual nanoparticle itself is the PS. Targeting ligands such as antibodies and peptides can be used to increase specificity. Gold and silver nanoparticles can provide plasmonic enhancement of PDT. Two-photon excitation or optical upconversion can be used instead of one-photon excitation to increase tissue penetration at longer wavelengths. Finally, after sections on in vivo studies and nanotoxicology, we attempt to answer the title question, “can nano-technology potentiate PDT?” PMID:26361572

  12. PEGylated Copper Nanowires as a Novel Photothermal Therapy Agent.

    PubMed

    Li, Kuei-Chang; Chu, Hsun-Chen; Lin, Yow; Tuan, Hsing-Yu; Hu, Yu-Chen

    2016-05-18

    Metal nanowires are promising for their applications including electrical connectors, transparent conductive electrodes and conductive additives, but the use of metal nanowires as photothermal agents to convert light to heat has yet to be reported. Here we synthesized dispersible polyethylene glycol-coated (PEGylated) copper nanowires (CuNWs) and showed for the first time that PEGylated CuNWs were able to convert near-infrared (NIR, 808 nm) light into heat at a photothermal efficiency of 12.5%. The PEGylated CuNWs exhibited good reusability and enabled rapid temperature rise to >50 °C in 6 min by NIR irradiation. The PEGylated CuNWs were flexible and intertwined around the cancer cells, which, upon NIR irradiation, allowed for direct heat transmission to cells and effectively triggered cancer cell ablation in vitro. Intratumoral injection of PEGylated CuNWs into colon tumor-bearing mice and ensuing NIR irradiation for 6 min significantly raised the local temperature to >50 °C, induced necrosis, and suppressed tumor growth. Compared with other NIR light absorbing noble metal-based nanomaterials, PEGylated CuNWs are relatively easy to synthesize in both laboratory and large scales using the low cost copper. This study demonstrated the potential of PEGylated CuNWs as a new cost-effective photothermal agent, and paved a new avenue to using CuNWs for cancer therapy. PMID:27111420

  13. Monitoring anticoagulant therapy with new oral agents.

    PubMed

    Ramos-Esquivel, Allan

    2015-12-26

    Thromboembolic disease is a major leading cause of mortality and morbidity in industrialized countries. Currently, the management of these patients is challenging due to the availability of new drugs with proven efficacy and security compared to traditional oral vitamin K antagonists. These compounds are characterized by a predictable pharmacokinetic profile for which blood monitoring is not routinely needed. Nevertheless, some data have suggested inter-patient variability in the anticoagulant effect of these drugs, raising concerns about their effectiveness and safety. Although mass-spectrometry is the gold standard to determine drug plasma concentrations, this method is not widely available in every-day practice and some coagulation assays are commonly used to determine the anticoagulant effect of these drugs. The present review aims to summarize the current knowledge regarding the clinical question of how and when to monitor patients with new anticoagulant oral agents. PMID:26713281

  14. Molecular targeting agents in cancer therapy: science and society.

    PubMed

    Shaikh, Asim Jamal

    2012-01-01

    The inception of targeted agents has revolutionized the cancer therapy paradigm, both for physicians and patients. A large number of molecular targeted agents for cancer therapy are currently available for clinical use today. Many more are in making, but there are issues that remain to be resolved for the scientific as well as social community before the recommendation of their widespread use in may clinical scenarios can be done, one such issue being cost and cost effectiveness, others being resistance and lack of sustained efficacy. With the current knowledge about available targeted agents, the growing knowledge of intricate molecular pathways and unfolding of wider spectrum of molecular targets that can really matter in the disease control, calls for only the just use of the agents available now, drug companies need to make a serious attempt to reduce the cost of the agents. Research should focus on agents that show sustained responses in preclinical data. More needs to be done in laboratories and by the pharmaceutical industries, before we can truly claim to have entered a new era of targeted therapy in cancer care.

  15. Terpenoids as potential chemopreventive and therapeutic agents in liver cancer

    PubMed Central

    Thoppil, Roslin J; Bishayee, Anupam

    2011-01-01

    Despite significant advances in medicine, liver cancer, predominantly hepatocellular carcinoma remains a major cause of death in the United States as well as the rest of the world. As limited treatment options are currently available to patients with liver cancer, novel preventive control and effective therapeutic approaches are considered to be reasonable and decisive measures to combat this disease. Several naturally occurring dietary and non-dietary phytochemicals have shown enormous potential in the prevention and treatment of several cancers, especially those of the gastrointestinal tract. Terpenoids, the largest group of phytochemicals, traditionally used for medicinal purposes in India and China, are currently being explored as anticancer agents in clinical trials. Terpenoids (also called “isoprenoids”) are secondary metabolites occurring in most organisms, particularly plants. More than 40 000 individual terpenoids are known to exist in nature with new compounds being discovered every year. A large number of terpenoids exhibit cytotoxicity against a variety of tumor cells and cancer preventive as well as anticancer efficacy in preclinical animal models. This review critically examines the potential role of naturally occurring terpenoids, from diverse origins, in the chemoprevention and treatment of liver tumors. Both in vitro and in vivo effects of these agents and related cellular and molecular mechanisms are highlighted. Potential challenges and future directions involved in the advancement of these promising natural compounds in the chemoprevention and therapy of human liver cancer are also discussed. PMID:21969877

  16. Status epilepticus: Using antioxidant agents as alternative therapies

    PubMed Central

    Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí

    2016-01-01

    The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state.

  17. Status epilepticus: Using antioxidant agents as alternative therapies

    PubMed Central

    Carmona-Aparicio, Liliana; Zavala-Tecuapetla, Cecilia; González-Trujano, María Eva; Sampieri, Aristides Iii; Montesinos-Correa, Hortencia; Granados-Rojas, Leticia; Floriano-Sánchez, Esaú; Coballase-Urrutía, Elvia; Cárdenas-Rodríguez, Noemí

    2016-01-01

    The epileptic state, or status epilepticus (SE), is the most serious situation manifested by individuals with epilepsy, and SE events can lead to neuronal damage. An understanding of the molecular, biochemical and physiopathological mechanisms involved in this type of neurological disease will enable the identification of specific central targets, through which novel agents may act and be useful as SE therapies. Currently, studies have focused on the association between oxidative stress and SE, the most severe epileptic condition. A number of these studies have suggested the use of antioxidant compounds as alternative therapies or adjuvant treatments for the epileptic state. PMID:27698680

  18. Simultaneous two-photon excitation of photodynamic therapy agents

    SciTech Connect

    Wachter, E.A.; Fisher, W.G. |; Partridge, W.P.; Dees, H.C.; Petersen, M.G.

    1998-01-01

    The spectroscopic and photochemical properties of several photosensitive compounds are compared using conventional single-photon excitation (SPE) and simultaneous two-photon excitation (TPE). TPE is achieved using a mode-locked titanium:sapphire laser, the near infrared output of which allows direct promotion of non-resonant TPE. Excitation spectra and excited state properties of both type 1 and type 2 photodynamic therapy (PDT) agents are examined.

  19. Beta-blocking agents during electroconvulsive therapy: a review.

    PubMed

    Boere, E; Birkenhäger, T K; Groenland, T H N; van den Broek, W W

    2014-07-01

    Electroconvulsive therapy (ECT) is associated with at least transient episodes of hypertension and tachycardia. Beta-blocking agents may be indicated to prevent cardiovascular complications and may shorten seizure duration. This review evaluates studies that used beta-blocking agents during ECT to determine which agent has the most favourable outcomes on cardiovascular variables and seizure duration. A Medline database search was made using the combined keywords 'adrenergic beta-antagonists' and 'electroconvulsive therapy'. The search was restricted to double-blind randomized controlled trials and yielded 29 original studies. With the use of esmolol, significant attenuating effects were found on cardiovascular parameters in the first 5 min after stimulation; its shortening effects on seizure duration may be dose-related. With the use of labetalol, findings on cardiovascular effects were inconsistent during the first minutes after stimulation but were significant after 5 min and thereafter; seizure duration was scarcely studied. Landiolol attenuates heart rate but with inconsistent findings regarding arterial pressure (AP); seizure duration was mostly unaffected. Esmolol appears to be effective in reducing the cardiovascular response, although seizure duration may be affected with higher dosages. Landiolol can be considered a suitable alternative, but effects on AP need further investigation. Labetalol has been studied to a lesser extent and may have prolonged cardiovascular effects. The included studies varied in design, methodology, and the amount of exact data provided in the publications. Further study of beta-blocking agents in ECT is clearly necessary.

  20. Novel agents in the future: Therapy beyond anti-TNF agents in inflammatory bowel disease.

    PubMed

    Peng, Jiang Chen; Shen, Jun; Ran, Zhi Hua

    2014-11-01

    Anti-tumor necrosis factor (TNF)-α agents emerge as the hot spot in the last decade for treating patients with inflammatory bowel disease (IBD). The effect of anti-TNF-α agents is satisfactory; however, some patients fail to achieve clinical response. Fortunately, in recent years, great efforts have been made and multiple novel therapies have been developed in the treatment for IBD. In this article, we aim to introduce anti-TNF-α drugs as well as other novel treatments currently undergoing clinical trials for IBD.

  1. The clinical development of molecularly targeted agents in combination with radiation therapy: a pharmaceutical perspective.

    PubMed

    Ataman, Ozlem U; Sambrook, Sally J; Wilks, Chris; Lloyd, Andrew; Taylor, Amanda E; Wedge, Stephen R

    2012-11-15

    This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the clinicaltrials.gov Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with clinicaltrials.gov protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such trials are

  2. The Clinical Development of Molecularly Targeted Agents in Combination With Radiation Therapy: A Pharmaceutical Perspective

    SciTech Connect

    Ataman, Ozlem U.; Sambrook, Sally J.; Wilks, Chris; Lloyd, Andrew; Taylor, Amanda E.; Wedge, Stephen R.

    2012-11-15

    Summary: This paper explores historical and current roles of pharmaceutical industry sponsorship of clinical trials testing radiation therapy combinations with molecularly targeted agents and attempts to identify potential solutions to expediting further combination studies. An analysis of clinical trials involving a combination of radiation therapy and novel cancer therapies was performed. Ongoing and completed trials were identified by searching the (clinicaltrials.gov) Web site, in the first instance, with published trials of drugs of interest identified through American Society of Clinical Oncology, European CanCer Organisation/European Society for Medical Oncology, American Society for Radiation Oncology/European Society for Therapeutic Radiology and Oncology, and PubMed databases and then cross-correlated with (clinicaltrials.gov) protocols. We examined combination trials involving radiation therapy with novel agents and determined their distribution by tumor type, predominant molecular mechanisms examined in combination to date, timing of initiation of trials relative to a novel agent's primary development, and source of sponsorship of such trials. A total of 564 studies of targeted agents in combination with radiation therapy were identified with or without concomitant chemotherapy. Most studies were in phase I/II development, with only 36 trials in phase III. The tumor site most frequently studied was head and neck (26%), followed by non-small cell lung cancer. Pharmaceutical companies were the sponsors of 33% of studies overall and provided support for only 16% of phase III studies. In terms of pharmaceutical sponsorship, Genentech was the most active sponsor of radiation therapy combinations (22%), followed by AstraZeneca (14%). Most radiation therapy combination trials do not appear to be initiated until after drug approval. In phase III studies, the most common (58%) primary endpoint was overall survival. Collectively, this analysis suggests that such

  3. Leukemia after therapy with alkylating agents for childhood cancer

    SciTech Connect

    Tucker, M.A.; Meadows, A.T.; Boice, J.D. Jr.; Stovall, M.; Oberlin, O.; Stone, B.J.; Birch, J.; Voute, P.A.; Hoover, R.N.; Fraumeni, J.F. Jr.

    1987-03-01

    The risk of leukemia was evaluated in 9,170 2-or-more-year survivors of childhood cancer in the 13 institutions of the Late Effects Study Group. Secondary leukemia occurred in 22 nonreferred individuals compared to 1.52 expected, based on general population rates (relative risk (RR) = 14; 95% confidence interval (CI), 9-22). The influence of therapy for the first cancer on subsequent leukemia risk was determined by a case-control study conducted on 25 cases and 90 matched controls. Treatment with alkylating agents was associated with a significantly elevated risk of leukemia (RR = 4.8; 95% CI, 1.2-18.9). A strong dose-response relationship was also observed between leukemia risk and total dose of alkylating agents, estimated by an alkylator score. The RR of leukemia reached 23 in the highest dose category. Radiation therapy, however, did not increase risk. Although doxorubicin was also identified as a possible risk factor, the excess risk of leukemia following treatment for childhood cancer appears almost entirely due to alkylating agents.

  4. Efficient synthesis of benzamide riboside, a potential anticancer agent.

    PubMed

    Bonnac, Laurent F; Gao, Guang-Yao; Chen, Liqiang; Patterson, Steven E; Jayaram, Hiremagalur N; Pankiewicz, Krzysztof W

    2007-01-01

    An efficient five step synthesis of benzamide riboside (BR) amenable for a large scale synthesis has been developed. It allows for extensive pre-clinical studies of BR as a potential anticancer agent. PMID:18066762

  5. 4-Aminoquinoline Derivatives as Potential Antileishmanial Agents.

    PubMed

    Antinarelli, Luciana M R; Dias, Rafael M P; Souza, Isabela O; Lima, Wallace P; Gameiro, Jacy; da Silva, Adilson D; Coimbra, Elaine S

    2015-10-01

    The leishmanicidal activity of a series of 4-aminoquinoline (AMQ) derivatives was assayed against Leishmania amazonensis. This activity against the intracellular parasite was found stronger than for L. amazonensis promastigotes. Neither compound was cytotoxic against macrophages. The compound AMQ-j, which exhibited a strong activity against promastigotes and amastigotes of L. amazonensis (IC50 values of 5.9 and 2.4 μg/mL, respectively) and similar leishmanicidal activity to reference drugs, was chosen for studies regarding its possible mechanism of action toward parasite death. The results showed that the compound AMQ-j induced depolarization of the mitochondrial membrane potential in promastigotes and in L. amazonensis-infected macrophages, but not in uninfected macrophages. Furthermore, the depolarization of the mitochondrial membrane potential was dose dependent in infected macrophages. We have established that promastigotes and L. amazonensis-infected macrophages treated with AMQ-j were submitted to oxidative stress. This is in line with the increase in the level of reactive oxygen species (ROS). Leishmania amazonensis-infected macrophages treated with AMQ-j did not show a significant increase in the production of nitric oxide. Our results indicate the effective and selective action of AMQ-j against L. amazonensis, and its mechanism of action appears to be mediated by mitochondrial dysfunction associated with ROS production. PMID:25682728

  6. Quinol derivatives as potential trypanocidal agents

    PubMed Central

    Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

    2012-01-01

    Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

  7. Rhizoma Coptidis: A Potential Cardiovascular Protective Agent

    PubMed Central

    Tan, Hui-Li; Chan, Kok-Gan; Pusparajah, Priyia; Duangjai, Acharaporn; Saokaew, Surasak; Mehmood Khan, Tahir; Lee, Learn-Han; Goh, Bey-Hing

    2016-01-01

    Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs. PMID:27774066

  8. Honey: A Potential Therapeutic Agent for Managing Diabetic Wounds

    PubMed Central

    Islam, Md. Asiful; Gan, Siew Hua; Khalil, Md. Ibrahim

    2014-01-01

    Diabetic wounds are unlike typical wounds in that they are slower to heal, making treatment with conventional topical medications an uphill process. Among several different alternative therapies, honey is an effective choice because it provides comparatively rapid wound healing. Although honey has been used as an alternative medicine for wound healing since ancient times, the application of honey to diabetic wounds has only recently been revived. Because honey has some unique natural features as a wound healer, it works even more effectively on diabetic wounds than on normal wounds. In addition, honey is known as an “all in one” remedy for diabetic wound healing because it can combat many microorganisms that are involved in the wound process and because it possesses antioxidant activity and controls inflammation. In this review, the potential role of honey's antibacterial activity on diabetic wound-related microorganisms and honey's clinical effectiveness in treating diabetic wounds based on the most recent studies is described. Additionally, ways in which honey can be used as a safer, faster, and effective healing agent for diabetic wounds in comparison with other synthetic medications in terms of microbial resistance and treatment costs are also described to support its traditional claims. PMID:25386217

  9. Unsafe and potentially safe herbal therapies.

    PubMed

    Klepser, T B; Klepser, M E

    1999-01-15

    Unsafe and potentially safe herbal therapies are discussed. The use of herbal therapies is on the rise in the United States, but most pharmacists are not adequately prepared educationally to meet patients' requests for information on herbal products. Pharmacists must also cope with an environment in which there is relatively little regulation of herbal therapies by FDA. Many herbs have been identified as unsafe, including borage, calamus, coltsfoot, comfrey, life root, sassafras, chaparral, germander, licorice, and ma huang. Potentially safe herbs include feverfew, garlic, ginkgo, Asian ginseng, saw palmetto, St. John's wort, and valerian. Clinical trials have been used to evaluate feverfew for migraine prevention and rheumatoid arthritis; garlic for hypertension, hyperlipidemia, and infections; ginkgo for circulatory disturbances and dementia; ginseng for fatigue and cancer prevention; and saw palmetto for benign prostatic hyperplasia. Also studied in formal trials have been St. John's wort for depression and valerian for insomnia. The clinical trial results are suggestive of efficacy of some herbal therapies for some conditions. German Commission E, a regulatory body that evaluates the safety and efficacy of herbs on the basis of clinical trials, cases, and other scientific literature, has established indications and dosage recommendations for many herbal therapies. Pharmacists have a responsibility to educate themselves about herbal therapies in order to help patients discern the facts from the fiction, avoid harm, and gain what benefits may be available.

  10. Modeling of gene therapy for regenerative cells using intelligent agents.

    PubMed

    Adly, Aya Sedky; Aboutabl, Amal Elsayed; Ibrahim, M Shaarawy

    2011-01-01

    Gene therapy is an exciting field that has attracted much interest since the first submission of clinical trials. Preliminary results were very encouraging and prompted many investigators and researchers. However, the ability of stem cells to differentiate into specific cell types holds immense potential for therapeutic use in gene therapy. Realization of this potential depends on efficient and optimized protocols for genetic manipulation of stem cells. It is widely recognized that gain/loss of function approaches using gene therapy are essential for understanding specific genes functions, and such approaches would be particularly valuable in studies involving stem cells. A significant complexity is that the development stage of vectors and their variety are still not sufficient to be efficiently applied in stem cell therapy. The development of scalable computer systems constitutes one step toward understanding dynamics of its potential. Therefore, the primary goal of this work is to develop a computer model that will support investigations of virus' behavior and organization on regenerative tissues including genetically modified stem cells. Different simulation scenarios were implemented, and their results were encouraging compared to ex vivo experiments, where the error rate lies in the range of acceptable values in this domain of application.

  11. [Bioterrorism, parasites as potential bioterrorism agents and biosecurity studies].

    PubMed

    Aksoy, Umit

    2006-01-01

    A variety of agents have a potential risk for being use as weapons of biological terrorism. However, the use of parasites as bioterrorism agents has not received so much attention. Parasites could contribute to the installation of fear in human population upon intentional addition to their food and water supplies. On the other hand, vector-borne parasites can also constitute risk of bioterrorism. Biosecurity issues are gaining importance as a consequence of globalization. Surveillance is critical in maintaining biosecurity and early detection of infectious disease agents is essential. In this review article, bioterrorism, the role of parasites as potential bioterrorism agents, studies on biosecurity and laboratory design for biosafety have been discussed under the light of recent literature.

  12. Monoclonal antibodies: new agents for cancer detection and targeted therapy

    SciTech Connect

    Baldwin, R.W.; Byers, V.S. )

    1991-01-01

    Antibodies directed against markers on cancer cells are gaining in importance for the purpose of targeting diagnostic and therapeutic agents. In the past, this approach has had very limited success principally because the classical methods for producing antibodies from blood serum of animals immunized with cancer cells or extracts were unsatisfactory. The situation has changed dramatically since 1975 following the design of procedures for 'immortalizing' antibody-producing cells (lymphocytes) by fusing them with cultured myeloma cells to form hybridomas which continuously secrete antibodies. Since these hybridomas produce antibodies coded for by a single antibody-producing cell, the antibodies are called monoclonal. Building on these advances in biomedical research, it is now possible to reproducibly manufacture monoclonal antibodies on a scale suitable for use in cancer detection and therapy.

  13. Phase-Change Contrast Agents for Imaging and Therapy

    PubMed Central

    Sheeran, Paul S.; Dayton, Paul A.

    2016-01-01

    Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized droplets undergo a phase-transition to the gaseous state and a volumetric expansion occurs. This phenomenon, termed acoustic droplet vaporization, has been proposed as a means to address a number of in vivo applications at the microscale and nanoscale. In this review, the history of PCCAs, physical mechanisms involved, and proposed applications are discussed with a summary of studies demonstrated in vivo. Factors that influence the design of PCCAs are discussed, as well as the need for future studies to characterize potential bioeffects for administration in humans and optimization of ultrasound parameters. PMID:22352770

  14. Targeting Microtubules by Natural Agents for Cancer Therapy

    PubMed Central

    Mukhtar, Eiman; Adhami, Vaqar Mustafa; Mukhtar, Hasan

    2014-01-01

    Natural compounds that target microtubules and disrupt the normal function of the mitotic spindle have proven to be one of the best classes of cancer chemotherapeutic drugs available in clinics to date. There is increasing evidence showing that even minor alteration of microtubule dynamics can engage the spindle checkpoint, arresting cell cycle progression at mitosis and subsequently leading to cell death. Our improved understanding of tumor biology and our continued appreciation for what the microtubule target agents (MTAs) can do has helped pave the way for a new era in the treatment of cancer. The effectiveness of these agents for cancer therapy has been impaired, however, by various side effects and drug resistance. Several new MTAs have shown potent activity against the proliferation of various cancer cells, including resistance to the existing MTAs. Sustained investigation of the mechanisms of action of MTAs, development and discovery of new drugs, and exploring new treatment strategies that reduce side effects and circumvent drug resistance could provide more effective therapeutic options for cancer patients. This review focuses on the successful cancer chemotherapy from natural compounds in clinical settings and the challenges that may abort their usefulness. PMID:24435445

  15. Insights into a microwave susceptible agent for minimally invasive microwave tumor thermal therapy.

    PubMed

    Shi, Haitang; Liu, Tianlong; Fu, Changhui; Li, Linlin; Tan, Longfei; Wang, Jingzhuo; Ren, Xiangling; Ren, Jun; Wang, Jianxin; Meng, Xianwei

    2015-03-01

    This work develops a kind of sodium alginate (SA) microcapsules as microwave susceptible agents for in vivo tumor microwave thermal therapy for the first time. Due to the excellent microwave susceptible properties and low bio-toxicity, excellent therapy efficiency can be achieved with the tumor inhibiting ratio of 97.85% after one-time microwave thermal therapy with ultralow power (1.8 W, 450 MHz). Meanwhile, the mechanism of high microwave heating efficiency was confirmed via computer-simulated model in theory, demonstrating that the spatial confinement efficiency of microcapsule walls endows the inside ions with high microwave susceptible properties. This strategy offers tremendous potential applications in clinical tumor treatment with the benefits of safety, reliability, effectiveness and minimally invasiveness.

  16. Primary screen for potential sheep scab control agents.

    PubMed

    Dunn, J A; Prickett, J C; Collins, D A; Weaver, R J

    2016-07-15

    The efficacy of potential acaricidal agents were assessed against the sheep scab mite Psoroptes ovis using a series of in vitro assays in modified test arenas designed initially to maintain P. ovis off-host. The mortality effects of 45 control agents, including essential oils, detergents, desiccants, growth regulators, lipid synthesis inhibitors, nerve action/energy metabolism disruptors and ecdysteroids were assessed against adults and nymphs. The most effective candidates were the desiccants (diatomaceous earth, nanoclay and sorex), the growth regulators (buprofezin, hexythiazox and teflubenzuron), the lipid synthesis inhibitors (spirodiclofen, spirotetramat and spiromesifen) and the nerve action and energy metabolism inhibitors (fenpyroximate, spinosad, tolfenpyrad, and chlorantraniliprole). PMID:27270393

  17. Alpharetroviral vectors: from a cancer-causing agent to a useful tool for human gene therapy.

    PubMed

    Suerth, Julia D; Labenski, Verena; Schambach, Axel

    2014-12-01

    Gene therapy using integrating retroviral vectors has proven its effectiveness in several clinical trials for the treatment of inherited diseases and cancer. However, vector-mediated adverse events related to insertional mutagenesis were also observed, emphasizing the need for safer therapeutic vectors. Paradoxically, alpharetroviruses, originally discovered as cancer-causing agents, have a more random and potentially safer integration pattern compared to gammaretro- and lentiviruses. In this review, we provide a short overview of the history of alpharetroviruses and explain how they can be converted into state-of-the-art gene delivery tools with improved safety features. We discuss development of alpharetroviral vectors in compliance with regulatory requirements for clinical translation, and provide an outlook on possible future gene therapy applications. Taken together, this review is a broad overview of alpharetroviral vectors spanning the bridge from their parental virus discovery to their potential applicability in clinical settings.

  18. Semimetal nanomaterials of antimony as highly efficient agent for photoacoustic imaging and photothermal therapy.

    PubMed

    Li, Wanwan; Rong, Pengfei; Yang, Kai; Huang, Peng; Sun, Kang; Chen, Xiaoyuan

    2015-03-01

    In this study we report semimetal nanomaterials of antimony (Sb) as highly efficient agent for photoacoustic imaging (PAI) and photothermal therapy (PTT). The Sb nanorod bundles have been synthesized through a facile route by mixing 1-octadecane (ODE) and oleyl amine (OAm) as the solvent. The aqueous dispersion of PEGylated Sb NPs, due to its broad and strong photoabsorption ranging from ultraviolet (UV) to near-infrared (NIR) wavelengths, is applicable as a photothermal agent driven by 808 nm laser with photothermal conversion efficiency up to 41%, noticeably higher than most of the PTT agents reported before. Our in vitro experiments also showed that cancer cell ablation effect of PEGylated Sb NPs was dependent on laser power. By intratumoral administration of PEGylated Sb NPs, 100% tumor ablation can be realized by using NIR laser irradiation with a lower power of 1 W/cm(2) for 5 min (or 0.5 W/cm(2) for 10 min) and no obvious toxic side effect is identified after photothermal treatment. Moreover, intense PA signal was also observed after intratumoral injection of PEGylated Sb NPs and NIR laser irradiation due to their strong NIR photoabsorption, suggesting PEGylated Sb NPs as a potential NIR PA agent. Based on the findings of this work, further development of using other semimetal nanocrystals as highly efficient NIR agents can be achieved for vivo tumor imaging and PTT.

  19. Potential biocontrol agents for biofouling on artificial structures.

    PubMed

    Atalah, Javier; Newcombe, Emma M; Hopkins, Grant A; Forrest, Barrie M

    2014-09-01

    The accumulation of biofouling on coastal structures can lead to operational impacts and may harbour problematic organisms, including non-indigenous species. Benthic predators and grazers that can supress biofouling, and which are able to be artificially enhanced, have potential value as augmentative biocontrol agents. The ability of New Zealand native invertebrates to control biofouling on marina pontoons and wharf piles was tested. Caging experiments evaluated the ability of biocontrol to mitigate established biofouling, and to prevent fouling accumulation on defouled surfaces. On pontoons, the gastropods Haliotis iris and Cookia sulcata reduced established biofouling cover by >55% and largely prevented the accumulation of new biofouling over three months. On wharf piles C. sulcata removed 65% of biofouling biomass and reduced its cover by 73%. C. sulcata also had better retention and survival rates than other agents. Augmentative biocontrol has the potential to be an effective method to mitigate biofouling on marine structures.

  20. Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity

    PubMed Central

    Gupta, Deepa; Jain, D. K.

    2015-01-01

    Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen–Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent. PMID:26317075

  1. Securinine, a Myeloid Differentiation Agent with Therapeutic Potential for AML

    PubMed Central

    Gupta, Kalpana; Chakrabarti, Amitabha; Rana, Sonia; Ramdeo, Ritu; Roth, Bryan L.; Agarwal, Munna L.; Tse, William; Agarwal, Mukesh K.; Wald, David N.

    2011-01-01

    As the defining feature of Acute Myeloid Leukemia (AML) is a maturation arrest, a highly desirable therapeutic strategy is to induce leukemic cell maturation. This therapeutic strategy has the potential of avoiding the significant side effects that occur with the traditional AML therapeutics. We identified a natural compound securinine, as a leukemia differentiation-inducing agent. Securinine is a plant-derived alkaloid that has previously been used clinically as a therapeutic for primarily neurological related diseases. Securinine induces monocytic differentiation of a wide range of myeloid leukemia cell lines as well as primary leukemic patient samples. Securinine's clinical potential for AML can be seen from its ability to induce significant growth arrest in cell lines and patient samples as well as its activity in significantly impairing the growth of AML tumors in nude mice. In addition, securinine can synergize with currently employed agents such as ATRA and decitabine to induce differentiation. This study has revealed securinine induces differentiation through the activation of DNA damage signaling. Securinine is a promising new monocytic differentiation inducing agent for AML that has seen previous clinical use for non-related disorders. PMID:21731671

  2. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    PubMed

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  3. Pyrazoles as potential anti-angiogenesis agents: a contemporary overview

    PubMed Central

    Kasiotis, Konstantinos M.; Tzanetou, Evangelia N.; Haroutounian, Serkos A.

    2014-01-01

    Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently, several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research. PMID:25250310

  4. Pyrazoles as potential anti-angiogenesis agents: A contemporary overview

    NASA Astrophysics Data System (ADS)

    Kasiotis, Konstantinos; Tzanetou, Evangelia; Haroutounian, Serkos

    2014-09-01

    Angiogenesis is a mulit-step process by which new blood vessels are formed from preexisting vasculature. It is a key rate limiting factor in tumor growth since new blood vessels are necessary to increase tumor size. In this context it has been shown that anti-angiogenic factors can be used in cancer therapy. Among the plethora of heterocyclic compounds administered as anti-angiogenesis agents, pyrazoles constitute one of the bottlenecks of this category. Currently several pyrazole based compounds are administered or are in Phase II and III trials and new targets emerge. It is highly possible that the advent of the next two decades will lead to the discovery and use of additional pyrazoles whose anti-angiogenic profile will position them in the forefront of the battle of various malignancies. The present review is an attempt to focus on those pyrazoles that arise as anti-angiogenesis agents commenting both on the chemistry and bioactivity that these exhibit aiming to contribute to the perspectives that they hold for future research.

  5. Regulation of MicroRNAs by Natural Agents: New Strategies in Cancer Therapies

    PubMed Central

    2014-01-01

    MicroRNAs (miRNAs) are short noncoding RNA which regulate gene expression by messenger RNA (mRNA) degradation or translation repression. The plethora of published reports in recent years demonstrated that they play fundamental roles in many biological processes, such as carcinogenesis, angiogenesis, programmed cell death, cell proliferation, invasion, migration, and differentiation by acting as tumour suppressor or oncogene, and aberrations in their expressions have been linked to onset and progression of various cancers. Furthermore, each miRNA is capable of regulating the expression of many genes, allowing them to simultaneously regulate multiple cellular signalling pathways. Hence, miRNAs have the potential to be used as biomarkers for cancer diagnosis and prognosis as well as therapeutic targets. Recent studies have shown that natural agents such as curcumin, resveratrol, genistein, epigallocatechin-3-gallate, indole-3-carbinol, and 3,3′-diindolylmethane exert their antiproliferative and/or proapoptotic effects through the regulation of one or more miRNAs. Therefore, this review will look at the regulation of miRNAs by natural agents as a means to potentially enhance the efficacy of conventional chemotherapy through combinatorial therapies. It is hoped that this would provide new strategies in cancer therapies to improve overall response and survival outcome in cancer patients. PMID:25254214

  6. Potential central nervous system antitumor agents. Aziridinylbenzoquinones. 1.

    PubMed

    Khan, A H; Driscoll, J S

    1976-02-01

    A series of 3,6-substituted 2,5-diaziridinyl-1,4-benzoquinones was prepared as potential CNS antitumor agents. Activity was evaluated in the murine leukemia L1210 system. The diurethane derivative 9 was found to have significant activity in that system as well as in the intraperitoneal P388 and B16 tumor models. Marginal Lewis lung activity was observed. Reproducible activity was seen in the intracerebral L1210 and P388 systems. Multiple cures were observed in the murine ependymoblastoma brain tumor model. The effect of substituent type on aziridinylquinone activity is discussed.

  7. Effects of antimicrobial agents used for therapy of CNS infections on dissociated brain cell cultures.

    PubMed

    Schaad, U B; Guenin, K; Steffen, C; Herschkowtiz, N

    1988-09-01

    The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity (p less than 0.001 or less than 0.01) and to a lesser extent (p less than 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections.

  8. Hypoglycemic agents and potential anti-inflammatory activity

    PubMed Central

    Kothari, Vishal; Galdo, John A; Mathews, Suresh T

    2016-01-01

    Current literature shows an association of diabetes and secondary complications with chronic inflammation. Evidence of these immunological changes include altered levels of cytokines and chemokines, changes in the numbers and activation states of various leukocyte populations, apoptosis, and fibrosis during diabetes. Therefore, treatment of diabetes and its complications may include pharmacological strategies to reduce inflammation. Apart from anti-inflammatory drugs, various hypoglycemic agents have also been found to reduce inflammation that could contribute to improved outcomes. Extensive studies have been carried out with thiazolidinediones (peroxisome proliferator-activated receptor-γ agonist), dipeptidyl peptidase-4 inhibitors, and metformin (AMP-activated protein kinase activator) with each of these classes of compounds showing moderate-to-strong anti-inflammatory action. Sulfonylureas and alpha glucosidase inhibitors appeared to exert modest effects, while the injectable agents, insulin and glucagon-like peptide-1 receptor agonists, may improve secondary complications due to their anti-inflammatory potential. Currently, there is a lack of clinical data on anti-inflammatory effects of sodium–glucose cotransporter type 2 inhibitors. Nevertheless, for all these glucose-lowering agents, it is essential to distinguish between anti-inflammatory effects resulting from better glucose control and effects related to intrinsic anti-inflammatory actions of the pharmacological class of compounds. PMID:27114714

  9. Underestimated potential of organometallic rhenium complexes as anticancer agents.

    PubMed

    Leonidova, Anna; Gasser, Gilles

    2014-10-17

    In the recent years, organometallic compounds have become recognized as promising anti-cancer drug candidates. While radioactive (186/188)Re compounds are already used in clinics for cancer treatment, cold Re organometallic compounds have mostly been explored as luminescent probes for cell imaging and photosensitizers in photocatalysis. However, a growing number of studies have recently revealed the potential of Re organometallic complexes as anti-cancer agents. Several compounds have displayed cytotoxicity equaling or exceeding that of the well-established anti-cancer drug cisplatin. In this review, we present the currently known Re organometallic complexes that have shown anti-proliferative activity on cancer cell lines. A particular emphasis is placed on their cellular uptake and localization as well as their potential mechanism of action.

  10. Artocarpus plants as a potential source of skin whitening agents.

    PubMed

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2011-09-01

    Artocarpus plants have been a focus of constant attention due to the potential for skin whitening agents. In the in vitro experiment, compounds from the Artocarpus plants, such as artocarpanone, norartocarpetin, artocarpesin, artogomezianol, andalasin, artocarbene, and chlorophorin showed tyrosinase inhibitory activity. Structure-activity investigations revealed that the 4-substituted resorcinol moiety in these compounds was responsible for their potent inhibitory activities on tyrosinase. In the in vitro assay, using B16 melanoma cells, the prenylated polyphenols isolated from Artocarpus plants, such as artocarpin, cudraflavone C, 6-prenylapigenin, kuwanon C, norartocarpin, albanin A, cudraflavone B, and brosimone I showed potent inhibitory activity on melanin formation. Structure-activity investigations revealed that the introduction of an isoprenoid moiety to a non-isoprenoid-substituted polyphenol enhanced the inhibitory activity of melanin production in B16 melanoma cells. In the in vivo investigation, the extract of the wood of Artocarpus incisus and a representative isolated compound from it, artocarpin had a lightening effect on the skin of guinea pigs' backs. Other in vivo experiments using human volunteers have shown that water extract of Artocarpus lakoocha reduced the melanin formation in the skin of volunteers. These results indicate that the extracts of Artocarpus plants are potential sources for skin whitening agents.

  11. Biological activities of phosphocitrate: a potential meniscal protective agent.

    PubMed

    Sun, Yubo; Roberts, Andrea; Mauerhan, David R; Sun, Andrew R; Norton, H James; Hanley, Edward N

    2013-01-01

    Phosphocitrate (PC) inhibited meniscal calcification and the development of calcium crystal-associated osteoarthritis (OA) in Hartley guinea pigs. However, the mechanisms remain elusive. This study sought to examine the biological activities of PC in the absence of calcium crystals and test the hypothesis that PC is potentially a meniscal protective agent. We found that PC downregulated the expression of many genes classified in cell proliferation, ossification, prostaglandin metabolic process, and wound healing, including bloom syndrome RecQ helicase-like, cell division cycle 7 homolog, cell division cycle 25 homolog C, ankylosis progressive homolog, prostaglandin-endoperoxide synthases-1/cyclooxygenase-1, and plasminogen activator urokinase receptor. In contrast, PC stimulated the expression of many genes classified in fibroblast growth factor receptor signaling pathway, collagen fibril organization, and extracellular structure organization, including fibroblast growth factor 7, collagen type I, alpha 1, and collagen type XI, alpha 1. Consistent with its effect on the expression of genes classified in cell proliferation, collagen fibril organization, and ossification, PC inhibited the proliferation of OA meniscal cells and meniscal cell-mediated calcification while stimulating the production of collagens. These findings indicate that PC is potentially a meniscal-protective agent and a disease-modifying drug for arthritis associated with severe meniscal degeneration. PMID:23936839

  12. The Effects of Glucose Therapy Agents-Apple Juice, Orange Juice, and Cola-on Enteral Tube Flow and Patency.

    PubMed

    Steinberg, Daphna J; Montreuil, Jasmine; Santoro, Andrea L; Zettas, Antonia; Lowe, Julia

    2016-06-01

    To develop evidence-based hypoglycemia treatment protocols in patients receiving total enteral nutrition, this study determined the effect on enteral tube flow of glucose therapy agents: apple juice, orange juice, and cola, and it also examined the effects of tube type and feed type with these glucose therapy agents. For this study, 12 gastrostomy tubes (6 polyethylene and 6 silicone) were set at 50 mL/h. Each feeding set was filled with Isosource HN with fibre or Novasource Renal. Each tube was irrigated with 1 glucose therapy agent, providing approximately 20 g of carbohydrate every 4 h. Flow-rate measurements were collected at 2 h intervals. The results showed that the glucose therapy agent choice affected flow rates: apple juice and cola had higher average flow rates than orange juice (P = 0.01). A significant difference was found between tube type and enteral formula: polyethylene tubes had higher average flow rates than silicone tubes (P < 0.0001), and Isosource HN with fibre had higher flow rates than Novasource Renal (P = 0.01). We concluded that apple juice and cola have less tube clogging potential than orange juice, and thus may be considered as primary treatment options for hypoglycemia in enterally fed patients. Polyethylene tubes and Isosource HN with fibre were less likely to clog than silicone tubes and Novasource Renal.

  13. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation

    PubMed Central

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-01-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility. PMID:25105845

  14. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation.

    PubMed

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-01-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce (1)O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of (1)O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.

  15. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation

    NASA Astrophysics Data System (ADS)

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-08-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen (1O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce 1O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of 1O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility.

  16. A graphene quantum dot photodynamic therapy agent with high singlet oxygen generation.

    PubMed

    Ge, Jiechao; Lan, Minhuan; Zhou, Bingjiang; Liu, Weimin; Guo, Liang; Wang, Hui; Jia, Qingyan; Niu, Guangle; Huang, Xing; Zhou, Hangyue; Meng, Xiangmin; Wang, Pengfei; Lee, Chun-Sing; Zhang, Wenjun; Han, Xiaodong

    2014-01-01

    Clinical applications of current photodynamic therapy (PDT) agents are often limited by their low singlet oxygen ((1)O2) quantum yields, as well as by photobleaching and poor biocompatibility. Here we present a new PDT agent based on graphene quantum dots (GQDs) that can produce (1)O2 via a multistate sensitization process, resulting in a quantum yield of ~1.3, the highest reported for PDT agents. The GQDs also exhibit a broad absorption band spanning the UV region and the entire visible region and a strong deep-red emission. Through in vitro and in vivo studies, we demonstrate that GQDs can be used as PDT agents, simultaneously allowing imaging and providing a highly efficient cancer therapy. The present work may lead to a new generation of carbon-based nanomaterial PDT agents with overall performance superior to conventional agents in terms of (1)O2 quantum yield, water dispersibility, photo- and pH-stability, and biocompatibility. PMID:25105845

  17. Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

    PubMed Central

    Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

    2015-01-01

    There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

  18. Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease.

    PubMed

    Li, Weibin; Lan, Xiaopeng

    2015-08-01

    Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides generated in vitro based on affinity for certain target molecules by a process known as Systematic Evolution of Ligands by Exponential Enrichment. Aptamers can bind their target molecules with high specificity and selectivity by means of structure compatibility, stacking of aromatic rings, electrostatic and van der Waals interactions, and hydrogen bonding. With several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch to batch variation, flexible modification and stability, lack of toxicity and low immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic agents. This review focuses on the development of aptamers as potential therapeutics for autoimmune diseases, including diabetes mellitus, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus. PMID:25993618

  19. Rapid, cell-based toxicity screen of potentially therapeutic post-transcriptional gene silencing agents.

    PubMed

    Kolniak, Tiffany A; Sullivan, Jack M

    2011-05-01

    Post-transcriptional gene silencing (PTGS) agents such as antisense, ribozymes and RNA interference (RNAi) have great potential as therapeutics for a variety of eye diseases including retinal and macular degenerations, glaucoma, corneal degenerations, inflammatory and viral conditions. Despite their great potential and over thirty years of academic and corporate research only a single PTGS agent is currently approved for human therapy for a single disease. Substantial challenges exist to achieving both efficacious and safe PTGS agents. Efficacy, as measured in specific target mRNA and protein knockdown, depends upon a number of complex factors including the identification of rare regions of target mRNA accessibility, cellular co-localization of the PTGS agent in sufficient concentration with the target mRNA, and stability of the PTGS agent in the target cells in which it is delivered or expressed. Safety is commonly measured by lack of cytotoxicity or other deleterious cellular responses in cells in which the PTGS agent is delivered or expressed. To relieve major bottlenecks in RNA drug discovery novel, efficient, inexpensive, and rapid tools are needed to facilitate lead identification of the most efficacious PTGS agent, rational optimization of efficacy of the lead agent, and lead agent safety determinations. We have developed a technological platform using cell culture expression systems that permits lead identification and efficacy optimization of PTGS agents against arbitrary disease target mRNAs under relatively high throughput conditions. Here, we extend the technology platform to include PTGS safety determinations in cultured human cells that are expected to represent the common cellular housekeeping microenvironment. We developed a high throughput screening (HTS) cytotoxicity assay in 96-well plate format based around the SYTOX Green dye which is excluded from healthy viable cells and becomes substantially fluorescent only after entering cells and binding

  20. Rapid, cell-based toxicity screen of potentially therapeutic post-transcriptional gene silencing agents.

    PubMed

    Kolniak, Tiffany A; Sullivan, Jack M

    2011-05-01

    Post-transcriptional gene silencing (PTGS) agents such as antisense, ribozymes and RNA interference (RNAi) have great potential as therapeutics for a variety of eye diseases including retinal and macular degenerations, glaucoma, corneal degenerations, inflammatory and viral conditions. Despite their great potential and over thirty years of academic and corporate research only a single PTGS agent is currently approved for human therapy for a single disease. Substantial challenges exist to achieving both efficacious and safe PTGS agents. Efficacy, as measured in specific target mRNA and protein knockdown, depends upon a number of complex factors including the identification of rare regions of target mRNA accessibility, cellular co-localization of the PTGS agent in sufficient concentration with the target mRNA, and stability of the PTGS agent in the target cells in which it is delivered or expressed. Safety is commonly measured by lack of cytotoxicity or other deleterious cellular responses in cells in which the PTGS agent is delivered or expressed. To relieve major bottlenecks in RNA drug discovery novel, efficient, inexpensive, and rapid tools are needed to facilitate lead identification of the most efficacious PTGS agent, rational optimization of efficacy of the lead agent, and lead agent safety determinations. We have developed a technological platform using cell culture expression systems that permits lead identification and efficacy optimization of PTGS agents against arbitrary disease target mRNAs under relatively high throughput conditions. Here, we extend the technology platform to include PTGS safety determinations in cultured human cells that are expected to represent the common cellular housekeeping microenvironment. We developed a high throughput screening (HTS) cytotoxicity assay in 96-well plate format based around the SYTOX Green dye which is excluded from healthy viable cells and becomes substantially fluorescent only after entering cells and binding

  1. Natural products for cancer-targeted therapy: citrus flavonoids as potent chemopreventive agents.

    PubMed

    Meiyanto, Edy; Hermawan, Adam; Anindyajati

    2012-01-01

    Targeted therapy has been a very promising strategy of drug development research. Many molecular mechanims of diseases have been known to be regulated by abundance of proteins, such as receptors and hormones. Chemoprevention for treatment and prevention of diseases are continuously developed. Pre-clinical and clinical studies in chemoprevention field yielded many valuable data in preventing the onset of disease and suppressing the progress of their growth, making chemoprevention a challenging and a very rational strategy in future researches. Natural products being rich of flavonoids are those fruits belong to the genus citrus. Ethanolic extract of Citrus reticulata and Citrus aurantiifolia peels showed anticarcinogenic, antiproliferative, co-chemotherapeutic and estrogenic effects. Several examples of citrus flavonoids that are potential as chemotherapeutic agents are tangeretin, nobiletin, hesperetin, hesperidin, naringenin, and naringin. Those flavonoids have been shown to possess inhibition activity on certain cancer cells' growth through various mechanisms. Moreover, citrus flavonoids also perform promising effect in combination with several chemotherapeutic agents against the growth of cancer cells. Some mechanisms involved in those activities are through cell cycle modulation, antiangiogenic effect, and apoptosis induction. Previous studies showed that tangeretin suppressed the growth of T47D breast cancer cells by inhibiting ERK phosphorylation. While in combination with tamoxifen, doxorubicin, and 5-FU, respectively, it was proven to be synergist on several cancer cells. Hesperidin and naringenin increased cytotoxicitity of doxorubicin on MCF-7 cells and HeLa cells. Besides, citrus flavonoids also performed estrogenic effect in vivo. One example is hesperidin having the ability to decrease the concentration of serum and hepatic lipid and reduce osteoporosis of ovariectomized rats. Those studies showed the great potential of citrus fruits as natural product

  2. Potential New Agents for the Management of Hyperkalemia.

    PubMed

    Packham, David K; Kosiborod, Mikhail

    2016-02-01

    Hyperkalemia is a common electrolyte disturbance with multiple potential etiologies. It is usually observed in the setting of reduced renal function. Mild to moderate hyperkalemia is usually asymptomatic, but is associated with poor prognosis. When severe, hyperkalemia may cause serious acute cardiac arrhythmias and conduction abnormalities, and may result in sudden death. The rising prevalence of conditions associated with hyperkalemia (heart failure, chronic kidney disease, and diabetes) and broad use of renin-angiotensin-aldosterone system (RAAS) inhibitors and mineralocorticoid receptor antagonists (MRAs), which improve patient outcomes but increase the risk of hyperkalemia, have led to a significant rise in hyperkalemia-related hospitalizations and deaths. Current non-invasive therapies for hyperkalemia either do not remove excess potassium or have poor efficacy and tolerability. There is a clear need for safer, more effective potassium-lowering therapies suitable for both acute and chronic settings. Patiromer sorbitex calcium and sodium zirconium cyclosilicate (ZS-9) are two new potassium-lowering compounds currently in development. Although they have not yet been approved by the US FDA, both have demonstrated efficacy and safety in recent trials. Patiromer sorbitex calcium is a polymer resin and sorbitol complex that binds potassium in exchange for calcium; ZS-9, a non-absorbed, highly selective inorganic cation exchanger, traps potassium in exchange for sodium and hydrogen. This review discusses the merits of both novel drugs and how they may help optimize the future management of patients with hyperkalemia.

  3. Curcumin: a potential neuroprotective agent in Parkinson's disease.

    PubMed

    Mythri, R B; Bharath, M M Srinivas

    2012-01-01

    Parkinson's disease (PD) is an age-associated neurodegenerative disease clinically characterized as a movement disorder. The motor symptoms in PD arise due to selective degeneration of dopaminergic neurons in the substantia nigra of the ventral midbrain thereby depleting the dopamine levels in the striatum. Most of the current pharmacotherapeutic approaches in PD are aimed at replenishing the striatal dopamine. Although these drugs provide symptomatic relief during early PD, many patients develop motor complications with long-term treatment. Further, PD medications do not effectively tackle tremor, postural instability and cognitive deficits. Most importantly, most of these drugs do not exhibit neuroprotective effects in patients. Consequently, novel therapies involving natural antioxidants and plant products/molecules with neuroprotective properties are being exploited for adjunctive therapy. Curcumin is a polyphenol and an active component of turmeric (Curcuma longa), a dietary spice used in Indian cuisine and medicine. Curcumin exhibits antioxidant, anti-inflammatory and anti-cancer properties, crosses the blood-brain barrier and is neuroprotective in neurological disorders. Several studies in different experimental models of PD strongly support the clinical application of curcumin in PD. The current review explores the therapeutic potential of curcumin in PD. PMID:22211691

  4. Drug therapy reviews: clinical use of hemostatic agents.

    PubMed

    Lowe, G D; Lawson, D H

    1978-04-01

    Systemic hemostatic agents are reviewed. Among the agents discussed are vitamin K preparations (phytonadione, menadione, menadione sodium bisulfite, menadiol sodium diphosphate); and blood products (whole blood, plasma, cryoprecipitate, factor VIII concentrates, factor IX concentrates and fibrinogen concentrates). Normal and abnormal hemostasis and fibrinolysis are discussed, as is the general management of systemic hemostatic defects. Specific disorders covered are clotting factor deficiencies, hemophilia A, factor VIII inhibitors, von Willebrand disease, hemophilia B (Christmas disease), other congenital coagulation disorders, acquired deficiency of factors II, VII, IX and X, and defibrination syndrome.

  5. Nutraceuticals as potential therapeutic agents for colon cancer: a review

    PubMed Central

    Kuppusamy, Palaniselvam; Yusoff, Mashitah M.; Maniam, Gaanty Pragas; Ichwan, Solachuddin Jauhari Arief; Soundharrajan, Ilavenil; Govindan, Natanamurugaraj

    2014-01-01

    Colon cancer is a world-wide health problem and the second-most dangerous type of cancer, affecting both men and women. The modern diet and lifestyles, with high meat consumption and excessive alcohol use, along with limited physical activity has led to an increasing mortality rate for colon cancer worldwide. As a result, there is a need to develop novel and environmentally benign drug therapies for colon cancer. Currently, nutraceuticals play an increasingly important role in the treatment of various chronic diseases such as colon cancer, diabetes and Alzheimer׳s disease. Nutraceuticals are derived from various natural sources such as medicinal plants, marine organisms, vegetables and fruits. Nutraceuticals have shown the potential to reduce the risk of colon cancer and slow its progression. These dietary substances target different molecular aspects of colon cancer development. Accordingly, this review briefly discusses the medicinal importance of nutraceuticals and their ability to reduce the risk of colorectal carcinogenesis. PMID:26579381

  6. Investigation of acetylated chitosan microspheres as potential chemoembolic agents.

    PubMed

    Zhou, Xuan; Kong, Ming; Cheng, Xiaojie; Li, Jingjing; Li, Jing; Chen, Xiguang

    2014-11-01

    The aim was to investigate the potential of chitosan microspheres (CMs) with different acetylation using as a chemoembolic agent. Chitosan microspheres (CMs) were prepared via water-in-oil (W/O) emulsification cross-linking method, and acetylated chitosan microspheres (ACMs) were obtained by acetylation of CMs. Next, we characterized the morphology, size, composition and degrees of deacetylation using scanning electron microscopy (TEM), dynamic laser light scattering (DLS), and Fourier transform infrared spectrometer (FTIR). All microspheres had smooth surfaces and good mechanical flexibility, and all could pass through a 5F catheter. The swelling rate (SR) of CMs decreased significantly with the increase of pH (4.0-10.0) but ACMs did not change under the same conditions. Protein absorption assays suggested that albumin was more greatly adsorbed on CMs than on ACMs. Furthermore, CMs caused more blood clots than ACMs. ACMs caused hemolysis less than CMs (<5% of the time). Data indicated that ACMs had more hemocompatibility. Cytotoxicity tests indicated that ACMs initially had less cell attached proliferation but increased with incubation. In contrast, the relative growth rate of mouse embryo fibroblasts (MEFs) on CMs decreased gradually. The results suggested that ACMs could stimulate the growth of MEFs, and CMs were not cytotoxic to MEFs. Thus, ACMs were more biocompatible with greater potential to be used as chemoembolic material.

  7. Development of Immune-Specific Interaction Potentials and Their Application in the Multi-Agent-System VaccImm

    PubMed Central

    Woelke, Anna Lena; von Eichborn, Joachim; Murgueitio, Manuela S.; Worth, Catherine L.; Castiglione, Filippo; Preissner, Robert

    2011-01-01

    Peptide vaccination in cancer therapy is a promising alternative to conventional methods. However, the parameters for this personalized treatment are difficult to access experimentally. In this respect, in silico models can help to narrow down the parameter space or to explain certain phenomena at a systems level. Herein, we develop two empirical interaction potentials specific to B-cell and T-cell receptor complexes and validate their applicability in comparison to a more general potential. The interaction potentials are applied to the model VaccImm which simulates the immune response against solid tumors under peptide vaccination therapy. This multi-agent system is derived from another immune system simulator (C-ImmSim) and now includes a module that enables the amino acid sequence of immune receptors and their ligands to be taken into account. The multi-agent approach is combined with approved methods for prediction of major histocompatibility complex (MHC)-binding peptides and the newly developed interaction potentials. In the analysis, we critically assess the impact of the different modules on the simulation with VaccImm and how they influence each other. In addition, we explore the reasons for failures in inducing an immune response by examining the activation states of the immune cell populations in detail. In summary, the present work introduces immune-specific interaction potentials and their application to the agent-based model VaccImm which simulates peptide vaccination in cancer therapy. PMID:21858048

  8. Inhaled therapy in cystic fibrosis: agents, devices and regimens

    PubMed Central

    Parrott, Helen

    2015-01-01

    Key points There have been significant advances in both inhalation medicines and delivery devices with “intelligent nebulisers” and “dry-powder inhalers” becoming commonplace in CF care. Inhaled medicines generate high levels of a drug within the airways with limited systemic effects, offering safe and convenient antibiotic and mucolytic therapy for individuals with CF. Variations in adherence are not unique to CF; however, treatment burden is high and therefore fast inhaled drug delivery devices may assist individuals in completing the prescribed treatment regimes. Prescribers of inhaled medicines have a responsibility to consider, in addition to efficacy, the appropriated drug/device combination for each individual in order to promote adherence and achieve the desired clinical benefit. Summary The recognised mainstay daily treatments for cystic fibrosis (CF) focus on inhaled and oral medications, airway clearance and optimised nutrition. This review discusses recent advances in inhaled therapies for the management of CF, including devices such as intelligent nebulisers, drug formulations and supporting evidence for inhaled antibiotics (for the management of chronic Pseudomonas aeruginosa) and muco-active drugs. We include practical advice for clinicians regarding the optimisation of inhalation technique and education. The influence of adherence on the use of inhaled therapies in CF is also reviewed. Educational aims To inform readers about the history and progression of inhaled therapies for people with CF with reference to the literature supporting current practice. To highlight the factors that may impact the success of inhaled therapies, including those which are device specific such as drug deposition and those which influence adherence. PMID:26306111

  9. Chromatin-modifying agents in anti-cancer therapy.

    PubMed

    Seidel, Carole; Florean, Cristina; Schnekenburger, Michael; Dicato, Mario; Diederich, Marc

    2012-11-01

    Epigenetic alterations are involved in every step of carcinogenesis. The development of chromatin-modifying agents (CMAs) has provided the ability to fight cancer by reversing these alterations. Currently, four CMAs have been approved for cancer treatment; two DNA demethylating agents and two deacetylase inhibitors. A number of promising CMAs are undergoing clinical trials in several cancer types. Moreover, already approved CMAs are still under clinical investigation to improve their efficacy and to extend their use to a broader panel of cancers. Combinatorial treatments with CMAs are already considered a promising strategy to improve clinical benefits and to limit side effects. The real mechanisms by which these CMAs allow the improvement and remission of patients are still obscure. A deeper analysis of the molecular features expressed by responding patients should be performed to reveal this information. In this review, we focus on clinical trials with CMAs, discussing the success and the pitfalls of this new class of anti-cancer drugs.

  10. The ophthalmological complications of targeted agents in cancer therapy: what do we need to know as ophthalmologists?

    PubMed

    Ho, Wing L; Wong, Hilda; Yau, Thomas

    2013-11-01

    Recently, there has been an increase in the use of targeted therapies for cancer treatments. Nevertheless, the ocular side-effects of the commonly used targeted agents are generally under-reported and not well studied in the literature. We conducted multiple searches in databases, including Medline, EMBASE, Cochrane Library and conference proceedings, using the following strings: 'name of targeted therapeutic agent (both generic and commercial names)' AND 'eye OR ocular OR vision OR ophthalmological'. Various targeted agents have been found to be associated with ocular side-effects due to their specific targeting of activities in the eye. Imatinib commonly causes periorbital oedema, epiphora and occasionally conjunctival haemorrhage. Cetuximab causes corneal lesions, meibomian gland dysfunction, periorbital and lid dermatitis, blepharitis and conjunctivitis. Erlotinib is related to various ocular toxicities, mainly on the ocular surface, and perifosine has been reported to be associated with severe keratitis. Bevacizumab could potentially disrupt intrinsic ocular circulation and lead to the development of thromboembolic events; there are rare reported cases of optic neuritis or optic neuropathy. Other targeted agents, such as trastuzumab, sunitinib and crizotinib, also have specific ocular toxicities. In conclusion, ocular effects of targeted agents are not uncommon in cancer patients receiving targeted therapy. Ophthalmologists should have high indexes of suspicion to diagnose and treat these complications promptly.

  11. Marine Diterpenoids as Potential Anti-Inflammatory Agents.

    PubMed

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E; Fernandez, Patricia L

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  12. Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

    SciTech Connect

    McConnell, D.S.

    1991-01-01

    R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium.

  13. Marine Diterpenoids as Potential Anti-Inflammatory Agents

    PubMed Central

    González, Yisett; Torres-Mendoza, Daniel; Jones, Gillian E.; Fernandez, Patricia L.

    2015-01-01

    The inflammatory response is a highly regulated process, and its dysregulation can lead to the establishment of chronic inflammation and, in some cases, to death. Inflammation is the cause of several diseases, including rheumatoid arthritis, inflammatory bowel diseases, multiple sclerosis, and asthma. The search for agents inhibiting inflammation is a great challenge as the inflammatory response plays an important role in the defense of the host to infections. Marine invertebrates are exceptional sources of new natural products, and among those diterpenoids secondary metabolites exhibit notable anti-inflammatory properties. Novel anti-inflammatory diterpenoids, exclusively produced by marine organisms, have been identified and synthetic molecules based on those structures have been obtained. The anti-inflammatory activity of marine diterpenoids has been attributed to the inhibition of Nuclear Factor-κB activation and to the modulation of arachidonic acid metabolism. However, more research is necessary to describe the mechanisms of action of these secondary metabolites. This review is a compilation of marine diterpenoids, mainly isolated from corals, which have been described as potential anti-inflammatory molecules. PMID:26538822

  14. Astaxanthin: a potential therapeutic agent in cardiovascular disease.

    PubMed

    Fassett, Robert G; Coombes, Jeff S

    2011-01-01

    Astaxanthin is a xanthophyll carotenoid present in microalgae, fungi, complex plants, seafood, flamingos and quail. It is an antioxidant with anti-inflammatory properties and as such has potential as a therapeutic agent in atherosclerotic cardiovascular disease. Synthetic forms of astaxanthin have been manufactured. The safety, bioavailability and effects of astaxanthin on oxidative stress and inflammation that have relevance to the pathophysiology of atherosclerotic cardiovascular disease, have been assessed in a small number of clinical studies. No adverse events have been reported and there is evidence of a reduction in biomarkers of oxidative stress and inflammation with astaxanthin administration. Experimental studies in several species using an ischaemia-reperfusion myocardial model demonstrated that astaxanthin protects the myocardium when administered both orally or intravenously prior to the induction of the ischaemic event. At this stage we do not know whether astaxanthin is of benefit when administered after a cardiovascular event and no clinical cardiovascular studies in humans have been completed and/or reported. Cardiovascular clinical trials are warranted based on the physicochemical and antioxidant properties, the safety profile and preliminary experimental cardiovascular studies of astaxanthin.

  15. Potential of Biological Agents in Decontamination of Agricultural Soil

    PubMed Central

    Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

    2016-01-01

    Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation. PMID:27293964

  16. Potential of Biological Agents in Decontamination of Agricultural Soil.

    PubMed

    Javaid, Muhammad Kashif; Ashiq, Mehrban; Tahir, Muhammad

    2016-01-01

    Pesticides are widely used for the control of weeds, diseases, and pests of cultivated plants all over the world, mainly since the period after the Second World War. The use of pesticides is very extensive to control harm of pests all over the globe. Persistent nature of most of the synthetic pesticides causes serious environmental concerns. Decontamination of these hazardous chemicals is very essential. This review paper elaborates the potential of various biological agents in decontamination of agricultural soils. The agricultural crop fields are contaminated by the periodic applications of pesticides. Biodegradation is an ecofriendly, cost-effective, highly efficient approach compared to the physical and chemical methods which are expensive as well as unfriendly towards environment. Biodegradation is sensitive to the concentration levels of hydrogen peroxide and nitrogen along with microbial community, temperature, and pH changes. Experimental work for optimum conditions at lab scale can provide very fruitful results about specific bacterial, fungal strains. This study revealed an upper hand of bioremediation over physicochemical approaches. Further studies should be carried out to understand mechanisms of biotransformation. PMID:27293964

  17. Nucleic Acid Aptamers as Potential Therapeutic and Diagnostic Agents for Lymphoma

    PubMed Central

    Shum, Ka-To; Zhou, Jiehua; Rossi, John J.

    2014-01-01

    Lymphomas are cancers that arise from white blood cells and usually present as solid tumors. Treatment of lymphoma often involves chemotherapy, and can also include radiotherapy and/or bone marrow transplantation. There is an un-questioned need for more effective therapies and diagnostic tool for lymphoma. Aptamers are single stranded DNA or RNA oligonucleotides whose three-dimensional structures are dictated by their sequences. The immense diversity in function and structure of nucleic acids enable numerous aptamers to be generated through an iterative in vitro selection technique known as Systematic Evolution of Ligands by EXponential enrichment (SELEX). Aptamers have several biochemical properties that make them attractive tools for use as potential diagnostic and pharmacologic agents. Isolated aptamers may directly inhibit the function of target proteins, or they can also be formulated for use as delivery agents for other therapeutic or imaging cargoes. More complex aptamer identification methods, using whole cancer cells (Cell-SELEX), may identify novel targets and aptamers to affect them. This review focuses on recent advances in the use of nucleic acid aptamers as diagnostic and therapeutic agents and as targeted delivery carriers that are relevant to lymphoma. Some representative examples are also discussed. PMID:25057429

  18. Therapies for neovascular age-related macular degeneration: current approaches and pharmacologic agents in development.

    PubMed

    Hanout, Mostafa; Ferraz, Daniel; Ansari, Mehreen; Maqsood, Natasha; Kherani, Saleema; Sepah, Yasir J; Rajagopalan, Nithya; Ibrahim, Mohamed; Do, Diana V; Nguyen, Quan Dong

    2013-01-01

    As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development.

  19. Therapies for Neovascular Age-Related Macular Degeneration: Current Approaches and Pharmacologic Agents in Development

    PubMed Central

    Ferraz, Daniel; Kherani, Saleema; Sepah, Yasir J.; Rajagopalan, Nithya; Ibrahim, Mohamed; Do, Diana V.; Nguyen, Quan Dong

    2013-01-01

    As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is to briefly review the available treatment modalities for neovascular AMD and then focus on promising new therapies that are currently in various stages of development. PMID:24319688

  20. Monitoring/Imaging and Regenerative Agents for Enhancing Tissue Engineering Characterization and Therapies.

    PubMed

    Santiesteban, Daniela Y; Kubelick, Kelsey; Dhada, Kabir S; Dumani, Diego; Suggs, Laura; Emelianov, Stanislav

    2016-03-01

    The past three decades have seen numerous advances in tissue engineering and regenerative medicine (TERM) therapies. However, despite the successes there is still much to be done before TERM therapies become commonplace in clinic. One of the main obstacles is the lack of knowledge regarding complex tissue engineering processes. Imaging strategies, in conjunction with exogenous contrast agents, can aid in this endeavor by assessing in vivo therapeutic progress. The ability to uncover real-time treatment progress will help shed light on the complex tissue engineering processes and lead to development of improved, adaptive treatments. More importantly, the utilized exogenous contrast agents can double as therapeutic agents. Proper use of these Monitoring/Imaging and Regenerative Agents (MIRAs) can help increase TERM therapy successes and allow for clinical translation. While other fields have exploited similar particles for combining diagnostics and therapy, MIRA research is still in its beginning stages with much of the current research being focused on imaging or therapeutic applications, separately. Advancing MIRA research will have numerous impacts on achieving clinical translations of TERM therapies. Therefore, it is our goal to highlight current MIRA progress and suggest future research that can lead to effective TERM treatments.

  1. Potential clinical application of interleukin-27 as an antitumor agent.

    PubMed

    Yoshimoto, Takayuki; Chiba, Yukino; Furusawa, Jun-Ichi; Xu, Mingli; Tsunoda, Ren; Higuchi, Kaname; Mizoguchi, Izuru

    2015-09-01

    Cancer immunotherapies such as sipuleucel-T and ipilimumab are promising new treatments that harness the power of the immune system to fight cancer and achieve long-lasting remission. Interleukin (IL)-27, a member of the IL-12 heterodimeric cytokine family, has pleiotropic functions in the regulation of immune responses with both pro-inflammatory and anti-inflammatory properties. Evidence obtained using a variety of preclinical mouse models indicates that IL-27 possesses potent antitumor activity against various types of tumors through multiple mechanisms without apparent adverse effects. These mechanisms include those mediated not only by CD8(+) T cells, natural killer cells and macrophages, but also by antibody-dependent cell-mediated cytotoxicity, antiangiogenesis, direct antiproliferative effects, inhibition of expression of cyclooxygenase-2 and prostaglandin E2 , and suppression of epithelial-mesenchymal transition, depending on the characteristics of individual tumors. However, the endogenous role of IL-27 subunits and one of its receptor subunits, WSX-1, in the susceptibility to tumor development after transplantation of tumor cell lines or endogenously arising tumors seems to be more complicated. IL-27 functions as a double-edged sword: IL-27 increases IL-10 production and the expression of programmed death ligand 1 and T-cell immunoglobulin and mucin domain-3, and promotes the generation of regulatory T cells, and IL-27 receptor α singling enhances transformation; IL-27 may augment protumor effects as well. Here, we review both facets of IL-27, antitumor effects and protumor effects, and discuss the potential clinical application of IL-27 as an antitumor agent.

  2. Disulfiram Attenuates Osteoclast Differentiation In Vitro: A Potential Antiresorptive Agent

    PubMed Central

    Cheng, Tak S.; Pavlos, Nathan J.; Rea, Sarah; Dai, Kerong; Zheng, Ming H.

    2015-01-01

    Disulfiram (DSF), a cysteine modifying compound, has long been clinically employed for the treatment of alcohol addiction. Mechanistically, DSF acts as a modulator of MAPK and NF-κB pathways signaling pathways. While these pathways are crucial for osteoclast (OC) differentiation, the potential influence of DSF on OC formation and function has not been directly assessed. Here, we explore the pharmacological effects of DSF on OC differentiation, activity and the modulation of osteoclastogenic signaling cascades. We first analyzed cytotoxicity of DSF on bone marrow monocytes isolated from C57BL/6J mice. Upon the establishment of optimal dosage, we conducted osteoclastogenesis and bone resorption assays in the presence or absence of DSF treatment. Luciferase assays in RAW264.7 cells were used to examine the effects of DSF on major transcription factors activation. Western blot, reverse transcription polymerase chain reaction, intracellular acidification and proton influx assays were employed to further dissect the underlying mechanism. DSF treatment dose-dependently inhibited both mouse and human osteoclastogenesis, especially at early stages of differentiation. This inhibition correlated with a decrease in the expression of key osteoclastic marker genes including CtsK, TRAP, DC-STAMP and Atp6v0d2 as well as a reduction in bone resorption in vitro. Suppression of OC differentiation was found to be due, at least in part, to the blockade of several key receptor activators of nuclear factor kappa-B ligand (RANKL)-signaling pathways including ERK, NF-κB and NFATc1. On the other hand, DSF failed to suppress intracellular acidification and proton influx in mouse and human osteoclasts using acridine orange quenching and microsome-based proton transport assays. Our findings indicate that DSF attenuates OC differentiation via the collective suppression of several key RANKL-mediated signaling cascades, thus making it an attractive agent for the treatment of OC

  3. Recent Development of Multifunctional Agents as Potential Drug Candidates for the Treatment of Alzheimer's Disease

    PubMed Central

    Guzior, Natalia; ckowska,, Anna Wię; Panek, Dawid; Malawska, Barbara

    2015-01-01

    Alzheimer’s disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid-β anti-aggregation activity, inhibition of β-secretase and monoamine oxidase, an antioxidant and metal chelating activity, NO-releasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD. PMID:25386820

  4. Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer's disease.

    PubMed

    Guzior, Natalia; Wieckowska, Anna; Panek, Dawid; Malawska, Barbara

    2015-01-01

    Alzheimer's disease (AD) is a complex and progressive neurodegenerative disorder. The available therapy is limited to the symptomatic treatment and its efficacy remains unsatisfactory. In view of the prevalence and expected increase in the incidence of AD, the development of an effective therapy is crucial for public health. Due to the multifactorial aetiology of this disease, the multi-target-directed ligand (MTDL) approach is a promising method in search for new drugs for AD. This review updates information on the development of multifunctional potential anti-AD agents published within the last three years. The majority of the recently reported structures are acetylcholinesterase inhibitors, often endowed with some additional properties. These properties enrich the pharmacological profile of the compounds giving hope for not only symptomatic but also causal treatment of the disease. Among these advantageous properties, the most often reported are an amyloid-β antiaggregation activity, inhibition of β-secretase and monoamine oxidase, an antioxidant and metal chelating activity, NOreleasing ability and interaction with cannabinoid, NMDA or histamine H3 receptors. The majority of novel molecules possess heterodimeric structures, able to interact with multiple targets by combining different pharmacophores, original or derived from natural products or existing therapeutics (tacrine, donepezil, galantamine, memantine). Among the described compounds, several seem to be promising drug candidates, while others may serve as a valuable inspiration in the search for new effective therapies for AD. PMID:25386820

  5. 188Re-ethylene dicysteine: a novel agent for possible use in endovascular radiation therapy.

    PubMed

    Das, T; Banerjee, S; Samuel, G; Sarma, H D; Ramamoorthy, N; Pillai, M R

    2000-10-01

    Several agents, such as 188ReO4-, 188Re-MAG3 and 188Re-DTPA are currently under investigation as radiation sources in liquid-filled balloons for prevention of restenosis following coronary angioplasty. Bearing in mind the risk factor associated with leakage of radioactivity in the event of balloon rupture, the criteria sought in selecting suitable agents for endovascular radiation therapy (EVRT) are rapid clearance and low dose to vital organs. Since 99Tcm labelled ethylene dicysteine (EC) is a well established agent for renal tubular function imaging, the use of 186Re-ethylene dicysteine as a potential agent for prevention of restenosis after angioplasty has been evaluated previously. Therefore, it was of interest to evaluate the applicability of the more potential isotope of rhenium, 188Re, a high energy beta-emitter (Ebetamax = 2.12 MeV) with a suitable T 1/2 = 16.9 h, obtainable carrier-free from the 188W-188Re generator, as an attractive and alternative radionuclide for labelling with L,L-EC. In this paper, the preparation and pharmacological behaviour of the 188Re complex of ethylene dicysteine are reported. The complex can be prepared in high yields (99.5%) under optimized conditions of pH 2-3, at a ligand concentration of 15 mM, 50 microg (0.18 mM) carrier rhenium and using 2 mg x mL(-1) stannous chloride. On storage at 4 degrees C, the RC purity was more than 97% after 48 h when prepared under optimum conditions. Biodistribution studies in Wistar rats showed the desired characteristics of fast blood clearance and low retention of activity in the vital organs (< 2% in intestine, < 1% in stomach, < 0.5% in liver) with a high renal excretion (90.65+/-0.6%) at 3 h post-injection. These results confirm the advantages of using the 188Re-EC complex compared with perrhenate and other rhenium radiopharmaceuticals currently being used in balloons for EVRT. PMID:11130335

  6. POTENTIAL OF HERBAL MEDICINES IN MODERN MEDICAL THERAPY

    PubMed Central

    Said, Hakim Mohammed

    1984-01-01

    The author discusses in this paper the potentialities of Herbal medicine in modern therapy. Also he throws some light on the importance of natural drugs which bring about cure without generation side-effects. PMID:22557447

  7. Potential to raise the efficiency of neutron and neutron-photon therapy using metal nonradioactive nanoparticles

    NASA Astrophysics Data System (ADS)

    Shmatov, M. L.

    2016-07-01

    The use of metal nonradioactive nanoparticles (specifically, gold ones) in neutron and neutron-photon cancer therapy is proposed. The minimum therapeutically effective average density of gold within a tumor subjected to neutron irradiation is estimated as a value on the order of 10-5-10-4 g/cm3. Potential benefits of the use of data obtained when using Peteosthor (a drug containing 224Ra and colloidal platinum) and Thorotrast (a radiopaque contrast agent containing thorium oxide nanoparticles) and its analogues in the analysis of safety and efficiency of application of nonradioactive nanoparticles in radiation therapy and diagnostics are discussed.

  8. Statin therapy: rationale for a new agent, rosuvastatin.

    PubMed

    Korlipara, K

    2002-06-01

    Cardiovascular disease (CVD) remains a major cause of death in industrialised societies, and elevated serum lipids are a significant, highly prevalent and undertreated risk factor for this condition. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have revolutionised the treatment of hyperlipidaemia, and results from large-scale, long-term clinical trials have shown that the substantial reductions in low-density lipoprotein cholesterol (LDL-C) achieved with these drugs are associated with dramatic decreases in cardiovascular risk. Results from recent comparative clinical trials that have included a new drug in this class, rosuvastatin (Crestor), have demonstrated that it is significantly superior to atorvastatin, pravastatin and simvastatin in reducing total cholesterol, LDL-C and apolipoprotein B (Apo B). It is also significantly more effective than atorvastatin in increasing high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I). Rosuvastatin was also superior to all these agents in helping patients meet European Atherosclerosis Society (EAS) and National Cholesterol Education Programme (NCEP) goals for LDL-C. The results of an increasing number of studies indicate that statins have a wide range of pleiotropic properties that almost certainly contribute to their ability to decrease cardiovascular risk and may also make them valuable for treatment of other diseases. These actions include plaque stabilisation, improvement of endothelial function, inhibition of smooth muscle cell proliferation and migration, reduction of expression of adhesion molecules, prevention of cholesterol esterification and accumulation, reduction of secretion of matrix metalloproteinases by macrophages, reduction of platelet activity, reduction of formation of thrombogenic factors, chemoprotection and induction of bone morphogenic protein-2 (BMP-2). Further exploration of these actions will provide key information about class effects

  9. Curcumin: potential for hepatic fibrosis therapy?

    PubMed Central

    O'Connell, M A; Rushworth, S A

    2007-01-01

    The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of curcumin have been well documented in relation to cancer and other chronic diseases. Recent evidence suggests that it may be of therapeutic interest in chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver disease, where normal hepatic tissue is replaced with collagen-rich extracellular matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver cirrhosis in a rodent model and exerts multiple biological effects in hepatic stellate cells (HSCs), which play a central role in the pathogenesis of hepatic fibrosis. In response to liver injury, these cells proliferate producing pro-inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix formation by enhancing HSC matrix metalloproteinase expression via PPARγ and suppressing connective tissue growth factor (CTGF) expression. In this issue, Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by inhibiting ERK and NF-κB activation. These studies suggest that curcumin modulates several intracellular signalling pathways in HSC and may be of future interest in hepatic fibrosis therapy. PMID:18037917

  10. Francisella tularensis as a potential agent of bioterrorism?

    PubMed

    Maurin, Max

    2015-02-01

    Francisella tularensis is a category A bioterrorism agent. It is the etiological agent of tularemia, a zoonotic disease found throughout the northern hemisphere. The intentional spread of F. tularensis aerosols would probably lead to severe and often fatal pneumonia cases, but also secondary cases from contaminated animals and environments. We are not ready to face such a situation. No vaccine is currently available. A few antibiotics are active against F. tularensis, but strains resistant to these antibiotics could be used in the context of bioterrorism. We need new therapeutic strategies to fight against category A bioterrorism agents, including development of new drugs inhibiting F. tularensis growth and/or virulence, or enhancing the host response to infection by this pathogen.

  11. Targeted Aucore-Agshell nanorods as a dual-functional contrast agent for photoacoustic imaging and photothermal therapy

    PubMed Central

    Shi, Yiwen; Peng, Dong; Wang, Kun; Chai, Xinyu; Ren, Qiushi; Tian, Jie; Zhou, Chuanqing

    2016-01-01

    Optimizing contrast enhancement is essential for producing specific signals in biomedical imaging and therapy. The potential of using Aucore-Agshell nanorods (Au@Ag NRs) as a dual-functional theranostic contrast agent is demonstrated for effective cancer imaging and treatments. Due to its strong NIR absorption and high efficiency of photothermal conversion, effects of both photoacoustic tomography (PAT) and photothermal therapy (PTT) are enhanced significantly. The PAT signal grows by 45.3% and 82% in the phantom and in vivo experiments, respectively, when compared to those using Au NRs. In PTT, The maximum increase of tissue temperature treated with Au@Ag NRs is 22.8 °C, twice that with Au NRs. Results of the current study show the feasibility of using Au@Ag NRs for synergetic PAT with PTT. And it will enhance the potential application on real-time PAT guided PTT, which will greatly benefit the customized PTT treatment of cancer. PMID:27231624

  12. Measuring the effects of topically applied skin optical clearing agents and modeling the effects and consequences for laser therapies

    NASA Astrophysics Data System (ADS)

    Verkruysse, Wim; Khan, Misbah; Choi, Bernard; Svaasand, Lars O.; Nelson, J. Stuart

    2005-04-01

    Human skin prepared with an optical clearing agent manifests reduced scattering as a result of de-hydration and refractive index matching. This has potentially large effects for laser therapies of several skin lesions such as port wine stain, hair removal and tattoo removal. With most topically applied clearing agents the clearing effect is limited because they penetrate poorly through the intact superficial skin layer (stratum corneum). Agent application modi other than topical are impractical and have limited the success of optical clearing in laser dermatology. In recent reports, however, a mixture of lipofylic and hydrofylic agents was shown to successfully penetrate through the intact stratum corneum layer which has raised new interest in this field. Immediately after application, the optical clearing effect is superficial and, as the agent diffuses through the skin, reduced scattering is manifested in deeper skin layers. For practical purposes as well as to maximize therapeutic success, it is important to quantify the reduced scattering as well as the trans-cutaneous transport dynamics of the agent. We determined the time and tissue depth resolved effects of optically cleared skin by inserting a microscopic reflector array in the skin. Depth dependent light intensity was measured by quantifying the signal of the reflector array with optical coherence tomography. A 1-dimensional mass diffusion model was used to estimate a trans-cutaneous transport diffusion constant for the clearing agent mixture. The results are used in Monte Carlo modeling to determine the optimal time of laser treatment after topical application of the optical clearing agent.

  13. Nanobodies as novel agents for disease diagnosis and therapy

    PubMed Central

    Siontorou, Christina G

    2013-01-01

    The discovery of naturally occurring, heavy-chain only antibodies in Camelidae, and their further development into small recombinant nanobodies, presents attractive alternatives in drug delivery and imaging. Easily expressed in microorganisms and amenable to engineering, nanobody derivatives are soluble, stable, versatile, and have unique refolding capacities, reduced aggregation tendencies, and high-target binding capabilities. This review outlines the current state of the art in nanobodies, focusing on their structural features and properties, production, technology, and the potential for modulating immune functions and for targeting tumors, toxins, and microbes. PMID:24204148

  14. Occupational exposures to potentially hazardous agents in the petroleum industry

    SciTech Connect

    Runion, H.E.

    1988-07-01

    This chapter has been created to acquaint the reader with occupational exposures that are more common in, and somewhat unique to, the petroleum industry. Both highly toxic materials capable of causing acute illness or even death following short-term exposure, and chemical and physical agents that pose risk of chronic and irreversible damage to health during prolonged exposure are addressed.

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

    PubMed Central

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

    2014-01-01

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

  16. A dual function theranostic agent for near-infrared photoacoustic imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Upputuri, Paul Kumar; Huang, Shuo; Wang, Mingfeng; Pramanik, Manojit

    2016-03-01

    Theranostic, defined as combining diagnostic and therapeutic agents, has attracted more attention in biomedical application. It is essential to monitor diseased tissue before treatment. Photothermal therapy (PTT) is a promising treatment of cancer tissue due to minimal invasion, unharmful to normal tissue and high efficiency. Photoacoustic tomography (PAT) is a hybrid nonionizing biomedical imaging modality that combines rich optical contrast and high ultrasonic resolution in a single imaging modality. The near infra-red (NIR) wavelengths, usually used in PAT, can provide deep penetration at the expense of reduced contrast, as the blood absorption drops in the NIR range. Exogenous contrast agents with strong absorption in the NIR wavelength range can enhance the photoacoustic imaging contrast as well as imaging depth. Most theranostic agents incorporating PAT and PTT are inorganic nanomaterials that suffer from poor biocompatibility and biodegradability. Herein, we present an benzo[1,2-c;4,5-c'] bis[1,2,5] thiadiazole (BBT), based theranostic agent which not only acts as photoacoustic contrast agent but also a photothermal therapy agent. Experiments were performed on animal blood and organic nanoparticles embedded in a chicken breast tissue using PAT imaging system at ~803 nm wavelengths. Almost ten time contrast enhancement was observed from the nanoparticle in suspension. More than 6.5 time PA signal enhancement was observed in tissue at 3 cm depth. HeLa cell lines was used to test photothermal effect showing 90% cells were killed after 10 min laser irradiation. Our results indicate that the BBT - based naoparticles are promising theranostic agents for PAT imaging and cancer treatment by photothermal therapy.

  17. Mass spectral investigations of boron neutron capture therapy (BNCT) agents

    SciTech Connect

    Miller, D.L.; Peterson-Wright, L.J.

    1988-01-01

    We examined the use of mass spectrometry incorporating fast atom bombardment ionization to determine if the potential existed for the development of a HPLC FAB/MS analytical procedure utilizing the new continuous-flow FAB inlet. All experiments were conducted on a KRATOS MS890 equipped with an 8 kV MS50-type FAB source. The MS890 was equipped with an Ion Tech (11NF) saddle field ion gun and xenon was used as the FAB gas. Initial experiments using BSH were conducted in both positive and negative ion modes using a variety of FAB matrices. Positive ion experiments were discontinued when no peaks indicative of the compound of interest were observed. The positive ion spectra were dominated by peaks arising from sodium reacting with the various matrices used. Experiments conducted in the negative ion mode proved to be much more productive. A variety of matrices were tested with BSH. These matrices included glycerol, thioglycerol, 3-nitrobenzyl alcohol, triethanolamine, and PEG-600. No peaks indicative of the BSH compound were observed when glycerol was used as the matrix, even though the BSH was readily soluble. For the remainder of the matrices tested, good solubility of the BSH was also observed, as well as peaks using BSH containing the natural isotopic abundance of boron (approximately 20% /sup 10/B and 80% /sup 11/B). When examined using thioglycerol as the matrix, a cluster of peaks indicative of boron was observed with the most intense peak occurring at M/Z 197.

  18. 6-Thioguanine: A Drug With Unrealized Potential for Cancer Therapy

    PubMed Central

    Munshi, Pashna N.; Lubin, Martin

    2014-01-01

    Sixty years ago, 6-thioguanine (6-TG) was introduced into the clinic. We suggest its full potential in therapy may not have been reached. In this paper, we contrast 6-TG and the more widely used 6-mercaptopurine; discuss 6-TG metabolism, pharmacokinetics, dosage and schedule; and summarize many of the early studies that have shown infrequent but nevertheless positive results with 6-TG treatment of cancers. We also consider studies that suggest that combinations of 6-TG with other agents may enhance antitumor effects. Although not yet tested in man, 6-TG has recently been proposed to treat a wide variety of cancers with a high frequency of homozygous deletion of the gene for methylthioadenosine phosphorylase (MTAP), often codeleted with the adjacent tumor suppressor CDKN2A (p16). Among the cancers with a high frequency of MTAP deficiency are leukemias, lymphomas, mesothelioma, melanoma, biliary tract cancer, glioblastoma, osteosarcoma, soft tissue sarcoma, neuroendocrine tumors, and lung, pancreatic, and squamous cell carcinomas. The method involves pretreatment with the naturally occurring nucleoside methylthioadenosine (MTA), the substrate for the enzyme MTAP. MTA pretreatment protects normal host tissues, but not MTAP-deficient cancers, from 6-TG toxicity and permits administration of doses of 6-TG that are much higher than can now be safely administered. The combination of MTA/6-TG has produced substantial shrinkage or slowing of growth in two different xenograft human tumor models: lymphoblastic leukemia and metastatic prostate carcinoma with neuroendocrine features. Further development and a clinical trial of the proposed MTA/6-TG treatment of MTAP-deficient cancers seem warranted. PMID:24928612

  19. Potential Benefits of Non-Pharmacological Therapies in Fibromyalgia

    PubMed Central

    Sueiro Blanco, F.; Estévez Schwarz, I.; Ayán, C.; Cancela, JM.; Martín, V.

    2008-01-01

    Fibromyalgia (FM) is an incurable common syndrome of non-articular origin, and with no effective treatment by now. A great deal of research has sought to assess the efficacy of different therapies, especially non-pharmacological and low-cost ones, in the reduction of the intensity of symptoms. Despite the availability of a wide range of alternative therapies nowadays, there is little scientific evidence of the potential benefits of most of them, with results being contradictories. The purpose of this paper is to review some of the less well known alternative therapies in FM treatment, to describe the more relevant clinical studies published in this matter, and to analyze the potential effects of the main alternative therapies, in order to verify their efficacy. PMID:19088863

  20. Theranostic Au Cubic Nano-aggregates as Potential Photoacoustic Contrast and Photothermal Therapeutic Agents

    PubMed Central

    Hu, Juan; Zhu, Xianglong; Li, Hui; Zhao, Zhenghuan; Chi, Xiaoqin; Huang, Guoming; Huang, Dengtong; Liu, Gang; Wang, Xiaomin; Gao, Jinhao

    2014-01-01

    Multifunctional nanostructures combining diagnosis and therapy modalities into one entity have drawn much attention in the biomedical applications. Herein, we report a simple and cost-effective method to synthesize a novel cubic Au nano-aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong near-infrared (NIR) absorption, excellent water-solubility, good photothermal stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min, the temperature of the solution containing Au-80 CNAs (100 μg/mL) increased by ~38 °C. The in vitro and in vivo studies demonstrated that Au-80 CNAs could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs shows great potentials for theranostic applications. Moreover, this facile and cost-effective synthetic method provides a new strategy to prepare stable Au nanomaterials with excellent optical properties for biomedical applications. PMID:24672584

  1. Potential Molecular Targets for Narrow-Spectrum Agents to Combat Mycoplasma pneumoniae Infection and Disease.

    PubMed

    Balish, Mitchell F; Distelhorst, Steven L

    2016-01-01

    As Mycoplasma pneumoniae macrolide resistance grows and spreads worldwide, it is becoming more important to develop new drugs to prevent infection or limit disease. Because other mycoplasma species have acquired resistance to other classes of antibiotics, it is reasonable to presume that M. pneumoniae can do the same, so switching to commonly used antibiotics like fluoroquinolones will not result in forms of therapy with long-term utility. Moreover, broad-spectrum antibiotics can have serious consequences for the patient, as these drugs may have severe impacts on the natural microbiota of the individual, compromising the health of the patient either short-term or long-term. Therefore, developing narrow-spectrum antibiotics that effectively target only M. pneumoniae and no more than a small portion of the microbiota is likely to yield impactful, positive results that can be used perhaps indefinitely to combat M. pneumoniae. Development of these agents requires a deep understanding of the basic biology of M. pneumoniae, in many areas deeper than what is currently known. In this review, we discuss potential targets for new, narrow-spectrum agents and both the positive and negative aspects of selecting these targets, which include toxic molecules, metabolic pathways, and attachment and motility. By gathering this information together, we anticipate that it will be easier for researchers to evaluate topics of priority for study of M. pneumoniae. PMID:26941728

  2. Potential Molecular Targets for Narrow-Spectrum Agents to Combat Mycoplasma pneumoniae Infection and Disease

    PubMed Central

    Balish, Mitchell F.; Distelhorst, Steven L.

    2016-01-01

    As Mycoplasma pneumoniae macrolide resistance grows and spreads worldwide, it is becoming more important to develop new drugs to prevent infection or limit disease. Because other mycoplasma species have acquired resistance to other classes of antibiotics, it is reasonable to presume that M. pneumoniae can do the same, so switching to commonly used antibiotics like fluoroquinolones will not result in forms of therapy with long-term utility. Moreover, broad-spectrum antibiotics can have serious consequences for the patient, as these drugs may have severe impacts on the natural microbiota of the individual, compromising the health of the patient either short-term or long-term. Therefore, developing narrow-spectrum antibiotics that effectively target only M. pneumoniae and no more than a small portion of the microbiota is likely to yield impactful, positive results that can be used perhaps indefinitely to combat M. pneumoniae. Development of these agents requires a deep understanding of the basic biology of M. pneumoniae, in many areas deeper than what is currently known. In this review, we discuss potential targets for new, narrow-spectrum agents and both the positive and negative aspects of selecting these targets, which include toxic molecules, metabolic pathways, and attachment and motility. By gathering this information together, we anticipate that it will be easier for researchers to evaluate topics of priority for study of M. pneumoniae. PMID:26941728

  3. Antioxidants: potential antiviral agents for Japanese encephalitis virus infection.

    PubMed

    Zhang, Yu; Wang, Zehua; Chen, Huan; Chen, Zongtao; Tian, Yanping

    2014-07-01

    Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE. PMID:24780919

  4. Plasmon-resonant nanorods as multimodal agents for two-photon luminescent imaging and photothermal therapy

    NASA Astrophysics Data System (ADS)

    Huff, Terry B.; Hansen, Matthew N.; Tong, Ling; Zhao, Yan; Wang, Haifeng; Zweifel, Daniel A.; Cheng, Ji-Xin; Wei, Alexander

    2007-02-01

    Plasmon-resonant gold nanorods have outstanding potential as multifunctional agents for image-guided therapies. Nanorods have large absorption cross sections at near-infrared (NIR) frequencies, and produce two-photon luminescence (TPL) when excited by fs-pulsed laser irradiation. The TPL signals can be detected with single-particle sensitivity, enabling nanorods to be imaged in vivo while passing through blood vessels at subpicomolar concentrations. Furthermore, cells labeled with nanorods become highly susceptible to photothermal damage when irradiated at plasmon resonance, often resulting in a dramatic blebbing of the cell membrane. However, the straightforward application of gold nanorods for cell-specific labeling is obstructed by the presence of CTAB, a cationic surfactant carried over from nanorod synthesis which also promotes their nonspecific uptake into cells. Careful exchange and replacement of CTAB can be achieved by introducing oligoethyleneglycol (OEG) units capable of chemisorption onto nanorod surfaces by in situ dithiocarbamate formation, a novel method of surface functionalization. Nanorods with a dense coating of methyl-terminated OEG chains are shielded from nonspecific cell uptake, whereas nanorods functionalized with folate-terminated OEG chains accumulate on the surface of tumor cells overexpressing their cognate receptor, with subsequent delivery of photoinduced cell damage at low laser fluence.

  5. Self-assembled polymeric chelate nanoparticles as potential theranostic agents.

    PubMed

    Škodová, M; Černoch, P; Štěpánek, P; Chánová, E; Kučka, J; Kálalová, Z; Kaňková, D; Hrubý, M

    2012-12-21

    Improvements in cancer diagnostics and therapy have recently attracted the interest of many different branches of science. This study presents one of the new possible approaches in the diagnostics and therapy of cancer by using polymeric chelates as carriers. Graft copolymers with a backbone containing 8-hydroxyquinoline-5-sulfonic acid chelating groups and poly(ethylene oxide) hydrophilic grafts are synthesized and characterized. The polymers assemble and form particles after the addition of a biometal cation, such as iron or copper. The obtained nanoparticles exhibit a hydrodynamic diameter of around 25 nm and a stability of at least several hours, which are counted as essential parameters for biomedical purposes. To prove their biodegradability, a model degradation with deferoxamine is performed and, together with high radiolabeling efficiency with copper-64, their possible use for nuclear medicine purposes is demonstrated.

  6. Systemic therapy with immunosuppressive agents and retinoids in hidradenitis suppurativa: a systematic review.

    PubMed

    Blok, J L; van Hattem, S; Jonkman, M F; Horváth, B

    2013-02-01

    Hidradenitis suppurativa (HS) is a difficult disease to treat. Although the pathogenesis of this inflammatory skin disease is largely unknown, the important role of the immune system has been demonstrated in both experimental and clinical studies. Clinicians are therefore increasingly prescribing systemic treatments with immunosuppressive agents, but the more traditionally used systemic retinoids, especially isotretinoin, also remain relatively common therapies. In order to provide an overview of all currently available systemic immunosuppressive agents and retinoids for the treatment of HS, a systematic search was performed using the Medline and Embase databases. All published papers concerning systemic retinoids or immunosuppressive treatments for HS in adults were included. The primary endpoints were the percentages of significant responders, moderate responders and nonresponders. Other endpoints were the relapse rate and adverse events. In total 87 papers were included, comprising 518 patients with HS who were treated with systemic retinoids, biological agents or another immunosuppressive agents, including colchicine, ciclosporin, dapsone or methotrexate. The highest response rates were observed with infliximab, adalimumab and acitretin. Overall, the quality of evidence was low and differed between the agents, making direct comparisons difficult. However, based on the amount of evidence, infliximab and adalimumab were the most effective agents. Acitretin was also effective in HS, although the quality of the evidence was low. The therapeutic effect of isotretinoin is questionable. Randomized controlled trials are needed to confirm the effectiveness of acitretin, and to identify the most effective immunosuppressive agents in HS.

  7. Current antiplatelet agents: place in therapy and role of genetic testing.

    PubMed

    Yang, Eugene

    2015-04-01

    Antiplatelet therapies play a central role in reducing the risk of cardiovascular events such as myocardial infarction and stroke. While aspirin, a cyclo-oxygenase-1 inhibitor has been the cornerstone of antithrombotic treatment for several decades, P2Y12 receptor inhibitors cangrelor, clopidogrel, prasugrel, and ticagrelor and protease-activated receptor-1 antagonist vorapaxar, have emerged as additional therapies to reduce the risk of recurrent cardiovascular events in high-risk patients. Recent clinical trials evaluating the role of these agents and major society guideline updates for use of antiplatelet therapies for secondary prevention of cardiovascular events will be examined. The latest studies regarding the appropriate duration of dual antiplatelet therapy after percutaneous coronary intervention will be presented. The current state of genetic and platelet function testing will be reviewed.

  8. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    SciTech Connect

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  9. Microtubule-Stabilizing Agents as Potential Therapeutics for Neurodegenerative Disease

    PubMed Central

    Brunden, Kurt R.; Trojanowski, John Q.; Smith, Amos B.; Lee, Virginia M.-Y.; Ballatore, Carlo

    2014-01-01

    Microtubules (MTs)1, cytoskeletal elements found in all mammalian cells, play a significant role in cell structure and in cell division. They are especially critical in the proper functioning of post-mitotic central nervous system neurons, where MTs serve as the structures on which key cellular constituents are trafficked in axonal projections. MTs are stabilized in axons by the MT-associated protein tau, and in several neurodegenerative diseases, including Alzheimer’s disease, frontotemporal lobar degeneration, and Parkinson’s disease, tau function appears to be compromised due to the protein dissociating from MTs and depositing into insoluble inclusions referred to as neurofibrillary tangles. This loss of tau function is believed to result in alterations of MT structure and function, resulting in aberrant axonal transport that likely contributes to the neurodegenerative process. There is also evidence of axonal transport deficiencies in other neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington’s disease, which may result, at least in part, from MT alterations. Accordingly, a possible therapeutic strategy for such neurodegenerative conditions is to treat with MT-stabilizing agents, such as those that have been used in the treatment of cancer. Here, we review evidence of axonal transport and MT deficiencies in a number of neurodegenerative diseases, and summarize the various classes of known MT-stabilizing agents. Finally, we highlight the growing evidence that small molecule MT-stabilizing agents provide benefit in animal models of neurodegenerative disease and discuss the desired features of such molecules for the treatment of these central nervous system disorders. PMID:24433963

  10. Investigation of Vietnamese plants for potential anticancer agents

    PubMed Central

    Pérez, Lynette Bueno; Still, Patrick C.; Naman, C. Benjamin; Ren, Yulin; Pan, Li; Chai, Hee-Byung; Carcache de Blanco, Esperanza J.; Ninh, Tran Ngoc; Van Thanh, Bui; Swanson, Steven M.; Soejarto, Djaja D.

    2014-01-01

    Higher plants continue to afford humankind with many new drugs, for a variety of disease types. In this review, recent phytochemical and biological progress is presented for part of a collaborative multi-institutional project directed towards the discovery of new antitumor agents. The specific focus is on bioactive natural products isolated and characterized structurally from tropical plants collected in Vietnam. The plant collection, identification, and processing steps are described, and the natural products isolated from these species are summarized with their biological activities. PMID:25395897

  11. Potential for laboratory exposures to biohazardous agents found in blood.

    PubMed Central

    Evans, M R; Henderson, D K; Bennett, J E

    1990-01-01

    The magnitude of risk for occupational exposures to biohazardous agents found in blood was assessed by 800 environmental samples taken from a total of 10 clinical and research laboratories at the National Institutes of Health (NIH). Thirty-one samples from 11 work stations in three laboratories contained hepatitis B virus surface antigen (HBsAg). Observations of workers indicated that environmental contamination arose from several sources. Among the 11 work stations with HBsAg environmental samples, eight had high work loads, seven had inappropriate behaviors, and nine had flawed laboratory techniques. This information suggests that a multifactorial approach is needed to minimize the risk of laboratory-associated infections. PMID:2316762

  12. Monocarboxylate Transporter 1 Inhibitors as Potential Anticancer Agents

    PubMed Central

    2015-01-01

    Potent monocarboxylate transporter 1 inhibitors (MCT1) have been developed based on α-cyano-4-hydroxycinnamic acid template. Structure–activity relationship studies demonstrate that the introduction of p-N, N-dialkyl/diaryl, and o-methoxy groups into cyanocinnamic acid has maximal MCT1 inhibitory activity. Systemic toxicity studies in healthy ICR mice with few potent MCT1 inhibitors indicate normal body weight gains in treated animals. In vivo tumor growth inhibition studies in colorectal adenocarcinoma (WiDr cell line) in nude mice xenograft models establish that compound 27 exhibits single agent activity in inhibiting the tumor growth. PMID:26005533

  13. Endocrine therapy as adjuvant or neoadjuvant therapy for breast cancer: selecting the best agents, the timing and duration of treatment.

    PubMed

    Li, Jun-Jie; Shao, Zhi-Min

    2016-06-01

    Hormone receptor (HR) positive breast cancers represent the vast majority of breast cancers. Adjuvant and/or neoadjuvant endocrine therapy is highly effective and appropriate for nearly all women with HR positive tumors. Adjuvant tamoxifen (TAM) is a major endocrine treatment option, which has been found to be effective in both premenopausal and postmenopausal patients. Considerable evidence has been accrued of a benefit for ovarian ablation or suppression (OA/S) in premenopausal patients, for aromatase inhibitors (AIS) in postmenopausal patients, for the longer duration of adjuvant endocrine therapy and for the clinical utility of neoadjuvant endocrine therapy. Clinical practice guidelines should keep changing with developing evidence-based practice guidelines pertaining to breast cancer care. The present publication conducted a comprehensive systematic review of the literature addressing the use of endocrine therapy as adjuvant or neoadjuvant therapy for HR positive breast cancer, focusing on selecting the best agents for both premenopausal and postmenopausal patients, as well as the optimal duration of such treatment.

  14. Recent advances in inhibitors of bacterial fatty acid synthesis type II (FASII) system enzymes as potential antibacterial agents.

    PubMed

    Wang, Yi; Ma, Shutao

    2013-10-01

    Bacterial infections are a constant and serious threat to human health. With the increase of multidrug resistance of clinically pathogenic bacteria, common antibiotic therapies have been less effective. Fatty acid synthesis type II (FASII) system enzymes are essential for bacterial membrane lipid biosynthesis and represent increasingly promising targets for the discovery of antibacterial agents with new mechanisms of action. This review highlights recent advances in inhibitors of bacterial FASII as potential antibacterial agents, paying special attention to the activities, mechanisms, and structure-activity relationships of those inhibitors that mainly target β-ketoacyl-ACP synthase, β-ketoacyl-ACP reductase, β-hydroxyacyl-ACP dehydratase, and enoyl-ACP reductase. Although inhibitors with low nanomolar and selective activity against various bacterial FASII have entered clinical trials, further research is needed to expand upon both available and yet unknown scaffolds to identify new FASII inhibitors that may have antibacterial potential, particularly against resistant bacterial strains.

  15. Quinine conjugates and quinine analogues as potential antimalarial agents.

    PubMed

    Jones, Rachel A; Panda, Siva S; Hall, C Dennis

    2015-06-01

    Malaria is a tropical disease, prevalent in Southeast Asia and Africa, resulting in over half a million deaths annually; efforts to develop new antimalarial agents are therefore particularly important. Quinine continues to play a role in the fight against malaria, but quinoline derivatives are more widely used. Drugs based on the quinoline scaffold include chloroquine and primaquine, which are able to act against the blood and liver stages of the parasite's life cycle. The purpose of this review is to discuss reported biologically active compounds based on either the quinine or quinoline scaffold that may have enhanced antimalarial activity. The review emphasises hybrid molecules, and covers advances made in the last five years. The review is divided into three sections: modifications to the quinine scaffold, modifications to aminoquinolines and finally metal-containing antimalarial compounds.

  16. Therapeutic Potential of Hydrazones as Anti-Inflammatory Agents

    PubMed Central

    Bala, Suman; Sharma, Neha; Saini, Vipin

    2014-01-01

    Hydrazones are a special class of organic compounds in the Schiff base family. Hydrazones constitute a versatile compound of organic class having basic structure (R1R2C=NNR3R4). The active centers of hydrazone, that is, carbon and nitrogen, are mainly responsible for the physical and chemical properties of the hydrazones and, due to the reactivity toward electrophiles and nucleophiles, hydrazones are used for the synthesis of organic compound such as heterocyclic compounds with a variety of biological activities. Hydrazones and their derivatives are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal, anti-HIV, and so forth. The present review summarizes the efficiency of hydrazones as potent anti-inflammatory agents. PMID:25383223

  17. Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.

    PubMed

    Zhou, Yinjian; Zhang, Chunling; Liang, Wei

    2014-11-10

    RNA interference (RNAi) was intensively studied in the past decades due to its potential in therapy of diseases. The target specificity and universal treatment spectrum endowed siRNA advantages over traditional small molecules and protein drugs. However, barriers exist in the blood circulation system and the diseased tissues blocked the actualization of RNAi effect, which raised function versatility requirements to siRNA therapeutic agents. Appropriate functionalization of siRNAs is necessary to break through these barriers and target diseased tissues in local or systemic targeted application. In this review, we summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation. Preclinical targeted siRNA delivery and the current status of siRNA based RNAi therapeutic agents in clinical trial were reviewed and finally the future of siRNA delivery was proposed. The valuable experience from the siRNA agent delivery study and the RNAi therapeutic agents in clinical trial paved ways for practical RNAi therapeutics to emerge early.

  18. Anti-inflammatory agents from plants: progress and potential.

    PubMed

    Recio, M C; Andujar, I; Rios, J L

    2012-01-01

    The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases.

  19. Anti-inflammatory agents from plants: progress and potential.

    PubMed

    Recio, M C; Andujar, I; Rios, J L

    2012-01-01

    The identification of substances that can promote the resolution of inflammation in a way that is homeostatic, modulatory, efficient, and well-tolerated by the body is of fundamental importance. Traditional medicines have long provided front-line pharmacotherapy for many millions of people worldwide. Medicinal extracts are a rich source of therapeutic leads for the pharmaceutical industry. The use of medicinal plant therapies to treat chronic illness, including rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), is thus widespread and on the rise.The aim of this review is to present recent progress in clinical anti-inflammatory studies of plant extracts and compound leads such as green tea polyphenols, curcumin, resveratrol, boswellic acid, and cucurbitacins, among others, against chronic inflammatory diseases, mainly RA and IBD. In this context, the present paper also highlights the most promising experimental data on those plant extracts and pure compounds active in animal models of the aforementioned diseases. PMID:22414101

  20. Epidermal growth factor (EGF) as a potential targeting agent for delivery of boron to malignant gliomas

    SciTech Connect

    Capala, J.; Barth, R.F.; Adams, D.M.; Bailey, M.Q.; Soloway, A.H.; Carlsson, J.

    1994-12-31

    The majority of high grade gliomas express an amplified epidermal growth factor receptor (EGFR) gene, and this often is associated with an increase in cell surface receptor expression. The rapid internalization and degradation of EGF-EGFR complexes, as well as their high affinity make EGF a potential targeting agent for delivery of {sup 10}B to tumor cells with an amplified number of EGFR. Human glioma cells can expresses as many as 10{sup 5} {minus}10{sup 6} EGF receptors per cell, and if these could be saturated with boronated EGF, then > 10{sup 8} boron atoms would be delivered per cell. Since EGF has a comparatively low molecular weight ({approximately} 6 kD), this has allowed us to construct relatively small bioconjugates containing {approximately} 900 boron atoms per EGF molecule{sup 3}, which also had high affinity for EGFR on tumor cells. In the present study, the feasibility of using EGF receptors as a potential target for therapy of gliomas was investigated by in vivo scintigraphic studies using {sup 131}I{minus} or {sup 99m}{Tc}-labeled EGF in a rat brain tumor model. Our results indicate that intratumorally delivered boron- EGF conjugates might be useful for targeting EGFR on glioma cells if the boron containing moiety of the conjugates persisted intracellularly. Further studies are required, however, to determine if this approach can be used for BNCT of the rat glioma.

  1. STATINS MORE THAN CHOLESTEROL LOWERING AGENTS IN ALZHEIMER DISEASE: THEIR PLEIOTROPIC FUNCTIONS AS POTENTIAL THERAPEUTIC TARGETS

    PubMed Central

    Barone, Eugenio; Domenico, Fabio Di; Butterfield, D. Allan

    2013-01-01

    Alzheimer disease (AD) is a progressive neurodegenerative disorder characterized by severe cognitive impairment, inability to perform activities of daily living and mood changes. Statins, long known to be beneficial in conditions where dyslipidemia occurs by lowering serum cholesterol levels, also have been proposed for use in neurodegenerative conditions, including AD. However, it is not clear that the purported effectiveness of statins in neurodegenerative disorders is directly related to cholesterol-lowering effects of these agents; rather, the pleiotropic functions of statins likely play critical roles. The aim of this review is to provide an overview on the new discoveries about the effects of statin therapy on the oxidative ad nitrosative stress levels as well as on the modulation of the heme oxygenase/biliverdin reductase (HO/BVR) system in the brain. We propose a novel mechanism of action for atorvastatin which, through the activation of HO/BVR-A system, may contribute to the neuroprotective effects thus suggesting a potential therapeutic role in AD and potentially accounting for the observation of decreased AD incidence with persons on statin. PMID:24231510

  2. Screening for potential anti-infective agents towards Burkholderia pseudomallei infection

    NASA Astrophysics Data System (ADS)

    Eng, Su Anne; Nathan, Sheila

    2014-09-01

    The established treatment for melioidosis is antibiotic therapy. However, a constant threat to this form of treatment is resistance development of the causative agent, Burkholderia pseudomallei, towards antibiotics. One option to circumvent this threat of antibiotic resistance is to search for new alternative anti-infectives which target the host innate immune system and/or bacterial virulence. In this study, 29 synthetic compounds were evaluated for their potential to increase the lifespan of an infected host. The nematode Caenorhabditis elegans was adopted as the infection model as its innate immune pathways are homologous to humans. Screens were performed in a liquid-based survival assay containing infected worms exposed to individual compounds and survival of untreated and compound-treated worms were compared. A primary screen identified nine synthetic compounds that extended the lifespan of B. pseudomallei-infected worms. Subsequently, a disc diffusion test was performed on these selected compounds to delineate compounds into those that enhanced the survival of worms via antimicrobial activity i.e. reducing the number of infecting bacteria, or into those that did not target pathogen viability. Out of the nine hits selected, two demonstrated antimicrobial effects on B. pseudomallei. Therefore, the findings from this study suggest that the other seven identified compounds are potential anti-infectives which could protect a host against B. pseudomallei infection without developing the risk of drug resistance.

  3. PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy.

    PubMed

    Cheng, Liang; Gong, Hua; Zhu, Wenwen; Liu, Jingjing; Wang, Xiaoyong; Liu, Gang; Liu, Zhuang

    2014-12-01

    Theranostic agents with both imaging and therapeutic functions have attracted enormous interests in cancer diagnosis and treatment in recent years. In this work, we develop a novel theranostic agent based on Prussian blue nanocubes (PB NCs), a clinically approved agent with strong near-infrared (NIR) absorbance and intrinsic paramagnetic property, for in vivo bimodal imaging-guided photothermal therapy. After being coated with polyethylene glycol (PEG), the obtained PB-PEG NCs are highly stable in various physiological solutions. In vivo T1-weighted magnetic resonance (MR) and photoacoustic tomography (PAT) bimodal imaging uncover that PB-PEG NCs after intravenous (i.v.) injection show high uptake in the tumor. Utilizing the strong and super stable NIR absorbance of PB, in vivo cancer treatment is then conducted upon i.v. injection of PB-PEG NCs followed by NIR laser irradiation of the tumors, achieving excellent therapeutic efficacy in a mouse tumor model. Comprehensive blood tests and careful histological examinations reveal no apparent toxicity of PB-PEG NCs to mice at our tested dose, which is two-fold of the imaging/therapy dose, within two months. Our work highlights the great promise of Prussian blue with well engineered surface coating as a multifunctional nanoprobe for imaging-guided cancer therapy. PMID:25239041

  4. Novel Targeted Agents in Hodgkin and Non-Hodgkin Lymphoma Therapy

    PubMed Central

    Grover, Natalie S.; Park, Steven I.

    2015-01-01

    There has been a recent emergence of novel targeted agents for treatment of Hodgkin and non-Hodgkin lymphoma. In particular, antibodies and antibody-drug conjugates directed against surface antigens, agents that block immune checkpoint pathways, and small molecule inhibitors directed against cell signaling pathways have shown significant promise in patients with relapsed and refractory disease and in the frontline setting. With the development of these new therapies, cytotoxic chemotherapy may be avoided entirely in some clinical settings. This review will present the latest information on these novel treatments in Hodgkin and non-Hodgkin lymphoma and will discuss both recently approved agents as well as drugs currently being studied in clinical trials. PMID:26393619

  5. Biological agents with potential for misuse: a historical perspective and defensive measures.

    PubMed

    Bhalla, Deepak K; Warheit, David B

    2004-08-15

    Biological and chemical agents capable of producing serious illness or mortality have been used in biowarfare from ancient times. Use of these agents has progressed from crude forms in early and middle ages, when snakes and infected cadavers were used as weapons in battles, to sophisticated preparations for use during and after the second World War. Cults and terrorist organizations have attempted the use of biological agents with an aim to immobilize populations or cause serious harm. The reasons for interest in these agents by individuals and organizations include relative ease of acquisition, potential for causing mass casualty or panic, modest financing requirement, availability of technology, and relative ease of delivery. The Centers for Disease Control and Prevention has classified Critical Biological Agents into three major categories. This classification was based on several criteria, which include severity of impact on human health, potential for delivery in a weapon, capacity to cause panic and special needs for development, and stockpiling of medication. Agents that could cause the greatest harm following deliberate use were placed in category A. Category B included agents capable of producing serious harm and significant mortality but of lower magnitude than category A agents. Category C included emerging pathogens that could be developed for mass dispersion in future and their potential as a major health threat. A brief description of the category A bioagents is included and the pathophysiology of two particularly prominent agents, namely anthrax and smallpox, is discussed in detail. The potential danger from biological agents and their ever increasing threat to human populations have created a need for developing technologies for their early detection, for developing treatment strategies, and for refinement of procedures to ensure survival of affected individuals so as to attain the ultimate goal of eliminating the threat from intentional use of

  6. Potential Role of Garcinol as an Anticancer Agent

    PubMed Central

    Saadat, Nadia; Gupta, Smiti V.

    2012-01-01

    Garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Although the fruit has been consumed traditionally over centuries, its biological activities, specifically its anticancer potential is a result of recent scientific investigations. The anticarcinogenic properties of garcinol appear to be moderated via its antioxidative, anti-inflammatory, antiangiogenic, and proapoptotic activities. In addition, garcinol displays effective epigenetic influence by inhibiting histone acetyltransferases (HAT 300) and by possible posttranscriptional modulation by mi RNA profiles involved in carcinogenesis. In vitro as well as some in vivo studies have shown the potential of this compound against several cancers types including breast, colon, pancreatic, and leukemia. Although this is a promising molecule in terms of its anticancer properties, investigations in relevant animal models, and subsequent human trials are warranted in order to fully appreciate and confirm its chemopreventative and/or therapeutic potential. PMID:22745638

  7. Neem components as potential agents for cancer prevention and treatment.

    PubMed

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  8. Neem components as potential agents for cancer prevention and treatment.

    PubMed

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2014-08-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment.

  9. Thymol and eugenol derivatives as potential antileishmanial agents.

    PubMed

    de Morais, Selene Maia; Vila-Nova, Nadja Soares; Bevilaqua, Claudia Maria Leal; Rondon, Fernanda Cristina; Lobo, Carlos Henrique; de Alencar Araripe Noronha Moura, Arlindo; Sales, Antônia Débora; Rodrigues, Ana Paula Ribeiro; de Figuereido, José Ricardo; Campello, Claudio Cabral; Wilson, Mary E; de Andrade, Heitor Franco

    2014-11-01

    In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5-10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis.

  10. Thymol and eugenol derivatives as potential antileishmanial agents.

    PubMed

    de Morais, Selene Maia; Vila-Nova, Nadja Soares; Bevilaqua, Claudia Maria Leal; Rondon, Fernanda Cristina; Lobo, Carlos Henrique; de Alencar Araripe Noronha Moura, Arlindo; Sales, Antônia Débora; Rodrigues, Ana Paula Ribeiro; de Figuereido, José Ricardo; Campello, Claudio Cabral; Wilson, Mary E; de Andrade, Heitor Franco

    2014-11-01

    In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5-10% of humans die despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100mg/kg/day for 30 days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67 ± 0.28 μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis. PMID:25281268

  11. Neem components as potential agents for cancer prevention and treatment

    PubMed Central

    Hao, Fang; Kumar, Sandeep; Yadav, Neelu; Chandra, Dhyan

    2016-01-01

    Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted. The key anticancer effects of neem components on malignant cells include inhibition of cell proliferation, induction of cell death, suppression of cancer angiogenesis, restoration of cellular reduction/oxidation (redox) balance, and enhancement of the host immune responses against tumor cells. While the underlying mechanisms of these effects are mostly unclear, the suppression of NF-κB signaling pathway is, at least partially, involved in the anticancer functions of neem components. Importantly, the anti-proliferative and apoptosis-inducing effects of neem components are tumor selective as the effects on normal cells are significantly weaker. In addition, neem extracts sensitize cancer cells to immunotherapy and radiotherapy, and enhance the efficacy of certain cancer chemotherapeutic agents. This review summarizes the current updates on the anticancer effects of neem components and their possible impact on managing cancer incidence and treatment. PMID:25016141

  12. Viruses as potential pathogenic agents in systemic lupus erythematosus.

    PubMed

    Nelson, P; Rylance, P; Roden, D; Trela, M; Tugnet, N

    2014-05-01

    Genetic and environmental factors appear to contribute to the pathogenesis of systemic lupus erythematosus (SLE). Viral infections have been reported to be associated with the disease. A number of exogenous viruses have been linked to the pathogenesis of SLE, of which Epstein-Barr virus (EBV) has the most evidence of an aetiological candidate. In addition, human endogenous retroviruses (HERV), HRES-1, ERV-3, HERV-E 4-1, HERV-K10 and HERV-K18 have also been implicated in SLE. HERVs are incorporated into human DNA, and thus can be inherited. HERVs may trigger an autoimmune reaction through molecular mimicry, since homology of amino acid sequences between HERV proteins and SLE autoantigens has been demonstrated. These viruses can also be influenced by oestrogen, DNA hypomethylation, and ultraviolet light (UVB) exposure which have been shown to enhance HERV activation or expression. Viral infection, or other environmental factors, could induce defective apoptosis, resulting in loss of immune tolerance. Further studies in SLE and other autoimmune diseases are needed to elucidate the contribution of both exogenous and endogenous viruses in the development of autoimmunity. If key peptide sequences could be identified as molecular mimics between viruses and autoantigens, then this might offer the possibility of the development of blocking peptides or antibodies as therapeutic agents in SLE and other autoimmune conditions.

  13. Potential benefits of cell therapy in coronary heart disease.

    PubMed

    Grimaldi, Vincenzo; Mancini, Francesco Paolo; Casamassimi, Amelia; Al-Omran, Mohammed; Zullo, Alberto; Infante, Teresa; Napoli, Claudio

    2013-11-01

    Cardiovascular disease is the leading cause of morbidity and mortality in the world. In recent years, there has been an increasing interest both in basic and clinical research regarding the field of cell therapy for coronary heart disease (CHD). Several preclinical models of CHD have suggested that regenerative properties of stem and progenitor cells might help restoring myocardial functions in the event of cardiac diseases. Here, we summarize different types of stem/progenitor cells that have been tested in experimental and clinical settings of cardiac regeneration, from embryonic stem cells to induced pluripotent stem cells. Then, we provide a comprehensive description of the most common cell delivery strategies with their major pros and cons and underline the potential of tissue engineering and injectable matrices to address the crucial issue of restoring the three-dimensional structure of the injured myocardial region. Due to the encouraging results from preclinical models, the number of clinical trials with cell therapy is continuously increasing and includes patients with CHD and congestive heart failure. Most of the already published trials have demonstrated safety and feasibility of cell therapies in these clinical conditions. Several studies have also suggested that cell therapy results in improved clinical outcomes. Numerous ongoing clinical trials utilizing this therapy for CHD will address fundamental issues concerning cell source and population utilized, as well as the use of imaging techniques to assess cell homing and survival, all factors that affect the efficacy of different cell therapy strategies.

  14. Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy.

    PubMed

    Zhou, Jiehua; Rossi, John J

    2014-06-17

    One hundred years ago, Dr. Paul Ehrlich popularized the "magic bullet" concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, "targeted therapy" that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.

  15. Chlorotoxin: Structure, activity, and potential uses in cancer therapy.

    PubMed

    Ojeda, Paola G; Wang, Conan K; Craik, David J

    2016-01-01

    Chlorotoxin is a disulfide-rich stable peptide from the venom of the Israeli scorpion Leiurus quinquestriatus, which has potential therapeutic applications in the treatment of cancer. Its ability to preferentially bind to tumor cells has been harnessed to develop an imaging agent to help visualize tumors during surgical resection. In addition, chlorotoxin has attracted interest as a vehicle to deliver anti-cancer drugs specifically to cancer cells. Given its interesting structural and biological properties, chlorotoxin also has the potential to be used in a variety of other biotechnology and biomedical applications. Here, we review the structure, activity and potential applications of chlorotoxin as a drug design scaffold.

  16. TLR Agonists as Modulators of the Innate Immune Response and Their Potential as Agents Against Infectious Disease

    PubMed Central

    Mifsud, Edin J.; Tan, Amabel C. L.; Jackson, David C.

    2014-01-01

    Immunotherapies that can either activate or suppress innate immune responses are being investigated as treatments against infectious diseases and the pathology they can cause. The objective of these therapies is to elicit protective immune responses thereby limiting the harm inflicted by the pathogen. The Toll-like receptor (TLR) signaling pathway plays critical roles in numerous host immune defenses and has been identified as an immunotherapeutic target against the consequences of infectious challenge. This review focuses on some of the recent advances being made in the development of TLR-ligands as potential prophylactic and/or therapeutic agents. PMID:24624130

  17. An in situ forming biodegradable hydrogel-based embolic agent for interventional therapies.

    PubMed

    Weng, Lihui; Rostambeigi, Nassir; Zantek, Nicole D; Rostamzadeh, Parinaz; Bravo, Mike; Carey, John; Golzarian, Jafar

    2013-09-01

    We present here the characteristics of an in situ forming hydrogel prepared from carboxymethyl chitosan and oxidized carboxymethyl cellulose for interventional therapies. Gelation, owing to the formation of Schiff bases, occurred both with and without the presence of a radiographic contrast agent. The hydrogel exhibited a highly porous internal structure (pore diameter 17±4 μm), no cytotoxicity to human umbilical vein endothelial cells, hemocompatibility with human blood, and degradability in lysozyme solutions. Drug release from hydrogels loaded with a sclerosant, tetracycline, was measured at pH 7.4, 6 and 2 at 37°C. The results showed that tetracycline was more stable under acidic conditions, with a lower release rate observed at pH 6. An anticancer drug, doxorubicin, was loaded into the hydrogel and a cumulative release of 30% was observed over 78 h in phosphate-buffered saline at 37°C. Injection of the hydrogel precursor through a 5-F catheter into a fusiform aneurysm model was feasible, leading to complete filling of the aneurysmal sac, which was visualized by fluoroscopy. The levels of occlusion by hydrogel precursors (1.8% and 2.1%) and calibrated microspheres (100-300 μm) in a rabbit renal model were compared. Embolization with hydrogel precursors was performed without clogging and the hydrogel achieved effective occlusion in more distal arteries than calibrated microspheres. In conclusion, this hydrogel possesses promising characteristics potentially beneficial for a wide range of vascular intervention procedures that involve embolization and drug delivery. PMID:23791672

  18. Image-guided synergistic photothermal therapy using photoresponsive imaging agent-loaded graphene-based nanosheets.

    PubMed

    Miao, Wenjun; Shim, Gayong; Kim, Gunwoo; Lee, Soondong; Lee, Hee-Jung; Kim, Young Bong; Byun, Youngro; Oh, Yu-Kyoung

    2015-08-10

    We report the image-guided synergistic photothermal antitumor effects of photoresponsive near-infrared (NIR) imaging agent, indocyanine green (ICG), by loading onto hyaluronic acid-anchored, reduced graphene oxide (HArGO) nanosheets. Loading of ICG onto either rGO (ICG/rGO) or HArGO (ICG/HArGO) substantially improved the photostability of photoresponsive ICG upon NIR irradiation. After 1min of irradiation, the NIR absorption peak of ICG almost disappeared whereas the peak of ICG on rGO or HArGO was retained even after 5min of irradiation. Compared with plain rGO, HArGO provided greater cellular delivery of ICG and photothermal tumor cell-killing effects upon laser irradiation in CD44-positive KB cells. The temperature of cell suspensions treated with ICG/HArGO was 2.4-fold higher than that of cells treated with free ICG. Molecular imaging revealed that intravenously administered ICG/HArGO accumulated in KB tumor tissues higher than ICG/rGO or free ICG. Local temperatures in tumor tissues of laser-irradiated KB cell-bearing nude mice were highest in those intravenously administered ICG/HArGO, and were sufficient to trigger thermal-induced complete tumor ablation. Immunohistologically stained tumors also showed the highest percentages of apoptotic cells in the group treated with ICG/HArGO. These results suggest that photoresponsive ICG-loaded HArGO nanosheets could serve as a potential theranostic nano-platform for image-guided and synergistic photothermal antitumor therapy.

  19. Copper-D-penicillamine complex as potential contrast agent for MRI.

    PubMed

    Kupka, T; Dziegielewski, J O; Pasterna, G; Małecki, J G

    1992-01-01

    In vitro and in vivo proton T1 data are reported that demonstrate that the paramagnetic copper-D-penicillamine complex can be applied as a potential contrast agent to magnetic resonance imaging. PMID:1461082

  20. Potential effects of cannabidiol as a wake-promoting agent.

    PubMed

    Murillo-Rodríguez, Eric; Sarro-Ramírez, Andrea; Sánchez, Daniel; Mijangos-Moreno, Stephanie; Tejeda-Padrón, Alma; Poot-Aké, Alwin; Guzmán, Khalil; Pacheco-Pantoja, Elda; Arias-Carrión, Oscar

    2014-05-01

    Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆(9)-tetrahydrocannabinol (∆(9)-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug. PMID:24851090

  1. Potential Effects of Cannabidiol as a Wake-Promoting Agent

    PubMed Central

    Murillo-Rodríguez, Eric; Sarro-Ramírez, Andrea; Sánchez, Daniel; Mijangos-Moreno, Stephanie; Tejeda-Padrón, Alma; Poot-Aké, Alwin; Guzmán, Khalil; Pacheco-Pantoja, Elda; Arias-Carrión, Oscar

    2014-01-01

    Over the last decades, the scientific interest in chemistry and pharmacology of cannabinoids has increased. Most attention has focused on ∆9-tetrahydrocannabinol (∆9-THC) as it is the psychoactive constituent of Cannabis sativa (C. sativa). However, in previous years, the focus of interest in the second plant constituent with non-psychotropic properties, cannabidiol (CBD) has been enhanced. Recently, several groups have investigated the pharmacological properties of CBD with significant findings; furthermore, this compound has raised promising pharmacological properties as a wake-inducing drug. In the current review, we will provide experimental evidence regarding the potential role of CBD as a wake-inducing drug. PMID:24851090

  2. Breakthrough therapies: Cystic fibrosis (CF) potentiators and correctors.

    PubMed

    Solomon, George M; Marshall, Susan G; Ramsey, Bonnie W; Rowe, Steven M

    2015-10-01

    Cystic Fibrosis is caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene resulting in abnormal protein function. Recent advances of targeted molecular therapies and high throughput screening have resulted in multiple drug therapies that target many important mutations in the CFTR protein. In this review, we provide the latest results and current progress of CFTR modulators for the treatment of cystic fibrosis, focusing on potentiators of CFTR channel gating and Phe508del processing correctors for the Phe508del CFTR mutation. Special emphasis is placed on the molecular basis underlying these new therapies and emerging results from the latest clinical trials. The future directions for augmenting the rescue of Phe508del with CFTR modulators are also emphasized.

  3. New trial designs and potential therapies for pulmonary artery hypertension.

    PubMed

    Gomberg-Maitland, Mardi; Bull, Todd M; Saggar, Rajeev; Barst, Robyn J; Elgazayerly, Amany; Fleming, Thomas R; Grimminger, Friedrich; Rainisio, Maurizio; Stewart, Duncan J; Stockbridge, Norman; Ventura, Carlo; Ghofrani, Ardeschir H; Rubin, Lewis J

    2013-12-24

    A greater understanding of the epidemiology, pathogenesis, and pathophysiology of pulmonary artery hypertension (PAH) has led to significant advances, but the disease remains fatal. Treatment options are neither universally available nor always effective, underscoring the need for development of novel therapies and therapeutic strategies. Clinical trials to date have provided evidence of efficacy, but were limited in evaluating the scope and duration of treatment effects. Numerous potential targets in varied stages of drug development exist, in addition to novel uses of familiar therapies. The pursuit of gene and cell-based therapy continues, and device use to help acute deterioration and chronic management is emerging. This rapid surge of drug development has led to multicenter pivotal clinical trials and has resulted in novel ethical and global clinical trial concerns. This paper will provide an overview of the opportunities and challenges that await the development of novel treatments for PAH.

  4. Annexin A5 multitasking: a potentially novel antiatherothrombotic agent?

    PubMed

    Cederholm, Anna; Frostegård, Johan

    2007-06-01

    Atherothrombosis, formed on an underlying atherosclerotic plaque, is the key pathogenic mechanism behind the majority of clinically evident cardiovascular ischemic diseases including acute coronary artery disease, cerebrovascular and peripheral arterial occlusion. Annexin A5 (ANXA5; previously annexin V), a member of the annexin superfamily, is a protein with potent and unique antithrombotic properties. The antithrombotic effect exerted by ANXA5 is thought to be mediated mainly by mechanical shielding of phospholipids, phosphatidylserine in particular, thereby reducing their availability for coagulation reactions. However, other intriguing properties of ANXA5 potentially contributing to its antithrombotic function, especially downregulation of surface expressed tissue factor, or interaction with additional ligands involved in hemostasis such as sulfatide and heparin, as well as upregulation of urokinase-type plasminogen activator were reported. The biological significance of ANXA5 as a member of endogenous antithrombotic system in vivo has been suggested recently for the large vasculature and for placental microcirculation. Antiatherothrombotic potential of ANXA5 deserves further attention and careful studies in order to determine its true physiological impact as well as its possible therapeutic applications.

  5. Synthesis, functionalization, and characterization of rod-shaped gold nanoparticles as potential optical contrast agents

    NASA Astrophysics Data System (ADS)

    Rayavarapu, R. G.; Petersen, W.; Le Gac, S.; Ungureanu, C.; van Leeuwen, T. G.; Manohar, S.

    2007-07-01

    Gold nanoparticles exhibit intense and narrow optical extinction bands due to the phenomenon of plasmon resonance making them useful as contrast agents for light-based imaging techniques. Localized heating results from the absorbed light energy, which shows potential for these particles in photothermal therapy as well. The bioconjugation of gold nanoparticles to appropriate antibodies targeted to tumors in vivo, could make highly selective detection and therapy of tumors possible. We have synthesised gold nanorods based on seed mediated protocols using two methods. The first method is based on using a mono-surfactant silver assisted method which produces gold nanorods having plasmon peaks between 670-850 nm within the "optical imaging and therapeutic window". These nanorods have aspect ratios between 2.3 - 3.7. A second method is a silver assisted bi-surfactant method which produce nanorods with peaks in the range of 850-1100 nm having aspect ratios between 5 - 11. Typical concentrations of these particles in aqueous dispersions are in the range of 1x10 10 - 1x10 11 particles per mL. We have bioconjugated these gold nanorods with anti-HER2/neu mouse monoclonal antibodies (MAb). Since the as-prepared CTAB-stabilized nanorods were found to be toxic to SKBR3 cells, we decided to coat the gold nanorods with polyethylene glycol (PEG). Characterization and size estimation of the nanoparticles were performed using electron microscopies, optical spectroscopy and confocal microscopy. We present these results and implications for use of these nanoparticles for in vivo biomedical applications.

  6. Choosing Initial Antiretroviral Therapy: Current Recommendations for Initial Therapy and Newer or Investigational Agents.

    PubMed

    Gulick, Roy M

    2015-01-01

    There is general consistency among US and European guidelines regarding the initiation of antiretroviral therapy for HIV-infected individuals. Recent and ongoing trials comparing regimens may lead to reevaluation of initial treatment choices. The choice of antiretroviral regimen will also likely be affected by development, evaluation, and availability of newer drugs. This article reviews currently recommended regimens and characteristics of selected current investigational drugs, including the nucleotide analogue reverse transcriptase inhibitor tenofovir alafenamide, the nonnucleoside reverse transcriptase inhibitor doravirine, the integrase strand transfer inhibitor cabotegravir, the HIV entry inhibitor BMS-663068, and the HIV maturation inhibitor BMS-955176. This article summarizes a presentation by Roy M. Gulick, MD, MPH, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in March 2015 and September 2015. PMID:26713502

  7. Potential of iron chelators as effective antiproliferative agents.

    PubMed

    Richardson, D R

    1997-01-01

    Initially the impetus to develop iron (Fe) chelators for clinical use was based upon the need for a drug to treat Fe-overload diseases such as beta-thalassemia. However, it has become clear that Fe chelators may be useful for the treatment of a wide variety of disease states, including cancer, malaria, and free radical mediated injury. In particular, over the last 10 years a number of studies have shown that Fe chelators may be of use in the treatment of a number of aggressive human cancers, including neuroblastoma and leukemia, and several clinical trials have substantiated their potential. In the current review the role of Fe in cellular proliferation will be discussed, followed by the possible sites and mechanism of action of some of the most effective ligands. Attention will then be turned to examine the Fe chelators shown to possess antiproliferative activity and the clinical trials performed to assess their efficacy.

  8. Melatonin as a Potential Agent in the Treatment of Sarcopenia

    PubMed Central

    Coto-Montes, Ana; Boga, Jose A.; Tan, Dun X.; Reiter, Russel J.

    2016-01-01

    Considering the increased speed at which the world population is aging, sarcopenia could become an epidemic in this century. This condition currently has no means of prevention or treatment. Melatonin is a highly effective and ubiquitously acting antioxidant and free radical scavenger that is normally produced in all organisms. This molecule has been implicated in a huge number of biological processes, from anticonvulsant properties in children to protective effects on the lung in chronic obstructive pulmonary disease. In this review, we summarize the data which suggest that melatonin may be beneficial in attenuating, reducing or preventing each of the symptoms that characterize sarcopenia. The findings are not limited to sarcopenia, but also apply to osteoporosis-related sarcopenia and to age-related neuromuscular junction dysfunction. Since melatonin has a high safety profile and is drastically reduced in advanced age, its potential utility in the treatment of sarcopenic patients and related dysfunctions should be considered. PMID:27783055

  9. Potential Antiviral Agents from Marine Fungi: An Overview.

    PubMed

    Moghadamtousi, Soheil Zorofchian; Nikzad, Sonia; Kadir, Habsah Abdul; Abubakar, Sazaly; Zandi, Keivan

    2015-07-22

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  10. Potential Antiviral Agents from Marine Fungi: An Overview

    PubMed Central

    Zorofchian Moghadamtousi, Soheil; Nikzad, Sonia; Abdul Kadir, Habsah; Abubakar, Sazaly; Zandi, Keivan

    2015-01-01

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity. PMID:26204947

  11. Potential Antiviral Agents from Marine Fungi: An Overview.

    PubMed

    Moghadamtousi, Soheil Zorofchian; Nikzad, Sonia; Kadir, Habsah Abdul; Abubakar, Sazaly; Zandi, Keivan

    2015-07-01

    Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity. PMID:26204947

  12. [Immunotropic activity of a potential antiparkinson agent himantane].

    PubMed

    Nezhinskaia, G I; Val'dman, E A; Nazarov, P G; Voronina, T A

    2001-01-01

    N-(Adamant-2-yl) hexamethyleneimine hydrochloride (A-7, himantane), a new potential antiparkinsonian drug belonging to the class of aminoadamantyl derivatives, exhibits pronounced immunomodulant activity in a therapeutic dose of 10 mg/kg. A single intraperitoneal injection of himantane stimulated a high B-lymphocyte activity in mice over a period of 21 days. The drug inhibited the reaction of delayed hypersensitivity with respect to the Freund adjuvant, while enhancing the immediate reaction with respect to horse serum in guinea pigs. Himantane increased the functional (absorption) activity of macrophages in the peritoneal exudate, while not affecting superoxide anion production by the macrophages. These results suggest that the immunomodulant activity of himantane may produce a positive neuroprotective and symptomatic effects in the course of parkinsonism. PMID:11548451

  13. Potential Antiosteoporotic Agents from Plants: A Comprehensive Review

    PubMed Central

    Jia, Min; Nie, Yan; Cao, Da-Peng; Xue, Yun-Yun; Wang, Jie-Si; Zhao, Lu; Rahman, Khalid; Zhang, Qiao-Yan; Qin, Lu-Ping

    2012-01-01

    Osteoporosis is a major health hazard and is a disease of old age; it is a silent epidemic affecting more than 200 million people worldwide in recent years. Based on a large number of chemical and pharmacological research many plants and their compounds have been shown to possess antiosteoporosis activity. This paper reviews the medicinal plants displaying antiosteoporosis properties including their origin, active constituents, and pharmacological data. The plants reported here are the ones which are commonly used in traditional medical systems and have demonstrated clinical effectiveness against osteoporosis. Although many plants have the potential to prevent and treat osteoporosis, so far, only a fraction of these plants have been thoroughly investigated for their physiological and pharmacological properties including their mechanism of action. An attempt should be made to highlight plant species with possible antiosteoporosis properties and they should be investigated further to help with future drug development for treating this disease. PMID:23365596

  14. Hyperbaric Oxygen Therapy as a Sole Agent Is Not Immunosuppressant in a Highly Immunogenic Mouse Model

    PubMed Central

    Gassas, Adam; Min, Weixian; Evans, A. Wayne; Carter, Susan; Sándor, George K.; Grunebaum, Eyal

    2011-01-01

    Background. Hyperbaric oxygen (HBO) therapy, which is used for many conditions, may also have immunosuppressive effects and could be used for prevention or treatment of graft-versus-host disease (GvHD). If HBO is immunosuppressant, then we hypothesize that HBO therapy will delay the T-cell mediated skin graft rejection. Methods. C57/BL6 black-coated (H2B) mice received skin graft from CBA (H2D) white-coated mice. Mice were treated with either 19 session of 240 kpa oxygen or 29 session of 300 kpa oxygen, for 90 minutes. Mice were housed either 4 per cage or separately, to prevent friction and mechanical factors that may affect graft survival. Skin grafts were assessed daily. Results. There was no difference in length of graft survival between mice that received either regimens of HBO therapy and mice that did not receive HBO therapy. Conclusions. HBO therapy, as a sole agent, did not delay skin graft rejection in a highly immunogenic mouse model. PMID:22046567

  15. Gene therapy in Alzheimer's disease - potential for disease modification.

    PubMed

    Nilsson, Per; Iwata, Nobuhisa; Muramatsu, Shin-ichi; Tjernberg, Lars O; Winblad, Bengt; Saido, Takaomi C

    2010-04-01

    Alzheimer's disease (AD) is the major cause of dementia in the elderly, leading to memory loss and cognitive decline. The mechanism underlying onset of the disease has not been fully elucidated. However, characteristic pathological manifestations include extracellular accumulation and aggregation of the amyloid beta-peptide (Abeta) into plaques and intracellular accumulation and aggregation of hyperphosphorylated tau, forming neurofibrillary tangles. Despite extensive research worldwide, no disease modifying treatment is yet available. In this review, we focus on gene therapy as a potential treatment for AD, and summarize recent work in the field, ranging from proof-of-concept studies in animal models to clinical trials. The multifactorial causes of AD offer a variety of possible targets for gene therapy, including two neurotrophic growth factors, nerve growth factor and brain-derived neurotrophic factor, Abeta-degrading enzymes, such as neprilysin, endothelin-converting enzyme and cathepsin B, and AD associated apolipoprotein E. This review also discusses advantages and drawbacks of various rapidly developing virus-mediated gene delivery techniques for gene therapy. Finally, approaches aiming at down-regulating amyloid precursor protein (APP) and beta-site APP cleaving enzyme 1 levels by means of siRNA-mediated knockdown are briefly summarized. Overall, the prospects appear hopeful that gene therapy has the potential to be a disease modifying treatment for AD.

  16. The preclinical pharmacokinetic disposition of a series of perforin-inhibitors as potential immunosuppressive agents.

    PubMed

    Bull, M R; Spicer, J A; Huttunen, K M; Denny, W A; Ciccone, A; Browne, K A; Trapani, J A; Helsby, N A

    2015-12-01

    The cytolytic protein perforin is a key component of the immune response and is implicated in a number of human pathologies and therapy-induced conditions. A novel series of small molecule inhibitors of perforin function have been developed as potential immunosuppressive agents. The pharmacokinetics and metabolic stability of a series of 16 inhibitors of perforin was evaluated in male CD1 mice following intravenous administration. The compounds were well tolerated 6 h after dosing. After intravenous administration at 5 mg/kg, maximum plasma concentrations ranged from 532 ± 200 to 10,061 ± 12 ng/mL across the series. Plasma concentrations were greater than the concentrations required for in vitro inhibitory activity for 11 of the compounds. Following an initial rapid distribution phase, the elimination half-life values for the series ranged from 0.82 ± 0.25 to 4.38 ± 4.48 h. All compounds in the series were susceptible to oxidative biotransformation. Following incubations with microsomal preparations, a tenfold range in in vitro half-life was observed across the series. The data suggests that oxidative biotransformation was not singularly responsible for clearance of the compounds and no direct relationship between microsomal clearance and plasma clearance was observed. Structural modifications however, do provide some information as to the relative microsomal stability of the compounds, which may be useful for further drug development.

  17. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 2.

    PubMed

    Sagar, S M; Yance, D; Wong, R K

    2006-06-01

    The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are expanding the clinical knowledge that is already documented in traditional texts. The herbs that are traditionally used for anti-cancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclo-oxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as adaptogens, potentially enhancing the efficacy of the conventional therapies or reducing toxicity. Their effectiveness may be increased when multiple agents are used in optimal combinations. New designs for trials to demonstrate activity in human subjects are required. Although controlled trials may be preferable, smaller studies with appropriate endpoints and

  18. Optimizing Treatment of Intra-amniotic Infection and Early-Onset Postpartum Endometritis: Advantages of Single-Agent Therapy

    PubMed Central

    Stiglich, Norma; Alston, Meredith; vanSwam, Simone

    2011-01-01

    Introduction: Intra-amniotic infection (IAI) and early-onset postpartum endometritis (PPE) require prompt antibiotic treatment and are generally treated by either of two regimens. A complicated multi-agent regimen is most commonly used, despite a lack of clear evidence that it produces better outcomes than a simpler single-agent regimen. Objective: We compared treatment outcomes between a multi-agent regimen of ampicillin, gentamicin, and clindamycin versus a single-agent regimen of ampicillin/sulbactam for IAI and early-onset PPE. Methods: We conducted an observational retrospective cohort study by collecting data from the records of all patients at Denver Health Medical Center treated for IAI or PPE during two 6-month periods: a baseline period during which a regimen of ampicillin, gentamicin, and clindamycin was used and a subsequent period when ampicillin/sulbactam was used. Primary outcomes were prolonged antibiotic treatment and readmission for endometritis or wound cellulitis. Results: Of potential study participants, 323 women met inclusion criteria; 179 were treated with the multi-agent regimen and 144 were treated with the single-agent regimen. The groups were statistically similar for demographic and intrapartum characteristics, except for a lower rate of premature rupture of membranes in the single-agent treatment group. Twelve patients required prolonged treatment, and 2 were readmitted; these subgroups were combined for statistical analyses. The primary outcomes were significantly associated with cesarean delivery and blood loss >500 mL for vaginal deliveries and >1000 mL for cesarean deliveries; however, there was no significant difference in the incidence of the primary outcomes between the 2 treatment groups when adjusted for these variables. Treatment with ampicillin/sulbactam resulted in fewer antibiotic doses administered to patients with an uncomplicated treatment course. Conclusion: Ampicillin/sulbactam treatment of IAI and early-onset PPE

  19. Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy

    PubMed Central

    Zhou, Jiehua; Rossi, John J.

    2014-01-01

    One hundred years ago, Dr. Paul Ehrlich popularized the “magic bullet” concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, “targeted therapy” that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges. PMID:24936916

  20. Remineralizing potential of various agents on dental erosion

    PubMed Central

    Somani, Rani; Jaidka, Shipra; Singh, Deepti Jawa; Arora, Vanika

    2014-01-01

    Aim The purpose of this study is to compare the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP, Tooth Mousse) containing and casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF, Tooth Mousse Plus) containing pastes on dental erosion. Materials and methods Thirty permanent non-carious premolars indicated for orthodontic extraction were included in this study and were sectioned in mesiodistal direction vertically. After immersion in the carbonated drink for 14 min, samples were treated with various remineralizing pastes which were CPP-ACP containing paste (Tooth Mousse) and CPP-ACPF containing paste (Tooth Mousse Plus) according to the manufacturer's instructions. Vickers Microhardness was recorded at baseline, after exposure to erosive drink and after treatment with remineralizing pastes. Data obtained was statistically analysed using Student t-test with a level of significance set at p < 0.05. Results CPP-ACP (Tooth Mousse) and CPP-ACP with fluoride (Tooth Mousse Plus) resulted in 30.52% and 38.98% increase in post-erosion microhardness values respectively. The remineralizing potential of CPP-ACP with fluoride containing paste (Tooth Mousse Plus) was significantly better than that of CPP-ACP containing paste (Tooth Mousse) (p < 0.05). Conclusion Casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF, Tooth Mousse Plus) can be recommended to be used in preventing erosive tooth wear from acidic beverages. PMID:25737926

  1. Morphine as a Potential Oxidative Stress-Causing Agent

    PubMed Central

    Skrabalova, Jitka; Drastichova, Zdenka; Novotny, Jiri

    2013-01-01

    Morphine exhibits important pharmacological effects for which it has been used in medical practice for quite a long time. However, it has a high addictive potential and can be abused. Long-term use of this drug can be connected with some pathological consequences including neurotoxicity and neuronal dysfunction, hepatotoxicity, kidney dysfunction, oxidative stress and apoptosis. Therefore, most studies examining the impact of morphine have been aimed at determining the effects induced by chronic morphine exposure in the brain, liver, cardiovascular system and macrophages. It appears that different tissues may respond to morphine diversely and are distinctly susceptible to oxidative stress and subsequent oxidative damage of biomolecules. Importantly, production of reactive oxygen/nitrogen species induced by morphine, which have been observed under different experimental conditions, can contribute to some pathological processes, degenerative diseases and organ dysfunctions occurring in morphine abusers or morphine-treated patients. This review attempts to provide insights into the possible relationship between morphine actions and oxidative stress. PMID:24376392

  2. Investigation of Stilbenoids as Potential Therapeutic Agents for Rotavirus Gastroenteritis.

    PubMed

    Ball, Judith M; Medina-Bolivar, Fabricio; Defrates, Katelyn; Hambleton, Emily; Hurlburt, Megan E; Fang, Lingling; Yang, Tianhong; Nopo-Olazabal, Luis; Atwill, Richard L; Ghai, Pooja; Parr, Rebecca D

    2015-01-01

    Rotavirus (RV) infections cause severe diarrhea in infants and young children worldwide. Vaccines are available but cost prohibitive for many countries and only reduce severe symptoms. Vaccinated infants continue to shed infectious particles, and studies show decreased efficacy of the RV vaccines in tropical and subtropical countries where they are needed most. Continuing surveillance for new RV strains, assessment of vaccine efficacy, and development of cost effective antiviral drugs remain an important aspect of RV studies. This study was to determine the efficacy of antioxidant and anti-inflammatory stilbenoids to inhibit RV replication. Peanut (A. hypogaea) hairy root cultures were induced to produce stilbenoids, which were purified by high performance countercurrent chromatography (HPCCC) and analyzed by HPLC. HT29.f8 cells were infected with RV in the presence stilbenoids. Cell viability counts showed no cytotoxic effects on HT29.f8 cells. Viral infectivity titers were calculated and comparatively assessed to determine the effects of stilbenoid treatments. Two stilbenoids, trans-arachidin-1 and trans-arachidin-3, show a significant decrease in RV infectivity titers. Western blot analyses performed on the infected cell lysates complemented the infectivity titrations and indicated a significant decrease in viral replication. These studies show the therapeutic potential of the stilbenoids against RV replication.

  3. Potentially Harmful Therapy and Multicultural Counseling: Bridging Two Disciplinary Discourses

    PubMed Central

    Wendt, Dennis C.; Gone, Joseph P.; Nagata, Donna K.

    2015-01-01

    In recent years psychologists have been increasingly concerned about potentially harmful therapy, yet this recent discourse has not addressed issues that have long been voiced by the multicultural counseling and psychotherapy movement. We aim to begin to bring these seemingly disparate discourses of harm into greater conversation with one another, in the service of placing the discipline on a firmer foothold in its considerations of potentially harmful therapy. After reviewing the two discourses and exploring reasons for their divergence, we argue that they operate according to differing assumptions pertaining to the sources, objects, and scope of harm. We then argue that these differences reveal the discipline’s need to better appreciate that harm is a social construct, that psychotherapy may be inherently ethnocentric, and that strategies for collecting evidence of harm should be integrated with a social justice agenda. PMID:26339075

  4. β-Nitrostyrenes as Potential Anti-leishmanial Agents.

    PubMed

    Shafi, Syed; Afrin, Farhat; Islamuddin, Mohammad; Chouhan, Garima; Ali, Intzar; Naaz, Faatima; Sharma, Kalicharan; Zaman, Mohammad S

    2016-01-01

    Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25-8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels. PMID:27635124

  5. β-Nitrostyrenes as Potential Anti-leishmanial Agents

    PubMed Central

    Shafi, Syed; Afrin, Farhat; Islamuddin, Mohammad; Chouhan, Garima; Ali, Intzar; Naaz, Faatima; Sharma, Kalicharan; Zaman, Mohammad S.

    2016-01-01

    Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25–8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels.

  6. Hypochlorous Acid as a Potential Wound Care Agent

    PubMed Central

    Wang, L; Bassiri, M; Najafi, R; Najafi, K; Yang, J; Khosrovi, B; Hwong, W; Barati, E; Belisle, B; Celeri, C; Robson, MC

    2007-01-01

    Objective: Hypochlorous acid (HOCl), a major inorganic bactericidal compound of innate immunity, is effective against a broad range of microorganisms. Owing to its chemical nature, HOCl has never been used as a pharmaceutical drug for treating infection. In this article, we describe the chemical production, stabilization, and biological activity of a pharmaceutically useful formulation of HOCl. Methods: Stabilized HOCl is in the form of a physiologically balanced solution in 0.9% saline at a pH range of 3.5 to 4.0. Chlorine species distribution in solution is a function of pH. In aqueous solution, HOCl is the predominant species at the pH range of 3 to 6. At pH values less than 3.5, the solution exists as a mixture of chlorine in aqueous phase, chlorine gas, trichloride (Cl3−), and HOCl. At pH greater than 5.5, sodium hypochlorite (NaOCl) starts to form and becomes the predominant species in the alkaline pH. To maintain HOCl solution in a stable form, maximize its antimicrobial activities, and minimize undesirable side products, the pH must be maintained at 3.5 to 5. Results: Using this stabilized form of HOCl, the potent antimicrobial activities of HOCl are demonstrated against a wide range of microorganisms. The in vitro cytotoxicity profile in L929 cells and the in vivo safety profile of HOCl in various animal models are described. Conclusion: On the basis of the antimicrobial activity and the lack of animal toxicity, it is predicted that stabilized HOCl has potential pharmaceutical applications in the control of soft tissue infection. PMID:17492050

  7. β-Nitrostyrenes as Potential Anti-leishmanial Agents

    PubMed Central

    Shafi, Syed; Afrin, Farhat; Islamuddin, Mohammad; Chouhan, Garima; Ali, Intzar; Naaz, Faatima; Sharma, Kalicharan; Zaman, Mohammad S.

    2016-01-01

    Development of new therapeutic approach to treat leishmaniasis has become a priority. In the present study, the antileishmanial effect of β-nitrostyrenes was investigated against in vitro promastigotes and amastigotes. A series of β-nitrostyrenes have been synthesized by using Henry reaction and were evaluated for their antimicrobial activities by broth microdilution assay and in vitro antileishmanial activities against Leishmania donovani promastigotes by following standard guidelines. The most active compounds were futher evaluated for their in vitro antileishmanial activities against intracellular amastigotes. Among the tested β-nitrostyrenes, compounds 7, 8, 9, 12, and 17 exhibited potential activities (MICs range, 0.25–8 μg/mL) against clinically significant human pathogenic fungi. However, the microbactericidal concentrations (MBCs) and the microfungicidal concentrations (MFCs) were found to be either similar or only two-fold greater than the MICs. Anti-leishmanial results demonstrated that compounds 9, 12, 14, and 18 were found to be most active among the tested samples and exhibited 50% inhibitory concentration (IC50) by 23.40 ± 0.71, 37.83 ± 3.74, 40.50 ± 1.47, 55.66 ± 2.84 nM against L. donovani promastigotes and 30.5 ± 3.42, 21.46 ± 0.96, 26.43 ± 2.71, and 61.63 ± 8.02 nM respectively against intracellular L. donovani promastigotes amastigotes respectively which are comparable with standard AmB (19.60 ± 1.71 nM against promastigotes and 27.83 ± 3.26 nM against amastigotes). Compounds 9, 12, 14, and 18 were found to have potent in vitro leishmanicidal activity against L. donovani and found to be non-toxic against mammalian macrophages even at a concentration of 25 μM. Nitric oxide (NO) estimation studies reveals that these compounds are moderately inducing NO levels. PMID:27635124

  8. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy.

    PubMed

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  9. Novel Cs-Based Upconversion Nanoparticles as Dual-Modal CT and UCL Imaging Agents for Chemo-Photothermal Synergistic Therapy

    PubMed Central

    Liu, Yuxin; Li, Luoyuan; Guo, Quanwei; Wang, Lu; Liu, Dongdong; Wei, Ziwei; Zhou, Jing

    2016-01-01

    Lanthanide-based contrast agents have attracted increasing attention for their unique properties and potential applications in cancer theranostics. To date, many of these agents have been studied extensively in cells and small animal models. However, performance of these theranostic nanoparticles requires further improvement. In this study, a novel CsLu2F7:Yb,Er,Tm-based visual therapeutic platform was developed for imaging-guided synergistic cancer therapy. Due to the presence of the heavy alkali metal Cesium (Cs) in host lattice, the nanoplatform can provide a higher resolution X-ray CT imaging than many other reported lanthanide-based CT contrast agents. Furthermore, by using the targeted RGD motif, chemotherapy drug alpha-tocopheryl succinate (α-TOS), and photothermal coupling agent ICG, this nanoplatform simultaneously provides multifunctional imaging and targeted synergistic therapy. To demonstrate the theranostic performance of this novel nanoplatform in vivo, visual diagnosis in the small animal model was realized by UCL/CT imaging which was further integrated with targeted chemo-photothermal synergistic therapy. These results provided evidence for the successful construction of a novel lanthanide-based nanoplatform coupled with multimodal imaging diagnosis and potential application in synergistic cancer theranostics. PMID:27446485

  10. Cationic porphycenes as potential photosensitizers for antimicrobial photodynamic therapy

    PubMed Central

    Ragàs, Xavier; Sánchez-García, David; Ruiz-González, Rubén; Dai, Tianhong; Agut, Montserrat; Hamblin, Michael R.; Nonell, Santi

    2010-01-01

    Structures of typical photosensitizers used in antimicrobial photodynamic therapy are based on porphyrins, phthalocyanines and phenothiazinium salts, with cationic charges at physiological pH values. However derivatives of the porphycene macrocycle (a structural isomer of porphyrin) have barely been investigated as antimicrobial agents. Therefore, we report the synthesis of the first tricationic water-soluble porphycene and its basic photochemical properties. We successfully tested it for in vitro photoinactivation of different Gram-positive and Gram-negative bacteria, as well as a fungal species (Candida) in a drug-dose and light-dose dependent manner. We also used the cationic porphycene in vivo to treat an infection model comprising mouse 3rd degree burns infected with a bioluminescent methicillin-resistant Staphylococcus aureus strain. There was a 2.6-log10 reduction (p < 0.001) of the bacterial bioluminescence for the PDT-treated group after irradiation with 180 J·cm-2 of red light. PMID:20936792

  11. Small conjugate-based theranostic agents: an encouraging approach for cancer therapy.

    PubMed

    Kumar, Rajesh; Shin, Weon Sup; Sunwoo, Kyoung; Kim, Won Young; Koo, Seyoung; Bhuniya, Sankarprasad; Kim, Jong Seung

    2015-10-01

    The advances in genomics, proteomics, and bioinformatics have directed the development of new anticancer agents to reduce drug abuse and increase safe and specific drug treatment. Theranostics, combining therapy and diagnosis, is an appealing approach for chemotherapy in medicine which exhibits improved biodistribution, selective cancer targeting ability, reduced toxicity, masked drug efficacy, and minimum side effects. The role of diagnosis tools in theranostics is to collect the information of the diseased state before and after specific treatment. Magnetic particle-, mesoporous silica-, various carbon allotrope-, and polymer nanoparticle-based theranostic systems are well accepted and clinically significant. Currently, small conjugate-based systems have received much attention for cancer treatment and diagnosis. The structural architecture of these systems is relatively simple, compact, biocompatible, and unidirectional. In this tutorial review, we summarize the latest developments on small conjugate based theranostic agents for tumor treatment and diagnosis using fluorescence and magnetic resonance imaging (MRI).

  12. Photo-activated Cancer Therapy: Potential for Treatment of Brain Tumors

    NASA Astrophysics Data System (ADS)

    Hirschberg, Henry

    The diffuse and infiltrative nature of high grade gliomas, such as glioblastoma multiforme (GBM), makes complete surgical resection virtually impossible. The propensity of glioma cells to migrate along white matter tracts suggests that a cure is possible only if these migratory cells can be eradicated. Approximately 80% of GBMs recur within 2 cm of the resection margin, suggesting that a reasonable approach for improving the prognosis of GBM patients would be the development of improved local therapies capable of eradicating glioma cells in the brain-adjacent-to-tumor (BAT). An additional complicating factor for the development of successful therapies is the presence of the blood-brain barrier (BBB) which is highly variable throughout the BAT—it is intact in some regions, while leaky in others. This variance in BBB patency has significant implications for the delivery of therapeutic agents. The results of a number of studies have shown that experimental light-based therapeutic modalities such as photochemical internalization (PCI) and photothermal therapy (PTT) may be useful in the treatment of gliomas. This chapter summarizes recent findings illustrating the potential of: (1) PCI for the delivery of therapeutic macromolecules such as chemotherapeutic agents and tumor suppressor genes, and (2) nanoshell-mediated PTT, including nanoparticle delivery approaches via macrophages.

  13. Cytokines in thyroid eye disease: potential for anticytokine therapy.

    PubMed

    Bahn, R S

    1998-05-01

    Interactions between between orbital fibroblasts and immunocompetent cells that infiltrate or reside within the orbit are thought to be important in the pathogenesis of thyroid eye disease (TED). These interactions are mediated primarily by cytokines; interferon-gamma, tumor necrosis factor-alpha, interleukin-1alpha and leukoregulin are of particular interest in this regard. These mediators induce or enhance the in vitro expression of immunomodulatory proteins in orbital fibroblasts, and stimulate proliferative and metabolic activities of these cells. The stimulation by particular cytokines of glycosaminoglycan synthesis in orbital fibroblasts is an important factor in the development of the clinical disease. A similarly important pathophysiological role for cytokines has been defined in rheumatoid arthritis. In this disease, the chronic erosive changes in the cartilage and bone of the joints result from cytokine-stimulated production of collegenases and other neutral proteases by synovial cells and articular chondrocytes. Advances in the understanding of the pathogenesis of rheumatologic joint disease has led to treatment trials aimed at immune-modulation, including trials of anticytokine therapy. Lessons learned in early clinical trials using these biological therapies in the treatment of rheumatoid arthritis can be applied to studies of similar agents in the treatment of TED. PMID:9623733

  14. Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

  15. Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol‑1 L s‑1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

  16. Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy.

    PubMed

    Trump, Donald L; Deeb, Kristin K; Johnson, Candace S

    2010-01-01

    Considerable preclinical and epidemiologic data suggest that vitamin D may play a role in the pathogenesis, progression, and therapy for cancer. Numerous epidemiologic studies support the hypothesis that individuals with lower serum vitamin D levels have a higher risk of a number of cancers. Measures of vitamin D level in such studies include both surrogate estimates of vitamin D level (residence in more northern latitudes, history of activity, and sun exposure) as well as measured serum 25(OH) cholecalciferol levels. Perhaps, the most robust of these epidemiologic studies is that of Giovannucci et al, who developed and validated an estimate of serum 25(OH) cholecalciferol level and reported that among >40,000 individuals in the Health Professionals Study, an increase in 25(OH) cholecalciferol level of 62.5 ng/mL was associated with a reduction in the risk of head/neck, esophagus, pancreas cancers, and acute leukemia by >50%. Unfortunately, very limited data are available to indicate whether or not giving vitamin D supplements reduces the risk of cancer. Many preclinical studies indicate that exposing cancer cells, as well as vascular endothelial cells derived from tumors, to high concentrations of active metabolites of vitamin D halts progression through cell cycle, induces apoptosis and will slow or stop the growth of tumors in vivo. There are no data that one type of cancer is more or less susceptible to the effects of vitamin D. Vitamin D also potentiates the antitumor activity of a number of types of cytotoxic anticancer agents in in vivo preclinical models. Vitamin D analogues initiate signaling through a number of important pathways, but the pathway(s) essential to the antitumor activities of vitamin D are unclear. Clinical studies of vitamin D as an antitumor agent have been hampered by the lack of a suitable pharmaceutical preparation for clinical study. All commercially available formulations are inadequate because of the necessity to administer large

  17. Vitamin D: Considerations in the Continued Development as an Agent for Cancer Prevention and Therapy

    PubMed Central

    Trump, Donald L.; Deeb, Kristen; Johnson, Candace S.

    2010-01-01

    Considerable preclinical and epidemiologic data suggest that vitamin D may play a role in the pathogenesis, progression and therapy of cancer. Numerous epidemiologic studies support the hypothesis that individuals with lower serum vitamin D levels have a higher risk of a number of cancers. Measures of vitamin D level in such studies include both surrogate estimates of vitamin D level (residence in more northern latitudes, history of activity and sun exposure) as well as measured serum 25(OH) cholecalciferol levels. Perhaps the most robust of these epidemiologic studies is that of Giovannucci and colleagues who developed and validated an estimate of serum 25(OH) cholecalciferol level and reported that among more than 40,000 individuals in the Health professionals Study an increase in 25(OH) cholecalciferol level of 62.5ng/mL was associated with a reduction in the risk of head/neck, esophagus, pancreas cancers and acute leukemia by >50%. Unfortunately very limited data are available to indicate whether or not giving vitamin D supplements reduces the risk of cancer. Many preclinical studies indicate that exposing cancer cells – as well as vascular endothelial cells derived from tumors - to high concentrations of active metabolites of vitamin D halts progression through cell cycle, induces apoptosis and will slow or stop the growth of tumors in vivo. There are no data that one type of cancer is more or less susceptible to the effects of vitamin D. Vitamin D also potentiates the antitumor activity of a number of types of cytotoxic anticancer agents in in vivo preclinical models. Vitamin D analogues initiate signaling through a number of important pathways, but the pathway(s) essential to the antitumor activities of vitamin D are unclear. Clinical studies of vitamin D as an antitumor agent have been hampered by the lack of a suitable pharmaceutical preparation for clinical study. All commercially available formulations are inadequate because of the necessity to

  18. Vitamin D: considerations in the continued development as an agent for cancer prevention and therapy.

    PubMed

    Trump, Donald L; Deeb, Kristin K; Johnson, Candace S

    2010-01-01

    Considerable preclinical and epidemiologic data suggest that vitamin D may play a role in the pathogenesis, progression, and therapy for cancer. Numerous epidemiologic studies support the hypothesis that individuals with lower serum vitamin D levels have a higher risk of a number of cancers. Measures of vitamin D level in such studies include both surrogate estimates of vitamin D level (residence in more northern latitudes, history of activity, and sun exposure) as well as measured serum 25(OH) cholecalciferol levels. Perhaps, the most robust of these epidemiologic studies is that of Giovannucci et al, who developed and validated an estimate of serum 25(OH) cholecalciferol level and reported that among >40,000 individuals in the Health Professionals Study, an increase in 25(OH) cholecalciferol level of 62.5 ng/mL was associated with a reduction in the risk of head/neck, esophagus, pancreas cancers, and acute leukemia by >50%. Unfortunately, very limited data are available to indicate whether or not giving vitamin D supplements reduces the risk of cancer. Many preclinical studies indicate that exposing cancer cells, as well as vascular endothelial cells derived from tumors, to high concentrations of active metabolites of vitamin D halts progression through cell cycle, induces apoptosis and will slow or stop the growth of tumors in vivo. There are no data that one type of cancer is more or less susceptible to the effects of vitamin D. Vitamin D also potentiates the antitumor activity of a number of types of cytotoxic anticancer agents in in vivo preclinical models. Vitamin D analogues initiate signaling through a number of important pathways, but the pathway(s) essential to the antitumor activities of vitamin D are unclear. Clinical studies of vitamin D as an antitumor agent have been hampered by the lack of a suitable pharmaceutical preparation for clinical study. All commercially available formulations are inadequate because of the necessity to administer large

  19. Potential Use of Biological Proteins for Liver Failure Therapy

    PubMed Central

    Taguchi, Kazuaki; Yamasaki, Keishi; Seo, Hakaru; Otagiri, Masaki

    2015-01-01

    Biological proteins have unlimited potential for use as pharmaceutical products due to their various biological activities, which include non-toxicity, biocompatibility, and biodegradability. Recent scientific advances allow for the development of novel innovative protein-based products that draw on the quality of their innate biological activities. Some of them hold promising potential for novel therapeutic agents/devices for addressing hepatic diseases such as hepatitis, fibrosis, and hepatocarcinomas. This review attempts to provide an overview of the development of protein-based products that take advantage of their biological activity for medication, and discusses possibilities for the therapeutic potential of protein-based products produced through different approaches to specifically target the liver (or hepatic cells: hepatocytes, hepatic stellate cells, liver sinusoidal endothelial cells, and Kupffer cells) in the treatment of hepatic diseases. PMID:26404356

  20. Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Shi, Changhong; Wu, Jason Boyang; Pan, Dongfeng

    2016-05-01

    A class of near-infrared fluorescence (NIRF) heptamethine cyanine dyes that are taken up and accumulated specifically in cancer cells without chemical conjugation have recently emerged as promising tools for tumor imaging and targeting. In addition to their fluorescence and nuclear imaging-based tumor-imaging properties, these dyes can be developed as drug carriers to safely deliver chemotherapy drugs to tumors. They can also be used as effective agents for photodynamic therapy with remarkable tumoricidal activity via photodependent cytotoxic activity. The preferential uptake of dyes into cancer but not normal cells is co-operatively mediated by the prevailing activation of a group of organic anion-transporting polypeptides on cancer cell membranes, as well as tumor hypoxia and increased mitochondrial membrane potential in cancer cells. Such mechanistic explorations have greatly advanced the current application and future development of NIRF dyes and their derivatives as anticancer theranostic agents. This review summarizes current knowledge and emerging advances in NIRF dyes, including molecular characterization, photophysical properties, multimodal development and uptake mechanisms, and their growing potential for preclinical and clinical use.

  1. Argon gas: a potential neuroprotectant and promising medical therapy.

    PubMed

    Nowrangi, Derek S; Tang, Jiping; Zhang, John H

    2014-02-17

    Argon is a noble gas element that has demonstrated narcotic and protective abilities that may prove useful in the medical field. The earliest records of argon gas have exposed its ability to exhibit narcotic symptoms at hyperbaric pressures greater than 10 atmospheres with more recent evidence seeking to display argon as a potential neuroprotective agent. The high availability and low cost of argon provide a distinct advantage over using similarly acting treatments such as xenon gas. Argon gas treatments in models of brain injury such as in vitro Oxygen-Glucose-Deprivation (OGD) and Traumatic Brain Injury (TBI), as well as in vivo Middle Cerebral Artery Occlusion (MCAO) have largely demonstrated positive neuroprotective behavior. On the other hand, some warning has been made to potential negative effects of argon treatments in cases of ischemic brain injury, where increases of damage in the sub-cortical region of the brain have been uncovered. Further support for argon use in the medical field has been demonstrated in its use in combination with tPA, its ability as an organoprotectant, and its surgical applications. This review seeks to summarize the history and development of argon gas use in medical research as mainly a neuroprotective agent, to summarize the mechanisms associated with its biological effects, and to elucidate its future potential.

  2. Potential of epigenetic therapies in non-cancerous conditions

    PubMed Central

    Mau, Theresa; Yung, Raymond

    2014-01-01

    There has been an explosion of knowledge in the epigenetics field in the past 20 years. The first epigenetic therapies have arrived in the clinic for cancer treatments. In contrast, much of the promise of epigenetic therapies for non-cancerous conditions remains in the laboratories. The current review will focus on the recent progress that has been made in understanding the pathogenic role of epigenetics in immune and inflammatory conditions, and how the knowledge may provide much needed new therapeutic targets for many autoimmune diseases. Dietary factors are increasingly recognized as potential modifiers of epigenetic marks that can influence health and diseases across generations. The current epigenomics revolution will almost certainly complement the explosion of personal genetics medicine to help guide treatment decisions and disease risk stratification. PMID:25566322

  3. The role of potential agents in making spatial perspective taking social

    PubMed Central

    Clements-Stephens, Amy M.; Vasiljevic, Katarina; Murray, Alexandra J.; Shelton, Amy L.

    2013-01-01

    A striking relationship between visual spatial perspective taking (VSPT) and social skills has been demonstrated for perspective-taking tasks in which the target of the imagined or inferred perspective is a potential agent, suggesting that the presence of a potential agent may create a social context for the seemingly spatial task of imagining a novel visual perspective. In a series of studies, we set out to investigate how and when a target might be viewed as sufficiently agent-like to incur a social influence on VSPT performance. By varying the perceptual and conceptual features that defined the targets as potential agents, we find that even something as simple as suggesting animacy for a simple wooden block may be sufficient. More critically, we found that experience with one potential agent influenced the performance with subsequent targets, either by inducing or eliminating the influence of social skills on VSPT performance. These carryover effects suggest that the relationship between social skills and VSPT performance is mediated by a complex relationship that includes the task, the target, and the context in which that target is perceived. These findings highlight potential problems that arise when identifying a task as belonging exclusively to a single cognitive domain and stress instead the highly interactive nature of cognitive domains and their susceptibility to cross-domain individual differences. PMID:24046735

  4. Local drug delivery agents as adjuncts to endodontic and periodontal therapy

    PubMed Central

    Puri, K; Puri, N

    2013-01-01

    Abstract In the treatment of intracanal and periodontal infections, the local application of antibiotics and other therapeutic agents in the root canal or in periodontal pockets may be a promising approach to achieve sustained/controlled drug release, high antimicrobial activity and low systemic side effects. The conventional method for the elimination of subgingival microbial infection includes mechanical debridement, irrigation with antimicrobial agents or surgical access. But, the effectiveness of conventional nonsurgical treatment is limited by lack of accessibility to bacteria in deeper periodontal pockets, and/or does not completely eliminate intracanal microorganisms. Surgical intervention may be beneficial but cannot be done in all cases, medically compromised cases and also in patients not willing to be subjected to surgical therapy. Development of local drug delivery systems provides an answer to all such difficulties. This comprehensive review tries to cover the detailed information about the latest advances in the various local drug delivery systems, their indications, contraindications and their advantages over systemic drug therapy. PMID:24868252

  5. Potential applications of pharmacogenomics to heart failure therapies.

    PubMed

    Parikh, Kishan S; Ahmad, Tariq; Fiuzat, Mona

    2014-10-01

    Pharmacogenomics explores one drug's varying effects on different patient genotypes. A better understanding of genomic variation's contribution to drug response can impact 4 arenas in heart failure (HF): (1) identification of patients most likely to receive benefit from therapy, (2) risk stratify patients for risk of adverse events, (3) optimize dosing of drugs, and (4) steer future clinical trial design and drug development. In this review, the authors explore the potential applications of pharmacogenomics in patients with HF in the context of these categories.

  6. Basal cell carcinoma — molecular biology and potential new therapies

    PubMed Central

    Kasper, Maria; Jaks, Viljar; Hohl, Daniel; Toftgård, Rune

    2012-01-01

    Basal cell carcinoma (BCC) of the skin, the most common malignancy in individuals of mixed European descent, is increasing in incidence due to an aging population and sun exposure habits. The realization that aberrant activation of Hedgehog signaling is a pathognomonic feature of BCC development has opened the way for exciting progress toward understanding BCC biology and translation of this knowledge to the clinic. Genetic mouse models closely mimicking human BCCs have provided answers about the tumor cell of origin, and inhibition of Hedgehog signaling is emerging as a potentially useful targeted therapy for patients with advanced or multiple BCCs that have hitherto lacked effective treatment. PMID:22293184

  7. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer—Part 1

    PubMed Central

    Sagar, S.M.; Yance, D.; Wong, R.K.

    2006-01-01

    An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose–response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or

  8. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-Part 1.

    PubMed

    Sagar, S M; Yance, D; Wong, R K

    2006-02-01

    An integrative approach for managing a patient with cancer should target the multiple biochemical and physiologic pathways that support tumour development and minimize normal-tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The present article focuses on products that have a high degree of anti-angiogenic activity, but it also describes some of the many other actions of these agents that can inhibit tumour progression and reduce the risk of metastasis. Natural health products target molecular pathways other than angiogenesis, including epidermal growth factor receptor, the HER2/neu gene, the cyclooxygenase-2 enzyme, the nuclear factor kappa-B transcription factor, the protein kinases, the Bcl-2 protein, and coagulation pathways. The herbs that are traditionally used for anticancer treatment and that are anti-angiogenic through multiple interdependent processes (including effects on gene expression, signal processing, and enzyme activities) include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking upon clinical trials. More data are required on dose-response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations. During active cancer therapy, they should generally be evaluated in combination with chemotherapy and radiation. In this role, they act as modifiers of biologic response or as

  9. Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers.

    PubMed

    Sinkovics, Joseph G; Horvath, Joseph C

    2008-12-01

    Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a

  10. Natural and genetically engineered viral agents for oncolysis and gene therapy of human cancers.

    PubMed

    Sinkovics, Joseph G; Horvath, Joseph C

    2008-12-01

    Based on personal acquaintances and experience dating back to the early 1950s, the senior author reviews the history of viral therapy of cancer. He points out the difficulties encountered in the treatment of human cancers, as opposed by the highly successful viral therapy of experimentally maintained tumors in laboratory animals, especially that of ascites carcinomas in mice. A detailed account of viral therapy of human tumors with naturally oncolytic viruses follows, emphasizing the first clinical trials with viral oncolysates. The discrepancy between the high success rates, culminating in cures, in the treatment of tumors of laboratory animals, and the moderate results, such as stabilizations of disease, partial responses, very rare complete remissions, and frequent relapses with virally treated human tumors is recognized. The preclinical laboratory testing against established human tumor cell lines that were maintained in tissue cultures for decades, and against human tumors extricated from their natural habitat and grown in xenografts, may not yield valid results predictive of the viral therapy applied against human tumors growing in their natural environment, the human host. Since the recent discovery of the oncosuppressive efficacy of bacteriophages, the colon could be regarded as the battlefield, where incipient tumor cells and bacteriophages vie for dominance. The inner environment of the colon will be the teaching ground providing new knowledge on the value of the anti-tumor efficacy of phage-induced innate anti-tumor immune reactions. Genetically engineered oncolytic viruses are reviewed next. The molecular biology of viral oncolysis is explained in details. Elaborate efforts are presented to elucidate how gene product proteins of oncolytic viruses switch off the oncogenic cascades of cancer cells. The facts strongly support the conclusion that viral therapy of human cancers will remain in the front lines of modern cancer therapeutics. It may be a

  11. [Antiplatelet therapy: resistance to traditional antiaggregation drugs and role of new antiplatelet agents].

    PubMed

    del Castillo-Carnevali, Hugo; Barrios Alonso, Vivencio; Zamorano Gómez, José Luis

    2014-09-01

    Platelet aggregation plays a key role in the development of major cardiovascular events (MACE) related to atherothrombosis. Since the appearance of coronary stenting, the importance of measuring and modulating platelet activity has considerably increased in the scientific literature during the last decade. Double antiplatelet therapy with aspirin and clopidogrel administrated to stent carriers has widely demonstrated its efficacy in the prevention of MACE compared with aspirin alone. These benefits are also present when a conservatory approach is chosen for acute coronary syndrome management. However, there are an important number of patients who develop MACE despite optimal dual antiplatelet therapy, most likely related to an incomplete platelet activity inhibition. Many studies suggest an important inter-individual variability in the response to the drugs, maybe related, at least in part, to the use of different assessment techniques of platelet aggregation. Other authors suggest an incomplete platelet inhibition as a possible explanation for the presence of MACE in patients under optimal antiplatelet therapy. Resistance to usual drugs has become a clinically relevant issue that requires an individual approach where new antiplatelet agents, such as prasugrel or ticagrelor, could play an important role as stated in current consensus documents. PMID:24342012

  12. [Antiplatelet therapy: resistance to traditional antiaggregation drugs and role of new antiplatelet agents].

    PubMed

    del Castillo-Carnevali, Hugo; Barrios Alonso, Vivencio; Zamorano Gómez, José Luis

    2014-09-01

    Platelet aggregation plays a key role in the development of major cardiovascular events (MACE) related to atherothrombosis. Since the appearance of coronary stenting, the importance of measuring and modulating platelet activity has considerably increased in the scientific literature during the last decade. Double antiplatelet therapy with aspirin and clopidogrel administrated to stent carriers has widely demonstrated its efficacy in the prevention of MACE compared with aspirin alone. These benefits are also present when a conservatory approach is chosen for acute coronary syndrome management. However, there are an important number of patients who develop MACE despite optimal dual antiplatelet therapy, most likely related to an incomplete platelet activity inhibition. Many studies suggest an important inter-individual variability in the response to the drugs, maybe related, at least in part, to the use of different assessment techniques of platelet aggregation. Other authors suggest an incomplete platelet inhibition as a possible explanation for the presence of MACE in patients under optimal antiplatelet therapy. Resistance to usual drugs has become a clinically relevant issue that requires an individual approach where new antiplatelet agents, such as prasugrel or ticagrelor, could play an important role as stated in current consensus documents.

  13. Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.

    PubMed

    Wang, Ping-Han; Zhao, Li-Xue; Wan, Jing-Yu; Zhang, Liang; Mao, Xiao-Na; Long, Fang-Yi; Zhang, Shuang; Chen, Chu; Du, Jun-Rong

    2016-03-01

    Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis. PMID:26704993

  14. Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.

    PubMed

    Wang, Ping-Han; Zhao, Li-Xue; Wan, Jing-Yu; Zhang, Liang; Mao, Xiao-Na; Long, Fang-Yi; Zhang, Shuang; Chen, Chu; Du, Jun-Rong

    2016-03-01

    Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.

  15. New potential chemotherapy for ovarian cancer - Combined therapy with WP 631 and epothilone B.

    PubMed

    Bukowska, Barbara; Rogalska, Aneta; Marczak, Agnieszka

    2016-04-15

    Despite more modern therapeutics approaches and the use of new drugs for chemotherapy, patients with ovarian cancer still have poor prognosis and therefore, new strategies for its cure are highly needed. One of the promising ways is combined therapy, which has many advantages as minimizing drug resistance, enhancing efficacy of treatment, and reducing toxicity. Combined therapy has rich and successful history in the field of ovarian cancer treatment. Currently use therapy is usually based on platinum-containing agent (carboplatin or cisplatin) and a member of taxanes (paclitaxel or docetaxel). In the mid-2000s this standard regimen has been expanded with bevacizumab, monoclonal antibody directed to Vascular Endothelial Growth Factor (VEGF). Another drug combination with promising perspectives is WP 631 given together with epothilone B (Epo B). WP 631 is a bisanthracycline composed of two molecules of daunorubicin linked with a p-xylenyl linker. Epo B is a 16-membered macrolide manifesting similar mechanism of action to taxanes. Their effectiveness against ovarian cancer as single agents is well established. However, the combination of WP 631 and Epo B appeared to act synergistically, meaning that it is much more potent than the single drugs. The mechanism lying under its efficacy includes disturbing essential cell cycle-regulating proteins leading to mitotic slippage and following apoptosis, as well as affecting EpCAM and HMGB1 expression. In this article, we summarized the current state of knowledge regarding combined therapy based on WP 631 and Epo B as a potential way of ovarian cancer treatment. PMID:26944437

  16. Potential Application of Temozolomide in Mesenchymal Stem Cell-Based TRAIL Gene Therapy Against Malignant Glioma

    PubMed Central

    Kim, Seong Muk; Woo, Ji Sun; Jeong, Chang Hyun; Ryu, Chung Heon; Jang, Jae-Deog

    2014-01-01

    Because the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells, it is one of the most promising candidates for cancer treatment. TRAIL-secreting human mesenchymal stem cells (MSC-TRAIL) provide targeted and prolonged delivery of TRAIL in glioma therapy. However, acquired resistance to TRAIL of glioma cells is a major problem to be overcome. We showed a potential therapy that used MSC-TRAIL combined with the chemotherapeutic agent temozolomide (TMZ). The antitumor effects of the combination with MSC-TRAIL and TMZ on human glioma cells were determined by using an in vitro coculture system and an in vivo experimental xenografted mouse model. Intracellular signaling events that are responsible for the TMZ-mediated sensitization to TRAIL-induced apoptosis were also evaluated. Treatment of either TRAIL-sensitive or -resistant human glioma cells with TMZ and MSC-TRAIL resulted in a significant enhancement of apoptosis compared with the administration of each agent alone. We demonstrated that TMZ effectively increased the sensitivity to TRAIL-induced apoptosis via extracellular signal-regulated kinase-mediated upregulation of the death receptor 5 and downregulation of antiapoptotic proteins, such as X-linked inhibitor of apoptosis protein and cellular FLICE-inhibitory protein. Subsequently, this combined treatment resulted in a substantial increase in caspase activation. Furthermore, in vivo survival experiments and bioluminescence imaging analyses showed that treatment using MSC-TRAIL combined with TMZ had greater therapeutic efficacy than did single-agent treatments. These results suggest that the combination of clinically relevant TMZ and MSC-TRAIL is a potential therapeutic strategy for improving the treatment of malignant gliomas. PMID:24436439

  17. Physicochemical properties of potential porphyrin photosensitizers for photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Kempa, Marta; Kozub, Patrycja; Kimball, Joseph; Rojkiewicz, Marcin; Kuś, Piotr; Gryczyński, Zugmunt; Ratuszna, Alicja

    2015-07-01

    This research evaluated the suitability of synthetic photosensitizers for their use as potential photosensitizers in photodynamic therapy using steady state and time-resolved spectroscopic techniques. Four tetraphenylporphyrin derivatives were studied in ethanol and dimethyl sulfoxide. The spectroscopic properties namely electronic absorption and emission spectra, ability to generate singlet oxygen, lifetimes of the triplet state, as well as their fluorescence quantum yield were determined. Also time-correlated single photon counting method was used to precisely determine fluorescence lifetimes for all four compounds. Tested compounds exhibit high generation of singlet oxygen, low generation of fluorescence and they are chemical stable during irradiation. The studies show that the tested porphyrins satisfy the conditions of a potential drug in terms of physicochemical properties.

  18. Macromolecular Imaging Agents Containing Lanthanides: Can Conceptual Promise Lead to Clinical Potential?

    PubMed Central

    Bryson, Joshua; Reineke, Jeffrey W.; Reineke, Theresa M.

    2012-01-01

    Macromolecular magnetic resonance imaging (MRI) contrast agents are increasingly being used to improve the resolution of this noninvasive diagnostic technique. All clinically-approved T1 contrast agents are small molecule chelates of gadolinium [Gd(III)] that affect bound water proton relaxivity. Both the small size and monomeric nature of these agents ultimately limits the image resolution enhancement that can be achieved for both contrast enhancement and pharmacokinetic/biodistribution reasons. The multimeric nature of macromolecules, such as polymers, dendrimers, and noncovalent complexes of small molecule agents with proteins, have been shown to significantly increase the image contrast and resolution due to their large size and ability to incorporate multiple Gd(III) chlelation sites. Also, macromolecular agents are advantageous as they have the ability to be designed to be nontoxic, hydrophilic, easily purified, aggregation-resistant, and have controllable three-dimensional macromolecular structure housing the multiple lanthanide chelation sites. For these reasons, large molecule diagnostics have the ability to significantly increase the relaxivity of water protons within the targeted tissues and thus the image resolution for many diagnostic applications. The FDA approval of a contrast agent that consists of a reversible, non-covalent coupling of a small Gd(III) chelate with serum albumin for blood pool imaging (marketed under the trade names of Vasovist and Ablivar) proved to be one of the first diagnostic agent to capitalize on these benefits from macromolecular association in humans. However, much research and development is necessary to optimize the safety of these unique agents for in vivo use and potential clinical development. To this end, recent work in the field of polymer, dendrimer, and noncovalent complex-based imaging agents are reviewed herein and the future outlook of this field is discussed. PMID:23467737

  19. Aminolevulinic Acid-Photodynamic Therapy Combined with Topically Applied Vascular Disrupting Agent Vadimezan Led to Enhanced Antitumor Responses

    PubMed Central

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor-vascular disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a non-invasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. Additionally, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA assays to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared to ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. PMID:21575001

  20. Berberine as a photosensitizing agent for antitumoral photodynamic therapy: Insights into its association to low density lipoproteins.

    PubMed

    Luiza Andreazza, Nathalia; Vevert-Bizet, Christine; Bourg-Heckly, Geneviève; Sureau, Franck; José Salvador, Marcos; Bonneau, Stephanie

    2016-08-20

    Recent years have seen a growing interest in Berberine, a phytochemical with multispectrum therapeutic activities, as anti-tumoral agent for photodynamic therapy (PDT). In this context, low density lipoproteins (LDL) play a key role in the delivery of the photosensitizer in tumor cells. We correlate the physicochemical parameters of the berberine association to LDL with the influence of LDL-delivery on its accumulation in a glioma cell line and on its photo-induced activity in view of antitumor PDT. Our results evidence an important binding of 400 berberine molecules per LDL. Changes in berberine and apoprotein fluorescence suggest different fixation types, involving various LDL compartments including the vicinity of the apoprotein. The berberine association to LDL does not affect their recognition by the specific B/E receptors, of which over-expression increases the cellular uptake of LDL-preloaded berberine. Fluorescence microscopy evidences the mitochondrial labeling of the glioma model cells, with no significant modification upon LDL-delivery. Moreover, the cellular delivery of berberine by LDL increases its photocytotoxic effects on such cells. So, this research illustrates the potential of berberine as a photosensitizing agent for PDT, in particular due to their behavior towards LDL as plasma vehicles, and gives insights into its mechanisms of cell uptake. PMID:27282536

  1. Synergistic potentiation of D-fraction with vitamin C as possible alternative approach for cancer therapy.

    PubMed

    Konno, Sensuke

    2009-01-01

    Maitake D-fraction or PDF is the bioactive extract of maitake mushroom (Grifola frondosa) and its active constituent is the protein-bound polysaccharide (proteoglucan), or more specifically known as beta-glucan. PDF has been extensively studied and a number of its medicinal potentials/properties have been unveiled and demonstrated. Those include various physiological benefits ranging from immunomodulatory and antitumor activities to treatment for hypertension, diabetes, hypercholesterolemia, viral infections (hepatitis B and human immunodeficiency virus), and obesity. Particularly, two major biological activities of PDF, immunomodulatory and antitumor activities, have been the main target for scientific and clinical research. To demonstrate and confirm such biological activities, numerous studies have been performed in vitro and in vivo or in clinical settings. These studies showed that PDF was indeed capable of modulating immunologic and hematologic parameters, inhibiting or regressing the cancer cell growth, and even improving quality of life of cancer patients. Synergistic potentiation of PDF with vitamin C demonstrated in vitro is rather interesting and may have clinical implication, because such combination therapy appears to help improve the efficacy of currently ongoing cancer therapies. Recently, intravenous administration of vitamin C has been often used to increase its physiological concentration and this useful procedure may further make this combination therapy feasible. Therefore, PDF may have great potential, either being used solely or combined with other agents, for cancer therapy. Such relevant and detailed studies will be described and discussed herein with a special focus on the combination of PDF and vitamin C as a viable therapeutic option.

  2. Management of immune thrombocytopenic purpura in children: potential role of novel agents.

    PubMed

    Bredlau, Amy Lee; Semple, John W; Segel, George B

    2011-08-01

    The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of bleeding or a platelet count <10 000/μL, then treatment with glucocorticoids, intravenous immunoglobulin (IVIg), or anti-D are possible initial choices. Glucocorticoid treatment is the least expensive and is our usual first choice of therapy. Its use assumes that the blood counts and blood film have been evaluated to ensure the absence of evidence of alternative diagnoses, such as thrombotic thrombocytopenic purpura or incipient acute leukemia. IVIg is expensive and often causes severe headache, nausea and vomiting, and requires hospitalization at our institution. Anti-D therapy is also expensive and can only be used in patients who are Rhesus D positive. These therapies, even if only transiently effective, can be repeated if necessary. Children usually recover from newly diagnosed ITP, with or without multiple courses of medical therapy. If the disease becomes 'persistent' with severe thrombocytopenia and/or bleeding, and is no longer responsive to the three first-line therapies, the next approach includes the use of thrombopoietin receptor agonists or rituximab. When the disease persists for more than 1 year, it is considered chronic, and, if symptomatic, it may become necessary to consider third-line therapies, including splenectomy, alternative immunosuppressive agents, or combination or investigative chemoimmunotherapy. This review considers the indications, mechanism of action, and effectiveness of the traditional and novel treatment options for patients with ITP.

  3. Imaging of hemorrhagic fever with renal syndrome: a potential bioterrorism agent of military significance.

    PubMed

    Bui-Mansfield, Liem T; Cressler, Dana K

    2011-11-01

    Hemorrhagic fever with renal syndrome (HFRS) is a potentially fatal infectious disease with worldwide distribution. Its etiologic agents are viruses of the genus Hantavirus of the virus family Bunyaviridae. Hypothetical ease of production and distribution of these agents, with their propensity to incapacitate victims and overwhelm health care resources, lend themselves as significant potential biological agents of terrorism. HFRS has protean clinical manifestations, which may mimic upper respiratory tract infection, nephrolithiasis, and Hantavirus pulmonary syndrome and may delay proper treatment. Sequelae of HFRS, such as hemorrhage, acute renal failure, retroperitoneal edema, pancreatitis, pulmonary edema, and neurologic symptoms, can be detected by different imaging modalities. Medical providers caring for HFRS patients must be aware of its radiologic features, which may help to confirm its clinical diagnosis. In this article, the authors review the epidemiology, pathophysiology, clinical presentation, diagnosis, treatment, and complications of HFRS. PMID:22165665

  4. Novel 1-Phenyl-3-hydroxy-4-pyridinone Derivatives as Multifunctional Agents for the Therapy of Alzheimer's Disease.

    PubMed

    Sheng, Rong; Tang, Li; Jiang, Liu; Hong, Lingjuan; Shi, Ying; Zhou, Naiming; Hu, Yongzhou

    2016-01-20

    A series of novel 1-phenyl-3-hydroxy-4-pyridinone derivatives were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy through incorporation of 3-hydroxy-4-pyridinone moiety from deferiprone into the scaffold of H3 receptor antagonists. Most of these new compounds displayed designed quadruple functions, H3 receptor antagonism, Aβ aggregation inhibition, metal ion chelation, and radical scavenging. Especially, the most promising compound 5c displayed nanomolar IC50 values in H3 receptor antagonism with high selectivity, efficient capability to interrupt the formation of Aβ(1-42) fibrils, good copper and iron chelating properties, and more potent 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging activity than Trolox. Further biological evaluation revealed that it did not show obvious cytotoxicity and hERG potassium channel inhibition at micromolar concentration. In addition, compound 5c demonstrated suitable pharmacokinetic properties and acceptable blood-brain barrier (BBB) permeability in vivo. All these results indicate that compound 5c is a potential multifunctional candidate for AD therapy. PMID:26479744

  5. Novel 1-Phenyl-3-hydroxy-4-pyridinone Derivatives as Multifunctional Agents for the Therapy of Alzheimer's Disease.

    PubMed

    Sheng, Rong; Tang, Li; Jiang, Liu; Hong, Lingjuan; Shi, Ying; Zhou, Naiming; Hu, Yongzhou

    2016-01-20

    A series of novel 1-phenyl-3-hydroxy-4-pyridinone derivatives were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy through incorporation of 3-hydroxy-4-pyridinone moiety from deferiprone into the scaffold of H3 receptor antagonists. Most of these new compounds displayed designed quadruple functions, H3 receptor antagonism, Aβ aggregation inhibition, metal ion chelation, and radical scavenging. Especially, the most promising compound 5c displayed nanomolar IC50 values in H3 receptor antagonism with high selectivity, efficient capability to interrupt the formation of Aβ(1-42) fibrils, good copper and iron chelating properties, and more potent 2,2'-azino-bis(3-ethyl-benzothiazoline-6-sulfonic acid) radical cation (ABTS(•+)) scavenging activity than Trolox. Further biological evaluation revealed that it did not show obvious cytotoxicity and hERG potassium channel inhibition at micromolar concentration. In addition, compound 5c demonstrated suitable pharmacokinetic properties and acceptable blood-brain barrier (BBB) permeability in vivo. All these results indicate that compound 5c is a potential multifunctional candidate for AD therapy.

  6. Progress in Nanotechnology Based Approaches to Enhance the Potential of Chemopreventive Agents

    PubMed Central

    Muqbil, Irfana; Masood, Ashiq; Sarkar, Fazlul H.; Mohammad, Ramzi M.; Azmi, Asfar S.

    2011-01-01

    Cancer chemoprevention is defined as the use of natural agents to suppress, reverse or prevent the carcinogenic process from turning into aggressive cancer. Over the last two decades, multiple natural dietary compounds with diverse chemical structures such flavonoids, tannins, curcumins and polyphenols have been proposed as chemopreventive agents. These agents have proven excellent anticancer potential in the laboratory setting, however, the observed effects in vitro do not translate in clinic where they fail to live up to their expectations. Among the various reasons for this discrepancy include inefficient systemic delivery and robust bioavailability. To overcome this barrier, researchers have focused towards coupling these agents with nano based encapsulation technology that in principle will enhance bioavailability and ultimately benefit clinical outcome. The last decade has witnessed rapid advancement in the development of nanochemopreventive technology with emergence of many nano encapsulated formulations of different dietary anticancer agents. This review summarizes the most up-to-date knowledge on the studies performed in nanochemoprevention, their proposed use in the clinic and future directions in which this field is heading. As the knowledge of the dynamics of nano encapsulation evolves, it is expected that researchers will bring forward newer and far more superior nanochemopreventive agents that may become standard drugs for different cancers. PMID:24212623

  7. Intelligent Agents and Their Potential for Future Design and Synthesis Environment

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K. (Compiler); Malone, John B. (Compiler)

    1999-01-01

    This document contains the proceedings of the Workshop on Intelligent Agents and Their Potential for Future Design and Synthesis Environment, held at NASA Langley Research Center, Hampton, VA, September 16-17, 1998. The workshop was jointly sponsored by the University of Virginia's Center for Advanced Computational Technology and NASA. Workshop attendees came from NASA, industry and universities. The objectives of the workshop were to assess the status of intelligent agents technology and to identify the potential of software agents for use in future design and synthesis environment. The presentations covered the current status of agent technology and several applications of intelligent software agents. Certain materials and products are identified in this publication in order to specify adequately the materials and products that were investigated in the research effort. In no case does such identification imply recommendation or endorsement of products by NASA, nor does it imply that the materials and products are the only ones or the best ones available for this purpose. In many cases equivalent materials and products are available and would probably produce equivalent results.

  8. Molecular effective coverage surface area of optical clearing agents for predicting optical clearing potential

    NASA Astrophysics Data System (ADS)

    Feng, Wei; Ma, Ning; Zhu, Dan

    2015-03-01

    The improvement of methods for optical clearing agent prediction exerts an important impact on tissue optical clearing technique. The molecular dynamic simulation is one of the most convincing and simplest approaches to predict the optical clearing potential of agents by analyzing the hydrogen bonds, hydrogen bridges and hydrogen bridges type forming between agents and collagen. However, the above analysis methods still suffer from some problem such as analysis of cyclic molecule by reason of molecular conformation. In this study, a molecular effective coverage surface area based on the molecular dynamic simulation was proposed to predict the potential of optical clearing agents. Several typical cyclic molecules, fructose, glucose and chain molecules, sorbitol, xylitol were analyzed by calculating their molecular effective coverage surface area, hydrogen bonds, hydrogen bridges and hydrogen bridges type, respectively. In order to verify this analysis methods, in vitro skin samples optical clearing efficacy were measured after 25 min immersing in the solutions, fructose, glucose, sorbitol and xylitol at concentration of 3.5 M using 1951 USAF resolution test target. The experimental results show accordance with prediction of molecular effective coverage surface area. Further to compare molecular effective coverage surface area with other parameters, it can show that molecular effective coverage surface area has a better performance in predicting OCP of agents.

  9. Circular RNAs as potential biomarkers for cancer diagnosis and therapy

    PubMed Central

    Wang, Fengling; Nazarali, Adil J; Ji, Shaoping

    2016-01-01

    Circular RNAs (circRNAs) are a naturally occurring type of universal and diverse endogenous noncoding RNAs which unlike linear RNAs, have covalently linked ends. They are usually stable, abundant, conserved RNA molecules and often exhibit tissue/developmental-stage specific expression. Functional circRNAs have been identified to act as microRNA sponges and RNA-binding protein (RBP) sequestering agents as well as transcriptional regulators. These multiple functional roles elicit a great potential for circRNAs in biological applications. Emerging evidence shows that circRNAs play important roles in several diseases, particularly in cancer where they act through regulating protein expression of the pivotal genes that are critical for carcinogenesis. The presence of abundant circRNAs in saliva, exosomes and clinical standard blood samples will make them potential diagnostic or predictive biomarkers for diseases, particularly for cancer development, progression and prognosis. Here, we review the current literature and provide evidence for the impact of circRNAs in cancers and their potential significance in cancer prognosis and clinical treatment. PMID:27429839

  10. Circular RNAs as potential biomarkers for cancer diagnosis and therapy.

    PubMed

    Wang, Fengling; Nazarali, Adil J; Ji, Shaoping

    2016-01-01

    Circular RNAs (circRNAs) are a naturally occurring type of universal and diverse endogenous noncoding RNAs which unlike linear RNAs, have covalently linked ends. They are usually stable, abundant, conserved RNA molecules and often exhibit tissue/developmental-stage specific expression. Functional circRNAs have been identified to act as microRNA sponges and RNA-binding protein (RBP) sequestering agents as well as transcriptional regulators. These multiple functional roles elicit a great potential for circRNAs in biological applications. Emerging evidence shows that circRNAs play important roles in several diseases, particularly in cancer where they act through regulating protein expression of the pivotal genes that are critical for carcinogenesis. The presence of abundant circRNAs in saliva, exosomes and clinical standard blood samples will make them potential diagnostic or predictive biomarkers for diseases, particularly for cancer development, progression and prognosis. Here, we review the current literature and provide evidence for the impact of circRNAs in cancers and their potential significance in cancer prognosis and clinical treatment. PMID:27429839

  11. Potential of epigenetic therapies in the management of solid tumors

    PubMed Central

    Valdespino, Victor; Valdespino, Patricia M

    2015-01-01

    Cancer is a complex disease with both genetic and epigenetic origins. The growing field of epigenetics has contributed to our understanding of oncogenesis and tumor progression, and has allowed the development of novel therapeutic drugs. First-generation epigenetic inhibitor drugs have obtained modest clinical results in two types of hematological malignancy. Second-generation epigenetic inhibitors are in development, and have intrinsically greater selectivity for their molecular targets. Solid tumors are more genetic and epigenetically complex than hematological malignancies, but the transcriptome and epigenome biomarkers have been identified for many of these malignancies. This solid tumor molecular aberration profile may be modified using specific or quasi-specific epidrugs together with conventional and innovative anticancer treatments. In this critical review, we briefly analyze the strategies to select the targeted epigenetic changes, enumerate the second-generation epigenetic inhibitors, and describe the main signs indicating the potential of epigenetic therapies in the management of solid tumors. We also highlight the work of consortia or academic organizations that support the undertaking of human epigenetic therapeutic projects as well as some examples of transcriptome/epigenome profile determination in clinical assessment of cancer patients treated with epidrugs. There is a good chance that epigenetic therapies will be able to be used in patients with solid tumors in the future. This may happen soon through collaboration of diverse scientific groups, making the selection of targeted epigenetic aberration(s) more rapid, the design and probe of drug candidates, accelerating in vitro and in vivo assays, and undertaking new cancer epigenetic-therapy clinical trails. PMID:26346546

  12. External Qi therapy to treat symptoms of Agent Orange Sequelae in Korean combat veterans of the Vietnam War.

    PubMed

    Lee, Myeong Soo; Woo, Won-Hong; Lim, Hyun-Ja; Hong, Sung-Soo; Kim, Hye-Jung; Moon, Sun-Rock

    2004-01-01

    We investigated the efficacy of Qi therapy as a non-pharmacological treatment for various symptoms presented by Korean combat veterans of the Vietnam War with Agent Orange Sequelae. Nine subjects volunteered to receive 30 minutes of Qi therapy, twice per day for 7 days. There was marked improvement in 89% of the patients with impaired physical activity, 86% of those with psychological disorder, 78% of those with heavy drug use, and 67% of those with fatigue, indigestion and high blood glucose levels. This data suggests that Qi therapy combined with conventional treatment has positive effects in reducing and managing the pain, psychosomatic disorders, and substance abuse in patients with Agent Orange Sequelae. We cannot completely discount the possible influence of the placebo effect, and more objective, clinical measures are needed to study the long-term effects of Qi therapy.

  13. External Qi therapy to treat symptoms of Agent Orange Sequelae in Korean combat veterans of the Vietnam War.

    PubMed

    Lee, Myeong Soo; Woo, Won-Hong; Lim, Hyun-Ja; Hong, Sung-Soo; Kim, Hye-Jung; Moon, Sun-Rock

    2004-01-01

    We investigated the efficacy of Qi therapy as a non-pharmacological treatment for various symptoms presented by Korean combat veterans of the Vietnam War with Agent Orange Sequelae. Nine subjects volunteered to receive 30 minutes of Qi therapy, twice per day for 7 days. There was marked improvement in 89% of the patients with impaired physical activity, 86% of those with psychological disorder, 78% of those with heavy drug use, and 67% of those with fatigue, indigestion and high blood glucose levels. This data suggests that Qi therapy combined with conventional treatment has positive effects in reducing and managing the pain, psychosomatic disorders, and substance abuse in patients with Agent Orange Sequelae. We cannot completely discount the possible influence of the placebo effect, and more objective, clinical measures are needed to study the long-term effects of Qi therapy. PMID:15344429

  14. Near-infrared Au nanorods in photodynamic therapy, hyperthermia agents, and near-infrared optical imaging

    NASA Astrophysics Data System (ADS)

    Kuo, Wen-Shuo; Chang, Chich-Neng; Chang, Yi-Ting; Yang, Meng-Heng; Chien, Yi-Hsin; Chen, Shean-Jen; Yeh, Chen-Sheng

    2011-03-01

    The development of multifunctional nanomaterials is currently a topic of interest in the field of nanotechnology. Integrated systems that incorporate therapeutics, molecular targeting, and diagnostic imaging capabilities are considered to be the next generation of multifunctional nanomedicine. In this work, we present the first example of using Au nanorods simultaneously serving not only as photodynamic and photothermal agents to destroy A549 malignant cells but also as optical contrast agents simultaneously to monitor cellular image. Au nanorods were successfully conjugated with hydrophilic photosensitizer, indocyanine green (ICG), to achieve photodynamic therapy (PDT) and hyperthermia. With the combination of PDT and hyperthermia proved to be efficiently killing cancer cells as compared to PDT or hyperthermia treatment alone and enhanced the effectiveness of photodestruction. Moreover, Au nanorods conjugated with ICG displayed high chemical stability and simultaneously acted as a promising cellular image probe. As a result, the preparation of Au nanorods conjugated with photosensitizers as well as their use in biomedical applications is valuable developments in multifunctional nanomaterials.

  15. Molecular Targeted Agents for Gastric Cancer: A Step Forward Towards Personalized Therapy

    PubMed Central

    Cidon, Esther Una; Ellis, Sara G; Inam, Yasir; Adeleke, Sola; Zarif, Sara; Geldart, Tom

    2013-01-01

    Gastric cancer (GC) represents a major cancer burden worldwide, and remains the second leading cause of cancer-related death. Due to its insidious nature, presentation is usually late and often carries a poor prognosis. Despite having improved treatment modalities over the last decade, for most patients only modest improvements have been seen in overall survival. Recent progress in understanding the molecular biology of GC and its signaling pathways, offers the hope of clinically significant promising advances for selected groups of patients. Patients with Her-2 overexpression or amplification have experienced benefit from the integration of monoclonal antibodies such as trastuzumab to the standard chemotherapy. Additionally, drugs targeting angiogenesis (bevacizumab, sorafenib, sunitinib) are under investigation and other targeted agents such as mTOR inhibitors, anti c-MET, polo-like kinase 1 inhibitors are in preclinical or early clinical development. Patient selection and the development of reliable biomarkers to accurately select patients most likely to benefit from these tailored therapies is now key. Future trials should focus on these advances to optimize the treatment for GC patients. This article will review recent progress and current status of targeted agents in GC. PMID:24216699

  16. Selecting a disease-modifying agent as platform therapy in the long-term management of multiple sclerosis.

    PubMed

    Stuart, William H; Cohan, Stanley; Richert, John R; Achiron, Anat

    2004-12-14

    Multiple sclerosis (MS) is a complex, incurable disease. Treatment consists of lifelong disease and symptom management. FDA-approved therapies for relapsing MS include subcutaneous (SC) interferon beta-1b (IFNbeta1b, Betaseron), IM interferon-beta-1a (Avonex), SC interferon-beta-1a (Rebif), glatiramer acetate (Copaxone), and mitoxantrone (Novantrone), all of which are known as disease-modifying agents (DMAs). DMAs that can be initiated and continued on a long-term basis can be referred to as platform therapies. During periods of disease instability with increased disease activity, corticosteroids or immunosuppressive agents can be used in combination with appropriate DMA platform therapy to help control symptoms. To date, long-term comparative studies of DMAs are not available. However, based on the effects of these agents on disability progression, relapse rates, MRI outcomes, and neutralizing antibodies observed in phase III randomized clinical trials, IFNbeta1a products are the DMAs of choice for platform therapy for MS. Evidence indicates that IFNbeta1a may also be beneficial in the early stages of the disease. Research is ongoing to identify other appropriate add-on agents (e.g., antigen-specific therapies) to be used in combination with existing DMAs to effectively manage MS.

  17. Anti-Inflammatory Dimethylfumarate: A Potential New Therapy for Asthma?

    PubMed Central

    Roth, Michael

    2013-01-01

    Asthma is a chronic inflammatory disease of the airways, which results from the deregulated interaction of inflammatory cells and tissue forming cells. Beside the derangement of the epithelial cell layer, the most prominent tissue pathology of the asthmatic lung is the hypertrophy and hyperplasia of the airway smooth muscle cell (ASMC) bundles, which actively contributes to airway inflammation and remodeling. ASMCs of asthma patients secrete proinflammatory chemokines CXCL10, CCL11, and RANTES which attract immune cells into the airways and may thereby initiate inflammation. None of the available asthma drugs cures the disease—only symptoms are controlled. Dimethylfumarate (DMF) is used as an anti-inflammatory drug in psoriasis and showed promising results in phase III clinical studies in multiple sclerosis patients. In regard to asthma therapy, DMF has been anecdotally reported to reduce asthma symptoms in patients with psoriasis and asthma. Here we discuss the potential use of DMF as a novel therapy in asthma on the basis of in vitro studies of its inhibitory effect on ASMC proliferation and cytokine secretion in ASMCs. PMID:23606796

  18. Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents

    PubMed Central

    Russo, Francesco; Gising, Johan; Åkerbladh, Linda; Roos, Annette K; Naworyta, Agata; Mowbray, Sherry L; Sokolowski, Anders; Henderson, Ian; Alling, Torey; Bailey, Mai A; Files, Megan; Parish, Tanya; Karlén, Anders; Larhed, Mats

    2015-01-01

    This is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the Mycobacterium tuberculosis (Mtb) proteasome. As part of the study, the structure–activity relationship of oxathiazolones as Mtb proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a good selectivity profile for Mtb compared to the human proteasome. The 5-styryl-oxathiazol-2-one inhibitors identified showed little activity against replicating Mtb, but were rapidly bactericidal against nonreplicating bacteria. (E)-5-(4-Chlorostyryl)-1,3,4-oxathiazol-2-one) was most effective, reducing the colony-forming units (CFU)/mL below the detection limit in only seven days at all concentrations tested. The results suggest that this new class of Mtb proteasome inhibitors has the potential to be further developed into novel antitubercular agents for synergistic combination therapies with existing drugs. PMID:26246997

  19. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B.; Sidell, F.R.; Leffingwell, S.S.

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  20. New 1,4-anthracene-9,10-dione derivatives as potential anticancer agents.

    PubMed

    Zagotto, G; Supino, R; Favini, E; Moro, S; Palumbo, M

    2000-01-01

    The amino-substituted anthracene-9,10-dione (9,10-anthraquinone) derivatives represent one of the most important classes of potential anticancer agents. To better understand the basic rules governing DNA sequence specificity, we have recently synthesized a new class of D- and L-aminoacyl-anthraquinone derivatives. We have tested these new compounds as cytotoxic agents, and we have correlated their activity with the configuration of the chiral aminoacyl moiety. Molecular modeling studies have been performed to compare the test drugs in terms of steric overlapping.

  1. Photodynamic therapy potentiates the paracrine endothelial stimulation by colorectal cancer

    NASA Astrophysics Data System (ADS)

    Lamberti, María Julia; Florencia Pansa, María; Emanuel Vera, Renzo; Belén Rumie Vittar, Natalia; Rivarola, Viviana Alicia

    2014-11-01

    Colorectal cancer (CRC) is the third most common cancer and the third leading cause of cancer death worldwide. Recurrence is a major problem and is often the ultimate cause of death. In this context, the tumor microenvironment influences tumor progression and is considered as a new essential feature that clearly impacts on treatment outcome, and must therefore be taken into consideration. Photodynamic therapy (PDT), oxygen, light and drug-dependent, is a novel treatment modality when CRC patients are inoperable. Tumor vasculature and parenchyma cells are both potential targets of PDT damage modulating tumor-stroma interactions. In biological activity assessment in photodynamic research, three-dimensional (3D) cultures are essential to integrate biomechanical, biochemical, and biophysical properties that better predict the outcome of oxygen- and drug-dependent medical therapies. Therefore, the objective of this study was to investigate the antitumor effect of methyl 5-aminolevulinic acid-PDT using a light emitting diode for the treatment of CRC cells in a scenario that mimics targeted tissue complexity, providing a potential bridge for the gap between 2D cultures and animal models. Since photodynamic intervention of the tumor microenvironment can effectively modulate the tumor-stroma interaction, it was proposed to characterize the endothelial response to CRC paracrine communication, if one of these two populations is photosensitized. In conclusion, we demonstrated that the dialogue between endothelial and tumor populations when subjected to lethal PDT conditions induces an increase in angiogenic phenotype, and we think that it should be carefully considered for the development of PDT therapeutic protocols.

  2. Evaluation of neutralized chemical agent identification sets (CAIS) for skin injury with an overview of the vesicant potential of agent degradation products.

    PubMed

    Olajos, E J; Olson, C T; Salem, H; Singer, A W; Hayes, T L; Menton, R G; Miller, T L; Rosso, T; MacIver, B

    1998-01-01

    Vesication and skin irritation studies were conducted in hairless guinea-pigs to determine the vesicant and skin irritation potential of chemically-neutralized Chemical Agent Identification Sets (CAIS). The CAIS are training items that contain chemical warfare-related material--sulfur mustard (HD), nitrogen mustard (HN) or lewisite (L)--and were declared obsolete in 1971. Animals were dosed topically with 'test article'--neat HD, 10% agent/chloroform solutions or product solutions (waste-streams) from neutralized CAIS--and evaluated for skin-damaging effects (gross and microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation. All agent-dosed (HD or agent/chloroform solutions) sites manifested microblisters as well as other histopathological lesions of the skin. Waste-streams from the neutralization of agent (agent/chloroform or agent/charcoal) were devoid of vesicant activity. Cutaneous effects (erythema and edema) were consistent with the skin-injurious activity associated with the neutralizing reagent 1,3-dichloro-5,5-dimethylhydantoin (DCDMH). Chemical neutralization of CAIS was effective in eliminating/reducing the vesicant property of CAIS containing agent in chloroform or agent on charcoal but was inefficient in reducing the vesicant potential of CAIS containing neat sulfur mustard.

  3. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

    NASA Astrophysics Data System (ADS)

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-08-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice.

  4. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments

    PubMed Central

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-01-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID:27561915

  5. The poultry red mite (Dermanyssus gallinae): a potential vector of pathogenic agents.

    PubMed

    Valiente Moro, Claire; De Luna, Carlos J; Tod, Alexander; Guy, Jonathan H; Sparagano, Olivier A E; Zenner, Lionel

    2009-06-01

    The poultry red mite, D. gallinae has been involved in the transmission of many pathogenic agents, responsible for serious diseases both in animals and humans. Nowadays, few effective methods are available to control the ectoparasite in poultry farms. Consequently, this is an emerging problem which must be taken into account to maintain good health in commercial egg production. This paper addresses the vector capacity of the ectoparasite with special emphasis on salmonellae, pathogenic agents responsible for many of the most important outbreaks of food-borne diseases worlwide. It has been experimentally shown that D. gallinae could act as a biological vector of S. enteritidis and natural carriage of these bacteria by the mite on poultry premises has also been reported. It was also found that D. gallinae carried other pathogens such as E. coli, Shigella sp., and Staphylococcus, thus increasing the list of pathogenic agents potentially transmitted by the mite.

  6. Novel Hydrogel Material as a Potential Embolic Agent in Embolization Treatments.

    PubMed

    Zhou, Feng; Chen, Liming; An, Qingzhu; Chen, Liang; Wen, Ying; Fang, Fang; Zhu, Wei; Yi, Tao

    2016-01-01

    We report a novel graphene-oxide (GO) enhanced polymer hydrogel (GPH) as a promising embolic agent capable of treating cerebrovascular diseases and malignant tumors, using the trans-catheter arterial embolization (TAE) technique. Simply composed of GO and generation five poly(amidoamine) dendrimers (PAMAM-5), our rheology experiments reveal that GPH exhibits satisfactory mechanical strength, which resist the high pressures of blood flow. Subcutaneous experiments on Sprague-Dawley (SD) rats demonstrate the qualified biocompatibility of GPH. Finally, our in vivo experiments on New Zealand rabbits, which mix GPH with the X-ray absorbing contrast agent, Iohexol, reveal complete embolization of the artery. We also note that GPH shortens embolization time and exhibits low toxicity in follow-up experiments. Altogether, our study demonstrates that GPH has many advantages over the currently used embolic agents and has potential applications in clinical practice. PMID:27561915

  7. Pharmacogenetics, enzyme probes and therapeutic drug monitoring as potential tools for individualizing taxane therapy.

    PubMed

    Krens, Stefanie D; McLeod, Howard L; Hertz, Daniel L

    2013-04-01

    The taxanes are a class of chemotherapeutic agents that are widely used in the treatment of various solid tumors. Although taxanes are highly effective in cancer treatment, their use is associated with serious complications attributable to large interindividual variability in pharmacokinetics and a narrow therapeutic window. Unpredictable toxicity occurrence necessitates close patient monitoring while on therapy and adverse effects frequently require decreasing, delaying or even discontinuing taxane treatment. Currently, taxane dosing is based primarily on body surface area, ignoring other factors that are known to dictate variability in pharmacokinetics or outcome. This article discusses three potential strategies for individualizing taxane treatment based on patient information that can be collected before or during care. The clinical implementation of pharmacogenetics, enzyme probes or therapeutic drug monitoring could enable clinicians to personalize taxane treatment to enhance efficacy and/or limit toxicity.

  8. Preparation and characterization of an iron oxide-hydroxyapatite nanocomposite for potential bone cancer therapy

    PubMed Central

    Sneha, Murugesan; Sundaram, Nachiappan Meenakshi

    2015-01-01

    Recently, multifunctional magnetic nanostructures have been found to have potential applications in biomedical and tissue engineering. Iron oxide nanoparticles are biocompatible and have distinctive magnetic properties that allow their use in vivo for drug delivery and hyperthermia, and as T2 contrast agents for magnetic resonance imaging. Hydroxyapatite is used frequently due to its well-known biocompatibility, bioactivity, and lack of toxicity, so a combination of iron oxide and hydroxyapatite materials could be useful because hydroxyapatite has better bone-bonding ability. In this study, we prepared nanocomposites of iron oxide and hydroxyapatite and analyzed their physicochemical properties. The results suggest that these composites have superparamagnetic as well as biocompatible properties. This type of material architecture would be well suited for bone cancer therapy and other biomedical applications. PMID:26491311

  9. Organ-Specific Cancer Metabolism and Its Potential for Therapy.

    PubMed

    Elia, Ilaria; Schmieder, Roberta; Christen, Stefan; Fendt, Sarah-Maria

    2016-01-01

    Targeting cancer metabolism has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, the aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor-positive breast cancer, early- and late-stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g., Warburg versus reverse Warburg metabolism). Yet, for each of the cancers, their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion.

  10. Organ-Specific Cancer Metabolism and Its Potential for Therapy.

    PubMed

    Elia, Ilaria; Schmieder, Roberta; Christen, Stefan; Fendt, Sarah-Maria

    2016-01-01

    Targeting cancer metabolism has the potential to lead to major advances in tumor therapy. Numerous promising metabolic drug targets have been identified. Yet, it has emerged that there is no singular metabolism that defines the oncogenic state of the cell. Rather, the metabolism of cancer cells is a function of the requirements of a tumor. Hence, the tissue of origin, the (epi)genetic drivers, the aberrant signaling, and the microenvironment all together define these metabolic requirements. In this chapter we discuss in light of (epi)genetic, signaling, and environmental factors the diversity in cancer metabolism based on triple-negative and estrogen receptor-positive breast cancer, early- and late-stage prostate cancer, and liver cancer. These types of cancer all display distinct and partially opposing metabolic behaviors (e.g., Warburg versus reverse Warburg metabolism). Yet, for each of the cancers, their distinct metabolism supports the oncogenic phenotype. Finally, we will assess the therapeutic potential of metabolism based on the concepts of metabolic normalization and metabolic depletion. PMID:25912014

  11. Functional Hyperbranched Polylysine as Potential Contrast Agent Probes for Magnetic Resonance Imaging.

    PubMed

    Zu, Guangyue; Liu, Min; Zhang, Kunchi; Hong, Shanni; Dong, Jingjin; Cao, Yi; Jiang, Bin; Luo, Liqiang; Pei, Renjun

    2016-06-13

    Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one-step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM(-1) s(-1)), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM(-1) s(-1)), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI. PMID:27187578

  12. Agent based modeling of the effects of potential treatments over the blood-brain barrier in multiple sclerosis.

    PubMed

    Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

    2015-12-01

    Multiple sclerosis is a disease of the central nervous system that involves the destruction of the insulating sheath of axons, causing severe disabilities. Since the etiology of the disease is not yet fully understood, the use of novel techniques that may help to understand the disease, to suggest potential therapies and to test the effects of candidate treatments is highly advisable. To this end we developed an agent based model that demonstrated its ability to reproduce the typical oscillatory behavior observed in the most common form of multiple sclerosis, relapsing-remitting multiple sclerosis. The model has then been used to test the potential beneficial effects of vitamin D over the disease. Many scientific studies underlined the importance of the blood-brain barrier and of the mechanisms that influence its permeability on the development of the disease. In the present paper we further extend our previously developed model with a mechanism that mimics the blood-brain barrier behavior. The goal of our work is to suggest the best strategies to follow for developing new potential treatments that intervene in the blood-brain barrier. Results suggest that the best treatments should potentially prevent the opening of the blood-brain barrier, as treatments that help in recovering the blood-brain barrier functionality could be less effective. PMID:26343337

  13. Discovery of wall teichoic acid inhibitors as potential anti-MRSA β-lactam combination agents.

    PubMed

    Wang, Hao; Gill, Charles J; Lee, Sang H; Mann, Paul; Zuck, Paul; Meredith, Timothy C; Murgolo, Nicholas; She, Xinwei; Kales, Susan; Liang, Lianzhu; Liu, Jenny; Wu, Jin; Santa Maria, John; Su, Jing; Pan, Jianping; Hailey, Judy; Mcguinness, Debra; Tan, Christopher M; Flattery, Amy; Walker, Suzanne; Black, Todd; Roemer, Terry

    2013-02-21

    Innovative strategies are needed to combat drug resistance associated with methicillin-resistant Staphylococcus aureus (MRSA). Here, we investigate the potential of wall teichoic acid (WTA) biosynthesis inhibitors as combination agents to restore β-lactam efficacy against MRSA. Performing a whole-cell pathway-based screen, we identified a series of WTA inhibitors (WTAIs) targeting the WTA transporter protein, TarG. Whole-genome sequencing of WTAI-resistant isolates across two methicillin-resistant Staphylococci spp. revealed TarG as their common target, as well as a broad assortment of drug-resistant bypass mutants mapping to earlier steps of WTA biosynthesis. Extensive in vitro microbiological analysis and animal infection studies provide strong genetic and pharmacological evidence of the potential effectiveness of WTAIs as anti-MRSA β-lactam combination agents. This work also highlights the emerging role of whole-genome sequencing in antibiotic mode-of-action and resistance studies.

  14. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials

    PubMed Central

    Xu, Liang; Wu, Xiaobo; Hu, Chun; Zhang, Zhiying; Zhang, Le; Liang, Shujing; Xu, Yingchun; Zhang, Fengchun

    2016-01-01

    Nowadays, the philosophy of treating metastatic breast cancer (MBC) is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015) comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS), and the secondary end points were the progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 toxicities. The pooled hazard ratio (HR) and pooled risk ratio (RR) were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84–0.96, P=0.002), PFS (HR 0.81, 95% CI 0.76–0.88, P<0.001), and ORR (RR 1.72, 95% CI 1.34–2.21, P<0.001). Notably, subgroup analysis failed to favor the targeted agent-based combination in terms of OS (HR 1.08, 95% CI 0.89–1.31, P=0.365), PFS (HR 1.09, 95% CI 0.88–1.35, P=0.433), and ORR (RR 1.60, 95% CI 0.69–3.71, P=0.278) compared with single agent. In addition, although more hematological and gastrointestinal toxicities were observed in the doublet agents group, they were acceptable and manageable. Taken together, when compared with single-agent therapy, doublet agents should be considered a treatment option because of the superior efficacy and the manageable safety profile for the prior anthracycline- and taxane-treated MBC patients. PMID:27445497

  15. A meta-analysis of combination therapy versus single-agent therapy in anthracycline- and taxane-pretreated metastatic breast cancer: results from nine randomized Phase III trials.

    PubMed

    Xu, Liang; Wu, Xiaobo; Hu, Chun; Zhang, Zhiying; Zhang, Le; Liang, Shujing; Xu, Yingchun; Zhang, Fengchun

    2016-01-01

    Nowadays, the philosophy of treating metastatic breast cancer (MBC) is slowly evolving. Especially for the anthracycline- and taxane-pretreated MBC patients, no standard therapy exists in this setting. Whether to choose doublet agents or single agent as salvage treatment remains fiercely debated. Thus, we conducted a meta-analysis to resolve this problem. Databases including PubMed, EMBASE, and Cochrane library were searched for Phase III randomized clinical trials (published before August 2015) comparing the efficacy and adverse effects between the combination therapy and single-agent therapy in anthracycline- and taxane-pretreated MBC patients. The primary end point was the overall survival (OS), and the secondary end points were the progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 toxicities. The pooled hazard ratio (HR) and pooled risk ratio (RR) were used to evaluate the efficacy. Analyses were also performed to estimate the side effects and safety of both groups. In all, nine eligible randomized clinical trials were included in this meta-analysis. Improvements were proven in the doublet agents group on OS (HR 0.90, 95% confidence interval [CI] 0.84-0.96, P=0.002), PFS (HR 0.81, 95% CI 0.76-0.88, P<0.001), and ORR (RR 1.72, 95% CI 1.34-2.21, P<0.001). Notably, subgroup analysis failed to favor the targeted agent-based combination in terms of OS (HR 1.08, 95% CI 0.89-1.31, P=0.365), PFS (HR 1.09, 95% CI 0.88-1.35, P=0.433), and ORR (RR 1.60, 95% CI 0.69-3.71, P=0.278) compared with single agent. In addition, although more hematological and gastrointestinal toxicities were observed in the doublet agents group, they were acceptable and manageable. Taken together, when compared with single-agent therapy, doublet agents should be considered a treatment option because of the superior efficacy and the manageable safety profile for the prior anthracycline- and taxane-treated MBC patients. PMID:27445497

  16. Efficacy of gallium phthalocyanine as a photosensitizing agent in photodynamic therapy for the treatment of cancer

    NASA Astrophysics Data System (ADS)

    Maduray, Kaminee; Odhav, Bharti

    2012-12-01

    Photodynamic therapy is a revolutionary treatment aimed at treating cancers without surgery or chemotherapy. It is based on the discovery that certain chemicals known as photosensitizing agents (e.g. porphyrins, phthalocyanines, etc.) can kill cancerous cells when exposed to low level laser light at a specific wavelength. The present study investigates the cellular uptake and photodynamic effect of gallium (III) phthalocyanine chloride (GaPcCl) on Caco-2 cancer cells. Caco-2 cells were treated with different concentrations of GaPcCl for 2 h before treatment with a diode laser (λ = 661 nm, laser power = 90 mW) delivering a light dose of 2.5 J/cm2, 4.5 J/cm2 or 8.5 J/cm2. After 24 h, the cell viability of post-irradiated cells was measured using the MTT assay. Cellular uptake studies were performed by photosensitizing cells with GaPcCl for 30 min, 2 h, 10 h, 12 h, 18 h and 24 h before lysing the treated cells into solution to measure the GaPcCl fluorescence emission at an excitation wavelength of 600 nm. Results showed an increase in fluorescence intensity of emission peaks at longer incubation times, indicating a greater cellular uptake of GaPcCl by Caco-2 cells at 24 h in comparison to 30 min. GaPcCl at a concentration of 100 μg/ml activated with a laser light dose of 8.5 J/cm2 reduced the cell viability of Caco-2 cells to 27%. This concludes that GaPcCl activated with low level laser light can be used as a photosensitizing agent for the in vitro PDT treatment of colon cancer.

  17. Single agent nanoparticle for radiotherapy and radio-photothermal therapy in anaplastic thyroid cancer.

    PubMed

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y; Li, Chun

    2015-07-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [(64)Cu]CuS NPs, in which the radiotherapeutic property of (64)Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG-[(64)Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[(64)Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[(64)Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC.

  18. Single Agent Nanoparticle for Radiotherapy and Radio-Photothermal Therapy in Anaplastic Thyroid Cancer

    PubMed Central

    Zhou, Min; Chen, Yunyun; Adachi, Makoto; Wen, Xiaoxia; Erwin, Bill; Mawlawi, Osama; Lai, Stephen Y.; Li, Chun

    2015-01-01

    Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human malignancies. The aggressive behavior of ATC and its resistance to traditional treatment limit the efficacy of radiotherapy, chemotherapy, and surgery. The purpose of this study is aimed at enhancing the therapeutic efficacy of radiotherapy (RT) combined with photothermal therapy (PTT) in murine orthotopic model of ATC, based on our developed single radioactive copper sulfide (CuS) nanoparticle platform. We prepare a new dual-modality therapy for ATC consisting of a single-compartment nanoplatform, polyethylene glycol-coated [64Cu]CuS NPs, in which the radiotherapeutic property of 64Cu is combined with the plasmonic properties of CuS NPs. Mice with Hth83 ATC were treated with PEG[64Cu]CuS NPs and/or near infrared laser. Antitumor effects were assessed by tumor growth and animal survival. We found that in mice bearing orthotopic human Hth83 ATC tumors, micro-PET/CT imaging and biodistribution studies showed that about 50% of the injected dose of PEG-[64Cu]CuS NPs was retained in tumor 48 h after intratumoral injection. Human absorbed doses were calculated from biodistribution data. In antitumor experiments, tumor growth was delayed by PEG-[64Cu]CuS NP-mediated RT, PTT, and combined RT/PTT, with combined RT/PTT being most effective. In addition, combined RT/PTT significantly prolonged the survival of Hth83 tumor-bearing mice compared to no treatment, laser treatment alone, or NP treatment alone without producing acute toxic effects. These findings indicate that this single-compartment multifunctional NPs platform merits further development as a novel therapeutic agent for ATC. PMID:25913249

  19. Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy

    PubMed Central

    Turrini, Eleonora; Ferruzzi, Lorenzo; Fimognari, Carmela

    2015-01-01

    Cancer is the second leading cause of death and is becoming the leading one in old age. Vegetable and fruit consumption is inversely associated with cancer incidence and mortality. Currently, interest in a number of fruits high in polyphenols has been raised due to their reported chemopreventive and/or chemotherapeutic potential. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. This review provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of pomegranate polyphenols as future anticancer agents. Pomegranate evokes antiproliferative, anti-invasive, and antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins, upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate blocks the activation of inflammatory pathways including, but not limited to, the NF-κB pathway. The strongest evidence for its anticancer activity comes from studies on prostate cancer. Accordingly, some exploratory clinical studies investigating pomegranate found a trend of efficacy in increasing prostate-specific antigen doubling time in patients with prostate cancer. However, the genotoxicity reported for pomegranate raised certain concerns over its safety and an accurate assessment of the risk/benefit should be performed before suggesting the use of pomegranate or its polyphenols for cancer-related therapeutic purposes. PMID:26180600

  20. Secukinumab for rheumatology: development and its potential place in therapy.

    PubMed

    Koenders, Marije I; van den Berg, Wim B

    2016-01-01

    Rheumatic disease is not a single disorder, but a group of more than 100 diseases that affect joints, connective tissues, and/or internal organs. Although rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS) differ in their pathogenesis and clinical presentation, the treatment of these inflammatory disorders overlaps. Non-steroid anti-inflammatory drugs are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs are prescribed to slowdown disease progression, and is in RA more frequently and effectively applied than in AS. Biologicals are a relatively new class of treatments that specifically target cytokines or cells of the immune system, like tumor necrosis factor alpha inhibitors or B-cell blockers. A new kid on the block is the interleukin-17 (IL-17) inhibitor secukinumab, which has been recently approved by the US Food and Drug Administration for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS. IL-17 is a proinflammatory cytokine that has an important role in host defense, but its proinflammatory and destructive effects have also been linked to pathogenic processes in autoimmune diseases like RA and psoriasis. Animal models have greatly contributed to further insights in the potential of IL-17 blockade in autoimmune and autoinflammatory diseases, and have resulted in the development of various potential drugs targeting the IL-17 pathway. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to IL-17A and recently entered the market under the brand name Cosentyx(®). By binding to IL-17A, secukinumab prevents it from binding to its receptor and inhibits its ability to trigger inflammatory responses that play a role in the development of various autoimmune diseases. With secukinumab being the first in class to receive Food and Drug Administration approval, this article will further focus on this new biologic agent and review the

  1. Secukinumab for rheumatology: development and its potential place in therapy

    PubMed Central

    Koenders, Marije I; van den Berg, Wim B

    2016-01-01

    Rheumatic disease is not a single disorder, but a group of more than 100 diseases that affect joints, connective tissues, and/or internal organs. Although rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS) differ in their pathogenesis and clinical presentation, the treatment of these inflammatory disorders overlaps. Non-steroid anti-inflammatory drugs are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs are prescribed to slowdown disease progression, and is in RA more frequently and effectively applied than in AS. Biologicals are a relatively new class of treatments that specifically target cytokines or cells of the immune system, like tumor necrosis factor alpha inhibitors or B-cell blockers. A new kid on the block is the interleukin-17 (IL-17) inhibitor secukinumab, which has been recently approved by the US Food and Drug Administration for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS. IL-17 is a proinflammatory cytokine that has an important role in host defense, but its proinflammatory and destructive effects have also been linked to pathogenic processes in autoimmune diseases like RA and psoriasis. Animal models have greatly contributed to further insights in the potential of IL-17 blockade in autoimmune and autoinflammatory diseases, and have resulted in the development of various potential drugs targeting the IL-17 pathway. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to IL-17A and recently entered the market under the brand name Cosentyx®. By binding to IL-17A, secukinumab prevents it from binding to its receptor and inhibits its ability to trigger inflammatory responses that play a role in the development of various autoimmune diseases. With secukinumab being the first in class to receive Food and Drug Administration approval, this article will further focus on this new biologic agent and review the milestones

  2. Secukinumab for rheumatology: development and its potential place in therapy.

    PubMed

    Koenders, Marije I; van den Berg, Wim B

    2016-01-01

    Rheumatic disease is not a single disorder, but a group of more than 100 diseases that affect joints, connective tissues, and/or internal organs. Although rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS) differ in their pathogenesis and clinical presentation, the treatment of these inflammatory disorders overlaps. Non-steroid anti-inflammatory drugs are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs are prescribed to slowdown disease progression, and is in RA more frequently and effectively applied than in AS. Biologicals are a relatively new class of treatments that specifically target cytokines or cells of the immune system, like tumor necrosis factor alpha inhibitors or B-cell blockers. A new kid on the block is the interleukin-17 (IL-17) inhibitor secukinumab, which has been recently approved by the US Food and Drug Administration for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS. IL-17 is a proinflammatory cytokine that has an important role in host defense, but its proinflammatory and destructive effects have also been linked to pathogenic processes in autoimmune diseases like RA and psoriasis. Animal models have greatly contributed to further insights in the potential of IL-17 blockade in autoimmune and autoinflammatory diseases, and have resulted in the development of various potential drugs targeting the IL-17 pathway. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to IL-17A and recently entered the market under the brand name Cosentyx(®). By binding to IL-17A, secukinumab prevents it from binding to its receptor and inhibits its ability to trigger inflammatory responses that play a role in the development of various autoimmune diseases. With secukinumab being the first in class to receive Food and Drug Administration approval, this article will further focus on this new biologic agent and review the

  3. Identification of endoplasmic reticulum stress-inducing agents by antagonizing autophagy: a new potential strategy for identification of anti-cancer therapeutics in B-cell malignancies.

    PubMed

    Mahoney, Emilia; Maddocks, Kami; Flynn, Joseph; Jones, Jeffrey; Cole, Sara L; Zhang, Xiaoli; Byrd, John C; Johnson, Amy J

    2013-12-01

    The endoplasmic reticulum (ER) plays a vital function in multiple cellular processes. There is a growing interest in developing therapeutic agents that can target the ER in cancer cells, inducing a stress response that leads to cell death. However, ER stress-inducing agents can also induce autophagy, a survival strategy of cancer cells. Therefore, by inhibiting autophagy we can increase the efficacy of the ER stress-inducing agents. Nelfinavir, a human immunodeficiency virus (HIV) protease inhibitor with anti-cancer properties, can induce ER stress. Nelfinavir's effects on chronic lymphocytic leukemia (CLL) are yet to be elucidated. Herein we demonstrate that nelfinavir induces ER morphological changes and stress response, along with an autophagic protective strategy. Our data reveal that chloroquine, an autophagy inhibitor, significantly increases nelfinavir cytotoxicity. These results identify a novel strategy potentially effective in CLL treatment, by repositioning two well-known drugs as a combinatorial therapy with anti-cancer properties.

  4. First In Vivo Evaluation of Liposome-encapsulated 223Ra as a Potential Alpha-particle-emitting Cancer Therapeutic Agent

    SciTech Connect

    Jonasdottir, Thora J.; Fisher, Darrell R.; Borrebaek, Jorgen; Bruland, Oyvind S.; Larsen, Roy H.

    2006-09-13

    Liposomes carrying chemotherapeutics have had some success in cancer treatment and may be suitable carriers for therapeutic radionuclides. This study was designed to evaluate the biodistribution of and to estimate the radiation doses from the alpha emitter 223Ra loaded into pegylated liposomes in selected tissues. 223Ra was encapsulated in pegylated liposomal doxorubicin by ionophore-mediated loading. The biodistribution of liposomal 223Ra was compared to free cationic 223Ra in Balb/C mice. We showed that liposomal 223 Ra circulated in the blood with an initial half-time in excess of 24 hours, which agreed well with that reported for liposomal doxorubicin in rodents, while the blood half-time of cationic 223Ra was considerably less than one hour. When liposomal 223 Ra was catabolized, the released 223Ra was either excreted or taken up in the skeleton. This skeletal uptake increased up to 14 days after treatment, but did not reach the level seen with free 223Ra. Pre-treatment with non-radioactive liposomal doxorubicin 4 days in advance lessened the liver uptake of liposomal 223 Ra. Dose estimates showed that the spleen, followed by bone surfaces, received the highest absorbed doses. Liposomal 223 Ra was relatively stable in vivo and may have potential for radionuclide therapy and combination therapy with chemotherapeutic agents.

  5. The use of marine-derived bioactive compounds as potential hepatoprotective agents

    PubMed Central

    Nair, Dileep G; Weiskirchen, Ralf; Al-Musharafi, Salma K

    2015-01-01

    The marine environment may be explored as a rich source for novel drugs. A number of marine-derived compounds have been isolated and identified, and their therapeutic effects and pharmacological profiles are characterized. In the present review, we highlight the recent studies using marine compounds as potential hepatoprotective agents for the treatment of liver fibrotic diseases and discuss the proposed mechanisms of their activities. In addition, we discuss the significance of similar studies in Oman, where the rich marine life provides a potential for the isolation of novel natural, bioactive products that display therapeutic effects on liver diseases. PMID:25500871

  6. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

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

    PubMed

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

    2015-08-01

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

  8. HBO: a possible supplementary therapy for oral potentially malignant disorders.

    PubMed

    Ye, Xiaojing; Zhang, Jing; Lu, Rui; Zhou, Gang

    2014-08-01

    Oral potentially malignant disorders (OPMDs) are chronic inflammatory diseases in which cells suffer hypoxia referring to deprivation of adequate oxygen supply. Hyperbaric oxygen treatment (HBO), which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve or cure disorders involving hypoxia. Although the applications of HBO in wound healings, acute ischemic stroke, radiation-induced soft tissue injury and cancers are extensively reported, there are only few studies on their effect in OPMDs. Not only does HBO furnish oxygen-it also possesses potent anti-inflammatory properties. At the cellular level, HBO can decrease lymphocyte proliferation and promote apoptosis of fibroblasts. At the molecular level, it can decrease expression of HIF, ICAM-1, TNF-α, TGF-β, and IFN-γ, as well as increase vascular VEGF expression and angiogenesis. Thus, we hypothesize that HBO may contribute to treat OPMDs, including oral lichen planus, oral leukoplakia, and oral submucous fibrosis both at the cellular level and the molecular level, and that it would be a safe and inexpensive therapeutic strategy. PMID:24908359

  9. Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

    NASA Astrophysics Data System (ADS)

    Wang, Yan J.; Strohm, Eric M.; Kolios, Michael C.

    2016-03-01

    In this study, multifunctional theranostic agents for photoacoustic (PA), ultrasound (US), fluorescent imaging, and for therapeutic drug delivery were developed and tested. These agents consisted of a shell made from a biodegradable Poly(lactide-co-glycolic acid) (PLGA) polymer, loaded with perfluorohexane (PFH) liquid and gold nanoparticles (GNPs) in the core, and lipophilic carbocyanines fluorescent dye DiD and therapeutic drug Paclitaxel (PAC) in the shell. Their multifunctional capacity was investigated in an in vitro study. The PLGA/PFH/DiD-GNPs particles were synthesized by a double emulsion technique. The average PLGA particle diameter was 560 nm, with 50 nm diameter silica-coated gold nano-spheres in the shell. MCF7 human breast cancer cells were incubated with PLGA/PFH/DiDGNPs for 24 hours. Fluorescent and PA images were recorded using a fluorescent/PA microscope using a 1000 MHz transducer and a 532 nm pulsed laser. For the particle vaporization and drug delivery test, MCF7 cells were incubated with the PLGA/PFH-GNPs-PAC or PLGA/PFH-GNPs particles for 6, 12 and 24 hours. The effects of particle vaporization and drug delivery inside the cells were examined by irradiating the cells with a laser fluence of 100 mJ/cm2, and cell viability quantified using the MTT assay. The PA images of MCF7 cells containing PLGA/PFH/DiD-GNPs were spatially coincident with the fluorescent images, and confirmed particle uptake. After exposure to the PLGA/PFHGNP- PAC for 6, 12 and 24 hours, the cell survival rate was 43%, 38%, and 36% respectively compared with the control group, confirming drug delivery and release inside the cells. Upon vaporization, cell viability decreased to 20%. The particles show potential as imaging agents and drug delivery vehicles.

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

    PubMed Central

    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

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

    PubMed

    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.

  12. Endoplasmic Reticulum-Localized Iridium(III) Complexes as Efficient Photodynamic Therapy Agents via Protein Modifications.

    PubMed

    Nam, Jung Seung; Kang, Myeong-Gyun; Kang, Juhye; Park, Sun-Young; Lee, Shin Jung C; Kim, Hyun-Tak; Seo, Jeong Kon; Kwon, Oh-Hoon; Lim, Mi Hee; Rhee, Hyun-Woo; Kwon, Tae-Hyuk

    2016-08-31

    Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen ((1)O2) and superoxide radical (O2(•-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes. PMID:27494510

  13. Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

    PubMed

    Wu, Man; Guo, Qiaoyan; Xu, Feng; Liu, Shujun; Lu, Xuehong; Wang, Jing; Gao, Hongwen; Luo, Ping

    2016-08-15

    Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine. PMID:27214146

  14. In vitro efficiency and mechanistic role of indocyanine green as photodynamic therapy agent for human melanoma

    SciTech Connect

    Mamoon, A.M.; Miller, L.; Gamal-Eldeen, A. M.; Ruppel, M. E.; Smith, R. J.; Tsang, T.; Miller, L. M.

    2009-05-02

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800 nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway. Human skin melanoma cells (Sk-Mel-28) were incubated with ICG and exposed to a low power Ti:Sapphire laser. Synchrotron-assisted Fourier transform infrared microspectroscopy and hierarchical cluster analysis were used to assess the cell damage and changes in lipid, protein, and nucleic acids. The cell death pathway was determined by analysis of cell viability and apoptosis and necrosis markers. In the cell death pathway, {sup 1}O{sub 2} generation evoked rapid multiple consequences that trigger apoptosis after laser exposure for only 15min including the release of cytochrome c, the activation of total caspases, caspase-3, and caspase-9, the inhibition of NF-{Kappa}B P65, and the enhancement of DNA fragmentation, and histone acetylation. ICG/PDT can efficiently and rapidly induce apoptosis in human melanoma cells and it can be considered as a new therapeutic approach for topical treatment of melanoma.

  15. Hybrid graphene/Au activatable theranostic agent for multimodalities imaging guided enhanced photothermal therapy.

    PubMed

    Gao, Shi; Zhang, Liwen; Wang, Guohao; Yang, Kai; Chen, Minglong; Tian, Rui; Ma, Qingjie; Zhu, Lei

    2016-02-01

    Photothermal therapy (PTT) has been increasingly investigated. However, there are still challenges in strategies that can further enhance photoconversion efficiency and improve photothermal tumor ablation effect of current nanomaterials. Herein, we developed a fluorescent/photoacoustic imaging guided PTT agent by seeding Gold (Au) nanoparticles onto graphene oxide (GO). Near infrared dye (Cy5.5) labeled-matrix metalloproteinase-14 (MMP-14) substrate (CP) was conjugated onto the GO/Au complex (GA) forming tumor targeted theranostic probe (CPGA), whereCy5.5 fluorescent signal is quenched by Surface Plasmon Resonance (SPR) capacity from both GO and Au, yet it can boost strong fluorescence signals after degradation by MMP-14. The photothermal effect of GA hybrid was found significantly elevated compared with Au or GO alone. After intravenous administration of CPGA into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.64 ± 0.51 for optical imaging and 2.5 ± 0.27 for PA imaging). The tumors were then irradiated with a laser, and an excellent tumor inhibition was observedwithoutrecurrence. Our studies further encourage applications of the hybrid nanocomposite for image-guided enhanced PTT in biomedical applications, especially in cancer theranostics. PMID:26691399

  16. Cobalt Zinc Ferrite Nanoparticles as a Potential Magnetic Resonance Imaging Agent: An In vitro Study

    PubMed Central

    Ghasemian, Zeinab; Shahbazi-Gahrouei, Daryoush; Manouchehri, Sohrab

    2015-01-01

    Background: Magnetic Nanoparticles (MNP) have been used for contrast enhancement in Magnetic Resonance Imaging (MRI). In recent years, research on the use of ferrite nanoparticles in T2 contrast agents has shown a great potential application in MR imaging. In this work, Co0.5Zn0.5Fe2O4 and Co0.5Zn0.5Fe2O4-DMSA magnetic nanoparticles, CZF-MNPs and CZF-MNPs-DMSA, were investigated as MR imaging contrast agents. Methods: Cobalt zinc ferrite nanoparticles and their suitable coating, DMSA, were investigated under in vitro condition. Human prostate cancer cell lines (DU145 and PC3) with bare (uncoated) and coated magnetic nanoparticles were investigated as nano-contrast MR imaging agents. Results: Using T2-weighted MR images identified that signal intensity of bare and coated MNPs was enhanced with increasing concentration of MNPs in water. The values of 1/T2 relaxivity (r2) for bare and coated MNPs were found to be 88.46 and 28.80 (mM−1 s−1), respectively. Conclusion: The results show that bare and coated MNPs are suitable as T2-weighted MR imaging contrast agents. Also, the obtained r2/r1 values (59.3 and 50) for bare and coated MNPs were in agreement with the results of other previous relevant works. PMID:26140183

  17. Quantum dots and potential therapy for Krabbe's disease.

    PubMed

    Dawson, Glyn

    2016-11-01

    Enzyme replacement therapy and substrate reduction therapy have proved useful in reversing many pathological consequences of many nonneural lysosomal storage diseases but have not yet reversed pathology or influenced disease outcome in Krabbe's disease (KD). This Review discusses the relative merits of stem cell therapy, molecular chaperone therapy, gene therapy, substrate reduction therapy, enzyme replacement therapy, and combination therapy. Given the limitations of these approaches, this Review introduces the idea of using tiny, 6-nm, intensely fluorescent quantum dots (QDs) to deliver a cell-penetrating peptide and 6 histidine residue-tagged β-D-galactocerebrosidase across the blood-brain barrier. We can therefore follow the fate of injected material and ensure that all targets are reached and that accumulated material is degraded. Uptake of lysosomal hydrolases is a complex process, and the cell-penetrating peptide JB577 is uniquely able to promote endosomal egress of the QD cargo. This Review further shows that uptake may depend on the charge of the coating of the QD, specifically, that negative charge directs the cargo to neurons. Because KD involves primarily glia, specifically oligodendroglia, we experiment with many coatings and discover a coating (polyethylene glycol 600 amino) that has a positive charge and targets oligodendrocytes. A similar effect is achieved by treating with chondroitinase ABC to degrade the extracellular matrix, indicating that enzyme replacement has several hurdles to overcome before it can become a routine CNS therapy. © 2016 Wiley Periodicals, Inc. PMID:27638611

  18. [Effect of antidepressive agents on serotonin secretion and membrane potential changes in thrombocytes].

    PubMed

    Pogady, J

    1983-06-01

    Antidepressants (Amitriptylin, Imipramine, Ludiomil, Alival) at the concentrations present in the blood during treatment do not inhibit serotonin secretion by human blood platelets. This also applies for the concentrations at which they are present in the blood during therapy. The same antidepressants do inhibit the changes in membrane potential accompanying serotonin secretion. This suggests that there is a weak interaction between the antidepressants and the secretion mechanism.

  19. mTOR Inhibitors and Their Potential Role in Therapy in Leukemia and Other Haematologic Malignancies

    PubMed Central

    Teachey, David T.; Grupp, Stephan A.; Brown, Valerie I.

    2009-01-01

    Summary The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that functions as a key regulator of cell growth, protein synthesis, and cell-cycle progression through interactions with a number of signaling pathways, including PI3K/AKT, ras, TCL1, and BCR/ABL. Many haematologic malignancies have aberrant activation of the mTOR and related signaling pathways. Accordingly, mTOR inhibitors, a class of signal transduction inhibitors that were originally developed as immunosuppressive agents, are being investigated in preclinical models and clinical trials for a number of haematologic malignancies. Sirolimus and second generation mTOR inhibitors such as temsirolimus and everolimus, are safe and relatively well-tolerated, making them potentially attractive as single agents or in combination with conventional cytotoxics and other targeted therapies. Promising early clinical data suggests activity of mTOR inhibitors in a number of haematologic diseases, including acute lymphoblastic leukemia, chronic myelogenous leukemia, mantle cell lymphoma, anaplastic large cell lymphoma, and lymphoproliferative disorders. This review describes the rationale for using mTOR inhibitors in a variety of haematologic diseases with a focus on their use in leukemia. PMID:19344392

  20. Synthesis and pharmacological evaluation of some new fluorine containing hydroxypyrazolines as potential anticancer and antioxidant agents.

    PubMed

    Dinesha; Viveka, Shivapura; Priya, Bolli Keerthi; Pai, K Sreedhara Ranganath; Naveen, Shivalingegowda; Lokanath, Neratur K; Nagaraja, Gundibasappa Karikannar

    2015-11-01

    Breast cancer is probably the most prevalent cancer in women. The development of resistance to therapeutic agents and lack of targeted therapy for breast cancer cells provide motivation to identify new compounds for the treatment. With this objective in mind, a new series of 3-fluoro-4-methoxyphenyl group based 1,3,5-trisubstituted aryl-5-hydroxypyrazoline analogues 4a-l was synthesized through multi-step reaction sequence. The structures of the newly synthesized compounds were confirmed by IR, (1)H NMR, (13)C NMR, LC-MS and elemental analysis. They were screened for their in vitro anticancer and in vitro antioxidant activities. Among the tested compounds 4h, 4c and particularly 4i displayed promising cytotoxic effect on breast cancer cell lines. The compounds were also found to possess antioxidant activity when tested against DPPH free radical. Overall, this work has contributed to the development of promising leads for anticancer and antioxidant activities.

  1. Design, synthesis, molecular modeling, and biological evaluation of sulfanilamide-imines derivatives as potential anticancer agents.

    PubMed

    Mohamed, Sofian S; Tamer, Abdalkarem R; Bensaber, Salah M; Jaeda, Mousa I; Ermeli, Nouri B; Allafi, Aemen Ali; Mrema, Ibrahim A; Erhuma, Mabrouk; Hermann, Anton; Gbaj, Abdul M

    2013-09-01

    A series of sulfanilamide Schiff base derivatives (1 to 15) have been designed as potential antitubulin agents depending on the chemical structures of combretastatine A-4 and isoquinoline sulfamate (antimitotic agents under investigation). The designed compounds were synthesized by microwave chemical synthesis, their purity was confirmed by melting point and HPLC and chemical structures were determined by FT-IR, UV, and 1H and 13C-NMR spectroscopic techniques. The synthesized compounds have been docked in the colchicine binding site of β-tubulin using molecular modeling programs and the antitumor activities were screened on human breast and lung cancer cells by cell counting assay. Some tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC50 range of 90 to 166 μM. With regarding broad-spectrum activity, compounds 4, 8, and 13 have shown potent antitumor activity against human breast and human lung cells with IC50 range of 96 to 140 μM. The obtained results suggest that the sulfanilamide Schiff base derivatives might potentially constitute an interesting novel class of anticancer agents, which deserve further studies. PMID:23708566

  2. Chitosan oligosaccharide based Gd-DTPA complex as a potential bimodal magnetic resonance imaging contrast agent.

    PubMed

    Huang, Yan; Cao, Juan; Zhang, Qi; Lu, Zheng-rong; Hua, Ming-qing; Zhang, Xiao-yan; Gao, Hu

    2016-01-01

    A new gadolinium diethylenetriamine pentaacetic acid (DTPA) complex (Gd-DTPA-DMABA-CS11) as a potential bimodal magnetic resonance imaging (MRI) contrast agent with fluorescence was synthesized. It was synthesized by the incorporation of 4-dimethylaminobenzaldehyde (DMABA) and chitosan oligosaccharide (CSn; n=11) with low polydispersity index to DTPA anhydride and then chelated with gadolinium chloride. The structure was characterized by Fourier transform infrared (FTIR), (1)H NMR, elemental analysis and size exclusion chromatography (SEC). MRI measurements in vitro were evaluated. The results indicated that Gd-DTPA-DMABA-CS11 provided higher molar longitudinal relaxivity (r1) (12.95mM(-1)·s(-1)) than that of commercial Gd-DTPA (3.63mM(-1)·s(-1)) at 0.5T. Gd-DTPA-DMABA-CS11 also emitted fluorescence, and the intensity was much stronger than that of Gd-DTPA. Therefore, it can be meanwhile used in fluorescent imaging for improving the sensitivity in clinic diagnosis. Gd-DTPA-DMABA-CS11 as a potential contrast agent is preliminarily stable in vitro. The results of thermodynamic action between Gd-DTPA-DMABA-CS11 and bovine serum albumin (BSA) illustrated that the binding process was exothermic and spontaneous, and the main force was van der Waals' interaction and hydrogen bond. The preliminary study suggested that Gd-DTPA-DMABA-CS11 could be used in both magnetic resonance and fluorescent imaging as a promising bimodal contrast agent.

  3. Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs

    PubMed Central

    Shan, T.; Ma, Q.; Guo, K.; Liu, J.; Li, W.; Wang, F.; Wu, E.

    2011-01-01

    Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent. PMID:21902651

  4. Synthesis and evaluation of novel tropane derivatives as potential PET imaging agents for the dopamine transporter

    PubMed Central

    Qiao, Hongwen; Zhu, Lin; Lieberman, Brian P.; Zha, Zhihao; Plössl, Karl; Kung, Hank F.

    2012-01-01

    A novel series of tropane derivatives containing a fluorinated tertiary amino or amide at the 2β position was synthesized, labeled with the positron-emitter fluorine-18 (T1/2 = 109.8 min), and tested as potential in vivo dopamine transporter (DAT) imaging agents. The corresponding chlorinated analogs were prepared and employed as precursors for radiolabeling leading to the fluorine-18-labeled derivatives via a one-step nucleophilic aliphatic substitution reaction. In vitro binding results showed that the 2β-amino compounds 6b, 6d and 7b displayed moderately high affinities to DAT (Ki < 10 nM). Biodistribution studies of [18F]6b and [18F]6d showed that the brain uptakes in rats were low. This is likely due to their low lipophilicities. Further structural modifications of these tropane derivatives will be needed to improve their in vivo properties as DAT imaging agents. PMID:22658558

  5. Novel C6-substituted 1,3,4-oxadiazinones as potential anti-cancer agents

    PubMed Central

    Jung, Yujin; Yun, Hye Jeong; Min, Hye-Young; Lee, Ho Jin; Pham, Phuong Chi; Moon, Jayoung; Kwon, Dah In; Lim, Bumhee; Suh, Young-Ger; Lee, Jeeyeon; Lee, Ho-Young

    2015-01-01

    The insulin-like growth factor 1 receptor (IGF-1R) is a membrane receptor tyrosine kinase over-expressed in a number of tumors. However, combating resistance is one of the main challenges in the currently available IGF-1R inhibitor-based cancer therapies. Increased Src activation has been reported to confer resistance to anti-IGF-1R therapeutics in various tumor cells. An urgent unmet need for IGF-1R inhibitors is to suppress Src rephosphorylation induced by current anti-IGF-1R regimens. In efforts to develop effective anticancer agents targeting the IGF-1R signaling pathway, we explored 2-aryl-1,3,4-oxadiazin-5-ones as a novel scaffold that is structurally unrelated to current tyrosine kinase inhibitors (TKIs). The compound, LL-2003, exhibited promising antitumor effects in vitro and in vivo; it effectively suppressed IGF-1R and Src and induced apoptosis in various non-small cell lung cancer cells. Further optimizations for enhanced potency in cellular assays need to be followed, but our strategy to identify novel IGF-1R/Src inhibitors may open a new avenue to develop more efficient anticancer agents. PMID:26515601

  6. Vitamin D compounds: clinical development as cancer therapy and prevention agents.

    PubMed

    Trump, Donald L; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2006-01-01

    While 1,25 dihydroxycholecalciferol (calcitriol) is best recognized for its effects on bone and mineral metabolism, epidemiological data indicate that low vitamin D levels may play a role in the genesis and progression of breast, lung, colorectal and prostate cancer, as well as malignant lymphoma and melanoma. Calcitriol has strong antiproliferative effects in prostate, breast, colorectal, head/neck and lung cancer, as well as lymphoma, leukemia and myeloma model systems. Antiproliferative effects are seen in vitro and in vivo. The mechanisms of these effects are associated with G0/G1 arrest, induction of apoptosis, differentiation and modulation of growth factor-mediated signaling in tumor cells. In addition to the direct effects on tumor cells, recent data strongly support the hypothesis that the stromal effects of vitamin D analogs (e.g., direct effects on tumor vasculature) are also important in the antiproliferative effects. Antitumor effects are seen in a wide variety of tumor types and there are few data to suggest that vitamin D-based approaches are more effective in any one tumor type. Glucocorticoids potentiate the antitumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. In addition, calcitriol potentiates the antitumor effects of many cytotoxic agents. Preclinical data indicate that maximal antitumor effects are seen with pharmacological doses of calcitriol and that such exposure can be safely achieved in animals using a high dose, intermittent schedule of administration. AUC and C(max) calcitriol concentrations of 32 ng.h/ml and 9.2 ng/ml are associated with striking antitumor effects in a murine squamous cell carcinoma model and there is increasing evidence from clinical trials that such exposures can be safely attained in patients. Another approach to maximizing intra-tumoral exposure to vitamin D analogs is to inhibit their catabolism. The data clearly indicate that agents which inhibit the major vitamin D catabolizing enzyme

  7. Vitamin D compounds: clinical development as cancer therapy and prevention agents.

    PubMed

    Trump, Donald L; Muindi, Josephia; Fakih, Marwan; Yu, Wei-Dong; Johnson, Candace S

    2006-01-01

    While 1,25 dihydroxycholecalciferol (calcitriol) is best recognized for its effects on bone and mineral metabolism, epidemiological data indicate that low vitamin D levels may play a role in the genesis and progression of breast, lung, colorectal and prostate cancer, as well as malignant lymphoma and melanoma. Calcitriol has strong antiproliferative effects in prostate, breast, colorectal, head/neck and lung cancer, as well as lymphoma, leukemia and myeloma model systems. Antiproliferative effects are seen in vitro and in vivo. The mechanisms of these effects are associated with G0/G1 arrest, induction of apoptosis, differentiation and modulation of growth factor-mediated signaling in tumor cells. In addition to the direct effects on tumor cells, recent data strongly support the hypothesis that the stromal effects of vitamin D analogs (e.g., direct effects on tumor vasculature) are also important in the antiproliferative effects. Antitumor effects are seen in a wide variety of tumor types and there are few data to suggest that vitamin D-based approaches are more effective in any one tumor type. Glucocorticoids potentiate the antitumor effect of calcitriol and decrease calcitriol-induced hypercalcemia. In addition, calcitriol potentiates the antitumor effects of many cytotoxic agents. Preclinical data indicate that maximal antitumor effects are seen with pharmacological doses of calcitriol and that such exposure can be safely achieved in animals using a high dose, intermittent schedule of administration. AUC and C(max) calcitriol concentrations of 32 ng.h/ml and 9.2 ng/ml are associated with striking antitumor effects in a murine squamous cell carcinoma model and there is increasing evidence from clinical trials that such exposures can be safely attained in patients. Another approach to maximizing intra-tumoral exposure to vitamin D analogs is to inhibit their catabolism. The data clearly indicate that agents which inhibit the major vitamin D catabolizing enzyme

  8. A whole-body pharmacokinetic model for the early assessment of targeted radionuclide therapy agents

    NASA Astrophysics Data System (ADS)

    Grudzinski, Joseph J.

    Early assessment of targeted radionuclide therapy (TRT) agent effectiveness based on its pharmacokinetic (PK) properties could provide a means to expedite agent development or rejection. A whole-body PK model was developed that not only simplifies the complex radiation dosimetry and physiology of TRT but also provides criteria for normal tissue and tumor PK parameters that achieve effective TRT while limiting toxicity. Because biologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumor response relationships, the model was expanded to include BED. The model consisted of two coupled normal body compartments and one decoupled tumor compartment. Differential equations were used to develop an equation that predicted TRT efficacy. PK scenarios were created by pairing normal body influx and efflux parameters with a range of tumor influx and efflux parameters. Each PK scenario yielded a maximum delivered tumor absorbed dose that limited the whole body dose to 2 Gy. The dose rate and repair rate were used for BED. The relationships between the tumor influx-to-efflux ratio (k34:k 43), central compartment efflux-to-influx ratio (k12:k 21), central elimination (ke1), and tumor repair rate (mu), and tumor BED were investigated. The model was used to find the PK parameters for NM404 and FLT within a xenograft model. The TCC of both Compartment 1 and tumor were fit to the equations of the model using Levenberg-Marquardt. The parameter errors were propagated into dosimetry uncertainties. Sensitivity functions were derived for each PK parameter that described the change in TCC as a result of a change in the PK parameter value at each time. Cramer-Rao Lower Bounds (CRLB) theory was used to derive optimal sampling schedules based on the sensitivity of the derived PK parameters. The experimental and optimal sampling schedules were compared by running simulations that measured the precision and accuracy of the measured PK parameters

  9. Use of cannabinoid receptor agonists in cancer therapy as palliative and curative agents.

    PubMed

    Pisanti, Simona; Malfitano, Anna Maria; Grimaldi, Claudia; Santoro, Antonietta; Gazzerro, Patrizia; Laezza, Chiara; Bifulco, Maurizio

    2009-02-01

    Cannabinoids (the active components of Cannabis sativa) and their derivatives have received renewed interest in recent years due to their diverse pharmacological activities. In particular, cannabinoids offer potential applications as anti-tumour drugs, based on the ability of some members of this class of compounds to limit cell proliferation and to induce tumour-selective cell death. Although synthetic cannabinoids may have pro-tumour effects in vivo due to their immunosuppressive properties, predominantly inhibitory effects on tumour growth and migration, angiogenesis, metastasis, and also inflammation have been described. Emerging evidence suggests that agonists of cannabinoid receptors expressed by tumour cells may offer a novel strategy to treat cancer. In this chapter we review the more recent results generating interest in the field of cannabinoids and cancer, and provide novel suggestions for the development, exploration and use of cannabinoid agonists for cancer therapy, not only as palliative but also as curative drugs.

  10. Cancer nanotechnology: a new commercialization pipeline for diagnostics, imaging agents, and therapies

    NASA Astrophysics Data System (ADS)

    Ptak, Krzysztof; Farrell, Dorothy; Hinkal, George; Panaro, Nicholas J.; Hook, Sara; Grodzinski, Piotr

    2011-06-01

    Nanotechnology - the science and engineering of manipulating matter at the molecular scale to create devices with novel chemical, physical and biological properties - has the potential to radically change oncology. Research sponsored by the NCI Alliance for Nanotechnology in Cancer has led to the development of nanomaterials as platforms of increasing complexity and devices of superior sensitivity, speed and multiplexing capability. Input from clinicians has guided researchers in the design of technologies to address specific needs in the areas of cancer therapy and therapeutic monitoring, in vivo imaging, and in vitro diagnostics. The promising output from the Alliance has led to many new companies being founded to commercialize their nanomedical product line. Furthermore, several of these technologies, which are discussed in this paper, have advanced to clinically testing.

  11. Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Pablico, Michele Huelar

    Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is

  12. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  13. Effects of Potential Therapeutic Agents on Copper Accumulations in Gill of Crassostrea virginica

    PubMed Central

    Luxama, Juan D.; Carroll, Margaret A.; Catapane, Edward J.

    2010-01-01

    Copper is an essential trace element for organisms, but when in excess, copper’s redox potential enhances oxyradical formation and increases cellular oxidative stress. Copper is a major pollutant in Jamaica Bay and other aquatic areas. Bivalves are filter feeders that accumulate heavy metals and other pollutants from their environment. Previously it was determined that seed from the bivalve Crassostrea virginica, transplanted from an oyster farm to Jamaica Bay readily accumulated copper and other pollutants into their tissues. In the present study we utilized Atomic Absorption Spectrometry to measure the uptake of copper into C. virginica gill in the presence and absence of three potential copper -blocking agents: diltiazem, lanthanum, and p-aminosalicyclic acid. Diltiazem and lanthanum are known calcium-channel blockers and p-aminosalicylic acid is an anti-infammarory agent with possible metal chelating properties. We also used the DMAB-Rhodanine histochemistry staining technique to confirm that copper was entering gill cells. Our result showed that diltiazem and p-aminosalicyclic acid reduced copper accumulations in the gill, while lanthanum did not. DMAB-Rhodanine histochemistry showed enhanced cellular copper staining in copper-treated samples and further demonstrated that diltiazem was able to reduce copper uptake. The accumulation of copper into oyster gill and its potential toxic effects could be of physiological significance to the growth and long term health of oysters and other marine animals living in a copper polluted environment. Identifying agents that block cellular copper uptake will further the understanding of metal transport mechanisms and may be beneficial in the therapeutic treatment of copper toxicity in humans. PMID:21841975

  14. Effects of Potential Therapeutic Agents on Copper Accumulations in Gill of Crassostrea virginica.

    PubMed

    Luxama, Juan D; Carroll, Margaret A; Catapane, Edward J

    2010-01-01

    Copper is an essential trace element for organisms, but when in excess, copper's redox potential enhances oxyradical formation and increases cellular oxidative stress. Copper is a major pollutant in Jamaica Bay and other aquatic areas. Bivalves are filter feeders that accumulate heavy metals and other pollutants from their environment. Previously it was determined that seed from the bivalve Crassostrea virginica, transplanted from an oyster farm to Jamaica Bay readily accumulated copper and other pollutants into their tissues. In the present study we utilized Atomic Absorption Spectrometry to measure the uptake of copper into C. virginica gill in the presence and absence of three potential copper -blocking agents: diltiazem, lanthanum, and p-aminosalicyclic acid. Diltiazem and lanthanum are known calcium-channel blockers and p-aminosalicylic acid is an anti-infammarory agent with possible metal chelating properties. We also used the DMAB-Rhodanine histochemistry staining technique to confirm that copper was entering gill cells. Our result showed that diltiazem and p-aminosalicyclic acid reduced copper accumulations in the gill, while lanthanum did not. DMAB-Rhodanine histochemistry showed enhanced cellular copper staining in copper-treated samples and further demonstrated that diltiazem was able to reduce copper uptake. The accumulation of copper into oyster gill and its potential toxic effects could be of physiological significance to the growth and long term health of oysters and other marine animals living in a copper polluted environment. Identifying agents that block cellular copper uptake will further the understanding of metal transport mechanisms and may be beneficial in the therapeutic treatment of copper toxicity in humans. PMID:21841975

  15. Complex of C60 Fullerene with Doxorubicin as a Promising Agent in Antitumor Therapy

    NASA Astrophysics Data System (ADS)

    Prylutska, Svitlana V.; Skivka, Larysa M.; Didenko, Gennadiy V.; Prylutskyy, Yuriy I.; Evstigneev, Maxim P.; Potebnya, Grygoriy P.; Panchuk, Rostyslav R.; Stoika, Rostyslav S.; Ritter, Uwe; Scharff, Peter

    2015-12-01

    The main aim of this work was to evaluate the effect of doxorubicin in complex with C60 fullerene (C60 + Dox) on the growth and metastasis of Lewis lung carcinoma in mice and to perform a primary screening of the potential mechanisms of C60 + Dox complex action. We found that volume of tumor from mice treated with the C60 + Dox complex was 1.4 times less than that in control untreated animals. The number of metastatic foci in lungs of animals treated with C60 + Dox complex was two times less than that in control untreated animals. Western blot analysis of tumor lysates revealed a significant decrease in the level of heat-shock protein 70 in animals treated with C60 + Dox complex. Moreover, the treatment of tumor-bearing mice was accompanied by the increase of cytotoxic activity of immune cells. Thus, the potential mechanisms of antitumor effect of C60 + Dox complex include both its direct action on tumor cells by inducing cell death and increasing of stress sensitivity and an immunomodulating effect. The obtained results provide a scientific basis for further application of C60 + Dox nanocomplexes as treatment agents in cancer chemotherapy.

  16. Quercetin and rutin as potential sunscreen agents: determination of efficacy by an in vitro method.

    PubMed

    Choquenet, Benjamin; Couteau, Céline; Paparis, Eva; Coiffard, Laurence J M

    2008-06-01

    Given that flavonoids are known for their ultraviolet (UV)B photoprotective properties in plants that contain them, we chose to study quercetin (1) and rutin (2) as agents that could potentially be used in sunscreen products. These two substances proved to behave in similar ways. When incorporated in oil-in-water emulsions, at a concentration of 10% (w/w), 1 and 2 give sun protection factor (SPF) values similar to that of homosalate, a standard substance. These two flavonoids also provided a non-negligible level of photoprotection in the UVA range. When used in association with titanium dioxide, the SPF obtained was around 30.

  17. Antioxidants as potential medical countermeasures for chemical warfare agents and toxic industrial chemicals.

    PubMed

    McElroy, Cameron S; Day, Brian J

    2016-01-15

    The continuing horrors of military conflicts and terrorism often involve the use of chemical warfare agents (CWAs) and toxic industrial chemicals (TICs). Many CWA and TIC exposures are difficult to treat due to the danger they pose to first responders and their rapid onset that can produce death shortly after exposure. While the specific mechanism(s) of toxicity of these agents are diverse, many are associated either directly or indirectly with increased oxidative stress in affected tissues. This has led to the exploration of various antioxidants as potential medical countermeasures for CWA/TIC exposures. Studies have been performed across a wide array of agents, model organisms, exposure systems, and antioxidants, looking at an almost equally diverse set of endpoints. Attempts at treating CWAs/TICs with antioxidants have met with mixed results, ranging from no effect to nearly complete protection. The aim of this commentary is to summarize the literature in each category for evidence of oxidative stress and antioxidant efficacy against CWAs and TICs. While there is great disparity in the data concerning methods, models, and remedies, the outlook on antioxidants as medical countermeasures for CWA/TIC management appears promising.

  18. Functional outcome after intracerebral haemorrhage - a review of the potential role of antiapoptotic agents.

    PubMed

    Salihu, Abubakar Tijjani; Muthuraju, Sangu; Idris, Zamzuri; Izaini Ghani, Abdul Rahman; Abdullah, Jafri Malin

    2016-04-01

    Intracerebral haemorrhage (ICH) is the second most common form of stroke and is associated with greater mortality and morbidity compared with ischaemic stroke. The current ICH management strategies, which mainly target primary injury mechanisms, have not been shown to improve patient's functional outcome. Consequently, multimodality treatment approaches that will focus on both primary and secondary pathophysiology have been suggested. During the last decade, a proliferation of experimental studies has demonstrated the role of apoptosis in secondary neuronal loss at the periphery of the clot after ICH. Subsequently, the value of certain antiapoptotic agents in reducing neuronal death and improving functional outcome following ICH was evaluated in animal models. Preliminary evidence from those studies strongly supports the potential role of antiapoptotic agents in reducing neuronal death and improving functional outcome after intracerebral haemorrhage. Expectedly, the ongoing and subsequent clinical trials will substantiate these findings and provide clear information on the most potent and safe antiapoptotic agents, their appropriate dosage, and temporal window of action, thereby making them suitable for the multimodality treatment approach. PMID:26641962

  19. Discovery of transition state factor Xa inhibitors as potential anticoagulant agents.

    PubMed

    Zhu, B Y; Huang, W; Su, T; Marlowe, C; Sinha, U; Hollenbach, S; Scarborough, R M

    2001-06-01

    Factor Xa is an attractive biological target in the discovery and development of either parenteral or orally active anticoagulant agents. Several strategies have been utilized at COR Therapeutics in the pursuit of tri-peptide based transition state mimetic factor Xa inhibitors with high aqueous solubility. Some of these inhibitors have displayed excellent in vitro potency in inhibiting factor Xa in the prothrombinase complex. More importantly, these compounds showed strong in vivo antithrombotic efficacy without significant bleeding complications in several animal thrombosis models. These results demonstrated that small molecule factor Xa inhibitors could be advantageous over Warfarin and LMWH. For the discovery and development of orally active anticoagulant agents, small organic molecules as reversible factor Xa inhibitors were explored. From a medicinal chemistry perspective, significant insight has been gained regarding the in vivo antithrombotic efficacy and pharmacokinetic behaviors of each class of factor Xa inhibitors. This review will focus on the design and discovery of transition state factor Xa inhibitors as potential parenteral anticoagulant agents. Several excellent comprehensive review articles on factor Xa inhibitors have appeared recently [1-4]. PMID:11899247

  20. Cardiocladius oliffi (Diptera: Chironomidae) as a potential biological control agent against Simulium squamosum (Diptera: Simuliidae)

    PubMed Central

    Boakye, Daniel A; Fokam, Eric; Ghansah, Anita; Amakye, Josef; Wilson, Michael D; Brown, Charles A

    2009-01-01

    Background The control of onchocerciasis in the African region is currently based mainly on the mass drug administration of ivermectin. Whilst this has been found to limit morbidity, it does not stop transmission. In the absence of a macrofilaricide, there is a need for an integrated approach for disease management, which includes vector control. Vector control using chemical insecticides is expensive to apply, and therefore the use of other measures such as biological control agents is needed. Immature stages of Simulium squamosum, reared in the laboratory from egg masses collected from the field at Boti Falls and Huhunya (River Pawnpawn) in Ghana, were observed to be attacked and fed upon by larvae of the chironomid Cardiocladius oliffi Freeman, 1956 (Diptera: Chironomidae). Methods Cardiocladius oliffi was successfully reared in the rearing system developed for S. damnosum s.l. and evaluated for its importance as a biological control agent in the laboratory. Results Even at a ratio of one C. oliffi to five S. squamosum, they caused a significant decrease in the number of adult S. squamosum emerging from the systems (treatments). Predation was confirmed by the amplification of Simulium DNA from C. oliffi observed to have fed on S. squamosum pupae. The study also established that the chironomid flies could successfully complete their development on a fish food diet only. Conclusion Cardiocladius oliffi has been demonstrated as potential biological control agent against S. squamosum. PMID:19393069

  1. Double layered hydroxides as potential anti-cancer drug delivery agents.

    PubMed

    Riaz, Ufana; Ashraf, S M

    2013-04-01

    The emergence of nanotechnology has changed the scenario of the medical world by revolutionizing the diagnosis, monitoring and treatment of cancer. This nanotechnology has been proved miraculous in detecting cancer cells, delivering chemotherapeutic agents and monitoring treatment from non-specific to highly targeted killing of tumor cells. In the past few decades, a number of inorganic materials have been investigated such as calcium phosphate, gold, carbon materials, silicon oxide, iron oxide, and layered double hydroxide (LDH) for examining their efficacy in targeting drug delivery. The reason behind the selection of these inorganic materials was their versatile and unique features efficient in drug delivery, such as wide availability, rich surface functionality, good biocompatibility, potential for target delivery, and controlled release of the drug from these inorganic nanomaterials. Although, the drug-LDH hybrids are found to be quite instrumental because of their application as advanced anti-cancer drug delivery systems, there has not been much research on them. This mini review is set to highlight the advancement made in the use of layered double hydroxides (LDHs) as anti-cancer drug delivery agents. Along with the advantages of LDHs as anti-cancer drug delivery agents, the process of interaction of some of the common anti-cancer drugs with LDH has also been discussed.

  2. ER maleate is a novel anticancer agent in oral cancer: implications for cancer therapy

    PubMed Central

    Fu, Guodong; Somasundaram, Raj Thani; Jessa, Fatima; Srivastava, Gunjan; MacMillan, Christina; Witterick, Ian; Walfish, Paul G.; Ralhan, Ranju

    2016-01-01

    ER maleate [10-(3-Aminopropyl)-3, 4-dimethyl-9(10H)-acridinone maleate] identified in a kinome screen was investigated as a novel anticancer agent for oral squamous cell carcinoma (OSCC). Our aim was to demonstrate its anticancer effects, identify putative molecular targets and determine their clinical relevance and investigate its chemosensitization potential for platinum drugs to aid in OSCC management. Biologic effects of ER maleate were determined using oral cancer cell lines in vitro and oral tumor xenografts in vivo. mRNA profiling, real time PCR and western blot revealed ER maleate modulated the expression of polo-like kinase 1 (PLK1) and spleen tyrosine kinase (Syk). Their clinical significance was determined in oral SCC patients by immunohistochemistry and correlated with prognosis by Kaplan-Meier survival and multivariate Cox regression analyses. ER maleate induced cell apoptosis, inhibited proliferation, colony formation, migration and invasion in oral cancer cells. Imagestream analysis revealed cell cycle arrest in G2/M phase and increased polyploidy, unravelling deregulation of cell division and cell death. Mechanistically, ER maleate decreased expression of PLK1 and Syk, induced cleavage of PARP, caspase9 and caspase3, and increased chemosensitivity to carboplatin; significantly suppressed tumor growth and increased antitumor activity of carboplatin in tumor xenografts. ER maleate treated tumor xenografts showed reduced PLK1 and Syk expression. Clinical investigations revealed overexpression of PLK1 and Syk in oral SCC patients that correlated with disease prognosis. Our in vitro and in vivo findings provide a strong rationale for pre-clinical efficacy of ER maleate as a novel anticancer agent and chemosensitizer of platinum drugs for OSCC. PMID:26934445

  3. In Vitro Efficacy and Mechanistic Role of Indocyanine Green as a Photodynamic Therapy Agent for Human Melanoma

    SciTech Connect

    Mamoon, A.; Gamal-Eldeen, A; Ruppel, M; Smith, R; Tsang, T; Miller, L

    2009-01-01

    Photodynamic therapy (PDT) is a promising treatment for superficial cancer. However, poor therapeutic results have been reported for melanoma, due to the high melanin content. Indocyanine green (ICG) has near infrared absorption (700-800nm) and melanins do not absorb strongly in this area. This study explores the efficiency of ICG as a PDT agent for human melanoma, and its mechanistic role in the cell death pathway.

  4. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression.

    PubMed

    Wargovich, M J; Jimenez, A; McKee, K; Steele, V E; Velasco, M; Woods, J; Price, R; Gray, K; Kelloff, G J

    2000-06-01

    We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal anti-inflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis. PMID:10837003

  5. Sugar-borate esters--potential chemical agents in prostate cancer chemoprevention.

    PubMed

    Scorei, Romulus Ion; Popa, Radu

    2013-07-01

    The potential value of sugar-borate esters (SBEs) in the chemo-preventive therapy of prostate cancer has been reviewed. We propose that SBEs act as boron (B) vehicles, increasing the concentration of borate inside cancer cells relative to normal cells. Increased intracellular concentration of borate activates borate transporters, but also leads to growth inhibition and apoptosis. The effects of SBEs on normal cells are less dramatic because SBEs are naturally-occurring biochemicals, common and abundant in some fruits and vegetables, and also because borate dissociated from SBEs in natural diet doses is easily exported from normal cells. Cancer cell lines that over-express sugar transporters or under-express borate export are potential targets for SBE-based therapy. With regard to efficiency against cancer cells and drug preparation requirements, trigonal cis-diol boric monoesters will be one of the most effective class of SBEs. Because negative correlation exists between borate intake and the incidence of prostate cancer, and because most cancer cells overexpress sugar transporters, SBEs are proposed as a potential chemopreventive avenue in the fight against primary and recurrent prostate cancer. PMID:23293883

  6. Metal chelators coupled with nanoparticles as potential therapeutic agents for Alzheimer's disease

    PubMed Central

    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A.

    2009-01-01

    Alzheimer's disease (AD) is a devastating neuro-degenerative disorder characterized by the progressive and irreversible loss of memory followed by complete dementia. Despite the disease's high prevalence and great economic and social burden, an explicative etiology or viable cure is not available. Great effort has been made to better understand the disease's pathogenesis, and to develop more effective therapeutic agents. However, success is greatly hampered by the presence of the blood-brain barrier that limits a large number of potential therapeutics from entering the brain. Nanoparticle-mediated drug delivery is one of the few valuable tools for overcoming this impediment and its application as a potential AD treatment shows promise. In this review, the current studies on nanoparticle delivery of chelation agents as possible therapeutics for AD are discussed because several metals are found excessive in the AD brain and may play a role in the disease development. Specifically, a novel approach involving transport of iron chelation agents into and out of the brain by nanoparticles is highlighted. This approach may provide a safer and more effective means of simultaneously reducing several toxic metals in the AD brain. It may also provide insights into the mechanisms of AD pathophysiology, and prove useful in treating other iron-associated neurodegenerative diseases such as Friedreich's ataxia, Parkinson's disease, Huntington's disease and Hallervorden-Spatz Syndrome. It is important to note that the use of nanoparticle-mediated transport to facilitate toxicant excretion from diseased sites in the body may advance nanoparticle technology, which is currently focused on targeted drug delivery for disease prevention and treatment. The application of nanoparticle-mediated drug transport in the treatment of AD is at its very early stages of development and, therefore, more studies are warranted. PMID:19936278

  7. Tumor-colonizing bacteria: a potential tumor targeting therapy.

    PubMed

    Zu, Chao; Wang, Jiansheng

    2014-08-01

    In 1813, Vautier published his observation of tumor regression in patients who had suffered from gas gangrene. Since then, many publications have described the use of bacteria as antitumor therapy. For example, Bifidobacterium and Clostridium have been shown to selectively colonize tumors and to reduce tumor size. In addition, recent studies have focused on the use of genetic engineering to induce the expression of pro-drug converting enzymes, cytokines, specific antibodies, or suicide genes in tumor-colonizing bacteria. Moreover, some animal experiments have reported the treatment of tumors with engineered bacteria, and few side effects were observed. Therefore, based on these advances in tumor targeting therapy, bacteria may represent the next generation of cancer therapy.

  8. Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential antitubercular agents.

    PubMed

    Bairwa, Ranjeet; Kakwani, Manoj; Tawari, Nilesh R; Lalchandani, Jaya; Ray, M K; Rajan, M G R; Degani, Mariam S

    2010-03-01

    In an attempt to identify potential new agents active against tuberculosis, 20 novel phenylacrylamide derivatives incorporating cinnamic acids and guanylhydrazones were synthesized using microwave assisted synthesis. Activity of the synthesized compounds was evaluated using resazurin microtitre plate assay (REMA) against Mycobacterium tuberculosis H37Rv. Based on empirical structure-activity relationship data it was observed that both steric and electronic parameters play major role in the activity of this series of compounds. Compound 7s (2E)-N-((-2-(3,4-dimethoxybenzylidene) hydrazinyl) (imino) methyl)-3-(4-methoxyphenyl) acrylamide showed MIC of 6.49microM along with good safety profile of >50-fold in VERO cell line. Thus, this compound could act as a potential lead for further antitubercular studies.

  9. Potential Anti-HPV and Related Cancer Agents from Marine Resources: An Overview

    PubMed Central

    Wang, Shi-Xin; Zhang, Xiao-Shuang; Guan, Hua-Shi; Wang, Wei

    2014-01-01

    Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail. PMID:24705500

  10. 4, 5-Dihydrooxazole-pyrazoline hybrids: Synthesis and their evaluation as potential antimalarial agents.

    PubMed

    Pandey, Ashutosh Kumar; Sharma, Supriya; Pandey, Minakshi; Alam, M Mumtaz; Shaquiquzzaman, M; Akhter, Mymoona

    2016-11-10

    A new series of oxazoline-pyrazoline hybrids (4a-p) were synthesized by condensation reaction of substituted oxazoline based chalcones (3a-m) and substituted hydrazines in methanol. Some of the compounds exhibited promising in vitro antimalarial activity for chloroquine sensitive CQ(S) (3D7) strain and chloroquine resistant CQ(R) (RKL9) strain. The most potent analogue 4i (IC50 0.322 μg/ml) exhibited significant in vivo antimalarial potential against Plasmodium berghei mouse model. The stable complex of 4i with hematin (1:1 stoichiometry) suggests that heme may be one possible target for these hybrid compounds. The study has revealed potential of title compounds as lead for the development of antimalarial agents. PMID:27494165

  11. Avena sativa (Oat), a potential neutraceutical and therapeutic agent: an overview.

    PubMed

    Singh, Rajinder; De, Subrata; Belkheir, Asma

    2013-01-01

    The aim of the present review article is to summarize the available information related to the availability, production, chemical composition, pharmacological activity, and traditional uses of Avena sativa to highlight its potential to contribute to human health. Oats are now cultivated worldwide and form an important dietary staple for the people in number of countries. Several varieties of oats are available. It is a rich source of protein, contains a number of important minerals, lipids, β-glucan, a mixed-linkage polysaccharide, which forms an important part of oat dietary fiber, and also contains various other phytoconstituents like avenanthramides, an indole alkaloid-gramine, flavonoids, flavonolignans, triterpenoid saponins, sterols, and tocols. Traditionally oats have been in use since long and are considered as stimulant, antispasmodic, antitumor, diuretic, and neurotonic. Oat possesses different pharmacological activities like antioxidant, anti-inflammatory, wound healing, immunomodulatory, antidiabetic, anticholesterolaemic, etc. A wide spectrum of biological activities indicates that oat is a potential therapeutic agent.

  12. Potential Bio-Control Agent from Rhodomyrtus tomentosa against Listeria monocytogenes

    PubMed Central

    Odedina, Grace Fiyinfoluwa; Vongkamjan, Kitiya; Voravuthikunchai, Supayang Piyawan

    2015-01-01

    Listeria monocytogenes is an important foodborne pathogen implicated in many outbreaks of listeriosis. This study aimed at screening for the potential use of Rhodomyrtus tomentosa ethanolic leaf extract as a bio-control agent against L. monocytogenes. Twenty-two L. monocytogenes isolates were checked with 16 commercial antibiotics and isolates displayed resistance to 10 antibiotics. All the tested isolates were sensitive to the extract with inhibition zones ranging from 14 to 16 mm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 16 to 32 µg/mL and 128 to 512 µg/mL, respectively. Time-kill assay showed that the extract had remarkable bactericidal effects on L. monocytogenes. The extract at a concentration of 16 µg/mL reduced tolerance to 10% NaCl in L. monocytogenes in 4 h. Stationary phase L. monocytogenes cells were rapidly inactivated by greater than 3-log units within 30 min of contact time with R. tomentosa extract at 128 µg/mL. Electron microscopy revealed fragmentary bacteria with changes in the physical and morphological properties. Our study demonstrates the potential of the extract for further development into a bio-control agent in food to prevent the incidence of L. monocytogenes contamination. PMID:26371033

  13. Synthesis and biological evaluation of oxindole linked indolyl-pyrimidine derivatives as potential cytotoxic agents.

    PubMed

    Prajapti, Santosh Kumar; Nagarsenkar, Atulya; Guggilapu, Sravanthi Devi; Gupta, Keshav Kumar; Allakonda, Lingesh; Jeengar, Manish Kumar; Naidu, V G M; Babu, Bathini Nagendra

    2016-07-01

    In our endeavor towards the development of effective cytotoxic agents, a series of oxindole linked indolyl-pyrimidine derivatives were synthesized and characterized by IR, (1)H NMR, (13)C NMR and Mass spectral analysis. All the newly synthesized target compounds were assessed against PA-1 (ovarian), U-87MG (glioblastoma), LnCaP (prostate), and MCF-7 (Breast) cancer cell lines for their cytotoxic potential, with majority of them showing inhibitory activity at low micro-molar concentrations. Significantly, compound 8e was found to be most potent amongst all the tested compounds with an IC50 value of (2.43±0.29μM) on PA-1 cells. The influence of the most active cytotoxic compound 8e on the cell cycle distribution was assessed on the PA-1 cell line, exhibiting a cell cycle arrest at the G2/M phase. Moreover, acridine orange/ethidium bromide staining and annexin V binding assay confirmed that compound 8e can induce cell apoptosis in PA-1 cells. These preliminary results persuade further investigation on the synthesized compounds aiming to the development of potential cytotoxic agents.

  14. Design, synthesis, and evaluation of novel galloyl pyrrolidine derivatives as potential anti-tumor agents.

    PubMed

    Li, Xun; Li, Yalin; Xu, Wenfang

    2006-03-01

    A series of novel galloyl pyrrolidine derivatives were synthesized as potential anti-tumor agents. Their inhibiting activities on gelatinase (MMP-2 and -9) were tested with succinylated gelatin as the substrate. Structure-activity analyses demonstrate that introduction of longer and more flexible side chains at the C(4) position of the pyrrolidine ring brings higher activity against gelatinase. Free phenol hydroxyl group is more favorable than the methylated one, which confirms the important role of the phenol hydroxyl group when inhibitors interact with gelatinase. In particular, (2S,4S)-4-(3-(3,4-dimethoxyphenyl)acrylamido)-N-hydroxy-1-(3,4,5- trimethoxybenzoyl)pyrrolidine-2-carboxamide (18) stood out as the most attractive compound (IC(50) = 0.9 nM). The anti-metastasis model of mice bearing H(22) tumor cells was used to evaluate their anti-tumor activities in vivo. The assay in vivo revealed that most of these inhibitors displayed favorable inhibitory activities (inhibitory rate >35%) and no significant toxic effects were observed. The inhibition for 62.37% of 19 indicates the strategy used to design MMP inhibitors (MMPIs) of galloyl pyrrolidine derivatives as potential anti-tumor agents is promising.

  15. Development and thermodynamic evaluation of novel lipid raft stationary phase chromatography for screening potential antitumor agents.

    PubMed

    Tong, Shanshan; Sun, Chaonan; Cao, Xia; Zheng, Qianfeng; Zhang, Huiyun; Firempong, Caleb Kesse; Feng, Yingshu; Yang, Yan; Yu, Jiangnan; Xu, Ximing

    2014-12-01

    Novel lipid raft stationary phase chromatography (LRSC), with lipid rafts that contain abundant tropomyosin-related tyrosine kinase A receptors immobilized on the stationary phase, was developed for a high-throughput screening of potentially active antitumor agents. Lestaurtinib was used as a model compound to determine the operational parameters of the LRSC. Of all the factors considered, the particle size of column packing, the column temperature and the flow rate were of immense importance in determining the performance of the established LRSC system. In order to profoundly comprehend the binding interaction between the model drug and the receptors on the column, thermodynamic studies were employed. The results revealed that the interaction was spontaneous and exothermic, a typical enthalpy-driven process. Additionally, the primary forces were hydrogen bonding and van der Waals forces. In evaluating the applicability of the method, active extracts from Albizziae Cortex were screened out using the LRSC system under the optimized conditions. The bioactive components were successfully confirmed by the MTT assay. In conclusion, it could be said that the LRSC is a good model for screening potential antitumor agents because of its viability, rapid response and scalable features.

  16. Potential Bio-Control Agent from Rhodomyrtus tomentosa against Listeria monocytogenes.

    PubMed

    Odedina, Grace Fiyinfoluwa; Vongkamjan, Kitiya; Voravuthikunchai, Supayang Piyawan

    2015-09-07

    Listeria monocytogenes is an important foodborne pathogen implicated in many outbreaks of listeriosis. This study aimed at screening for the potential use of Rhodomyrtus tomentosa ethanolic leaf extract as a bio-control agent against L. monocytogenes. Twenty-two L. monocytogenes isolates were checked with 16 commercial antibiotics and isolates displayed resistance to 10 antibiotics. All the tested isolates were sensitive to the extract with inhibition zones ranging from 14 to 16 mm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranged from 16 to 32 µg/mL and 128 to 512 µg/mL, respectively. Time-kill assay showed that the extract had remarkable bactericidal effects on L. monocytogenes. The extract at a concentration of 16 µg/mL reduced tolerance to 10% NaCl in L. monocytogenes in 4 h. Stationary phase L. monocytogenes cells were rapidly inactivated by greater than 3-log units within 30 min of contact time with R. tomentosa extract at 128 µg/mL. Electron microscopy revealed fragmentary bacteria with changes in the physical and morphological properties. Our study demonstrates the potential of the extract for further development into a bio-control agent in food to prevent the incidence of L. monocytogenes contamination.

  17. Potential water-quality effects from iron cyanide anticaking agents in road salt

    SciTech Connect

    Paschka, M.G.; Ghosh, R.S.; Dzombak, D.A.

    1999-10-01

    Water-soluble iron cyanide compounds are widely used as anticaking agents in road salt, which creates potential contamination of surface and groundwater with these compounds when the salt dissolves and is washed off roads in runoff. This paper presents a summary of available information on iron cyanide use in road salt and its potential effects on water quality. Also, estimates of total cyanide concentrations in snow-melt runoff from roadways are presented as simple mass-balance calculations. Although available information does not indicate a widespread problem, it also is clear that the water-quality effects of cyanide in road salt have not been examined much. Considering the large, and increasing, volume of road salt used for deicing, studies are needed to determine levels of total and free cyanide in surface and groundwater adjacent to salt storage facilities and along roads with open drainage ditches. Results could be combined with current knowledge of the fate and transport of cyanide to assess water-quality effects of iron cyanide anticaking agents used in road salt.

  18. Effect of hypobaric hypoxia on cognitive functions and potential therapeutic agents.

    PubMed

    Muthuraju, Sangu; Pati, Soumya

    2014-12-01

    High altitude (HA), defined as approximately 3000-5000 m, considerably alters physiological and psychological parameters within a few hours. Chronic HA-mediated hypoxia (5000 m) results in permanent neuronal damage to the human brain that persists for one year or longer, even after returning to sea level. At HA, there is a decrease in barometric pressure and a consequential reduction in the partial pressure of oxygen (PO2), an extreme environmental condition to which humans are occasionally exposed. This condition is referred to as hypobaric hypoxia (HBH), which represents the most unfavourable characteristics of HA. HBH causes the disruption of oxygen availability to tissue. However, no review article has explored the impact of HBH on cognitive functions or the potential therapeutic agents for HBH. Therefore, the present review aimed to describe the impact of HBH on both physiological and cognitive functions, specifically learning and memory. Finally, the potential therapeutic agents for the treatment of HBH-induced cognitive impairment are discussed. PMID:25941462

  19. Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.

    PubMed

    Conlon, J Michael; Mechkarska, Milena; Lukic, Miodrag L; Flatt, Peter R

    2014-07-01

    Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms. PMID:24793775

  20. Potential therapeutic applications of multifunctional host-defense peptides from frog skin as anti-cancer, anti-viral, immunomodulatory, and anti-diabetic agents.

    PubMed

    Conlon, J Michael; Mechkarska, Milena; Lukic, Miodrag L; Flatt, Peter R

    2014-07-01

    Frog skin constitutes a rich source of peptides with a wide range of biological properties. These include host-defense peptides with cytotoxic activities against bacteria, fungi, protozoa, viruses, and mammalian cells. Several hundred such peptides from diverse species have been described. Although attention has been focused mainly on antimicrobial activity, the therapeutic potential of frog skin peptides as anti-infective agents remains to be realized and no compound based upon their structures has yet been adopted in clinical practice. Consequently, alternative applications are being explored. Certain naturally occurring frog skin peptides, and analogs with improved therapeutic properties, show selective cytotoxicity against tumor cells and viruses and so have potential for development into anti-cancer and anti-viral agents. Some peptides display complex cytokine-mediated immunomodulatory properties. Effects on the production of both pro-inflammatory and anti-inflammatory cytokines by peritoneal macrophages and peripheral blood mononuclear cells have been observed so that clinical applications as anti-inflammatory, immunosuppressive, and immunostimulatory agents are possible. Several frog skin peptides, first identified on the basis of antimicrobial activity, have been shown to stimulate insulin release both in vitro and in vivo and so show potential as incretin-based therapies for treatment of patients with Type 2 diabetes mellitus. This review assesses the therapeutic possibilities of peptides from frogs belonging to the Ascaphidae, Alytidae, Pipidae, Dicroglossidae, Leptodactylidae, Hylidae, and Ranidae families that complement their potential role as anti-infectives for use against multidrug-resistant microorganisms.

  1. Potential of Gene Therapy for the Treatment of Pituitary Tumors

    PubMed Central

    Goya, R G.; Sarkar, D.K.; Brown, O.A.; Hereñú, C.B.

    2010-01-01

    Pituitary adenomas constitute the most frequent neuroendocrine pathology, comprising up to 15% of primary intracranial tumors. Current therapies for pituitary tumors include surgery and radiotherapy, as well as pharmacological approaches for some types. Although all of these approaches have shown a significant degree of success, they are not devoid of unwanted side effects, and in most cases do not offer a permanent cure. Gene therapy—the transfer of genetic material for therapeutic purposes—has undergone an explosive development in the last few years. Within this context, the development of gene therapy approaches for the treatment of pituitary tumors emerges as a promising area of research. We begin by presenting a brief account of the genesis of prolactinomas, with particular emphasis on how estradiol induces prolactinomas in animals. In so doing, we discuss the role of each of the recently discovered growth inhibitory and growth stimulatory substances and their interactions in estrogen action. We also evaluate the cell-cell communication that may govern these growth factor interactions and subsequently promote the growth and survival of prolactinomas. Current research efforts to implement gene therapy in pituitary tumors include the treatment of experimental prolactinomas or somatomammotropic tumors with adenoviral vector-mediated transfer of the suicide gene for the herpes simplex type 1 (HSV1) thymidine kinase, which converts the prodrug ganciclovir into a toxic metabolite. In some cases, the suicide transgene has been placed under the control of pituitary cell-type specific promoters, like the human prolactin or human growth hormone promoters. Also, regulatable adenoviral vector systems are being assessed in gene therapy approaches for experimental pituitary tumors. In a different type of approach, an adenoviral vector, encoding the human retinoblastoma suppressor oncogene, has been successfully used to rescue the phenotype of spontaneous pituitary

  2. Clinical potential of gene therapy: towards meeting the demand.

    PubMed

    Macpherson, J L; Rasko, J E J

    2014-03-01

    Since the discovery that new genetic material could be transferred into human cells resulting in induced expression of genes and proteins, clinicians and scientists have been working to harness the technology for clinical outcomes. This article provides a summary of the current status of developments within the broad discipline of clinical gene therapy. In pursuing the treatment of diverse clinical conditions, a wide variety of therapeutics, each tailor-made, may be required. Gene therapy offers the possibility of accurately and specifically targeting particular genetic abnormalities through gene correction, addition or replacement. It represents a compelling idea that adds a new dimension to our portfolio of credible therapeutic choices.

  3. Complete genome sequence analysis of two Pseudomonas plecoglossicida phages, potential therapeutic agents.

    PubMed

    Kawato, Yasuhiko; Yasuike, Motoshige; Nakamura, Yoji; Shigenobu, Yuya; Fujiwara, Atushi; Sano, Motohiko; Nakai, Toshihiro

    2015-02-01

    Pseudomonas plecoglossicida is a lethal pathogen of ayu (Plecoglossus altivelis) in Japan and is responsible for substantial economic costs to ayu culture. Previously, we demonstrated the efficacy of phage therapy against P. plecoglossicida infection using two lytic phages (PPpW-3 and PPpW-4) (S. C. Park, I. Shimamura, M. Fukunaga, K. Mori, and T. Nakai, Appl Environ Microbiol 66:1416-1422, 2000, http://dx.doi.org/10.1128/AEM.66.4.1416-1422.2000; S. C. Park and T. Nakai, Dis Aquat Org 53:33-39, 2003, http://dx.doi.org/10.3354/dao053033). In the present study, the complete genome sequences of these therapeutic P. plecoglossicida phages were determined and analyzed for deleterious factors as therapeutic agents. The genome of PPpW-3 (myovirus) consisted of 43,564 bp with a GC content of 61.1% and 66 predicted open reading frames (ORFs). Approximately half of the genes were similar to the genes of the Escherichia coli phage vB_EcoM_ECO1230-10 (myovirus). The genome of PPpW-4 (podovirus) consisted of 41,386 bp with a GC content of 56.8% and 50 predicted ORFs. More than 70% of the genes were similar to the genes of Pseudomonas fluorescens phage ϕIBB-PF7A and Pseudomonas putida phage ϕ15 (podoviruses). The whole-genome analysis revealed that no known virulence genes were present in PPpW-3 and PPpW-4. An integrase gene was found in PPpW-3, but other factors used for lysogeny were not confirmed. The PCR detection of phage genes in phage-resistant variants provided no evidence of lysogenic activity in PPpW-3 and PPpW-4. We conclude that these two lytic phages qualify as therapeutic agents. PMID:25416766

  4. Complete genome sequence analysis of two Pseudomonas plecoglossicida phages, potential therapeutic agents.

    PubMed

    Kawato, Yasuhiko; Yasuike, Motoshige; Nakamura, Yoji; Shigenobu, Yuya; Fujiwara, Atushi; Sano, Motohiko; Nakai, Toshihiro

    2015-02-01

    Pseudomonas plecoglossicida is a lethal pathogen of ayu (Plecoglossus altivelis) in Japan and is responsible for substantial economic costs to ayu culture. Previously, we demonstrated the efficacy of phage therapy against P. plecoglossicida infection using two lytic phages (PPpW-3 and PPpW-4) (S. C. Park, I. Shimamura, M. Fukunaga, K. Mori, and T. Nakai, Appl Environ Microbiol 66:1416-1422, 2000, http://dx.doi.org/10.1128/AEM.66.4.1416-1422.2000; S. C. Park and T. Nakai, Dis Aquat Org 53:33-39, 2003, http://dx.doi.org/10.3354/dao053033). In the present study, the complete genome sequences of these therapeutic P. plecoglossicida phages were determined and analyzed for deleterious factors as therapeutic agents. The genome of PPpW-3 (myovirus) consisted of 43,564 bp with a GC content of 61.1% and 66 predicted open reading frames (ORFs). Approximately half of the genes were similar to the genes of the Escherichia coli phage vB_EcoM_ECO1230-10 (myovirus). The genome of PPpW-4 (podovirus) consisted of 41,386 bp with a GC content of 56.8% and 50 predicted ORFs. More than 70% of the genes were similar to the genes of Pseudomonas fluorescens phage ϕIBB-PF7A and Pseudomonas putida phage ϕ15 (podoviruses). The whole-genome analysis revealed that no known virulence genes were present in PPpW-3 and PPpW-4. An integrase gene was found in PPpW-3, but other factors used for lysogeny were not confirmed. The PCR detection of phage genes in phage-resistant variants provided no evidence of lysogenic activity in PPpW-3 and PPpW-4. We conclude that these two lytic phages qualify as therapeutic agents.

  5. Complete Genome Sequence Analysis of Two Pseudomonas plecoglossicida Phages, Potential Therapeutic Agents

    PubMed Central

    Yasuike, Motoshige; Nakamura, Yoji; Shigenobu, Yuya; Fujiwara, Atushi; Sano, Motohiko; Nakai, Toshihiro

    2014-01-01

    Pseudomonas plecoglossicida is a lethal pathogen of ayu (Plecoglossus altivelis) in Japan and is responsible for substantial economic costs to ayu culture. Previously, we demonstrated the efficacy of phage therapy against P. plecoglossicida infection using two lytic phages (PPpW-3 and PPpW-4) (S. C. Park, I. Shimamura, M. Fukunaga, K. Mori, and T. Nakai, Appl Environ Microbiol 66:1416–1422, 2000, http://dx.doi.org/10.1128/AEM.66.4.1416-1422.2000; S. C. Park and T. Nakai, Dis Aquat Org 53:33–39, 2003, http://dx.doi.org/10.3354/dao053033). In the present study, the complete genome sequences of these therapeutic P. plecoglossicida phages were determined and analyzed for deleterious factors as therapeutic agents. The genome of PPpW-3 (myovirus) consisted of 43,564 bp with a GC content of 61.1% and 66 predicted open reading frames (ORFs). Approximately half of the genes were similar to the genes of the Escherichia coli phage vB_EcoM_ECO1230-10 (myovirus). The genome of PPpW-4 (podovirus) consisted of 41,386 bp with a GC content of 56.8% and 50 predicted ORFs. More than 70% of the genes were similar to the genes of Pseudomonas fluorescens phage ϕIBB-PF7A and Pseudomonas putida phage ϕ15 (podoviruses). The whole-genome analysis revealed that no known virulence genes were present in PPpW-3 and PPpW-4. An integrase gene was found in PPpW-3, but other factors used for lysogeny were not confirmed. The PCR detection of phage genes in phage-resistant variants provided no evidence of lysogenic activity in PPpW-3 and PPpW-4. We conclude that these two lytic phages qualify as therapeutic agents. PMID:25416766

  6. Encapsulation of magnetotactic bacteria for targeted and controlled delivery of anticancer agents for tumor therapy.

    PubMed

    Afkhami, Fatemeh; Taherkhani, Samira; Mohammadi, Mahmood; Martel, Sylvain

    2011-01-01

    We showed that magnetotactic bacteria (MTB) have great potentials to be used as microcarriers for targeted delivery of therapeutic agents. Indeed, magnetotaxis inherent in MTB can be exploited to direct them towards a tumor while being propelled by their own flagellated molecular motors. Nonetheless, although the thrust propelling force above 4 pN of the MC-1 MTB showed to be superior compared to other technologies for displacement in the microvasculature, MTB becomes much less efficient when travelling in larger blood vessels due to higher blood flow. In the latter case, a new technique developed by our group and referred to as Magnetic Resonance Navigation (MRN), has been successfully applied in larger vessels using synthetic microcarriers nut proved to be less efficient in the microvasculature due mainly to technological constraints. These findings called for the need to integrate both approaches by encapsulating MTB in special MRN-compatible microcarriers to be release in the vicinity of microvascular networks where they becomes more effective for targeting purposes in tumoral lesions. In this study Magnetococcus strain MC-1 were encapsulated in giant vesicles. The survival of the encapsulated bacteria was monitored. The release of bacteria from giant vesicles was also studied in different time intervals and conditions.

  7. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Correction for `Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g.

  8. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents.

    PubMed

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguyen Thi Kim

    2016-02-21

    Correction for 'Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g. PMID:26823197

  9. Marathon Group Therapy: Potential for University Counseling Centers and Beyond

    ERIC Educational Resources Information Center

    Stanger, Thomas; Harris, Rafael S., Jr.

    2005-01-01

    A descriptive analysis of marathon group therapy was conducted, specifying issues of set-up, screening, preparation, start-up, introduction to group process, facilitating therapeutic moments throughout the weekend, termination, and follow-up. Factors and dynamics unique to this modality are outlined for marathon groups in university counseling…

  10. Potentials of interferon therapy in the treatment of pancreatic cancer.

    PubMed

    Booy, Stephanie; Hofland, Leo; van Eijck, Casper

    2015-05-01

    Pancreatic cancer is a highly aggressive malignancy with limited treatment options. To improve survival for patients with pancreatic cancer, research has focused on other treatment modalities like adding biological modulators such as type-I interferons (IFNs). Type I IFNs (ie, IFN-α/IFN-β) have antiproliferative, antiviral, and immunoregulatory activities. Furthermore, they are able to induce apoptosis, exert cell cycle blocking, and sensitize tumor cells for chemo- and radiotherapy. A few years ago in vitro, in vivo, and several clinical trials have been described regarding adjuvant IFN-α therapy in the treatment of pancreatic cancer. Some studies reported a remarkable increase in the 2- and 5-year survival. Unfortunately, the only randomized clinical trial did not show a significant increase in overall survival, although the increased median survival implicated that some patients in the experimental group benefited from the adjuvant IFN-α therapy. Furthermore, encouraging in vitro and in vivo data points to a possible role for adjuvant IFN therapy. However, up till now, the use of IFNs in the treatment of pancreatic cancer remains controversial. This review, therefore, aims to describe, based on the available data, whether there is a distinct role for IFN therapy in the treatment of pancreatic cancer.

  11. Anti-metastatic therapy by urinary trypsin inhibitor in combination with an anti-cancer agent.

    PubMed Central

    Kobayashi, H.; Shinohara, H.; Gotoh, J.; Fujie, M.; Fujishiro, S.; Terao, T.

    1995-01-01

    We have demonstrated that urinary trypsin inhibitor (UTI) purified from human urine is able to inhibit lung metastasis of mouse Lewis lung carcinoma (3LL) cells in experimental and spontaneous metastasis models. In this study, we have investigated whether UTI in combination with an anti-cancer drug, etoposide, can prevent tumour metastasis and show an enhanced therapeutic effect. Subcutaneous (s.c.) implantation of 3LL cells (1 x 10(6) cells) in the abdominal wall of C57BL/6 female mice resulted in macroscopic lung metastasis within 21 days. Microscopic lung metastasis was established by day 14 after tumour cell inoculation, and surgical treatment alone after this time resulted in no inhibition of lung metastasis. The number of lung tumour colonies in the group of mice which received surgery at day 21 was greater than in mice which had tumours left in situ (P = 0.0017). Surgical treatment on day 7, followed by UTI administration (s.c.) for 7 days, led to a decrease in lung metastasis compared with untreated animals. A significant inhibition of the formation of pulmonary metastasis was obtained with daily s.c. injections of UTI for 7 days immediately after tumour cell inoculation. UTI administration did not affect the primary tumour size at the time of operation. In addition, etoposide treatment alone led to a smaller primary tumours and yielded reduction of the formation of lung metastasis in the group of mice which received surgery at day 14 (P = 0.0026). Even in mice which received surgical treatment on day 14, followed by the combination of UTI (500 micrograms per mouse, days 14, 15, 16, 17, 18, 19 and 20) with etoposide (40 mg kg-1, days 14, 18 and 22), there was significant reduction of the formation of lung metastasis (P = 0.0001). Thus, the combination of an anti-metastatic agent with an anti-cancer drug, etoposide, might provide a therapeutically promising basis for anti-metastatic therapy. PMID:7577458

  12. Ethanol gastric lesion aggravated by lung injury in rat. Therapy effect of antiulcer agents.

    PubMed

    Stancic-Rokotov, D; Sikiric, P; Seiwerth, S; Slobodnjak, Z; Aralica, J; Aralica, G; Perovic, D; Anic, T; Zoricic, I; Buljat, G; Prkacin, I; Gjurasin, M; Rucman, R; Petek, M; Turkovic, B; Ivasovic, Z; Jagic, V; Staresinic, M; Boban-Blagaic, A

    2001-01-01

    Hemorrhagic mucosal lesions in the stomach in the rat induced by an intragastrical application of 1 ml of 50 or 75% ethanol were aggravated by preceding lung damage provoked by an intratracheal instillation of pyrogen-free saline or HCl (pH 1.75) or 50-h exposure to 100% oxygen. Due to the particular preceding aggravating circumstances, these lesions were taken to be of a special kind, rather than ordinary. So far, it is not known whether and how antiulcer agents may influence these lesions. Rats received an intratracheal (i.t.) HCl instillation [1.5 ml/kg HCl (pH 1.75)] (lung-lesion), and an intragastric instillation of 96% ethanol (gastric lesion; 1 ml/rat, 24 h after i.t. HCl instillation), and were sacrificed 1 h after ethanol. Basically, in lung injured rats, the subsequent ethanol-gastric lesion was markedly aggravated. This aggravation, however, in turn, did not affect the severity of the lung lesions in the further period, at least for a 1-h observation. Taking intratracheal HCl-instillation as time 0, a gastric pentadecapeptide, GEPPPGKPADDAGLV, M.W.1419, coded BPC 157 (PL-10, PLD-116; 10 microg, 10 ng, 10 pg), ranitidine (10 mg), atropine (10 mg), omeprazole (10 mg), were given [/kg, intraperitoneally (i.p.)] (1) once, only prophylactically [as a pre-treatment (at -1 h), or as a co-treatment (at 0)], or only therapeutically (at +18 h or +24 h); (2) repeatedly, combining prophylactic/therapeutic regimens [(-1 h)+(+24 h) or (0)+(+24 h)], or therapeutic/therapeutic regimens [(+18 h)+(+24 h)]. In general, the antiulcer agents did protect against ethanol gastric lesions regardless of the presence of the severe lung injury, in all of the used regimens. Of note, combining their prophylactic and salutary regimens (at -1 h/+24 h, or at 0/+24 h) may increase the antiulcer potential, and the effect that had been not seen already with single application, became prominent after repeated treatment. PMID:11595452

  13. Advances in bypassing agent therapy for hemophilia patients with inhibitors to close care gaps and improve outcomes.

    PubMed

    Shapiro, Amy D; Hedner, Ulla

    2011-10-01

    In the past, patients with hemophilia and inhibitors have had less-than-optimal treatment and have experienced more orthopedic complications than patients without inhibitors. Bypassing agents offer the potential to close treatment gaps between inhibitor and noninhibitor patients by helping the former better attain key treatment goals, including: facilitating early initiation of treatment and hemostatic control in hemarthroses; providing effective treatment in serious hemorrhagic episodes; and performance of major surgery. Effective treatment with a bypassing agent minimizes joint and/or muscle damage and potentially can serve as an effective prophylactic agent to minimize the number of hemarthroses experienced per year, thereby mitigating the development of arthropathy. The reported efficacy of the currently available bypassing agents ranges from approximately 50-80% (50-64% in controlled studies) for plasma-derived activated prothrombin complex concentrate (pd-aPCC) and 81-91% (in controlled studies) for recombinant activated factor VII (rFVIIa), including use in major orthopedic surgery. Both bypassing agents have undergone key improvements in their formulation and/or properties in recent years. The nanofiltered, vapor-heated formulation of pd-aPCC has diminished the risk of acquiring blood-borne viral infections and the room temperature stable formulation of rFVIIa allows more convenient storage, increased ease to dissolve and inject, and smaller volumes, thereby increasing overall ease of administration. Use of recommended dosing has been demonstrated to provide effective hemostasis with a minimal number of injections for both agents. In this paper, we review the individual characteristics of pd-aPCC and rFVIIa and discuss clinical data from studies conducted in inhibitor patients that demonstrate the potential benefits of these bypassing agents in this difficult-to-treat population, and underscore the potential opportunities to close the gap in care between

  14. Use of novel metalloporphyrins as imageable tumor-targeting agents for radiation therapy

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    2005-10-04

    The present invention covers halogenated derivatives of boronated phorphyrins containing multiple carborane cages having the formula ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron-capture therapy and photodynamic therapy. The present invention also covers methods for using these halogenated derivatives of boronated porphyrins in tumor imaging and cancer treatment.

  15. Metalloporphyrins and their uses as imageable tumor-targeting agents for radiation therapy

    DOEpatents

    Miura, Michiko; Slatkin, Daniel N.

    2003-05-20

    The present invention covers halogenated derivatives of boronated porphyrins containing multiple carborane cages having the formula ##STR1## which selectively accumulate in neoplastic tissue within the irradiation volume and thus can be used in cancer therapies including, but not limited to, boron neutron- capture therapy and photodynamic therapy. The present invention also covers methods for using these halogenated derivatives of boronated porphyrins in tumor imaging and cancer treatment.

  16. ROS-Responsive Activatable Photosensitizing Agent for Imaging and Photodynamic Therapy of Activated Macrophages

    PubMed Central

    Kim, Hyunjin; Kim, Youngmi; Kim, In-Hoo; Kim, Kyungtae; Choi, Yongdoo

    2014-01-01

    The optical properties of macrophage-targeted theranostic nanoparticles (MacTNP) prepared from a Chlorin e6 (Ce6)-hyaluronic acid (HA) conjugate can be activated by reactive oxygen species (ROS) in macrophage cells. MacTNP are nonfluorescent and nonphototoxic in their native state. However, when treated with ROS, especially peroxynitrite, they become highly fluorescent and phototoxic. In vitro cell studies show that MacTNP emit near-infrared (NIR) fluorescence inside activated macrophages. The NIR fluorescence is quenched in the extracellular environment. MacTNP are nontoxic in macrophages up to a Ce6 concentration of 10 μM in the absence of light. However, MacTNP become phototoxic upon illumination in a light dose-dependent manner. In particular, significantly higher phototoxic effect is observed in the activated macrophage cells compared to human dermal fibroblasts and non-activated macrophages. The ROS-responsive MacTNP, with their high target-to-background ratio, may have a significant potential in selective NIR fluorescence imaging and in subsequent photodynamic therapy of atherosclerosis with minimum side effects. PMID:24396511

  17. Isoindoline-1,3-dione derivatives targeting cholinesterases: design, synthesis and biological evaluation of potential anti-Alzheimer's agents.

    PubMed

    Guzior, Natalia; Bajda, Marek; Rakoczy, Jurand; Brus, Boris; Gobec, Stanislav; Malawska, Barbara

    2015-04-01

    Alzheimer's disease is a fatal neurodegenerative disorder with a complex etiology. Because the available therapy brings limited benefits, the effective treatment for Alzheimer's disease remains the unmet challenge. Our aim was to develop a new series of donepezil-based compounds endowed with inhibitory properties against cholinesterases and β-amyloid aggregation. We designed the target compounds as dual binding site acetylcholinesterase inhibitors with N-benzylamine moiety interacting with the catalytic site of the enzyme and an isoindoline-1,3-dione fragment interacting with the peripheral anionic site of the enzyme. The results of pharmacological evaluation lead us to identify a compound 3b as the most potent and selective human acetylcholinesterase inhibitor (hAChE IC50=0.361μM). Kinetic studies revealed that 3b inhibited acetylcholinesterase in non-competitive mode. The result of the parallel artificial membrane permeability assay for the blood-brain barrier indicated that the compound 3b would be able to cross the blood-brain barrier and reach its biological targets in the central nervous system. The selected compound 3b represents a potential lead structure for further development of anti-Alzheimer's agents. PMID:25707322

  18. Photophysical studies of tin(IV)-protoporphyrin: Potential phototoxicity of a chemotherapeutic agent proposed for the prevention of neonatal jaundice

    SciTech Connect

    Land, E.J.; McDonagh, A.F.; McGarvey, D.J.; Truscott, T.G. )

    1988-07-01

    The strongly light-absorbing metalloporphyrin tin(IV)-protoporphyrin IX (SnPP) is currently being considered as a chemotherapeutic agent for preventing severe hyperbilirubinemia in newborns, a condition usually treated by phototherapy with visible light. To assess the potential phototoxicity of SnPP the authors studied the photophysics of the drug in aqueous and nonaqueous solutions using laser flash photolysis and pulse radiolysis. Quantum yields for formation of triplet-state excited SnPP were measured, along with triplet lifetimes and extinction coefficients. In addition, they measured quantum yields for the SnPP-photosensitized formation of singlet oxygen in MeO{sup 2}H and in {sup 2}H{sub 2}O containing cetyltrimethylammonium bromide, using a time-resolved luminescence technique. Quantum yields for formation of triplet SnPP from monomeric ground-state SnPP are high, and triplet lifetimes are long. SnPP-photosensitized formation of singlet oxygen in aqueous and nonaqueous solvents was confirmed by the detection of the characteristic luminescence at 1270 nm. These observations suggest that cutaneous photosensitivity arising from singlet-oxygen damage is likely to be an undesirable side-effect of SnPP therapy.

  19. Aptamer-conjugated, fluorescent gold nanorods as potential cancer theradiagnostic agents.

    PubMed

    Gallina, Maria Elena; Zhou, Yu; Johnson, Christopher J; Harris-Birtill, David; Singh, Mohan; Zhao, Hailin; Ma, Daqing; Cass, Tony; Elson, Daniel S

    2016-02-01

    GNRs are emerging as a new class of probes for theradiagnostic applications thanks to their unique optical properties. However, the achievement of proper nanoconstructs requires the synthesis of highly pure GNRs with well-defined aspect ratio (AR), in addition to extensive surface chemistry modification to provide them with active targeting and, possibly, multifunctionality. In this work, we refined the method of the seed mediated growth and developed a robust procedure for the fabrication of GNRs with specific AR. We also revealed and characterized unexplored aging phenomena that follow the synthesis and consistently alter GNRs' final AR. Such advances appreciably improved the feasibility of GNRs fabrication and offered useful insights on the growth mechanism. We next produced fluorescent, biocompatible, aptamer-conjugated GNRs by performing ligand exchange followed by bioconjugation to anti-cancer oligonucleotide AS1411. In vitro studies showed that our nanoconstructs selectively target cancer cells while showing negligible cytotoxicity. As a result, our aptamer-conjugated GNRs constitute ideal cancer-selective multifunctional probes and promising candidates as photothermal therapy agents.

  20. Identification of a Novel Class of Covalent Modifiers of Hemoglobin as Potential Antisickling Agents

    PubMed Central

    Omar, A. M.; Mahran, M. A.; Ghatge, M. S.; Chowdhury, N.; Bamane, F. H. A.; El-Araby, M. E.; Abdulmalik, O.; Safo, M. K.

    2015-01-01

    Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds--designated as KAUS (imidazolylacryloyl derivatives)--that we hypothesized would bind covalently to βCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition reaction between the β-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with βCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, however showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation to the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. PMID:25974708

  1. Aptamer-conjugated, fluorescent gold nanorods as potential cancer theradiagnostic agents.

    PubMed

    Gallina, Maria Elena; Zhou, Yu; Johnson, Christopher J; Harris-Birtill, David; Singh, Mohan; Zhao, Hailin; Ma, Daqing; Cass, Tony; Elson, Daniel S

    2016-02-01

    GNRs are emerging as a new class of probes for theradiagnostic applications thanks to their unique optical properties. However, the achievement of proper nanoconstructs requires the synthesis of highly pure GNRs with well-defined aspect ratio (AR), in addition to extensive surface chemistry modification to provide them with active targeting and, possibly, multifunctionality. In this work, we refined the method of the seed mediated growth and developed a robust procedure for the fabrication of GNRs with specific AR. We also revealed and characterized unexplored aging phenomena that follow the synthesis and consistently alter GNRs' final AR. Such advances appreciably improved the feasibility of GNRs fabrication and offered useful insights on the growth mechanism. We next produced fluorescent, biocompatible, aptamer-conjugated GNRs by performing ligand exchange followed by bioconjugation to anti-cancer oligonucleotide AS1411. In vitro studies showed that our nanoconstructs selectively target cancer cells while showing negligible cytotoxicity. As a result, our aptamer-conjugated GNRs constitute ideal cancer-selective multifunctional probes and promising candidates as photothermal therapy agents. PMID:26652380

  2. [Conservative therapy of female urinary incontinence--potential and effect].

    PubMed

    Horcicka, L; Chmel, R; Novácková, M

    2005-01-01

    Non-surgical treatment of female stress urinary incontinence is not as effective as surgical methods but it is very successful in indicated cases. Rehabilitation of the pelvic floor muscles (Kegel exercises, vaginal cones, and electrostimulation of the pelvic floor muscles), drug treatment (alfa-mimetics, tricyclic antidepressives, estrogens, duloxetin), pessarotherapy and uretral obturator devices represent possibilities of conservative therapy of the stress incontinence. Conservative therapy is the method of choice in the treatment of urge incontinence. The most successful are anticholinergic drugs but they have very frequent serious side effects (dryness of the mucous membranes, accommodation disorders, constipation). Spasmolytics, estrogens and tricyclic antidepressives are the other popular used drugs. Life style modification, bladder training and electrostimulation represent very important parts of the conservative treatment. Effectiveness of the non-surgical treatment of both urge and stress urinary incontinence can not reach 100 percent but it helps very much in the quality of life improvement of incontinent women.

  3. POTENTIAL FUTURE NEUROPROTECTIVE THERAPIES FOR NEURODEGENERATIVE DISORDERS AND STROKE

    PubMed Central

    Tarawneh, Rawan; Galvin, James E.

    2009-01-01

    The cellular mechanisms underlying neuronal loss and neurodegeneration have been an area of interest in the last decade. Although neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD) each have distinct clinical symptoms and pathologies, they all share common mechanisms such as protein aggregation, oxidative injury, inflammation, apoptosis and mitochondrial injury that contribute to neuronal loss. Although cerebrovascular disease is due to etiologies quite different from the neurodegenerative disorders, many of the same common disease mechanisms come into play following a stroke. Novel therapies that target each of these mechanisms may be effective in decreasing the risk of disease, abating symptoms or slowing down their progression. While most of these therapies are experimental, and require further investigation, a few seem to offer promise in the near future. PMID:20176298

  4. Clinical potential for vitamin D as a neoadjuvant for photodynamic therapy of nonmelanoma skin cancer

    NASA Astrophysics Data System (ADS)

    Maytin, Edward V.; Anand, Sanjay; Rollakanti, Kishore

    2015-03-01

    Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of human cancer worldwide. Effective therapies include surgical excision, cryotherapy, and ionizing radiation, but all of these cause scarring. ALA-based PDT is a non-scarring modality used routinely for NMSC in Europe but not in the USA, primarily due to lingering uncertainties about efficacy. We have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can be used as neoadjuvants, i.e., can be given as a pretreatment prior to ALA-PDT, to improve the efficacy of tumor killing in mouse models of NMSC. Vitamin D (VD3) is the most recent neoadjuvant on this list. In this presentation we make the case that VD3 may be superior to the other agents to improve results of ALA-PDT skin cancer treatment. The active form of VD3 (calcitriol) is available topically as a pharmaceutical grade cream or ointment (FDA-approved for psoriasis), and works well for boosting ALA-PDT tumor treatment in mouse models. For deep tumors not reachable by a topical route, calcitriol can be given systemically and is very effective, but carries a risk of causing hypercalcemia as a side effect. To circumvent this risk, we have conducted experiments with the natural dietary form of VD3 (cholecalciferol), and showed that this improves ALA-PDT efficacy almost to the same extent as calcitriol. Because cholecalciferol does not increase serum calcium levels, this represents a potentially extremely safe approach. Data in mouse models of BCC and SCC will be presented.

  5. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent.

    PubMed

    Thangamani, Shankar; Mohammad, Haroon; Abushahba, Mostafa F N; Hamed, Maha I; Sobreira, Tiago J P; Hedrick, Victoria E; Paul, Lake N; Seleem, Mohamed N

    2015-01-01

    The rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad-spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin's ability to suppress production of key MRSA toxins (α-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. PMID:26553420

  6. Bismuth@US-tubes as a Potential Contrast Agent for X-ray Imaging Applications

    PubMed Central

    Rivera, Eladio J.; Tran, Lesa A.; Hernández-Rivera, Mayra; Yoon, Diana; Mikos, Antonios G.; Rusakova, Irene A.; Cheong, Benjamin Y.; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Wilson, Lon J.

    2013-01-01

    The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking. PMID:24288589

  7. Understanding Virulence in the Brucellae and Francisellae: Towards Efficacious Treatments for Two Potential Biothreat Agents

    SciTech Connect

    Rasley, A; Parsons, D A; El-Etr, S; Roux, C; Tsolis, R

    2009-12-30

    Francisella tularensis, Yersinia pestis and Brucellae species are highly infectious pathogens classified as select agents by the Centers for Disease Control and Prevention (CDC) with the potential for use in bioterrorism attacks. These organisms are known to be facultative intracellular pathogens that preferentially infect human monocytes. As such, understanding how the host responds to infection with these organisms is paramount in detecting and combating human disease. We have compared the ability of fully virulent strains of each pathogen and their non-pathogenic near neighbors to enter and survive inside the human monocytic cell line THP-1 and have quantified the cellular response to infection with the goal of identifying both unique and common host response patterns. We expanded the scope of these studies to include experiments with pathogenic and non-pathogenic strains of Y. pestis, the causative agent of plague. Nonpathogenic strains of each organism were impaired in their ability to survive intracellularly compared with their pathogenic counterparts. Furthermore, infection of THP-1 cells with pathogenic strains of Y. pestis and F. tularensis resulted in marked increases in the secretion of the inflammatory chemokines IL-8, RANTES, and MIP-1{beta}. In contrast, B. melitensis infection failed to elicit any significant increases in a panel of cytokines tested. These differences may underscore distinct strategies in pathogenic mechanisms employed by these pathogens.

  8. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent

    PubMed Central

    Thangamani, Shankar; Mohammad, Haroon; Abushahba, Mostafa F. N.; Hamed, Maha I.; Sobreira, Tiago J. P.; Hedrick, Victoria E.; Paul, Lake N.; Seleem, Mohamed N.

    2015-01-01

    The rapid rise of bacterial resistance to traditional antibiotics combined with the decline in discovery of novel antibacterial agents has created a global public health crisis. Repurposing existing drugs presents an alternative strategy to potentially expedite the discovery of new antimicrobial drugs. The present study demonstrates that simvastatin, an antihyperlipidemic drug exhibited broad-spectrum antibacterial activity against important Gram-positive (including methicillin-resistant Staphylococcus aureus (MRSA)) and Gram-negative pathogens (once the barrier imposed by the outer membrane was permeabilized). Proteomics and macromolecular synthesis analyses revealed that simvastatin inhibits multiple biosynthetic pathways and cellular processes in bacteria, including selective interference of bacterial protein synthesis. This property appears to assist in simvastatin’s ability to suppress production of key MRSA toxins (α-hemolysin and Panton-Valentine leucocidin) that impair healing of infected skin wounds. A murine MRSA skin infection experiment confirmed that simvastatin significantly reduces the bacterial burden and inflammatory cytokines in the infected wounds. Additionally, simvastatin exhibits excellent anti-biofilm activity against established staphylococcal biofilms and demonstrates the ability to be combined with topical antimicrobials currently used to treat MRSA skin infections. Collectively the present study lays the foundation for further investigation of repurposing simvastatin as a topical antibacterial agent to treat skin infections. PMID:26553420

  9. Amphiphilic cationic β(3R3)-peptides: membrane active peptidomimetics and their potential as antimicrobial agents.

    PubMed

    Mosca, Simone; Keller, Janos; Azzouz, Nahid; Wagner, Stefanie; Titz, Alexander; Seeberger, Peter H; Brezesinski, Gerald; Hartmann, Laura

    2014-05-12

    We introduce a novel class of membrane active peptidomimetics, the amphiphilic cationic β(3R3)-peptides, and evaluate their potential as antimicrobial agents. The design criteria, the building block and oligomer synthesis as well as a detailed structure-activity relationship (SAR) study are reported. Specifically, infrared reflection absorption spectroscopy (IRRAS) was employed to investigate structural features of amphiphilic cationic β(3R3)-peptide sequences at the hydrophobic/hydrophilic air/liquid interface. Furthermore, Langmuir monolayers of anionic and zwitterionic phospholipids have been used to model the interactions of amphiphilic cationic β(3R3)-peptides with prokaryotic and eukaryotic cellular membranes in order to predict their membrane selectivity and elucidate their mechanism of action. Lastly, antimicrobial activity was tested against Gram-positive M. luteus and S. aureus as well as against Gram-negative E. coli and P. aeruginosa bacteria along with testing hemolytic activity and cytotoxicity. We found that amphiphilic cationic β(3R3)-peptide sequences combine high and selective antimicrobial activity with exceptionally low cytotoxicity in comparison to values reported in the literature. Overall, this study provides further insights into the SAR of antimicrobial peptides and peptidomimetics and indicates that amphiphilic cationic β(3R3)-peptides are strong candidates for further development as antimicrobial agents with high therapeutic index.

  10. Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants.

    PubMed

    Ntie-Kang, Fidele; Simoben, Conrad Veranso; Karaman, Berin; Ngwa, Valery Fuh; Judson, Philip Neville; Sippl, Wolfgang; Mbaze, Luc Meva'a

    2016-01-01

    Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner-Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa's expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space. PMID:27445461

  11. Potential of Pseudomonas chlororaphis subsp. aurantiaca Strain Pcho10 as a Biocontrol Agent Against Fusarium graminearum.

    PubMed

    Hu, Weiqun; Gao, Qixun; Hamada, Mohamed Sobhy; Dawood, Dawood Hosni; Zheng, Jingwu; Chen, Yun; Ma, Zhonghua

    2014-12-01

    To develop an effective biocontrol strategy for management of Fusarium head blight on wheat caused by Fusarium graminearum, the bacterial biocontrol agent Pcho10 was selected from more than 1,476 wheat-head-associated bacterial strains according to its antagonistic activity in vitro. This strain was subsequently characterized as Pseudomonas chlororaphis subsp. aurantiaca based on 16S ribosomal DNA sequence analysis, assays of the BIOLOG microbial identification system, and unique pigment production. The major antifungal metabolite produced by Pcho10 was further identified as phenazine-1-carboxamide (PCN) on the basis of nuclear magnetic resonance data. The core PCN biosynthesis gene cluster in Pcho10 was cloned and sequenced. PCN showed strong inhibitory activity against F. graminearum conidial germination, mycelial growth, and deoxynivalenol production. Tests both under growth chamber conditions and in field trials showed that Pcho10 well colonized on the wheat head and effectively controlled the disease caused by F. graminearum. Results of this study indicate that P. chlororaphis subsp. aurantiaca Pcho10 has high potential to be developed as a biocontrol agent against F. graminearum. To our knowledge, this is the first report of the use of P. chlororaphis for the management of Fusarium head blight.

  12. Pseudopterosin A: Protection of Synaptic Function and Potential as a Neuromodulatory Agent

    PubMed Central

    Caplan, Stacee Lee; Zheng, Bo; Dawson-Scully, Ken; White, Catherine A.; West, Lyndon M.

    2016-01-01

    Natural products have provided an invaluable source of inspiration in the drug discovery pipeline. The oceans are a vast source of biological and chemical diversity. Recently, this untapped resource has been gaining attention in the search for novel structures and development of new classes of therapeutic agents. Pseudopterosins are group of marine diterpene glycosides that possess an array of potent biological activities in several therapeutic areas. Few studies have examined pseudopterosin effects during cellular stress and, to our knowledge, no studies have explored their ability to protect synaptic function. The present study probes pseudopterosin A (PsA) for its neuromodulatory properties during oxidative stress using the fruit fly, Drosophila melanogaster. We demonstrate that oxidative stress rapidly reduces neuronal activity, resulting in the loss of neurotransmission at a well-characterized invertebrate synapse. PsA mitigates this effect and promotes functional tolerance during oxidative stress by prolonging synaptic transmission in a mechanism that differs from scavenging activity. Furthermore, the distribution of PsA within mammalian biological tissues following single intravenous injection was investigated using a validated bioanalytical method. Comparable exposure of PsA in the mouse brain and plasma indicated good distribution of PsA in the brain, suggesting its potential as a novel neuromodulatory agent. PMID:26978375

  13. A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2.

    PubMed

    Huang, Zih-Rou; Tsai, Chia-Ling; Huang, Ya-Yao; Shiue, Chyng-Yann; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Hsin, Ling-Wei

    2016-01-01

    In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains. PMID:27612194

  14. A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2

    PubMed Central

    Huang, Zih-Rou; Tsai, Chia-Ling; Huang, Ya-Yao; Shiue, Chyng-Yann; Tzen, Kai-Yuan; Yen, Ruoh-Fang; Hsin, Ling-Wei

    2016-01-01

    In the early 1990s, 9-(+)-11C-dihydrotetrabenazine (9-(+)-11C-DTBZ) was shown to be a useful positron emission tomography (PET) imaging agent for various neurodegenerative disorders. Here, we described the radiosynthesis and evaluation of the 9-(+)-11C-DTBZ analog, 10-(+)-11C-DTBZ, as a vesicular monoamine transporter 2 (VMAT2) imaging agent and compare it with 9-(+)-11C-DTBZ. 10-(+)-11C-DTBZ was obtained by 11C-MeI methylation with its 10 hydroxy precursor in the presence of 5 M NaOH. It had a slightly better average radiochemical yield of 35.3 ± 3.6% (decay-corrected to end of synthesis (EOS)) than did 9-(+)-11C-DTBZ (30.5 ± 2.3%). MicroPET studies showed that 10-(+)-11C-DTBZ had a striatum-to-cerebellum ratio of 3.74 ± 0.21 at 40 min post-injection, while the ratio of 9-(+)-11C-DTBZ was 2.50 ± 0.33. This indicated that 10-(+)-11C-DTBZ has a higher specific uptake in VMAT2-rich brain regions, and 10-(+)-11C-DTBZ may be a potential VMAT2 radioligand. Our experiment is the first study of 10-(+)-11C-DTBZ to include dynamic brain distribution in rat brains. PMID:27612194

  15. Potential of Pseudomonas chlororaphis subsp. aurantiaca Strain Pcho10 as a Biocontrol Agent Against Fusarium graminearum.

    PubMed

    Hu, Weiqun; Gao, Qixun; Hamada, Mohamed Sobhy; Dawood, Dawood Hosni; Zheng, Jingwu; Chen, Yun; Ma, Zhonghua

    2014-12-01

    To develop an effective biocontrol strategy for management of Fusarium head blight on wheat caused by Fusarium graminearum, the bacterial biocontrol agent Pcho10 was selected from more than 1,476 wheat-head-associated bacterial strains according to its antagonistic activity in vitro. This strain was subsequently characterized as Pseudomonas chlororaphis subsp. aurantiaca based on 16S ribosomal DNA sequence analysis, assays of the BIOLOG microbial identification system, and unique pigment production. The major antifungal metabolite produced by Pcho10 was further identified as phenazine-1-carboxamide (PCN) on the basis of nuclear magnetic resonance data. The core PCN biosynthesis gene cluster in Pcho10 was cloned and sequenced. PCN showed strong inhibitory activity against F. graminearum conidial germination, mycelial growth, and deoxynivalenol production. Tests both under growth chamber conditions and in field trials showed that Pcho10 well colonized on the wheat head and effectively controlled the disease caused by F. graminearum. Results of this study indicate that P. chlororaphis subsp. aurantiaca Pcho10 has high potential to be developed as a biocontrol agent against F. graminearum. To our knowledge, this is the first report of the use of P. chlororaphis for the management of Fusarium head blight. PMID:24941327

  16. Pharmacophore modeling and in silico toxicity assessment of potential anticancer agents from African medicinal plants

    PubMed Central

    Ntie-Kang, Fidele; Simoben, Conrad Veranso; Karaman, Berin; Ngwa, Valery Fuh; Judson, Philip Neville; Sippl, Wolfgang; Mbaze, Luc Meva’a

    2016-01-01

    Molecular modeling has been employed in the search for lead compounds of chemotherapy to fight cancer. In this study, pharmacophore models have been generated and validated for use in virtual screening protocols for eight known anticancer drug targets, including tyrosine kinase, protein kinase B β, cyclin-dependent kinase, protein farnesyltransferase, human protein kinase, glycogen synthase kinase, and indoleamine 2,3-dioxygenase 1. Pharmacophore models were validated through receiver operating characteristic and Güner–Henry scoring methods, indicating that several of the models generated could be useful for the identification of potential anticancer agents from natural product databases. The validated pharmacophore models were used as three-dimensional search queries for virtual screening of the newly developed AfroCancer database (~400 compounds from African medicinal plants), along with the Naturally Occurring Plant-based Anticancer Compound-Activity-Target dataset (comprising ~1,500 published naturally occurring plant-based compounds from around the world). Additionally, an in silico assessment of toxicity of the two datasets was carried out by the use of 88 toxicity end points predicted by the Lhasa’s expert knowledge-based system (Derek), showing that only an insignificant proportion of the promising anticancer agents would be likely showing high toxicity profiles. A diversity study of the two datasets, carried out using the analysis of principal components from the most important physicochemical properties often used to access drug-likeness of compound datasets, showed that the two datasets do not occupy the same chemical space. PMID:27445461

  17. Nanoparticle and Iron Chelators as a Potential Novel Alzheimer Therapy

    PubMed Central

    Liu, Gang; Men, Ping; Perry, George; Smith, Mark A.

    2010-01-01

    Current therapies for Alzheimer disease (AD) such as the acetylcholinesterase inhibitors and the latest NMDA receptor inhibitor, Namenda, provide moderate symptomatic delay at various stages of the disease, but do not arrest the disease progression or bring in meaningful remission. New approaches to the disease management are urgently needed. Although the etiology of AD is largely unknown, oxidative damage mediated by metals is likely a significant contributor since metals such as iron, aluminum, zinc, and copper are dysregulated and/or increased in AD brain tissue and create a pro-oxidative environment. This role of metal ion-induced free radical formation in AD makes chelation therapy an attractive means of dampening the oxidative stress burden in neurons. The chelator desferrioxamine, FDA approved for iron overload, has shown some benefit in AD, but like many chelators, it has a host of adverse effects and substantial obstacles for tissue-specific targeting. Other chelators are under development and have shown various strengths and weaknesses. Here, we propose a novel system of chelation therapy through the use of nanoparticles. Nanoparticles conjugated to chelators show unique ability to cross the blood–brain barrier (BBB), chelate metals, and exit through the BBB with their corresponding complexed metal ions. This method may provide a safer and more effective means of reducing the metal load in neural tissue, thus attenuating the harmful effects of oxidative damage and its sequelae. Experimental procedures are presented in this chapter. PMID:20013176

  18. Potential role of mind-body therapies in cancer survivorship.

    PubMed

    Monti, Daniel A; Sufian, Meryl; Peterson, Caroline

    2008-06-01

    The use of complementary and alternative medicine (CAM) by cancer survivors is high, particularly among those with psychosocial distress, poor quality of life, culturally based health beliefs, and those who experience health disparities in the mainstream healthcare system. As the number of cancer survivors continues to increase, so does the diversity of the survivorship population, making it increasingly important to understand and address the CAM culture in different survivor groups. Given the known communication barriers between cancer patients and their physicians regarding CAM, it would be useful for oncology providers to have a platform from which to discuss CAM-related issues. It is proposed that mind-body therapies with some basis in evidence could provide such a platform and also serve as a possible means of connecting cancer survivors to psychosocial supportive services. This article reviews a few mind-body therapies that may have particular relevance to cancer survivors, such as hypnosis and meditation practices. A theoretical foundation by which such therapies provide benefit is presented, with particular emphasis on self-regulation.

  19. Bridge with intravenous antiplatelet therapy during temporary withdrawal of oral agents for surgical procedures: a systematic review.

    PubMed

    Morici, Nuccia; Moja, Lorenzo; Rosato, Valentina; Sacco, Alice; Mafrici, Antonio; Klugmann, Silvio; D'Urbano, Maurizio; La Vecchia, Carlo; De Servi, Stefano; Savonitto, Stefano

    2014-03-01

    Patients needing surgery within 1 year after drug-eluting cardiac stent implantation are challenging to manage because of an increased thrombotic and bleeding risk. A "bridge therapy" with short-acting antiplatelet agents in the perioperative period is an option. We assessed the outcome and safety of such a bridge therapy in cardiovascular and non-cardiovascular surgery. We performed a comprehensive search of MEDLINE, EMBASE, the Cochrane Library, and ongoing trial registers, irrespective of type of design. Our primary outcome was the success rate of bridge therapy in terms of freedom from cardiac ischaemic adverse events, whereas secondary outcome was freedom from bleeding/transfusion. We also performed combined success rate for each bridge therapy drug (tirofiban, eptifibatide, and cangrelor). We included eight case series and one randomised controlled trial. Among the 420 patients included, the technique was effective 96.2 % of the times [95 % confidence interval (CI) 94.4-98.0 %]. The success rate was 100 % for tirofiban (4 studies), 93.8 % for eptifibatide (4 studies), and 96.2 % for cangrelor (1 study). Freedom from bleeding/transfusion events was observed in 72.6 % of the times (95 % CI 68.4-76.9 %), and was higher with cangrelor (88.7 %; 95 % CI 82.7-94.7 %) than with other drugs (81.0 % for tirofiban and 58.6 % for eptifibatide). Evidence from case series and one randomised controlled trial suggests that, in patients with recent coronary stenting undergoing major surgery, perioperative bridge therapy with intravenous antiplatelet agents is an effective and safe treatment option to ensure low rate of ischaemic events.

  20. Synthesis and biological evaluation of new boron-containing chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.

    PubMed

    Asano, Ryuji; Nagami, Amon; Fukumoto, Yuki; Miura, Kaori; Yazama, Futoshi; Ito, Hideyuki; Sakata, Isao; Tai, Akihiro

    2014-03-01

    New boron-containing chlorin derivatives 9 and 13 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized from photoprotoporphyrin IX dimethyl ester (2) and L-4-boronophenylalanine-related compounds. The in vivo biodistribution and clearance of 9 and 13 were investigated in tumor-bearing mice. The time to maximum accumulation of compound 13 in tumor tissue was one-fourth of that of compound 9, and compound 13 showed rapid clearance from normal tissues within 24h after injection. The in vivo therapeutic efficacy of PDT using 13 was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 3h after injection of 13. Tumor growth was significantly inhibited by PDT using 13. These results suggested that 13 might be a good candidate for both PDT and BNCT of cancer.

  1. Design and evaluation of novel oxadiazole derivatives as potential prostate cancer agents

    PubMed Central

    Qi, Xin; Euynni, Suresh; Sikazwi, Donald; Mateeva, Nelly; Soliman, Karam F.

    2016-01-01

    Various 1,3,4-oxadiazole derivatives have been synthesized and their antiproliferative properties have been studied. The in vitro screening was performed against androgen dependent (LNCaP) and androgen independent (PC-3) prostate cancer cell lines. Most of the compounds showed promising activity. Among them, compounds 2d (IC50 = 0.22 and 1.3 μM) and 2a (IC50 = 8.34 and 2,5 μM) have shown significant activities on PC-3 and LNCaP cell lines respectively. To investigate the mechanism of cell death we performed cell apoptosis staining and cell cycle arrest assay on more sensitive PC-3 cell lines on 2d. The results demonstrated that 2d induced apoptosis and shifted the cells to the sub G0/G1 and S phase. Our study evidently identified the potency of compound 2d as potential anti-prostate cancer agent. PMID:27156770

  2. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    PubMed Central

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-01-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents. PMID:27671769

  3. Sodium arsenite potentiates the clastogenicity and mutagenicity of DNA cross linking agents

    SciTech Connect

    Lee, T.C.; Lee, K.C.; Tzeng, Y.J.; Huang, R.Y.; Jan, K.Y.

    1986-01-01

    To see if sodium arsenite enhances the clastogenicity and the mutagenicity of DNA crosslinking agents, Chinese hamster ovary (CHO) cells and human skin fibroblasts were exposed to cis-diamminedichloroplatinum (II) (cis-Pt(II)) or 8-methoxypsoralen (8-MOP) plus long-wave ultraviolet light (UVA) and then to sodium arsenite. The results indicate that the clastogenicity of cis-Pt(II) and 8-MOP pllus UVA are enhanced by the post-treatment with sodium arsenite. Chromatid breaks and exchanges are predominantly increased in doubly treated cells. Furthermore, the mutagenicity of cis-Pt(II) at the hypoxanthine-guanine phosphoribosyl transferase locus is also potentiated by sodium arsenite in CHO cells

  4. 227Th-EDTMP: a potential therapeutic agent for bone metastasis.

    PubMed

    Washiyama, Kohshin; Amano, Ryohei; Sasaki, Jun; Kinuya, Seigo; Tonami, Norihisa; Shiokawa, Yoshinobu; Mitsugashira, Toshiaki

    2004-10-01

    The biodistribution of 227Th-EDTMP and retention of its daughter nuclide 223Ra were examined. 227Th-EDTMP was found to show high uptake and long-term retention in bone. The clearance of 227Th-EDTMP from blood and soft tissues was rapid and the femur-to-tissue uptake ratios reached more than 100 within 30 min for all tissues except the kidney. Seven and 14 days after injection of 227Th-EDTMP, the retention index of 223Ra in bone showed high values, and the differences between these time points were not significant. Therefore, 227Th-EDTMP is a potential radiotherapeutic agent for bone metastasis. PMID:15464392

  5. Chitosan as a potential stabilizing agent for titania nanoparticle dispersions for preparation of multifunctional cotton fabric.

    PubMed

    Goyal, Nidhi; Rastogi, Deepali; Jassal, Manjeet; Agrawal, Ashwini K

    2016-12-10

    Titania (TiO2) nanoparticle dispersions in water were prepared using chitosan (CS) as the stabilizing agent. The dispersion stability was evaluated with respect to storage time, hydrodynamic particle size, and zeta potential. The effect of the molecular weight of CS and presence of non-ionic polymers (poly(vinyl alcohol) and poly(ethylene glycol)) as co-dispersants was investigated. Despite the increase in size of dispersed particles, the long-term storage stability of the dispersions improved with increasing concentration and molecular weight of CS. The TiO2/CS dispersions were applied on cotton fabric and characterized. The presence of CS did not seriously affect the photocatalytic self-cleaning activity (SCA) of TiO2; with CS, a SCA of 89% was achieved compared with a value of 96% without CS. In addition, the TiO2/CS-treated cotton fabrics provided UV protection and significant antimicrobial activity. PMID:27577907

  6. Potential Relevance of Melatonin Against Some Infectious Agents: A Review and Assessment of Recent Research.

    PubMed

    Elmahallawy, Ehab Kotb; Luque, Javier Ortega; Aloweidi, Abdelkarim Saleh; Gutiérrez-Fernández, José; Sampedro-Martínez, Antonio; Rodriguez-Granger, Javier; Kaki, Abdullah; Agil, Ahmad

    2015-01-01

    Melatonin, a tryptophan-derived neurohormone found in animals, plants, and microbes, participates in various biological and physiological functions. Among other properties, numerous in vitro or in vivo studies have reported its therapeutic potential against many parasites, bacteria and viruses. In this concern, melatonin was found to be effective against many parasites such as Plasmodium, Toxoplasma gondii, and Trypansoma cruzi, via various mechanisms such as modulation of calcium level and/or host immune system. Likewise, a recent investigation has reported in vitro activity of melatonin against Leishmania infantum promastigotes which is the causative agent of fascinating visceral Leishmaniasis. This review was initially undertaken to summarize some facts about certain physiological and therapeutic effects of melatonin. It also reviews the effects and action mechanisms of melatonin in bacterial and viral infection besides biology of different parasites which may provide a promising strategy for control of many diseases of public health importance.

  7. Preparation and in vitro evaluation of benzylsulfanyl benzoxazole derivatives as potential antituberculosis agents.

    PubMed

    Klimesová, Vera; Kocí, Jan; Waisser, Karel; Kaustová, Jarmila; Möllmann, Ute

    2009-05-01

    A set of 2-benzylsulfanyl derivatives of benzoxazole was synthesized and evaluated for their in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria and multidrug-resistant M. tuberculosis. The activities were expressed as the minimum inhibitory concentration (MIC) in mmol/L. The substances showed similar activity against all tested strains. The lead compounds in the set, dinitro derivatives exhibited significant activity against both sensitive and resistant strains of M. tuberculosis and also against non-tuberculous mycobacteria. To facilitate drug design of benzoxazole as potential antituberculosis agent, we have explored the quantitative structure-activity relationship (QSAR). We demonstrated that lower lipophilicity has significant contribution to activity. Dinitrobenzylsulfanyl derivative of benzoxazole represents the promising small-molecule synthetic antimycobacterials.

  8. Microtubule Stabilizing Agents as Potential Treatment for Alzheimer’s Disease and Related Neurodegenerative Tauopathies

    PubMed Central

    Ballatore, Carlo; Brunden, Kurt R.; Huryn, Donna M.; Trojanowski, John Q.; Lee, Virginia M.-Y.; Smith, Amos B.

    2012-01-01

    The microtubule (MT)-associated protein tau, which is highly expressed in the axons of neurons, is an endogenous MT-stabilizing agent that plays an important role in the axonal transport. Loss of MT-stabilizing tau function, caused by misfolding, hyperphosphorylation and sequestration of tau into insoluble aggregates, leads to axonal transport deficits with neuropathological consequences. Several in vitro and preclinical in vivo studies have shown that MT-stabilizing drugs can be utilized to compensate for the loss of tau function and to maintain/restore an effective axonal transport. These findings indicate that MT-stabilizing compounds hold considerable promise for the treatment of Alzheimer disease and related tauopathies. The present article provides a synopsis of the key findings demonstrating the therapeutic potential of MT-stabilizing drugs in the context of neurodegenerative tauopathies, as well as an overview of the different classes of MT-stabilizing compounds. PMID:23020671

  9. New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

    DOEpatents

    Katti, Kattesh V.; Volkert, Wynn A.; Ketring, Alan R.; Singh, Prahlad R.

    1997-01-01

    A class of diagnostic and therapeutic compounds derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g. .sup.99m Tc or .sup.186 Re/.sup.188 Re) or late transition metals (e.g., .sup.105 Rh or .sup.109 Pd). The complexes with these metals .sup.186 Re/.sup.188 Re, .sup.99m Tc and .sup.109 Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g. Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

  10. Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

    NASA Astrophysics Data System (ADS)

    Zhang, Qingchun; Jin, Bo; Shi, Zhaotao; Wang, Xiaofang; Liu, Qiangqiang; Lei, Shan; Peng, Rufang

    2016-09-01

    A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

  11. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential

    PubMed Central

    Zasloff, Michael; Adams, A. Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M.; Weaver, Scott C.; Wong, Gerard C. L.

    2011-01-01

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored. PMID:21930925

  12. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential.

    PubMed

    Zasloff, Michael; Adams, A Paige; Beckerman, Bernard; Campbell, Ann; Han, Ziying; Luijten, Erik; Meza, Isaura; Julander, Justin; Mishra, Abhijit; Qu, Wei; Taylor, John M; Weaver, Scott C; Wong, Gerard C L

    2011-09-20

    Antiviral compounds that increase the resistance of host tissues represent an attractive class of therapeutic. Here, we show that squalamine, a compound previously isolated from the tissues of the dogfish shark (Squalus acanthias) and the sea lamprey (Petromyzon marinus), exhibits broad-spectrum antiviral activity against human pathogens, which were studied in vitro as well as in vivo. Both RNA- and DNA-enveloped viruses are shown to be susceptible. The proposed mechanism involves the capacity of squalamine, a cationic amphipathic sterol, to neutralize the negative electrostatic surface charge of intracellular membranes in a way that renders the cell less effective in supporting viral replication. Because squalamine can be readily synthesized and has a known safety profile in man, we believe its potential as a broad-spectrum human antiviral agent should be explored. PMID:21930925

  13. A potential therapeutic strategy for inhibition of corneal neovascularization with new anti-VEGF agents.

    PubMed

    Hosseini, Hamid; Nejabat, Mahmood

    2007-01-01

    The factors triggering corneal neovascularization involve various growth factors. The data supporting a causal role for vascular endothelial growth factor (VEGF) in corneal neovascularization are extensive. One possible strategy for treating corneal neovascularization is to inhibit VEGF activity by competitively binding VEGF with a specific neutralizing anti-VEGF antibody. The vireo-retinal service in the recent years enjoyed a high level of success in managing choroidal neovascularization using anti-VEGF strategies. Efficacy and tolerability have been demonstrated for drugs targeting VEGF. We herein hypothesize that topical application of new anti-VEGF agents such as pegaptanib, ranibizumab and bevacizumab are potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations are needed to place these medical treatments alongside corneal neovascularization therapeutics. PMID:17107753

  14. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    PubMed

    Gupta, Abhishek; de Campo, Liliana; Rehmanjan, Beenish; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-02-01

    Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

  15. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    PubMed

    Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  16. Arbuscular mycorrhizal fungi: potential biocontrol agents against the damaging root hemiparasite Pedicularis kansuensis?

    PubMed

    Sui, Xiao-Lin; Li, Ai-Rong; Chen, Yan; Zhuo, Lu; Liu, Yan-Yan

    2014-04-01

    Spatial expansion of root hemiparasitic Pedicularis kansuensis in Bayanbulak Grassland of Xinjiang Uygur Autonomous Region (China) has caused great loss of herbage yield and has threatened the local livestock industry. Current management practices using manual eradication and chemical control have been proved problematic. Arbuscular mycorrhizal (AM) fungi have been suggested to be potential biocontrol agents against a number of plant pests, but experimental evidence is lacking against weedy P. kansuensis. In this study, we tested the hypothesis that inoculation with AM fungi will cause growth depression in P. kansuensis and reduce its damage to host plants. Based on the confirmation of AM status and host community of the hemiparasite in the field, a pot cultivation experiment was conducted to test the influence of an AM fungus (Glomus mosseae) on growth of P. kansuensis and the parasitized host (Elymus nutans). AM colonization was observed in roots of P. kansuensis, but the levels were much lower than those of its adjacent host species. A negative correlation between AM levels and the numbers of haustoria was detected for the field samples of the hemiparasite. Strong suppression of haustorium formation, a significant reduction in plant dry weight (DW), as well as marked reduction in the survival rate of P. kansuensis after inoculation with AM fungi was observed. In contrast, inoculation with G. mosseae increased root DW and whole plant DW of parasitized host plants. Our findings demonstrated significantly repressive effects of AM fungi on growth performance of P. kansuensis with and without the presence of a host. The potential of AM fungi as biocontrol agents against the damaging hemiparasite was confirmed.

  17. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies

    PubMed Central

    Ashraf, Zaman; Bais, Abdul; Manir, Md. Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents. PMID:26267242

  18. Race-based therapy for hypertension: possible benefits and potential pitfalls.

    PubMed

    Ferdinand, Keith C; Ferdinand, Daphne P

    2008-11-01

    Hypertension is a leading risk factor for cardiovascular disease, which includes coronary heart disease, heart failure and stroke. This article examines the possible benefits and potential pitfalls of utilizing race-based categories for antihypertensive therapy. Although the use of race and ethnicity to guide antihypertensive treatment is fraught with difficulty and is, to a large extent, inadequate, there may be benefit in recognizing specific aspects of race and ethnicity when approaching patients with hypertension. Evidence from clinical trials, including drug efficacy and safety comparisons and cardiovascular outcomes, has demonstrated some differences based on race/ethnicity. American federal standards strongly encourage capturing data on race/ethnicity, and most of the current data are available for self-described African-Americans. International studies increasingly identify race/ethnicity, although the data are not as robust as in US trials. Current guidelines recommend thiazide diuretics and/or long-acting calcium channel blockers as initial treatment for Blacks, although medications for compelling indications agents should be prescribed, regardless of race/ethnicity.

  19. A quantitative structure activity/dose response relationship for contact allergic potential of alkyl group transfer agents.

    PubMed

    Roberts, D W; Basketter, D A

    1990-11-01

    As part of the investigation of structure activity relationships in contact allergy, it has been shown that methyl transfer agents are capable of acting as skin sensitizers. This work has now been extended to a more general examination of alkyl transfer reactions. The modified single injection adjuvant test has been used to investigate the sensitization potential of C12, C16 and unsaturated C18 alkyl transfer agents. Dose responses to challenge and the patterns of cross-reactivity between these materials and methyl transfer agents have been studied. All alkyl transfer agents examined were potent sensitizers in the guinea pig. There was evidence of mutual cross-reactivity between all alkyl transfer agents examined (including methyl transfer agents). Analysis of the data in terms of a modified relative alkylation index showed evidence of an overload effect. The sensitization data has been accurately modelled using a mathematical equation. These results emphasize the possibilities for relating physicochemical parameters and skin sensitization potential. Further studies with alkyl transfer agents are in progress of amplify the observations and conclusions presented in this report. No in vitro model is available for the prediction of skin sensitization potential. Therefore an approach based on a model using physicochemical criteria is the most likely route to a reduced requirement for animal testing. PMID:1965716

  20. Antiplatelet therapy in acute coronary syndromes: current agents and impact on patient outcomes

    PubMed Central

    Tayeb, Hussam M; Nelson, Adam J; Willoughby, Scott R; Worthley, Matthew I

    2011-01-01

    Platelets play a central role in atherothrombosis and subsequent development of acute coronary syndromes (ACS). The understanding of this process has driven a large body of evidence demonstrating the mortality and morbidity benefits of antiplatelet agents in the ACS population. As expected, however, these agents come with an intrinsically increased risk of bleeding which underlies the vast majority of their complications and adverse effects. In today’s setting of compounding comorbidities and broadening indications, finding the balance between thrombosis prevention and bleeding risk remains the challenge for all clinicians considering these medications. This article reviews the current main antiplatelet agents that are available for clinical use and outlines their impact on ACS outcome. We also outline factors which affect the response to these agents and discuss strategies to optimize clinical outcomes. PMID:22915965

  1. Physical agent modalities in physical therapy and rehabilitation of small animals.

    PubMed

    Hanks, June; Levine, David; Bockstahler, Barbara

    2015-01-01

    Physical agent modalities can be effective components of the overall rehabilitation of small animals. This article reviews the effects, indications, contraindications, and precautions of cold, superficial heat, therapeutic ultrasound, and electrical stimulation.

  2. Natural products as potential cancer therapy enhancers: A preclinical update

    PubMed Central

    Agbarya, Abed; Ruimi, Nili; Epelbaum, Ron; Ben-Arye, Eran

    2014-01-01

    Cancer is a multifactorial disease that arises as a consequence of alterations in many physiological processes. Recently, hallmarks of cancer were suggested that include sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis, along with two emerging hallmarks including reprogramming energy metabolism and escaping immune destruction. Treating multifactorial diseases, such as cancer with agents targeting a single target, might provide partial treatment and, in many cases, disappointing cure rates. Epidemiological studies have consistently shown that the regular consumption of fruits and vegetables is strongly associated with a reduced risk of developing chronic diseases, such as cardiovascular diseases and cancer. Since ancient times, plants, herbs, and other natural products have been used as healing agents. Moreover, the majority of the medicinal substances available today have their origin in natural compounds. Traditionally, pharmaceuticals are used to cure diseases, and nutrition and herbs are used to prevent disease and to provide an optimal balance of macro- and micro-nutrients needed for good health. We explored the combination of natural products, dietary nutrition, and cancer chemotherapeutics for improving the efficacy of cancer chemotherapeutics and negating side effects. PMID:26770737

  3. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser

    PubMed Central

    Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

    2015-01-01

    Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer. PMID:26251596

  4. Gold nanorods/mesoporous silica-based nanocomposite as theranostic agents for targeting near-infrared imaging and photothermal therapy induced with laser.

    PubMed

    Liu, Yang; Xu, Ming; Chen, Qing; Guan, Guannan; Hu, Wen; Zhao, Xiuli; Qiao, Mingxi; Hu, Haiyang; Liang, Ying; Zhu, Heyun; Chen, Dawei

    2015-01-01

    Photothermal therapy (PTT) is widely regarded as a promising technology for cancer treatment. Gold nanorods (GNRs), as excellent PTT agent candidates, have shown high-performance photothermal conversion ability under laser irradiation, yet two major obstacles to their clinical application are the lack of selective accumulation in the target site following systemic administration and the greatly reduced photothermal conversion efficiency caused by self-aggregating in aqueous environment. Herein, we demonstrate that tLyp-1 peptide-functionalized, indocyanine green (ICG)-containing mesoporous silica-coated GNRs (I-TMSG) possessed dual-function as tumor cells-targeting near-infrared (NIR) fluorescent probe and PTT agents. The construction of the nanostructure began with synthesis of GNRs by seed-mediated growth method, followed by the coating of mesoporous silica, the chemical conjugation of PEG and tLyp-1 peptide, and the enclosure of ICG as an NIR imaging agent in the mesoporous. The as-prepared nanoparticles could shield the GNRs against their self-aggregation, improve the stability of ICG, and exhibit negligible dark cytotoxicity. More importantly, such a theranostic nanocomposite could realize the combination of GNRs-based photothermal ablation under NIR illumination, ICG-mediated fluorescent imaging, and tLyp-1-enabled more easy endocytosis into breast cancer cells. All in all, I-TMSG nanoparticles, in our opinion, possessed the strong potential to realize the effective diagnosis and PTT treatment of human mammary cancer. PMID:26251596

  5. Viruses of the Bunya- and Togaviridae families: potential as bioterrorism agents and means of control.

    PubMed

    Sidwell, Robert W; Smee, Donald F

    2003-01-01

    When considering viruses of potential importance as tools for bioterrorism, several viruses in the Bunya- and Togaviridae families have been cited. Among those in the Bunyaviridae family are Rift Valley fever, Crimean-Congo hemorrhagic fever, hanta, and sandfly fever viruses, listed in order of priority. Those particularly considered in the Togaviridae family are Venezuelan, eastern and western equine encephalitis viruses. Factors affecting the selection of these viruses are the ability for them to induce a fatal or seriously incapacitating illness, their ease of cultivation in order to prepare large volumes, their relative infectivity in human patients, their ability to be transmitted by aerosol, and the lack of measures available for their control. Each factor is fully considered in this review. Vaccines for the control of infections induced by these viruses are in varying stages of development, with none universally accepted to date. Viruses in the Bunyaviridae family are generally sensitive to ribavirin, which has been recommended as an emergency therapy for infections by viruses in this family although has not yet been FDA-approved. Interferon and interferon inducers also significantly inhibit these virus infections in animal models. Against infections induced by viruses in the Togaviridae family, interferon-alpha would appear to currently be the most useful for therapy.

  6. Consolidation and Maintenance Therapies for Newly Diagnosed Multiple Myeloma in the Era of Novel Agents.

    PubMed

    Nathwani, Nitya; Larsen, Jeremy T; Kapoor, Prashant

    2016-04-01

    Advances in therapy in multiple myeloma have resulted in significant improvements in patient outcomes; however, relapse remains problematic. Strategies to improve outcomes following autologous stem cell transplantation (ASCT) include consolidation to intensify therapy and improve depth of response and maintenance therapy to achieve long-term disease control. Immunomodulatory drugs (IMiDs), including thalidomide and lenalidomide, are appealing as maintenance therapy given their oral administration; however, the cumulative toxicities of thalidomide have limited its efficacy in maintenance therapy. Maintenance lenalidomide is better tolerated, and multiple studies have demonstrated an improvement in progression-free survival (PFS), but its impact on overall survival (OS) remains controversial. Additional concerns regarding the risk of second primary malignancies and significant cost of long-term lenalidomide therapy have also been raised. Proteasome inhibitors, particularly, bortezomib have also been incorporated in consolidation and maintenance regimens alone or in combination with an IMiD. Preliminary studies have suggested bortezomib maintenance may benefit patients with adverse cytogenetics, including t(4;14) and deletion 17p. Determination of the optimal consolidation and maintenance regimen and duration of therapy post-transplantation is a focus of several ongoing randomized studies.

  7. The Quest for a Simple Bioactive Analog of Paclitaxel as a Potential Anticancer Agent

    PubMed Central

    2015-01-01

    Conspectus Paclitaxel (PTX), introduced into the clinic in 1991, has revealed itself as an effective antimicrotubule drug for treatment of a range of otherwise intractable cancers. Along with docetaxel (DTX) and in combination with other agents such as cisplatin, it has proven to be a first-line therapy. Unfortunately, PTX and DTX carry severe liabilities such as debilitating side effects, rapid onset of resistance, and rather complex molecular structures offering substantial challenges to ease of synthetic manipulation. Consequently, the past 15 years has witnessed many efforts to synthesize and test highly modified analogs based on intuitive structural similarity relationships with the PTX molecular skeleton, as well as efforts to mimic the conformational profile of the ligand observed in the macromolecular tubulin–PTX complex. Highly successful improvements in potency, up to 50-fold increases in IC50, have been achieved by constructing bridges between distal centers in PTX that imitate the conformer of the electron crystallographic binding pose. Much less successful have been numerous attempts to truncate PTX by replacing the baccatin core with simpler moieties to achieve PTX-like potencies and applying a wide range of flexible synthesis-based chemistries. Reported efforts, characterized by a fascinating array of baccatin substitutes, have failed to surpass the bioactivities of PTX in both microtubule disassembly assays and cytotoxicity measurements against a range of cell types. Most of the structures retain the main elements of the PTX C13 side chain, while seeking a smaller rigid bicycle as a baccatin replacement adorned with substituents to mimic the C2 benzoyl moiety and the oxetane ring. We surmise that past studies have been handicapped by solubility and membrane permeability issues, but primarily by the existence of an expansive taxane binding pocket and the discrepancy in molecular size between PTX and the pruned analogs. A number of these molecules

  8. Combination of the vascular targeting agent ZD6126 with boron neutron capture therapy

    SciTech Connect

    Masunaga, Shin-ichiro . E-mail: smasuna@rri.kyoto-u.ac.jp; Sakurai, Yoshinori; Suzuki, Minoru; Nagata, Kenji; Maruhashi, Akira; Kinash, Yuko; Ono, Koji

    2004-11-01

    Purpose: The aim of this study was to evaluate the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) in the rodent squamous cell carcinoma (SCC) VII carcinoma model, in combination with boron neutron capture therapy (BNCT). Methods and materials: Sodium borocaptate-{sup 10}B (BSH, 125 mg/kg, i.p.) or l-p-boronophenylalanine-{sup 10}B (BPA, 250 mg/kg, i.p.) was injected into SCC VII tumor-bearing mice, and 15 min later, ZD6126 (100 mg/kg, i.p.) was administered. Then, the {sup 10}B concentrations in tumors and normal tissues were measured by prompt {gamma}-ray spectrometry. On the other hand, for the thermal neutron beam exposure experiment, SCC VII tumor-bearing mice were continuously given 5-bromo-2'-deoxyuridine (BrdU) to label all proliferating (P) cells in the tumors, followed by treatment with a {sup 10}B-carrier and ZD6126 in the same manner as the above-mentioned {sup 10}B pharmacokinetics analyses. To obtain almost similar intratumor {sup 10}B concentrations during neutron exposure, thermal neutron beam irradiation was started from the time point of 30 min after injection of BSH only, 90 min after BSH injection for combination with ZD6126, 120 min after the injection of BPA only, and 180 min after BPA injection for combination with ZD6126. Right after irradiation, the tumors were excised, minced, and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (quiescent [Q] cells) was determined using immunofluorescence staining for BrdU. Meanwhile, the MN frequency in total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. The clonogenic cell survival assay was also performed in mice given no BrdU. Results: Pharmacokinetics analyses showed that combination with ZD6126 greatly increased the {sup 10}B concentrations in tumors after 60 min after BSH injection and

  9. Double-targeting using a TrkC ligand conjugated to dipyrrometheneboron difluoride (BODIPY) based photodynamic therapy (PDT) agent.

    PubMed

    Kamkaew, Anyanee; Burgess, Kevin

    2013-10-10

    A molecule 1 (IY-IY-PDT) was designed to contain a fragment (IY-IY) that targets the TrkC receptor and a photosensitizer that acts as an agent for photodynamic therapy (PDT). Molecule 1 had submicromolar photocytotoxicities to cells that were engineered to stably express TrkC (NIH3T3-TrkC) or that naturally express high levels of TrkC (SY5Y neuroblastoma lines). Control experiments showed that 1 is not cytotoxic in the dark and has significantly less photocytotoxicity toward cells that do not express TrkC (NIH3T3-WT). Other controls featuring a similar agent 2 (YI-YI-PDT), which is identical and isomeric with 1 except that the targeting region is scrambled (a YI-YI motif, see text), showed that 1 is considerably more photocytotoxic than 2 on TrkC(+) cells. Imaging live TrkC(+) cells after treatment with a fluorescent agent 1 (IY-IY-PDT) proved that 1 permeates into TrkC(+) cells and is localized in the lysosomes. This observation indirectly indicates that agent 1 enters the cells via the TrkC receptor. Consistent with this, the dose-dependent PDT effects of 1 can be competitively reduced by the natural TrkC ligand, neurotrophin NT3.

  10. FePt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells.

    PubMed

    Zheng, Yanhong; Tang, Yunlan; Bao, Zhirong; Wang, Hui; Ren, Feng; Guo, Mingxiong; Quan, Hong; Jiang, Changzhong

    2015-01-01

    Nanomaterials have an advantage in "personalized" therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration <250 μg/mL. Meanwhile, the FePt NPs showed negative/positive contrast enhancement for MRI/CT molecule imaging at the end of the study. Therefore, the combined results implied that FePt NPs might potentially serve as a promising nanoprobe for the integration of tumor diagnosis and chemoradiotherapy.

  11. FePt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells

    PubMed Central

    Zheng, Yanhong; Tang, Yunlan; Bao, Zhirong; Wang, Hui; Ren, Feng; Guo, Mingxiong; Quan, Hong; Jiang, Changzhong

    2015-01-01

    Nanomaterials have an advantage in “personalized” therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration <250 μg/mL. Meanwhile, the FePt NPs showed negative/positive contrast enhancement for MRI/CT molecule imaging at the end of the study. Therefore, the combined results implied that FePt NPs might potentially serve as a promising nanoprobe for the integration of tumor diagnosis and chemoradiotherapy. PMID:26604740

  12. FePt nanoparticles as a potential X-ray activated chemotherapy agent for HeLa cells.

    PubMed

    Zheng, Yanhong; Tang, Yunlan; Bao, Zhirong; Wang, Hui; Ren, Feng; Guo, Mingxiong; Quan, Hong; Jiang, Changzhong

    2015-01-01

    Nanomaterials have an advantage in "personalized" therapy, which is the ultimate goal of tumor treatment. In order to investigate the potential ability of FePt nanoparticles (NPs) in the diagnosis and chemoradiotherapy treatment of malignant tumors, superparamagnetic, monodispersed FePt (~3 nm) alloy NPs were synthesized, using cysteamine as a capping agent. The NPs were characterized by means of X-ray diffraction; transmission electron microscopy, Physical Property Measurement System, and Fourier transform infrared spectroscopy. The cytotoxicity of FePt NPs on Vero cells was assessed using an MTT assay, and tumor cell proliferation inhibited by individual FePt NPs and FePt NPs combined with X-ray beams were also collected using MTT assays; HeLa human cancer cell lines were used as in vitro models. Further confirmation of the combined effect of FePt NPs and X-rays was verified using HeLa cells, after which, the cellular uptake of FePt NPs was captured by transmission electron microscopy. The results indicated that the growth of HeLa cells was significantly inhibited by FePt NPs in a concentration-dependent manner, and the growth was significantly more inhibited by FePt NPs combined with a series of X-ray beam doses; the individual NPs did not display any remarkable cytotoxicity on Vero cells at a concentration <250 μg/mL. Meanwhile, the FePt NPs showed negative/positive contrast enhancement for MRI/CT molecule imaging at the end of the study. Therefore, the combined results implied that FePt NPs might potentially serve as a promising nanoprobe for the integration of tumor diagnosis and chemoradiotherapy. PMID:26604740

  13. Achromatopsia as a potential candidate for gene therapy.

    PubMed

    Pang, Ji-Jing; Alexander, John; Lei, Bo; Deng, Wentao; Zhang, Keqing; Li, Qiuhong; Chang, Bo; Hauswirth, William W

    2010-01-01

    Achromatopsia is an autosomal recessive retinal disease involving loss of cone function that afflicts approximately 1 in 30,000 individuals. Patients with achromatopsia usually have visual acuities lower than 20/200 because of the central vision loss, photophobia, complete color blindness and reduced cone-mediated electroretinographic (ERG) amplitudes. Mutations in three genes have been found to be the primary causes of achromatopsia, including CNGB3 (beta subunit of the cone cyclic nucleotide-gated cation channel), CNGA3 (alpha subunit of the cone cyclic nucleotide-gated cation channel), and GNAT2 (cone specific alpha subunit of transducin). Naturally occurring mouse models with mutations in Cnga3 (cpfl5 mice) and Gnat2 (cpfl3 mice) were discovered at The Jackson Laboratory. A natural occurring canine model with CNGB3 mutations has also been found. These animal models have many of the central phenotypic features of the corresponding human diseases. Using adeno-associated virus (AAV)-mediated gene therapy, we and others show that cone function can be restored in all three models. These data suggest that human achromatopsia may be a good candidate for corrective gene therapy. PMID:20238068

  14. Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

    SciTech Connect

    Kabalka, G. W.

    2005-06-28

    The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

  15. Hydrophilic MoSe2 Nanosheets as Effective Photothermal Therapy Agents and Their Application in Smart Devices.

    PubMed

    Lei, Zhouyue; Zhu, Wencheng; Xu, Shengjie; Ding, Jian; Wan, Jiaxun; Wu, Peiyi

    2016-08-17

    A facile poly(vinylpyrrolidone) (PVP)-assisted exfoliation method is utilized to simultaneously exfoliate and noncovalently modify MoSe2 nanosheets. The resultant hydrophilic nanosheets are shown to be promising candidates for biocompatible photothermal therapy (PTT) agents, and they could also be encapsulated into a hydrogel matrix for some intelligent devices. This work not only provides novel insights into exfoliation and modification of transition metal dichalcogenide (TMD) nanosheets but also might spark more research into engineering multifunctional TMD-related nanocomposites, which is in favor of further exploiting the attractive properties of these emerging layered two-dimensional (2D) nanomaterials. PMID:27467718

  16. Synergistic Combination Agent for Cancer Therapy | NCI Technology Transfer Center | TTC

    Cancer.gov

    The Nanotechnology Characterization Laboratory of the Frederick National Laboratory for Biomedical Research seeks parties interested in collaborative research to co-develop a ceramide and vinca alkaloid combination therapy for treatment of cancer.

  17. Mathematical analysis of multiscale models for hepatitis C virus dynamics under therapy with direct-acting antiviral agents.

    PubMed

    Rong, Libin; Perelson, Alan S

    2013-09-01

    Chronic hepatitis C virus (HCV) infection remains a world-wide public health problem. Therapy with interferon and ribavirin leads to viral elimination in less than 50% of treated patients. New treatment options aiming at a higher cure rate are focused on direct-acting antiviral agents (DAAs), which directly interfere with different steps in the HCV life cycle. In this paper, we describe and analyze a recently developed multiscale model that predicts HCV dynamics under therapy with DAAs. The model includes both intracellular viral RNA replication and extracellular viral infection. We calculate the steady states of the model and perform a detailed stability analysis. With certain assumptions we obtain analytical approximations of the viral load decline after treatment initiation. One approximation agrees well with the prediction of the model, and can conveniently be used to fit patient data and estimate parameter values. We also discuss other possible ways to incorporate intracellular viral dynamics into the multiscale model.

  18. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy

    PubMed Central

    Yan, Sijing; LU, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-01-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic. PMID:27535093

  19. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy

    NASA Astrophysics Data System (ADS)

    Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-08-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic.

  20. HematoPorphyrin Monomethyl Ether polymer contrast agent for ultrasound/photoacoustic dual-modality imaging-guided synergistic high intensity focused ultrasound (HIFU) therapy.

    PubMed

    Yan, Sijing; Lu, Min; Ding, Xiaoya; Chen, Fei; He, Xuemei; Xu, Chunyan; Zhou, Hang; Wang, Qi; Hao, Lan; Zou, Jianzhong

    2016-01-01

    This study is to prepare a hematoporphyrin monomethyl ether (HMME)-loaded poly(lactic-co-glycolic acid) (PLGA) microcapsules (HMME/PLGA), which could not only function as efficient contrast agent for ultrasound (US)/photoacoustic (PA) imaging, but also as a synergistic agent for high intensity focused ultrasound (HIFU) ablation. Sonosensitizer HMME nanoparticles were integrated into PLGA microcapsules with the double emulsion evaporation method. After characterization, the cell-killing and cell proliferation-inhibiting effects of HMME/PLGA microcapsules on ovarian cancer SKOV3 cells were assessed. The US/PA imaging-enhancing effects and synergistic effects on HIFU were evaluated both in vitro and in vivo. HMME/PLGA microcapsules were highly dispersed with well-defined spherical morphology (357 ± 0.72 nm in diameter, PDI = 0.932). Encapsulation efficiency and drug-loading efficiency were 58.33 ± 0.95% and 4.73 ± 0.15%, respectively. The HMME/PLGA microcapsules remarkably killed the SKOV3 cells and inhibited the cell proliferation, significantly enhanced the US/PA imaging results and greatly enhanced the HIFU ablation effects on ovarian cancer in nude mice by the HMME-mediated sono-dynamic chemistry therapy (SDT). HMME/PLGA microcapsules represent a potential multifunctional contrast agent for HIFU diagnosis and treatment, which might provide a novel strategy for the highly efficient imaging-guided non-invasive HIFU synergistic therapy for cancers by SDT in clinic. PMID:27535093

  1. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent.

    PubMed

    Lozano, Neus; Al-Ahmady, Zahraa S; Beziere, Nicolas S; Ntziachristos, Vasilis; Kostarelos, Kostas

    2015-03-30

    Indocyanine green (ICG) is an FDA-approved, strongly photo-absorbent/fluorescent probe that has been incorporated into a clinically-relevant PEGylated liposome as a flexible optoacoustic contrast agent platform. This study describes the engineering of targeted PEGylated liposome-ICG using the anti-MUC-1 "humanized" monoclonal antibody (MoAb) hCTM01 as a tumour-specific theranostic system. We aimed to visualise non-invasively the tumour accumulation of these MoAb-targeted liposomes over time in tumour-bearing mice using multispectral optoacoustic tomography (MSOT). Preferential accumulation of targeted PEGylated liposome-ICG was studied after intravenous administration in comparison to non-targeted PEGylated liposome-ICG using both fast growing (4T1) and slow growing (HT-29) MUC-1 positive tumour models. Monitoring liposomal ICG in the tumour showed that both targeted and non-targeted liposome-ICG formulations preferentially accumulated into the tumour models studied. Rapid accumulation was observed for targeted liposomes at early time points mainly in the periphery of the tumour volume suggesting binding to available MUC-1 receptors. In contrast, non-targeted PEGylated liposomes showed accumulation at the centre of the tumour at later time points. In an attempt to take this a step further, we successfully encapsulated the anticancer drug, doxorubicin (DOX) into both targeted and non-targeted PEGylated liposome-ICG. The engineering of DOX-loaded targeted ICG liposome systems present a novel platform for combined tumour-specific therapy and diagnosis. This can open new possibilities in the design of advanced image-guided cancer therapeutics.

  2. Monoclonal antibody-targeted PEGylated liposome-ICG encapsulating doxorubicin as a potential theranostic agent.

    PubMed

    Lozano, Neus; Al-Ahmady, Zahraa S; Beziere, Nicolas S; Ntziachristos, Vasilis; Kostarelos, Kostas

    2015-03-30

    Indocyanine green (ICG) is an FDA-approved, strongly photo-absorbent/fluorescent probe that has been incorporated into a clinically-relevant PEGylated liposome as a flexible optoacoustic contrast agent platform. This study describes the engineering of targeted PEGylated liposome-ICG using the anti-MUC-1 "humanized" monoclonal antibody (MoAb) hCTM01 as a tumour-specific theranostic system. We aimed to visualise non-invasively the tumour accumulation of these MoAb-targeted liposomes over time in tumour-bearing mice using multispectral optoacoustic tomography (MSOT). Preferential accumulation of targeted PEGylated liposome-ICG was studied after intravenous administration in comparison to non-targeted PEGylated liposome-ICG using both fast growing (4T1) and slow growing (HT-29) MUC-1 positive tumour models. Monitoring liposomal ICG in the tumour showed that both targeted and non-targeted liposome-ICG formulations preferentially accumulated into the tumour models studied. Rapid accumulation was observed for targeted liposomes at early time points mainly in the periphery of the tumour volume suggesting binding to available MUC-1 receptors. In contrast, non-targeted PEGylated liposomes showed accumulation at the centre of the tumour at later time points. In an attempt to take this a step further, we successfully encapsulated the anticancer drug, doxorubicin (DOX) into both targeted and non-targeted PEGylated liposome-ICG. The engineering of DOX-loaded targeted ICG liposome systems present a novel platform for combined tumour-specific therapy and diagnosis. This can open new possibilities in the design of advanced image-guided cancer therapeutics. PMID:25445515

  3. An information potential approach for tracking and surveilling multiple moving targets using mobile sensor agents

    NASA Astrophysics Data System (ADS)

    Lu, W.; Zhang, G.; Ferrari, S.; Fierro, R.; Palunko, I.

    2011-05-01

    The problem of surveilling moving targets using mobile sensor agents (MSAs) is applicable to a variety of fields, including environmental monitoring, security, and manufacturing. Several authors have shown that the performance of a mobile sensor can be greatly improved by planning its motion and control strategies based on its sensing objectives. This paper presents an information potential approach for computing the MSAs' motion plans and control inputs based on the feedback from a modified particle filter used for tracking moving targets. The modified particle filter, as presented in this paper implements a new sampling method (based on supporting intervals of density functions), which accounts for the latest sensor measurements and adapts, accordingly, a mixture representation of the probability density functions (PDFs) for the target motion. It is assumed that the target motion can be modeled as a semi-Markov jump process, and that the PDFs of the Markov parameters can be updated based on real-time sensor measurements by a centralized processing unit or MSAs supervisor. Subsequently, the MSAs supervisor computes an information potential function that is communicated to the sensors, and used to determine their individual feedback control inputs, such that sensors with bounded field-of-view (FOV) can follow and surveil the target over time.

  4. Boronated antibodies and promazine derivatives for potential neutron capture therapy

    SciTech Connect

    Alam, F.; Soloway, A.H.; Barth, R.F.; Adams, D.M.; Mafune, N.

    1986-01-01

    The theoretical basis for boron neutron capture therapy (BNCT) derives from the irradiation of /sup 10/B with thermal neutrons, resulting in a fission reaction yielding /sup 7/Li and alpha particles. The fission products have short path lengths and high linear energy transfer (LET). Each component of this binary system, thermal neutrons and /sup 10/B, independently are nontumoricidal, but together they can be highly lethal. Success depends on localizing enough of the /sup 10/B (approx.20 ..mu..g/g of tumor) and delivering a requisite fluence of thermal neutrons (approx.10/sup 13/ n/cm/sup 9/) at the site of the tumor. This report describes the boronation of antibodies and the development of boron-containing promazine derivatives to selectively deliver /sup 10/B to tumor cells for BNCT.

  5. Visceral Blood Flow Modulation: Potential Therapy for Morbid Obesity

    SciTech Connect

    Harris, Tyler J.; Murphy, Timothy P.; Jay, Bryan S.; Hampson, Christopher O.; Zafar, Abdul M.

    2013-06-15

    We present this preliminary investigation into the safety and feasibility of endovascular therapy for morbid obesity in a swine model. A flow-limiting, balloon-expandable covered stent was placed in the superior mesenteric artery of three Yorkshire swine after femoral arterial cutdown. The pigs were monitored for between 15 and 51 days after the procedure and then killed, with weights obtained at 2-week increments. In the two pigs in which the stent was flow limiting, a reduced rate of weight gain (0.42 and 0.53 kg/day) was observed relative to the third pig (0.69 kg/day), associated with temporary food aversion and signs of mesenteric ischemia in one pig.

  6. Is EGR1 a potential target for prostate cancer therapy?

    PubMed Central

    Gitenay, Delphine; Baron, Véronique T

    2009-01-01

    Prostate cancer is a major cause of cancer-related death in American men, for which finding new therapeutic strategies remains a challenge. Early growth response-1 (EGR1) is a transcription factor involved in cell proliferation and in the regulation of apoptosis. Although it has long been considered a tumor suppressor, a wealth of new evidence shows that EGR1 promotes the progression of prostate cancer. This review addresses the paradoxes of EGR1 function. While EGR1 mediates apoptosis in response to stress and DNA damage by regulating a tumor suppressor network, it also promotes the proliferation of prostate cancer cells by a mechanism that is not fully understood. Thus, EGR1 might be targeted for prostate cancer therapy either by ectopic expression in combination with radiotherapy or chemotherapy, or by direct inhibition for systemic treatment. Possible strategies to antagonize EGR1 function in a therapeutic setting are discussed. PMID:19792968

  7. A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms.

    PubMed

    George, Blassan Plackal Adimuriyil; Abrahamse, Heidi

    2016-01-01

    This review article presents an extensive examination of risk factors for breast cancer, treatment strategies with special attention to photodynamic therapy and natural product based treatments. Breast cancer remains the most commonly occurring cancer in women worldwide and the detection, treatment, and prevention are prominent concerns in public health. Background information on current developments in treatment helps to update the approach towards risk assessment. Breast cancer risk is linked to many factors such as hereditary, reproductive and lifestyle factors. Minimally invasive Photodynamic therapy (PDT) can be used in the management of various cancers; it uses a light sensitive drug (a photosensitizer, PS) and a light of visible wavelength, to destroy targeted cancer cells. State of the art analyses has been carried out to investigate advancement in the search for the cure and control of cancer progression using natural products. Traditional medicinal plants have been used as lead compounds for drug discovery in modern medicine. Both PDT and plant derived drugs induce cell death via different mechanisms including apoptosis, necrosis, autophagy, cell cycle regulation and even the regulation of various cell signalling pathways. PMID:26499768

  8. A Novel Bacteriophage Targeting Cronobacter sakazakii Is a Potential Biocontrol Agent in Foods

    PubMed Central

    Lee, Ju-Hoon; Bai, Jaewoo; Shin, Hakdong; Kim, Yeran; Park, Bookyung; Heu, Sunggi

    2015-01-01

    Cronobacter sakazakii is an important pathogen that causes high mortality in infants. Due to its occasional antibiotic resistance, a bacteriophage approach might be an alternative effective method for the control of this pathogen. To develop a novel biocontrol agent using bacteriophages, the C. sakazakii-infecting phage CR5 was newly isolated and characterized. Interestingly, this phage exhibited efficient and relatively durable host lysis activity. In addition, a specific gene knockout study and subsequent complementation experiment revealed that this phage infected the host strain using the bacterial flagella. The complete genome sequence analysis of phage CR5 showed that its genome contains 223,989 bp of DNA, including 231 predicted open reading frames (ORFs), and it has a G+C content of 50.06%. The annotated ORFs were classified into six functional groups (structure, packaging, host lysis, DNA manipulation, transcription, and additional functions); no gene was found to be related to virulence or toxin or lysogen formation, but >80% of the predicted ORFs are unknown. In addition, a phage proteomic analysis using SDS-PAGE and matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) revealed that seven phage structural proteins are indeed present, supporting the ORF predictions. To verify the potential of this phage as a biocontrol agent against C. sakazakii, it was added to infant formula milk contaminated with a C. sakazakii clinical isolate or food isolate, revealing complete growth inhibition of the isolates by the addition of phage CR5 when the multiplicity of infection (MOI) was 105. PMID:26497465

  9. Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats.

    PubMed

    Jevtovic-Todorovic, V; Benshoff, N; Olney, J W

    2000-08-01

    For general anaesthesia, patients usually receive a combination of drugs, all of which are classified as gamma-amino-butyric acid (GABA) agonists, with two notable exceptions - ketamine and nitrous oxide (laughing gas, N(2)O) - which are antagonists of N-methyl-D-aspartate (NMDA) glutamate receptors. At clinically relevant doses both ketamine and N(2)O, like other NMDA antagonists, have the potential to induce psychotomimetic reactions in humans and to cause pathomorphological changes in cerebrocortical neurons in rat brain. Because drug combinations used in clinical anaesthesia sometimes include both ketamine and N(2)O, we undertook experiments to evaluate whether augmented neurotoxicity results from their combined use. Ketamine and N(2)O were administered alone or in combination by various dosing regimens to adult female rats for a duration of 3 h and the severity of cerebrocortical neurotoxic changes was quantified histologically. Because GABA agonists are known to protect against the psychotomimetic and neurotoxic effects of NMDA antagonists, we also evaluated whether the combined neurotoxicity of ketamine+N(2)O can be prevented by certain commonly used GABA agonists. When ketamine and N(2)O were used in combination the neurotoxic reaction was enhanced to a degree much greater than can be explained by simple additivity. The apparent synergistic interaction was particularly striking when low doses of the agents were combined, the degree of toxic synergism at higher doses being masked by a ceiling effect. GABA agonists protected against ketamine/N(2)O neurotoxicity. It is recommended that this information be taken into consideration in the selection of drugs to be used in multi-agent protocols for general anaesthesia. PMID:10928976

  10. High mitochondrial redox potential may promote induction and activation of UCP2 in hepatocytes during hepatothermic therapy.

    PubMed

    McCarty, Mark F

    2005-01-01

    Although uncoupling protein-1 is a key mediator of thermogenesis in activated brown fat, the more recently characterized uncoupling proteins-2 and -3 do not appear to influence basal metabolism, but rather may function to diminish excessive mitochondrial superoxide production when mitochondrial redox potential is high. Under these circumstances, superoxide within the mitochondrial matrix directly activates uncoupling protein-2 (UCP2), and may also promote induction of this protein. Normal healthy hepatocytes do not express UCP2, but this protein is induced in hepatocytes that are steatotic or that are treated with agents that boost superoxide production. It is proposed that induction and activation of UCP2 may play a role in the thermogenesis evoked by hepatothermic therapy, a strategy designed to decrease body fat by maximizing hepatic fatty acid oxidation. Under these conditions, high mitochondrial redox potential would be expected, and induction of UCP2's uncoupling activity would represent a homeostatically appropriate antioxidant response. PMID:15823721

  11. [A short history of anti-rheumatic therapy--VII. Biological agents].

    PubMed

    Pasero, G; Marson, P; Gatto, B

    2011-11-09

    The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF) and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

  12. Vitamin D as a potential therapy in amyotrophic lateral sclerosis.

    PubMed

    Gianforcaro, Alexandro; Hamadeh, Mazen J

    2014-02-01

    Vitamin D has been demonstrated to influence multiple aspects of amyotrophic lateral sclerosis (ALS) pathology. Both human and rodent central nervous systems express the vitamin D receptor (VDR) and/or its enzymatic machinery needed to fully activate the hormone. Clinical research suggests that vitamin D treatment can improve compromised human muscular ability and increase muscle size, supported by loss of motor function and muscle mass in animals following VDR knockout, as well as increased muscle protein synthesis and ATP production following vitamin D supplementation. Vitamin D has also been shown to reduce the expression of biomarkers associated with oxidative stress and inflammation in patients with multiple sclerosis, rheumatoid arthritis, congestive heart failure, Parkinson's disease and Alzheimer's disease; diseases that share common pathophysiologies with ALS. Furthermore, vitamin D treatment greatly attenuates hypoxic brain damage in vivo and reduces neuronal lethality of glutamate insult in vitro; a hallmark trait of ALS glutamate excitotoxicity. We have recently shown that high-dose vitamin D3 supplementation improved, whereas vitamin D3 restriction worsened, functional capacity in the G93A mouse model of ALS. In sum, evidence demonstrates that vitamin D, unlike the antiglutamatergic agent Riluzole, affects multiple aspects of ALS pathophysiology and could provide a greater cumulative effect. PMID:24428861

  13. Self-regulated magnetic fluid hyperthermia: A potential cancer therapy

    NASA Astrophysics Data System (ADS)

    Bagaria, Hitesh Ghanshyam

    An emerging cancer therapy, self-regulated magnetic fluid hyperthermia (MFH), is the motivation for this work. In this therapy, cancer is annihilated by heating the tumor to desired therapeutic temperatures (˜45°C) by using magnetic nanoparticles of controlled Curie temperatures (Tc). This work was aimed at preparing and characterizing FePt, NiPd and NiPt nanoparticles for self-regulated MFH because their Tc could be tuned by changing their composition. Based on the excellent colloidal stability, size tunability and toxicity considerations, FePt was an obvious choice for self-regulated MFH. The 3.2 nm Fe61Pt39 particles displayed a Tc of 151°C, which is well below the Tc of bulk Fe61Pt39 (˜327°C). To reach the desired Tc of 45°C the composition of iron needs to be increased. However, a major obstacle was the formation of iron oxide shells with increase in iron composition of the particles. A recent finding that the composition of individual FePt particles deviated significantly from the average value encouraged us to study the mechanism of formation of FePt particles. Our analysis showed that early in the reaction the particles were Pt-rich and as the reaction proceeded the Fe content increased. It was found that the wide distribution in the composition of individual particles started early in the synthesis, suggesting that the compositional variability may be attributed to the Pt nuclei. The synthesized FePt particles are unsuitable for biological applications because of their hydrophobic surface. Hence, their surface was modified by ligand exchange with mercapto alkanoic acids. After ligand exchange, stable FePt dispersions could be formed in alkaline water. The study revealed that both the carboxylate and thiol groups were required to form stable FePt dispersions. In addition, 15 nm gold particles were successfully conjugated to genetically modified adenoviruses that selectively bind to cancer tumors. We also modeled the thermal transport in tissues during

  14. Synthesis and evaluation of 18F labeled alanine derivatives as potential tumor imaging agents

    PubMed Central

    Wang, Limin; Zha, Zhihao; Qu, Wenchao; Qiao, Hongwen; Lieberman, Brian P.; Plössl, Karl; Kung, Hank F.

    2012-01-01

    Introduction This paper reports the synthesis and labeling of 18F alanine derivatives. We also investigate their biological characteristics as potential tumor imaging agents mediated by alanine-serine-cysteine preferring (ASC) transporter system. Methods Three new 18F alanine derivatives were prepared from corresponding tosylate-precursors through a two-step labelling reaction. In vitro uptake studies to evaluate and to compare these three analogs were carried out in 9L glioma and PC-3 prostate cancer cell lines. Potential transport mechanisms, protein incorporation and stability of 3-(1-[18F]fluoromethyl)-L-alanine (L[18F]FMA) were investigated in 9L glioma cells. Its biodistribution was determined in a rat-bearing 9L tumor model. PET imaging studies were performed on rat bearing 9L glioma tumors and transgenic mouse carrying spontaneous generated M/tomND tumor (mammary gland adenocarcinoma). Results New 18F alanine derivatives were prepared with 7–34% uncorrected radiochemical yields, excellent enantiomeric purity (>99%) and good radiochemical purity (>99%). In vitro uptake of the L-[18F]FMA in 9L glioma and PC-3 prostate cancer cells was higher than those observed for other two alanine derivatives and [18F]FDG in first 1 h. Inhibition of cell uptake studies suggested that L-[18F]FMA uptake in 9L glioma was predominantly via transport system ASC. After entering into cells, L-[18F]FMA remained stable and was not incorporated into protein within 2 h. In vivo biodistribution studies demonstrated that L-[18F]FMA had relatively high uptake in liver and kidney. Tumor uptake was fast, reaching a maximum within 30 min. The tumor-to-muscle, tumor-to-blood and tumor-to-brain ratios at 60 min post injection were 2.2, 1.9 and 3.0, respectively. In PET imaging studies, tumors were visualized with L-[18F]FMA in both 9L rat and transgenic mouse. Conclusion L-[18F]FMA showed promising properties as a PET imaging agent for up-regulated ASC transporter associated with tumor

  15. Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g-1). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM-1 s-1 and 185.58 mM-1 s-1 respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high

  16. Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus

    PubMed Central

    Abdalla, Maher Y.; Switzer, Barbara L.; Goss, Christopher H.; Aitken, Moira L.; Singh, Pradeep K.

    2015-01-01

    The rapidly growing nontuberculous mycobacterial species Mycobacterium abscessus has recently emerged as an important pathogen in patients with cystic fibrosis (CF). Treatment options are limited because of the organism's innate resistance to standard antituberculous antibiotics, as well as other currently available antibiotics. New antibiotic approaches to the treatment of M. abscessus are urgently needed. The goal of the present study was to assess the growth-inhibitory activity of different Ga compounds against an American Type Culture Collection (ATCC) strain and clinical isolates of M. abscessus obtained from CF and other patients. In our results, using Ga(NO3)3 and all of the other Ga compounds tested inhibited the growth of ATCC 19977 and clinical isolates of M. abscessus. Inhibition was mediated by disrupting iron uptake, as the addition of exogenous iron (Fe) restored basal growth. There were modest differences in inhibition among the isolates for the same Ga chelates, and for most Ga chelates there was only a slight difference in potency from Ga(NO3)3. In contrast, Ga-protoporphyrin completely and significantly inhibited the ATCC strain and clinical isolates of M. abscessus at much lower concentrations than Ga(NO3)3. In in vitro broth culture, Ga-protoporphyrin was more potent than Ga(NO3)3. When M. abscessus growth inside the human macrophage THP-1 cell line was assessed, Ga-protoporphyrin was >20 times more active than Ga(NO3)3. The present work suggests that Ga exhibits potent growth-inhibitory capacity against the ATCC strain, as well as against antibiotic-resistant clinical isolates of M. abscessus, including the highly antibiotic-resistant strain MC2638. Ga-based therapy offers the potential for further development as a novel therapy against M. abscessus. PMID:26033732

  17. Gallium Compounds Exhibit Potential as New Therapeutic Agents against Mycobacterium abscessus.

    PubMed

    Abdalla, Maher Y; Switzer, Barbara L; Goss, Christopher H; Aitken, Moira L; Singh, Pradeep K; Britigan, Bradley E

    2015-08-01

    The rapidly growing nontuberculous mycobacterial species Mycobacterium abscessus has recently emerged as an important pathogen in patients with cystic fibrosis (CF). Treatment options are limited because of the organism's innate resistance to standard antituberculous antibiotics, as well as other currently available antibiotics. New antibiotic approaches to the treatment of M. abscessus are urgently needed. The goal of the present study was to assess the growth-inhibitory activity of different Ga compounds against an American Type Culture Collection (ATCC) strain and clinical isolates of M. abscessus obtained from CF and other patients. In our results, using Ga(NO3)3 and all of the other Ga compounds tested inhibited the growth of ATCC 19977 and clinical isolates of M. abscessus. Inhibition was mediated by disrupting iron uptake, as the addition of exogenous iron (Fe) restored basal growth. There were modest differences in inhibition among the isolates for the same Ga chelates, and for most Ga chelates there was only a slight difference in potency from Ga(NO3)3. In contrast, Ga-protoporphyrin completely and significantly inhibited the ATCC strain and clinical isolates of M. abscessus at much lower concentrations than Ga(NO3)3. In in vitro broth culture, Ga-protoporphyrin was more potent than Ga(NO3)3. When M. abscessus growth inside the human macrophage THP-1 cell line was assessed, Ga-protoporphyrin was >20 times more active than Ga(NO3)3. The present work suggests that Ga exhibits potent growth-inhibitory capacity against the ATCC strain, as well as against antibiotic-resistant clinical isolates of M. abscessus, including the highly antibiotic-resistant strain MC2638. Ga-based therapy offers the potential for further development as a novel therapy against M. abscessus.

  18. In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

    PubMed Central

    Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

    2014-01-01

    In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

  19. Mipomersen as a potential adjunctive therapy for hypercholesterolemia.

    PubMed

    Patel, Neeraj; Hegele, Robert A

    2010-10-01

    Mipomersen, an antisense oligonucleotide directed against apolipoprotein B-100 (apoB), was investigated for its safety and efficacy in reducing low-density lipoprotein (LDL) cholesterol (C) as adjunctive treatment for patients with homozygous familial hypercholesterolemia (HoFH) in a Phase III, double-blind, randomized, controlled trial. HoFH patients are very rare in the general population (∼ 1:1,000,000) and have very high risk for cardiovascular events. HoFH patients respond poorly to statins and most other existing lipid-lowering therapies. Mipomersen (200 or 160 mg) administered subcutaneously to 34 HoFH patients for 26 weeks significantly reduced LDL-C by 24.7% from baseline. In addition, mipomersen lowered plasma lipoprotein (a). In most patients, mipomersen administration was most associated with injection-site reactions; influenza-like symptoms were also more common in mipomersen-treated patients. Four patients had elevated serum alanine aminotransferase (ALT) concentrations, one of whom also had a significant increase in intrahepatic triglyceride content. Another patient met the stopping rules for increased ALT concentrations. No patient developed steatohepatitis during the study. Thus, so far short-term data indicate that mipomersen is safe and effective as an adjunctive drug for lowering LDL-C. Despite these promising results, the longer-term safety and efficacy of mipomersen still needs to be determined. PMID:20707601

  20. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential

    PubMed Central

    Running, Alice

    2015-01-01

    Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75–90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose. PMID:26170887

  1. Decreased Cortisol and Pain in Breast Cancer: Biofield Therapy Potential.

    PubMed

    Running, Alice

    2015-01-01

    Breast cancer is one of the leading causes of cancer death among women of all races. Pain is a common symptom associated with cancer; 75-90% of cancer patients experience pain during their illness and up to 50% of that pain is undertreated. Unrelieved pain leads to increased levels of the stress hormone cortisol. The purpose of this study was to examine the impact of bioenergy on fecal cortisol levels for mice injected with murine mammary carcinoma 4T1 in two separate pilot studies. Using a multiple experimental group design, six to eight week old female BALB/c mice were injected with tumor and randomly assigned, in groups of 10, to daily treatment, every other day treatment, and no treatment groups. Five days after tumor cell injection, bioenergy interventions were begun for a period of ten consecutive days. Fecal samples were collected for each study and ELISA analysis was conducted at the end of both studies. For both studies, cortisol levels were decreased in the every other day treatment groups but remained high in the no treatment groups. Future studies utilizing bioenergy therapies on cortisol levels in a murine breast cancer model can begin to describe pain outcomes and therapeutic dose.

  2. Signal transduction molecule patterns indicating potential glioblastoma therapy approaches

    PubMed Central

    Cruceru, Maria Linda; Enciu, Ana-Maria; Popa, Adrian Claudiu; Albulescu, Radu; Neagu, Monica; Tanase, Cristiana Pistol; Constantinescu, Stefan N

    2013-01-01

    Purpose The expression of an array of signaling molecules, along with the assessment of real-time cell proliferation, has been performed in U87 glioma cell line and in patients’ glioblastoma established cell cultures in order to provide a better understanding of cellular and molecular events involved in glioblastoma pathogenesis. Experimental therapy was performed using a phosphatidylinositol-3′-kinase (PI3K) inhibitor. Patients and methods xMAP technology was employed to assess expression levels of several signal transduction molecules and real-time xCELLigence platform for cell behavior. Results PI3K inhibition induced the most significant effects on global signaling pathways in patient-derived cell cultures, especially on members of the mitogen-activated protein-kinase family, P70S6 serine-threonine kinase, and cAMP response element-binding protein expression and further prevented tumor cell proliferation. Conclusion The PI3K pathway might be a prime target for glioblastoma treatment. PMID:24348050

  3. The role of cytokines in immunological tolerance: potential for therapy.

    PubMed

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  4. MODULATION OF AUTOPHAGY AND ITS POTENTIAL FOR CANCER THERAPY

    PubMed Central

    Claerhout, Sofie; Lorenzi, Philip L.; Weinstein, John N.; Mills, Gordon B.

    2014-01-01

    SUMMARY Autophagy is a process in which cellular contents are captured in specialized, membrane-bounded vesicles and delivered to lysosomes for final degradation. Most studies support an inherent connection between autophagy and survival, but increasing evidence also suggests an association between autophagy and cell death. The therapeutic potential of targeting the autophagy pathway in cancer seems clear, but specific strategies for achieving successful eradication of cancer cells are less obvious. Recent developments in the fields of autophagy and programmed cell death, nevertheless, have shed light on therapeutic strategies with significant potential. In this review, we provide an overview of the autophagy process, pathways that modulate autophagy, and promising autophagy-based therapeutic strategies for cancer. PMID:25419038

  5. Electrical stimulation of the hypoglossal nerve: a potential therapy.

    PubMed

    Schwartz, Alan R; Smith, Philip L; Oliven, Arie

    2014-02-01

    Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse, which result from a decrease in pharyngeal dilator muscle tone. The genioglossus is a major pharyngeal dilator that maintains airway patency during sleep. Early studies in animal and humans have demonstrated that electrical stimulation of this muscle reduces pharyngeal collapsibility, increases airflow, and mitigates obstructive sleep apnea. These findings impelled the development of fully implantable hypoglossal nerve stimulating systems (HGNS), for which feasibility trial results are now available. These pilot studies have confirmed that hypoglossal nerve stimulation can prevent pharyngeal collapse without arousing patients from sleep. Potentially, a substantial segment of the patient population with obstructive sleep apnea can be treated with this novel approach. Furthermore, the feasibility trial findings suggest that the therapeutic potential of HGNS can be optimized by selecting patients judiciously, titrating the stimulus intensity optimally, and characterizing the underlying function and anatomy of the pharynx. These strategies are currently being examined in ongoing pivotal trials of HGNS.

  6. Hendra and Nipah Infection: Pathology, Models and Potential Therapies

    PubMed Central

    Vigant, Frederic; Lee, Benhur

    2011-01-01

    The Paramyxoviridae family comprises of several genera that contain emerging or re-emerging threats for human and animal health with no real specific effective treatment available. Hendra and Nipah virus are members of a newly identified genus of emerging paramyxoviruses, Henipavirus. Since their discovery in the 1990s, henipaviruses outbreaks have been associated with high economic and public health threat potential. When compared to other paramyxoviruses, henipaviruses appear to have unique characteristics. Henipaviruses are zoonotic paramyxoviruses with a broader tropism than most other paramyxoviruses, and can cause severe acute encephalitis with unique features among viral encephalitides. There are currently no approved effective prophylactic or therapeutic treatments for henipavirus infections. Although ribavirin was empirically used and seemed beneficial during the biggest outbreak caused by one of these viruses, the Nipah virus, its efficacy is disputed in light of its lack of efficacy in several animal models of henipavirus infection. Nevertheless, because of its highly pathogenic nature, much effort has been spent in developing anti-henipavirus therapeutics. In this review we describe the unique features of henipavirus infections and the different strategies and animal models that have been developed so far in order to identify and test potential drugs to prevent or treat henipavirus infections. Some of these components have the potential to be broad-spectrum antivirals as they target effectors of viral pathogenecity common to other viruses. We will focus on small molecules or biologics, rather than vaccine strategies, that have been developed as anti-henipaviral therapeutics. PMID:21488828

  7. Electrophilic PPARγ ligands inhibit corneal fibroblast to myofibroblast differentiation in vitro: a potentially novel therapy for corneal scarring.

    PubMed

    Kuriyan, A E; Lehmann, G M; Kulkarni, A A; Woeller, C F; Feldon, S E; Hindman, H B; Sime, P J; Huxlin, K R; Phipps, R P

    2012-01-01

    A critical component of corneal scarring is the TGFβ-induced differentiation of corneal keratocytes into myofibroblasts. Inhibitors of this differentiation are potentially therapeutic for corneal scarring. In this study, we tested the relative effectiveness and mechanisms of action of two electrophilic peroxisome proliferator-activated receptor gamma (PPARγ) ligands: cyano-3,12-dioxolean-1,9-dien-28-oic acid-methyl ester (CDDO-Me) and 15-deoxy-Δ(-12,14)-prostaglandin J(2) (15d-PGJ(2)) for inhibiting TGFβ-induced myofibroblast differentiation in vitro. TGFβ was used to induce myofibroblast differentiation in cultured, primary human corneal fibroblasts. CDDO-Me and 15d-PGJ(2) were added to cultures to test their ability to inhibit this process. Myofibroblast differentiation was assessed by measuring the expression of myofibroblast-specific proteins (αSMA, collagen I, and fibronectin) and mRNA (αSMA and collagen III). The role of PPARγ in the inhibition of myofibroblast differentiation by these agents was tested in genetically and pharmacologically manipulated cells. Finally, we assayed the importance of electrophilicity in the actions of these agents on TGFβ-induced αSMA expression via Western blotting and immunofluorescence. Both electrophilic PPARγ ligands (CDDO-Me and 15d-PGJ(2)) potently inhibited TGFβ-induced myofibroblast differentiation, but PPARγ was only partially required for inhibition of myofibroblast differentiation by either agent. Electrophilic PPARγ ligands were able to inhibit myofibroblast differentiation more potently than non-electrophilic PPARγ ligands, suggesting an important role of electrophilicity in this process. CDDO-Me and 15d-PGJ(2) are strong inhibitors of TGFβ-induced corneal fibroblast to myofibroblast differentiation in vitro, suggesting this class of agents as potential novel therapies for corneal scarring warranting further study in pre-clinical animal models.

  8. Acute myeloid leukemia after myelodysplastic syndrome and failure of therapy with hypomethylating agents: an emerging entity with a poor prognosis.

    PubMed

    Jabbour, Elias; Ghanem, Hady; Huang, Xuelin; Ravandi, Farhad; Garcia-Manero, Guillermo; O'Brien, Susan; Faderl, Stephan; Pierce, Sherry; Choi, Sangbum; Verstovsek, Srdan; Brandt, Mark; Cortes, Jorge; Kantarjian, Hagop

    2014-04-01

    We assessed the outcomes of 63 patients with acute myeloid leukemia (AML) arising from myelodysplastic syndrome (MDS) after hypomethylating agent failure. Their median age was 63 years. All 63 patients had received ≥ 1 salvage regimens for AML, and 35 patients (55%) had received ≥ 2. Of the 31 patients (49%) who had received high-dose cytarabine (HDAC) at first relapse, 2 (6%) achieved complete remission (CR) and 4 (13%) CR with incomplete platelet recovery (overall response rate, 19%). Of the 32 patients (51%) who had received other treatments, including investigational agents, 4 (12%) achieved CR and 4 (12%) CR with incomplete platelet recovery (overall response rate, 24%). The median response duration was 20 weeks. With a median follow-up of 42 months from the AML diagnosis, the median survival (21 weeks) was similar between the 2 groups. The 1- and 2-year survival rate was 19% and 8%, respectively. Multivariate analysis identified low albumin, HDAC treatment, and platelet count < 50 × 10(9)/L as independent adverse factors for CR and a platelet count < 50 × 10(9)/L and age > 65 years as independent adverse factors for survival. Thus, the outcome of AML evolving from MDS after hypomethylating agent failure is poor and not improved with HDAC. Novel therapies directed toward this emerging entity are urgently needed.

  9. Molecular Modeling Studies of Thiophenyl C-Aryl Glucoside SGLT2 Inhibitors as Potential Antidiabetic Agents

    PubMed Central

    Sharma, Mukesh C.; Sharma, Smita

    2014-01-01

    A QSAR study on thiophenyl derivatives as SGLT2 inhibitors as potential antidiabetic agents was performed with thirty-three compounds. Comparison of the obtained results indicated the superiority of the genetic algorithm over the simulated annealing and stepwise forward-backward variable method for feature selection. The best 2D QSAR model showed satisfactory statistical parameters for the data set (r2 = 0.8499, q2 = 0.8267, and pred_r2 = 0.7729) with four descriptors describing the nature of substituent groups and the environment of the substitution site. Evaluation of the model implied that electron-rich substitution position improves the inhibitory activity. The good predictive 3D-QSAR models by k-nearest neighbor (kNN) method for molecular field analysis (MFA) have cross-validated coefficient q2 value of 0.7663 and predicted r2 value of 0.7386. The results have showed that thiophenyl groups are necessary for activity and halogen, bulky, and less bulky groups in thiophenyl nucleus enhanced the biological activity. These studies are promising for the development of novel SGLT2 inhibitor, which may have potent antidiabetic activity. PMID:25574393

  10. Evaluation of Se-75 BISTAES as a potential articular cartilage imaging agent

    SciTech Connect

    Yu, S.W.K.

    1987-01-01

    The potential of Se-75 bis (..beta..-N,N,N-trimethylamino)-ethyl) selenide diiodide (Se-75 BISTAES) as an articular cartilage imaging agent for the early diagnosis of osteoarthritis was evaluated. The compound was synthesized and the identity was established. The radiochemical purity and stability were determined initially and over a two-month period of storage at three temperatures. The biodistribution of Se-75 BISTAES in rabbits and guinea pigs was studied. A high concentration of radioactivity was found in the knee and shoulder cartilage. The radioactivity in the cartilage was the highest at 15 minutes to one hour post-injection. In rabbits, the highest ratio of radioactivity in the cartilage to the surrounding tissues was about 30. A minimal ratio of 10 is required for nuclear medicine imaging. Nuclear medicine imaging conducted on rabbits demonstrated increased radioactivity in the articular cartilage in the knee and shoulder. The impression from the nuclear medicine images and the findings of the biodistribution study indicated that the route of excretion of Se-75 BISTAES was the urine. The in vitro binding between Se-75 BISTAES and chondroitin sulfate was determined by an equilibrium dialysis technique.

  11. Human recombinant truncated RNASET2, devoid of RNase activity; A potential cancer therapeutic agent

    PubMed Central

    Nesiel-Nuttman, Liron; Schwartz, Betty; Shoseyov, Oded

    2014-01-01

    Human RNASET2 has been implicated in antitumorigenic and antiangiogenic activities, independent of its ribonuclease capacities. We constructed a truncated version of human RNASET2, starting at E50 (trT2-50) and devoid of ribonuclease activity. trT2-50 maintained its ability to bind actin and to inhibit angiogenesis and tumorigenesis. trT2-50 binds to cell surface actin and formed a complex with actin in vitro. The antiangiogenic effect of this protein was demonstrated in human umbilical vein endothelial cells (HUVECs) by its ability to arrest tube formation on Matrigel, induced by angiogenic factors. Immunofluorescence staining of HUVECs showed nuclear and cytosolic RNASET2 protein that was no longer detectable inside the cell following trT2-50 treatment. This effect was associated with disruption of the intracellular actin network. trT2-50 co-localized with angiogenin, suggesting that both molecules bind (or compete) for similar cellular epitopes. Moreover, trT2-50 led to a significant inhibition of tumor development. Histological analysis demonstrated abundant necrotic tissue and a substantial loss of endothelial structure in trT2-50-treated tumors. Collectively, the present results indicate that trT2-50, a molecule engineered to be deficient of its catalytic activity, still maintained its actin binding and anticancer-related biological activities. We therefore suggest that trT2-50 may serve as a potential cancer therapeutic agent. PMID:25426551

  12. Scaffold Hopping Toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as Potential Antidepressant Agents

    NASA Astrophysics Data System (ADS)

    Yang, Yang; Ang, Wei; Long, Haiyue; Chang, Ying; Li, Zicheng; Zhou, Liangxue; Yang, Tao; Deng, Yong; Luo, Youfu

    2016-10-01

    A scaffold-hopping strategy toward Agomelatine based on in silico screening and knowledge analysis was employed to design novel antidepressant agents. A series of 3, 4-dihydroisoquinoline compounds were selected for chemical synthesis and biological assessment. Three compounds (6a-1, 6a-2, 6a-9) demonstrated protective effects on corticosterone-induced lesion of PC12 cells. Compound 6a-1 also displayed low inhibitory effects on the growth of HEK293 and L02 normal cells and it was further evaluated for its potential antidepressant effects in vivo. The forced swim test (FST) results revealed that compound 6a-1 remarkably reduced the immobility time of rats and the open field test (OFT) results indicated a better general locomotor activity of the rats treated with compound 6a-1 than those with Agomelatine or Fluoxetine. Mechanism studies implied that compound 6a-1 can significantly reduce PC12 cell apoptosis by up-regulation of GSH and down-regulation of ROS in corticosterone-induced lesion of PC12 cells. Meanwhile, the down-regulation of calcium ion concentration and up-regulation of BDNF level in PC12 cells may account for the neuroprotective effects. Furthermore, compound 6a-1 can increase cell survival and cell proliferation, promote cell maturation in the rat hippocampus after chronic treatment. The acute toxicity data in vivo indicated compound 6a-1 exhibited less hepatotoxicity than Agomelatine.

  13. Biorelevant reactions of the potential anti-tumor agent vanadocene dichloride.

    PubMed

    Sanna, Daniele; Serra, Maria; Ugone, Valeria; Manca, Laura; Pirastru, Monica; Buglyó, Péter; Bíró, Linda; Micera, Giovanni; Garribba, Eugenio

    2016-05-01

    The interaction of the potential anti-tumor agent vanadocene dichloride ([Cp2VCl2] or VDC) with some relevant bioligands of the cytosol such as proteins (Hb), amino acids (glycine and histidine), NADH derivatives (NADH, NADPH, NAD(+) and NADP(+)), reductants (GSH and ascorbic acid), phosphates (HPO4(2-), P2O7(4-), cAMP, AMP, ADP and ATP) and carboxylate derivatives (lactate) and its uptake by red blood cells were studied. The results indicated that [Cp2VCl2] transforms at physiological pH into [Cp2V(OH)2] and that only HPO4(2-), P2O7(4-), lactate, ATP and ADP form mixed species with the [Cp2V](2+) moiety replacing the two hydroxide ions. EPR and electronic absorption spectroscopy, agarose gel electrophoresis and spin trapping measurements allow excluding any direct interaction and/or intercalation with DNA and the formation of reactive oxygen species (ROS) in Fenton-like reactions. Uptake experiments by erythrocytes suggested that VDC crosses the membrane and enters inside the cells, whereas 'bare' V(IV) transforms into V(IV)O species with loss of the two cyclopentadienyl rings. This transformation in the cellular environment could be related to the mechanism of action of VDC. PMID:27121101

  14. Potential of Submergedly Cultivated Mycelia of Ganoderma spp. as Antioxidant and Antimicrobial Agents.

    PubMed

    Ćilerdžić, Jasmina; Stajic, Mirjana; Vukojevic, Jelena

    2016-01-01

    The study aimed to evaluate the antiradical and antimicrobial (antibacterial and antifungal) potentials of ethanol mycelial extracts of selected Ganoderma species and strains and to define interand intraspecies diversity among Ganoderma species and strains. Ganoderma lucidum strains were good DPPH• scavengers (neutralizing up to 57.12% radicals), contrary to G. applanatum (20.35%) and G. carnosum (17.04%). High correlations between the activities and contents of total phenols in the extracts showed that these compounds were carriers of the activity. Results obtained by both discdiffusion and microdilution methods indicated that the extract of G. lucidum BEOFB 433 was the most potent antibacterial agent that inhibited growth of almost all bacterial species at a concentration of 1.0 mg/mL. Salmonella typhimurium was the most sensitive species to the mycelium extracts. Extracts of G. lucidum BEOFB 431 and BEOFB 434 showed the best antifungal activity since in concentration of 0.5 mg/mL inhibited the growth of Aspergillus glaucus (BEOFB 431) and the growth of A. glaucus and Trichoderma viride (BEOFB 434). Extracts of G. applanatum and G. lucidum BEOFB 431 had the strongest fungicidal effects, with lethal outcomes for A. glaucus and T. viride, respectively, being noted at a concentration of 1.17 mg/mL. Aspergillus niger was proved as the most resistant species. PMID:26420047

  15. Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food biopreservative.

    PubMed

    Chopra, Lipsy; Singh, Gurdeep; Kumar Jena, Kautilya; Sahoo, Debendra K

    2015-01-01

    The emergence of antibiotic resistant bacteria has led to exploration of alternative therapeutic agents such as ribosomally synthesized bacterial peptides known as bacteriocins. Biofilms, which are microbial communities that cause serious chronic infections, form environments that enhance antimicrobial resistance. Bacteria in biofilm can be upto thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. In this study, sonorensin, predicted to belong to the heterocycloanthracin subfamily of bacteriocins, was found to be effectively killing active and non-multiplying cells of both Gram-positive and Gram-negative bacteria. Sonorensin showed marked inhibition activity against biofilm of Staphylococcus aureus. Fluorescence and electron microscopy suggested that growth inhibition occurred because of increased membrane permeability. Low density polyethylene film coated with sonorensin was found to effectively control the growth of food spoilage bacteria like Listeria monocytogenes and S. aureus. The biopreservative effect of sonorensin coated film showing growth inhibition of spoilage bacteria in chicken meat and tomato samples demonstrated the potential of sonorensin as an alternative to current antibiotics/ preservatives. PMID:26292786

  16. Rapid screening of potential autophagic inductor agents using mammalian cell lines.

    PubMed

    Martins, Waleska K; Severino, Divinomar; Souza, Cleidiane; Stolf, Beatriz S; Baptista, Maurício S

    2013-06-01

    Recent progress in understanding the molecular basis of autophagy has demonstrated its importance in several areas of human health. Affordable screening techniques with higher sensitivity and specificity to identify autophagy are, however, needed to move the field forward. In fact, only laborious and/or expensive methodologies such as electron microscopy, dye-staining of autophagic vesicles, and LC3-II immunoblotting or immunoassaying are available for autophagy identification. Aiming to fulfill this technical gap, we describe here the association of three widely used assays to determine cell viability - Crystal Violet staining (CVS), 3-[4, 5-dimethylthiaolyl]-2, 5-diphenyl-tetrazolium bromide (MTT) reduction, and neutral red uptake (NRU) - to predict autophagic cell death in vitro. The conceptual framework of the method is the superior uptake of NR in cells engaging in autophagy. NRU was then weighted by the average of MTT reduction and CVS allowing the calculation of autophagic arbitrary units (AAU), a numeric variable that correlated specifically with the autophagic cell death. The proposed strategy is very useful for drug discovery, allowing the investigation of potential autophagic inductor agents through a rapid screening using mammalian cell lines B16-F10, HaCaT, HeLa, MES-SA, and MES-SA/Dx5 in a unique single microplate.

  17. Child as change agent. The potential of children to increase healthy food purchasing.

    PubMed

    Wingert, Katherine; Zachary, Drew A; Fox, Monica; Gittelsohn, Joel; Surkan, Pamela J

    2014-10-01

    Shoppers make many food choices while buying groceries. Children frequently accompany caregivers, giving them the potential to influence these choices. We aimed to understand low-income shoppers' perceptions of how children influence caregivers' purchasing decisions and how the supermarket environment could be manipulated to allow children to serve as change agents for healthy food purchasing in a primarily African-American community. We conducted thirty in-depth interviews, five follow-up interviews, one supermarket walk-through interview, and four focus groups with adult supermarket shoppers who were regular caregivers for children under age 16. We conducted one focus group with supermarket employees and one in-depth interview with a supermarket manager. Qualitative data were analyzed using iterative thematic coding and memo writing. Caregivers approached grocery shopping with efforts to save money, prevent waste and purchase healthy food for their families, but described children as promoting unplanned, unhealthy food purchases. This influence was exacerbated by the supermarket environment, which participants found to promote unhealthy options and provide limited opportunities for children to interact with healthier foods. Caregivers' suggestions for promoting healthy purchasing for shoppers with children included manipulating the placement of healthy and unhealthy foods and offering opportunities for children to taste and interact with healthy options. PMID:24996593

  18. Potential of Submergedly Cultivated Mycelia of Ganoderma spp. as Antioxidant and Antimicrobial Agents.

    PubMed

    Ćilerdžić, Jasmina; Stajic, Mirjana; Vukojevic, Jelena

    2016-01-01

    The study aimed to evaluate the antiradical and antimicrobial (antibacterial and antifungal) potentials of ethanol mycelial extracts of selected Ganoderma species and strains and to define interand intraspecies diversity among Ganoderma species and strains. Ganoderma lucidum strains were good DPPH• scavengers (neutralizing up to 57.12% radicals), contrary to G. applanatum (20.35%) and G. carnosum (17.04%). High correlations between the activities and contents of total phenols in the extracts showed that these compounds were carriers of the activity. Results obtained by both discdiffusion and microdilution methods indicated that the extract of G. lucidum BEOFB 433 was the most potent antibacterial agent that inhibited growth of almost all bacterial species at a concentration of 1.0 mg/mL. Salmonella typhimurium was the most sensitive species to the mycelium extracts. Extracts of G. lucidum BEOFB 431 and BEOFB 434 showed the best antifungal activity since in concentration of 0.5 mg/mL inhibited the growth of Aspergillus glaucus (BEOFB 431) and the growth of A. glaucus and Trichoderma viride (BEOFB 434). Extracts of G. applanatum and G. lucidum BEOFB 431 had the strongest fungicidal effects, with lethal outcomes for A. glaucus and T. viride, respectively, being noted at a concentration of 1.17 mg/mL. Aspergillus niger was proved as the most resistant species.

  19. N-( sup 18 F)fluoroacetyl-D-glucosamine: A potential agent for cancer diagnosis

    SciTech Connect

    Fujiwara, T.; Kubota, K.; Sato, T.; Matsuzawa, T.; Tada, M.; Iwata, R.; Itoh, M.; Hatazawa, J.; Sato, K.; Fukuda, H. )

    1990-10-01

    Positron labeled substrates such as sugars, amino acids, and nucleosides have been investigated for the in-vivo evaluation of biochemical processes in cancerous tissue. Hexosamines are obligatory structural components of many biologically important macromolecules, including membrane glycoproteins and mucopolysaccharide. We evaluated a new synthesized pharmaceutical, N-({sup 18}F)fluoroacetyl-D-glucosamine ({sup 18}F-FAG), which is a structural analog of N-acetyl-D-glucosamine. C3H/HeMsNRS mice bearing spontaneous hepatomas were used for the tissue distribution study. At 60 min after injection, high uptakes were found in tumor (5.16, mean value of %dose/g), liver (3.71), and kidney (3.27). The tumor uptake of 18F-FAG showed the highest value in all tissue. In the PET study, VX-2 carcinoma of the rabbit was clearly visualized. Our preliminary results suggest that {sup 18}F-FAG has potential as a new agent for tumor imaging.

  20. Scaffold Hopping Toward Agomelatine: Novel 3, 4-Dihydroisoquinoline Compounds as Potential Antidepressant Agents

    PubMed Central

    Yang, Yang; Ang, Wei; Long, Haiyue; Chang, Ying; Li, Zicheng; Zhou, Liangxue; Yang, Tao; Deng, Yong; Luo, Youfu

    2016-01-01

    A scaffold-hopping strategy toward Agomelatine based on in silico screening and knowledge analysis was employed to design novel antidepressant agents. A series of 3, 4-dihydroisoquinoline compounds were selected for chemical synthesis and biological assessment. Three compounds (6a-1, 6a-2, 6a-9) demonstrated protective effects on corticosterone-induced lesion of PC12 cells. Compound 6a-1 also displayed low inhibitory effects on the growth of HEK293 and L02 normal cells and it was further evaluated for its potential antidepressant effects in vivo. The forced swim test (FST) results revealed that compound 6a-1 remarkably reduced the immobility time of rats and the open field test (OFT) results indicated a better general locomotor activity of the rats treated with compound 6a-1 than those with Agomelatine or Fluoxetine. Mechanism studies implied that compound 6a-1 can significantly reduce PC12 cell apoptosis by up-regulation of GSH and down-regulation of ROS in corticosterone-induced lesion of PC12 cells. Meanwhile, the down-regulation of calcium ion concentration and up-regulation of BDNF level in PC12 cells may account for the neuroprotective effects. Furthermore, compound 6a-1 can increase cell survival and cell proliferation, promote cell maturation in the rat hippocampus after chronic treatment. The acute toxicity data in vivo indicated compound 6a-1 exhibited less hepatotoxicity than Agomelatine. PMID:27698414

  1. Animals living in polluted environments are potential source of antimicrobials against infectious agents

    PubMed Central

    Lee, Simon; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2012-01-01

    The antimicrobials crisis is a ticking time bomb which could lead to millions of people dying from untreatable infections. With the worsening trends of antimicrobial resistance, we are heading towards a pre-antibiotic era. Thus, there is a need for newer and more powerful antibiotic agents. The search for new antibiotic compounds originating from natural resources is a promising research area. Animals living in germ-infested environments are a potent source of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of bacteria, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances which show potent activity in the nervous system. We hope that the discovery of antimicrobial activity in the cockroach brain will stimulate research in finding antimicrobials from unusual sources, and has potential for the development of novel antibiotics. Nevertheless, intensive research in the next few years will be required to approach or realize these expectations. PMID:23265422

  2. Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food biopreservative

    PubMed Central

    Chopra, Lipsy; Singh, Gurdeep; Kumar Jena, Kautilya; Sahoo, Debendra K.

    2015-01-01

    The emergence of antibiotic resistant bacteria has led to exploration of alternative therapeutic agents such as ribosomally synthesized bacterial peptides known as bacteriocins. Biofilms, which are microbial communities that cause serious chronic infections, form environments that enhance antimicrobial resistance. Bacteria in biofilm can be upto thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. In this study, sonorensin, predicted to belong to the heterocycloanthracin subfamily of bacteriocins, was found to be effectively killing active and non-multiplying cells of both Gram-positive and Gram-negative bacteria. Sonorensin showed marked inhibition activity against biofilm of Staphylococcus aureus. Fluorescence and electron microscopy suggested that growth inhibition occurred because of increased membrane permeability. Low density polyethylene film coated with sonorensin was found to effectively control the growth of food spoilage bacteria like Listeria monocytogenes and S. aureus. The biopreservative effect of sonorensin coated film showing growth inhibition of spoilage bacteria in chicken meat and tomato samples demonstrated the potential of sonorensin as an alternative to current antibiotics/ preservatives. PMID:26292786

  3. New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

    DOEpatents

    Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

    1997-02-11

    A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

  4. Sonorensin: A new bacteriocin with potential of an anti-biofilm agent and a food biopreservative.

    PubMed

    Chopra, Lipsy; Singh, Gurdeep; Kumar Jena, Kautilya; Sahoo, Debendra K

    2015-01-01

    The emergence of antibiotic resistant bacteria has led to exploration of alternative therapeutic agents such as ribosomally synthesized bacterial peptides known as bacteriocins. Biofilms, which are microbial communities that cause serious chronic infections, form environments that enhance antimicrobial resistance. Bacteria in biofilm can be upto thousand times more resistant to antibiotics than the same bacteria circulating in a planktonic state. In this study, sonorensin, predicted to belong to the heterocycloanthracin subfamily of bacteriocins, was found to be effectively killing active and non-multiplying cells of both Gram-positive and Gram-negative bacteria. Sonorensin showed marked inhibition activity against biofilm of Staphylococcus aureus. Fluorescence and electron microscopy suggested that growth inhibition occurred because of increased membrane permeability. Low density polyethylene film coated with sonorensin was found to effectively control the growth of food spoilage bacteria like Listeria monocytogenes and S. aureus. The biopreservative effect of sonorensin coated film showing growth inhibition of spoilage bacteria in chicken meat and tomato samples demonstrated the potential of sonorensin as an alternative to current antibiotics/ preservatives.

  5. Curcumin derivatives as metal-chelating agents with potential multifunctional activity for pharmaceutical applications.

    PubMed

    Ferrari, Erika; Benassi, Rois; Sacchi, Stefania; Pignedoli, Francesca; Asti, Mattia; Saladini, Monica

    2014-10-01

    Curcuminoids represent new perspectives for the development of novel therapeutics for Alzheimer's disease (AD), one probable mechanism of action is related to their metal complexing ability. In this work we examined the metal complexing ability of substituted curcuminoids to propose new chelating molecules with biological properties comparable with curcumin but with improved stability as new potential AD therapeutic agents. The K2T derivatives originate from the insertion of a -CH2COOC(CH3)3 group on the central atom of the diketonic moiety of curcumin. They retain the diketo-ketoenol tautomerism which is solvent dependent. In aqueous solution the prevalent form is the diketo one but the addition of metal ion (Ga(3+), Cu(2+)) causes the dissociation of the enolic proton creating chelate complexes and shifting the tautomeric equilibrium towards the keto-enol form. The formation of metal complexes is followed by both NMR and UV-vis spectroscopy. The density functional theory (DFT) calculations on K2T21 complexes with Ga(3+) and Cu(2+) are performed and compared with those on curcumin complexes. [Ga(K2T21)2(H2O)2](+) was found more stable than curcumin one. Good agreement is detected between calculated and experimental (1)H and (13)C NMR data. The calculated OH bond dissociation energy (BDE) and the OH proton dissociation enthalpy (PDE), allowed to predict the radical scavenging ability of the metal ion complexed with K2T21, while the calculated electronic affinity (EA) and ionization potential (IP) represent yardsticks of antioxidant properties. Eventually theoretical calculations suggest that the proton-transfer-associated superoxide-scavenging activity is enhanced after binding metal ions, and that Ga(3+) complexes display possible superoxide dismutase (SOD)-like activity.

  6. Novel glyoxalase-I inhibitors possessing a “zinc-binding feature” as potential anticancer agents

    PubMed Central

    Al-Balas, Qosay A; Hassan, Mohammad A; Al-Shar’i, Nizar A; Mhaidat, Nizar M; Almaaytah, Ammar M; Al-Mahasneh, Fatima M; Isawi, Israa H

    2016-01-01

    Background The glyoxalase system including two thiol-dependent enzymes, glyoxalase I (Glo-I) and glyoxalase II, plays an important role in a ubiquitous metabolic pathway involved in cellular detoxification of cytotoxic 2-oxoaldehydes. Tumor cells have high glycolytic activity, leading to increased cellular levels of these toxic metabolites. The increased activity of the detoxification system in cancerous cells makes this pathway a viable target for developing novel anticancer agents. In this study, we examined the potential utility of non-glutathione-based inhibitors of the Glo-I enzyme as novel anticancer drugs. Methods Computer-aided drug design techniques, such as customized pharmacophoric features, virtual screening, and flexible docking, were used to achieve the project goals. Retrieved hits were extensively filtered and subsequently docked into the active site of the enzyme. The biological activities of retrieved hits were assessed using an in vitro assay against Glo-I. Results Since Glo-I is a zinc metalloenzyme, a customized Zn-binding pharmacophoric feature was used to search for selective inhibitors via virtual screening of a small-molecule database. Seven hits were selected, purchased, and biologically evaluated. Three of the seven hits inhibited Glo-I activity, the most effective of which exerted 76.4% inhibition at a concentration of 25 µM. Conclusion We successfully identified a potential Glo-I inhibitor that can serve as a lead compound for further optimization. Moreover, our in silico and experimental results were highly correlated. Hence, the docking protocol adopted in this study may be efficiently employed in future optimization steps. PMID:27574401

  7. Volatile Organic Compounds from Native Potato-associated Pseudomonas as Potential Anti-oomycete Agents

    PubMed Central

    De Vrieze, Mout; Pandey, Piyush; Bucheli, Thomas D.; Varadarajan, Adithi R.; Ahrens, Christian H.; Weisskopf, Laure; Bailly, Aurélien

    2015-01-01

    The plant kingdom represents a prominent biodiversity island for microbes that associate with the below- or aboveground organs of vegetal species. Both the root and the leaf represent interfaces where dynamic biological interactions influence plant life. Beside well-studied communication strategies based on soluble compounds and protein effectors, bacteria were recently shown to interact both with host plants and other microbial species through the emissions of volatile organic compounds (VOCs). Focusing on the potato late blight-causing agent Phytophthora infestans, this work addresses the potential role of the bacterial volatilome in suppressing plant diseases. In a previous study, we isolated and identified a large collection of strains with anti-Phytophthora potential from both the phyllosphere and the rhizosphere of potato. Here we report the characterization and quantification of their emissions of biogenic volatiles, comparing 16 Pseudomonas strains differing in (i) origin of isolation (phyllosphere vs. rhizosphere), (ii) in vitro inhibition of P. infestans growth and sporulation behavior, and (iii) protective effects against late blight on potato leaf disks. We systematically tested the pharmacological inhibitory activity of core and strain-specific single compounds against P. infestans mycelial growth and sporangial behavior in order to identify key effective candidate molecules present in the complex natural VOCs blends. We envisage the plant bacterial microbiome as a reservoir for functional VOCs and establish the basis for finding the primary enzymatic toolset that enables the production of active components of the volatile bouquet in plant-associated bacteria. Comprehension of these functional interspecies interactions will open perspectives for the sustainable control of plant diseases in forthcoming agriculture. PMID:26635763

  8. Combination Therapy with Systemic Steroids, an Antiviral Agent, Anticoagulants, and Stellate Ganglion Block for Treatment of Sudden Sensorineural Hearing Loss

    PubMed Central

    Lee, Chi-Kyou; Lee, Jong Dae; Park, Moo Kyun; Lee, Byung Don

    2012-01-01

    Background and Objectives Sudden sensorineural hearing loss (SSNHL) is commonly defined as a loss of at least 30 dB in three contiguous frequencies occurring within 3 days. Systemic steroid administration has become the most widely accepted treatment option for SSNHL. Since viral infection and vascular compromise are considered specific causes of SSNHL, antiviral agents, anticoagulants, and stellate ganglion block have been used for its treatment, although the evidence of their effectiveness is weak. The present study evaluated the hearing recovery rate in the combination therapy group (systemic steroids, antiviral agent, anticoagulants, and stellate ganglion block) in comparison with patients treated with systemic steroids alone. Subjects and Methods A total of 85 patients diagnosed with SSNHL were treated with combination therapy (group A, 46 patients) or systemic steroids only (group B, 39 patients). Hearing improvement was defined as a hearing gain of more than slight improvement using Siegel's criteria. All patients were treated with a 10-day course of systemic steroids (10-mg dexamethasone for 5 days, followed by tapering for 5 days). Acyclovir, heparin, and stellate ganglion block were included in the group A treatment regimen. Results The overall rate of hearing improvement was 60.9% (28/46 patients) in group A, which was significantly higher than that (38.5%, 15/39 patients) in group B. The distribution of prognostic factors was not significantly different between the two groups with the exception of the degree of initial hearing loss, which was more severe in group A. Upon analysis according to prognostic factors, group A showed a better hearing improvement recovery rate than group B in patients with hearing loss >70 dB, age >41 years, dizziness, and early treatment (<1 week). Conclusions Thus SSNHL patients treated with combination therapy have a higher likelihood of hearing improvement than those treated with systemic steroids alone. PMID:24653874

  9. Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent.

    PubMed

    Dewi, Novriana; Yanagie, Hironobu; Zhu, Haito; Demachi, Kazuyuki; Shinohara, Atsuko; Yokoyama, Kazuhito; Sekino, Masaki; Sakurai, Yuriko; Morishita, Yasuyuki; Iyomoto, Naoko; Nagasaki, Takeshi; Horiguchi, Yukichi; Nagasaki, Yukio; Nakajima, Jun; Ono, Minoru; Kakimi, Kazuhiro; Takahashi, Hiroyuki

    2013-07-01

    Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 μg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.

  10. Potential applications for antiviral therapy and prophylaxis in bovine medicine.

    PubMed

    Newcomer, Benjamin W; Walz, Paul H; Givens, M Daniel

    2014-06-01

    Viral disease is one of the major causes of financial loss and animal suffering in today's cattle industry. Increases in global commerce and average herd size, urbanization, vertical integration within the industry and alterations in global climate patterns have allowed the spread of pathogenic viruses, or the introduction of new viral species, into regions previously free of such pathogens, creating the potential for widespread morbidity and mortality in naïve cattle populations. Despite this, no antiviral products are currently commercially licensed for use in bovine medicine, although significant progress has been made in the development of antivirals for use against bovine viral diarrhea virus (BVDV), foot and mouth disease virus (FMDV) and bovine herpesvirus (BHV). BVDV is extensively studied as a model virus for human antiviral studies. Consequently, many compounds with efficacy have been identified and a few have been successfully used to prevent infection in vivo although commercial development is still lacking. FMDV is also the subject of extensive antiviral testing due to the importance of outbreak containment for maintenance of export markets. Thirdly, BHV presents an attractive target for antiviral development due to its worldwide presence. Antiviral studies for other bovine viral pathogens are largely limited to preliminary studies. This review summarizes the current state of knowledge of antiviral compounds against several key bovine pathogens and the potential for commercial antiviral applications in the prevention and control of several selected bovine diseases. PMID:24810855

  11. Potential applications for antiviral therapy and prophylaxis in bovine medicine.

    PubMed

    Newcomer, Benjamin W; Walz, Paul H; Givens, M Daniel

    2014-06-01

    Viral disease is one of the major causes of financial loss and animal suffering in today's cattle industry. Increases in global commerce and average herd size, urbanization, vertical integration within the industry and alterations in global climate patterns have allowed the spread of pathogenic viruses, or the introduction of new viral species, into regions previously free of such pathogens, creating the potential for widespread morbidity and mortality in naïve cattle populations. Despite this, no antiviral products are currently commercially licensed for use in bovine medicine, although significant progress has been made in the development of antivirals for use against bovine viral diarrhea virus (BVDV), foot and mouth disease virus (FMDV) and bovine herpesvirus (BHV). BVDV is extensively studied as a model virus for human antiviral studies. Consequently, many compounds with efficacy have been identified and a few have been successfully used to prevent infection in vivo although commercial development is still lacking. FMDV is also the subject of extensive antiviral testing due to the importance of outbreak containment for maintenance of export markets. Thirdly, BHV presents an attractive target for antiviral development due to its worldwide presence. Antiviral studies for other bovine viral pathogens are largely limited to preliminary studies. This review summarizes the current state of knowledge of antiviral compounds against several key bovine pathogens and the potential for commercial antiviral applications in the prevention and control of several selected bovine diseases.

  12. Antitumor Agents 250.† Design and Synthesis of New Curcumin Analogs as Potential Anti-Prostate Cancer Agents

    PubMed Central

    Lin, Li; Shi, Qian; Nyarko, Alexander K.; Bastow, Kenneth F.; Wu, Chin-Chung; Su, Ching-Yuan; Shih, Charles C.-Y; Lee, Kuo-Hsiung

    2008-01-01

    In a continuing study of curcumin analogs as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogs classified into four series: monophenyl analogs (series A), heterocycle-containing analogs (series B), analogs bearing various substituents on the phenyl rings (series C) and analogs with various linkers (series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells; seven only against LNCaP; and one solely against PC-3. This study established an advanced structure-activity relationship (SAR), and these correlations will guide the further design of new curcumin analogs with better anti-prostate cancer activity. PMID:16789753

  13. Vaccinium myrtillus leaves and Frangula alnus bark derived extracts as potential antistaphylococcal agents.

    PubMed

    Sadowska, Beata; Paszkiewicz, Małgorzata; Podsędek, Anna; Redzynia, Małgorzata; Różalska, Barbara

    2014-01-01

    Due to constantly increasing antibiotic resistance of pathogens and participation of the biofilms they make in various types of infections, a development of alternative therapeutic strategies becomes an urgent need. Taking advantage of the biological activity of plant-derived compounds can solve this problem. In this study antimicrobial, including those synergistic with classic antibiotics, and cytotoxic properties of newly-obtained extracts from Vaccinium myrtillus leaves (VLE) and Frangula alnus bark (FBE) were evaluated. Both tested extracts exhibited relevant antistaphylococcal activity (MIC range 0.75-1.5 mg/mL) accompanied by a relativly low cytotoxic effect on mammalian cells (BI > 1). Phytochemical analysis of the extracts tested showed a high total content of phenolic compounds with the predominance of hydroxycinnamic acids in VLE and hydroxybenzoic acids and flavanols in FBE. Widely described in the literature antimicrobial properties of phenolics were probably connected with the biological activity of the extracts tested. We also report that the presence of VLE or FBE at sub-MIC concentrations enhances biocidal potential of vancomycin and linezolid. Therefore, we are considering a possibility of an alternative therapy for local infections caused by S. aureus by combining classic antibiotics with plant-derived extracts. PMID:24649485

  14. Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents$

    PubMed Central

    Magesh, Sadagopan; Chen, Yu; Hu, Longqin

    2012-01-01

    Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress and xenobiotic damage. Activation of Nrf2 signaling induces the transcriptional regulation of ARE-dependent expression of various detoxifying and antioxidant defense enzymes and proteins. Keap1-Nrf2-ARE signaling has become an attractive target for the prevention and treatment of oxidative stress-related diseases and conditions including cancer, neurodegenerative, cardiovascular, metabolic and inflammatory diseases. Over the last few decades, numerous Nrf2 inducers have been developed and some of them are currently undergoing clinical trials. Recently, over-activation of Nrf2 has been implicated in cancer progression as well as in drug resistance to cancer chemotherapy. Thus, Nrf2 inhibitors could potentially be used to improve the effectiveness of cancer therapy. Herein, we review the signaling mechanism of Keap1-Nrf2-ARE pathway, its disease relevance, and currently known classes of small molecule modulators. We also discuss several aspects of Keap1-Nrf2 interaction, Nrf2-based peptide inhibitor design, and the screening assays currently used for the discovery of direct inhibitors of Keap1-Nrf2 interaction. PMID:22549716

  15. Natural products as anti-glycation agents: possible therapeutic potential for diabetic complications.

    PubMed

    Elosta, Abdulhakim; Ghous, Tahseen; Ahmed, Nessar

    2012-03-01

    Diabetes mellitus is characterised by hyperglycaemia, lipidaemia and oxidative stress and predisposes affected individuals to long-term complications afflicting the eyes, skin, kidneys, nerves and blood vessels. Increased protein glycation and the subsequent build-up of tissue advanced glycation endproducts (AGEs) contribute towards the pathogenesis of diabetic complications. Protein glycation is accompanied by generation of free radicals through autoxidation of glucose and glycated proteins and via interaction of AGEs with their cell surface receptors (referred to as RAGE). Glycationderived free radicals can damage proteins, lipids and nucleic acids and contribute towards oxidative stress in diabetes. There is interest in compounds with anti-glycation activity as they may offer therapeutic potential in delaying or preventing the onset of diabetic complications. Although many different compounds are under study, only a few have successfully entered clinical trials but none have yet been approved for clinical use. Whilst the search for new synthetic inhibitors of glycation continues, little attention has been paid to anti-glycation compounds from natural sources. In the last few decades the traditional system of medicine has become a topic of global interest. Various studies have indicated that dietary supplementation with combined anti-glycation and antioxidant nutrients may be a safe and simple complement to traditional therapies targeting diabetic complications. Data for forty two plants/constituents studied for anti-glycation activity is presented in this review and some commonly used medicinal plants that possess anti-glycation activity are discussed in detail including their active ingredients, mechanism of action and therapeutic potential. PMID:22268395

  16. The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges

    PubMed Central

    Goodman, Michael A.; Malik, Punam

    2016-01-01

    Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are a heterogeneous group of commonly inherited disorders affecting the function or levels of hemoglobin. Disease phenotype can be severe with substantial morbidity and mortality. Bone marrow transplantation is curative, but limited to those patients with an appropriately matched donor. Genetic therapy, which utilizes a patient’s own cells, is thus an attractive therapeutic option. Numerous therapies are currently in clinical trials or in development, including therapies utilizing gene replacement therapy using lentiviruses and the latest gene editing techniques. In addition, methods are being developed that may be able to expand gene therapies to those with poor access to medical care, potentially significantly decreasing the global burden of disease. PMID:27695619

  17. Anesthesia-Related Carbon Monoxide Exposure: Toxicity and Potential Therapy.

    PubMed

    Levy, Richard J

    2016-09-01

    Exposure to carbon monoxide (CO) during general anesthesia can result from volatile anesthetic degradation by carbon dioxide absorbents and rebreathing of endogenously produced CO. Although adherence to the Anesthesia Patient Safety Foundation guidelines reduces the risk of CO poisoning, patients may still experience subtoxic CO exposure during low-flow anesthesia. The consequences of such exposures are relatively unknown. In contrast to the widely recognized toxicity of high CO concentrations, the biologic activity of low concentration CO has recently been shown to be cytoprotective. As such, low-dose CO is being explored as a novel treatment for a variety of different diseases. Here, we review the concept of anesthesia-related CO exposure, identify the sources of production, detail the mechanisms of overt CO toxicity, highlight the cellular effects of low-dose CO, and discuss the potential therapeutic role for CO as part of routine anesthetic management. PMID:27537758

  18. Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.

    PubMed

    Zhang, Liwen; Gao, Shi; Zhang, Fan; Yang, Kai; Ma, Qingjie; Zhu, Lei

    2014-12-23

    Photothermal therapy (PTT) is an emerging treatment modality that is under intensive preclinical investigations for the treatment of various medical conditions, including cancer. However, the lack of targeting function of PTT agents hampers its clinical application. An effective and nontoxic delivery vehicle that can carry PTT agents into tumor areas is still needed urgently. In this study, we developed a multifunctional nanocomposite by loading copper sulfide (CuS) into Cy5.5-conjugated hyaluronic acid nanoparticles (HANP), obtaining an activatable Cy5.5-HANP/CuS (HANPC) nanocomposite. In this system, Cy5.5 fluorescent signal is quenched by CuS inside the particle until the whole nanocomposite is degraded by hyaluronidase present in tumor, giving strong fluorescence signals delineating the tumor. Importantly, CuS with strong NIR absorbance appears to be an excellent contrast agent for photoacoustic (PA) imaging and an effective PTT agent. After intravenous administration of HANPC into SCC7 tumor-bearing mice, high fluorescence and PA signals were observed in the tumor area over time, which peaked at the 6 h time point (tumor-to-normal tissue ratio of 3.25±0.25 for optical imaging and 3.8±0.42 for PA imaging). The tumors were then irradiated with a laser, and a good tumor inhibition rate (89.74% on day 5) was observed. Our studies further encourage application of this HA-based multifunctional nanocomposite for image-guided PTT in biomedical applications, especially in cancer theranostics. PMID:25402600

  19. Gold nanorods as photothermal agents and autofluorescence enhancer to track cell death during plasmonic photothermal therapy

    NASA Astrophysics Data System (ADS)

    Kannadorai, Ravi Kumar; Chiew, Geraldine Giap Ying; Luo, Kathy Qian; Liu, Quan

    2015-07-01

    The transverse and longitudinal plasmon resonance in gold nanorods can be exploited to localize the photothermal therapy and influence the fluorescence to monitor the treatment outcome at the same time. While the longitudinal plasmon peak contributes to the photothermal effect, the transverse peak can enhance fluorescence. After cells take in PEGylated nanorods through endocytosis, autofluorescence from endogenous fluorophores such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the mitochondria is enhanced two times, which is a good indicator of the respiratory status of the cell. When cells are illuminated continuously with near infrared laser, the temperature reaches the hyperthermic region within the first four minutes, which demonstrates the efficiency of gold nanorods in photothermal therapy. The cell viability test and autofluorescence intensity show good correlation indicating the progress of cell death over time.

  20. Therapy effect of antiulcer agents on new chronic cysteamine colon lesion in rat.

    PubMed

    Sikiric, P; Seiwerth, S; Aralica, G; Perovic, D; Staresinic, M; Anic, T; Gjurasin, M; Prkacin, I; Separovic, J; Stancic-Rokotov, D; Lovric-Bencic, M; Mikus, D; Turkovic, B; Rotkvic, I; Mise, S; Rucman, R; Petek, M; Ziger, T; Sebecic, B; Ivasovic, Z; Jagic, V; Komericki, L; Balen, I; Boban-Blagaic, A; Sjekavica, I

    2001-01-01

    After demonstration that cysteamine induced duodenal lesions in gastrectomized rats, while a number of antiulcer drugs mitigated these lesions, it was shown that one single intrarectal (i.r.) cysteamine application produced severe colon lesions in acute studies in rats. Thus, the further focus was on the protracted effect of cysteamine challenge (400 mg/kg b.w. i.r.) and therapy influence in chronic experiments in female rats. Regularly, cysteamine colon lesions were markedly mitigated by ranitidine (10), omeprazole (10), atropine (10), methylprednisolone (1), sulphasalazine (50; mg/kg), pentadecapeptide BPC 157 (PL-10, PLD-116; 10 microg or 10 ng/kg). Specifically, after 1 or 3 months following initial challenge (cysteamine 400 mg/kg i.r.) in female rat, the therapy [BPC 157 (PL-10, PLD-116 (10.0 microg or 10.0 ng/kg; i.g., i.p., i.r.), ranitidine, omeprazole, atropine, methylprednisolone, sulphasalazine (i.p.)] reversed the protracted cysteamine colon injury: the 1 week-regimen (once daily application) started after 1 month post-cysteamine, as well as the 2 weeks-regimen (once daily application), which started after 3 months. The effect on recidive lesion was also tested. These cysteamine lesions may reappear after stopping therapy (after stopping therapy for 3 weeks at the end of 2-weeks regimen started in 3 months-cysteamine female rats) in sulphasalazine group, while this reappearance is markedly antagonized in pentadecapeptide BPC 157 (PL-10, PLD-116)-rats (cysteamine-colon lesion still substantially low). PMID:11595451

  1. Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions

    SciTech Connect

    Tirand, Loraine; Bastogne, Thierry; Bechet, Denise M.Sc.; Linder, Michel; Thomas, Noemie; Frochot, Celine; Guillemin, Francois; Barberi-Heyob, Muriel

    2009-09-01

    Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm{sup 2}; fluence rate, 85 mW/cm{sup 2}). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent. Conclusions: Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.

  2. Combination therapy with biologic agents in rheumatic diseases: current and future prospects

    PubMed Central

    Inui, Kentaro; Koike, Tatsuya

    2016-01-01

    Strategies in rheumatoid arthritis (RA) based on ‘treat to target’ aim to control disease activity, minimize structural damage, and promote longer life. Several disease-modifying antirheumatic drugs (DMARDs) have been shown to be effective including biological DMARDs (bDMARDs). Treatment guidelines and recommendations for RA have also been published. According to those guidelines, conventional synthetic DMARDs (csDMARDs), as monotherapy or combination therapy, should be used in DMARD-naïve patients, irrespective of the addition of glucocorticoids (GCs). Combination therapies with bDMARDs are also essential for conducting treatment strategies for RA, because in every recommendation or guideline for the management of RA, combination therapies of csDMARDs with bDMARDs are recommended for RA patients with moderate or high disease activity after failure of csDMARD treatment. bDMARDs are more efficacious if used concomitantly with methotrexate (MTX) than with MTX monotherapy or bDMARD monotherapy. Thus, retention has been reported to be longer when combined with MTX. The superior efficacy of combination therapy compared with MTX monotherapy or bDMARD monotherapy could be because: (1) it could help to minimize MTX toxicity by reducing the dose of MTX, thus retention rate of the same therapeutic regimen would become high; (2) anti-bDMARD antibodies are observed at lower concentrations when using MTX concomitantly, so less clearance of bDMARDs via less formation of bDMARD and an anti-bDMARD immune complex; (3) of the additive effects of MTX to bDMARD, especially the combination of tumor necrosis factor inhibitors (TNFis) with MTX. Hence, evidence suggests that combination therapy with bDMARDs is more efficacious than monotherapy using a csDMARD or bDMARD, and that MTX is the best drug for this purpose (if MTX is not contraindicated). Finding the most effective drug regimen at the lowest cost will be the aim of RA treatment in the future. PMID:27721905

  3. Potential of Microbispora sp. V2 as biocontrol agent against Sclerotium rolfsii, the causative agent of southern blight of Zea mays L (Baby corn)--in vitro studies.

    PubMed

    Patil, N N; Waghmode, M S; Gaikwad, P S; Gajbhiye, M H; Gunjal, A B; Nawani, N N; Kapadnis, B P

    2014-11-01

    The study was undertaken with the aim of exploring novel and beneficial agro activities of rare actinomycetes like Microbispora sp. V2. The antagonistic activity of Microbispora sp. V2 was evaluated as a biocontrol agents against Sclerotium rolfsii, a soil-borne fungal plant pathogen. The methodology performed for evaluation of biocontrol agent was in vitro evaluation assay which comprised of three tests viz., cellophane overlay technique, seed germination test and Thiram (fungicide) tolerance of Microbispora sp. V2. The isolate was found to inhibit the fungal pathogen Sclerotium rolfsii to 91.43% in cellophane assay. In seed germination assay, Microbispora sp. V2 treated seeds resulted in 25.75% increased germination efficiency, as compared to seeds infected by Sclerotium rolfsii. The isolate Microbispora sp. V2 could tolerate 1000 microg mL(-1) of Thiram (fungicide). The in vitro assay studies proved that Microbispora sp. V2 can be used as antifungal antagonist and thus posses' great potential as biocontrol agent against southern blight caused by Sclerotium rolfsii in Zea mays L (Baby corn) which causes large economical losses.

  4. Vital Pulp Therapy with Three Different Pulpotomy Agents in Immature Molars: A Case Report

    PubMed Central

    Harandi, Azadeh; Forghani, Maryam; Ghoddusi, Jamileh

    2013-01-01

    Introduction This case report describes apexogenesis treatment of three molar teeth of an 8-year-old boy using three different pulpotomy agents. Methods Pulpotomy was performed on decayed immature molar teeth with established irreversible pulpitis and the remaining pulp was capped with either zinc oxide eugenol, ProRoot mineral trioxide aggregate or calcium-enriched mixture (CEM) cement. Teeth were restored with stainless steel crowns. Results Eighteen months clinical and radiographic follow-up revealed successful preservation of pulpal vitality with continued root development in all treated teeth. Conclusion Based on this case report, CEM cement may be an alternative option for pulpotomy treatment of immature permanent molars. PMID:23922578

  5. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer.

    PubMed

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P N; Nangia-Makker, Pratima

    2014-11-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is unexplored. The primary objectives of this investigation are (i) to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (ii) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemoresistant; CR) colon cancer cells, highly enriched in CSCs, were used for this study. Although EPA alone was effective, combination of EPA and FuOx was more potent in (i) inhibiting cell growth, colonosphere formation, and sphere-forming frequency, (ii) increasing sphere disintegration, (iii) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (iv) decreasing proinflammatory metabolites in mice. In addition, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization, and transcriptional activity by EPA suggests a role for the PTEN-Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring colorectal cancer.

  6. Identification of novel class of falcipain-2 inhibitors as potential antimalarial agents.

    PubMed

    Chakka, Sai Kumar; Kalamuddin, Mohammad; Sundararaman, Srividhya; Wei, Lianhu; Mundra, Sourabh; Mahesh, Radhakrishnan; Malhotra, Pawan; Mohmmed, Asif; Kotra, Lakshmi P

    2015-05-01

    Falcipain-2 is a papain family cysteine protease and an emerging antimalarial drug target. A pseudo-tripeptide scaffold I was designed using in silico screening tools and the three dimensional structures of falcipain-2, falcipain-3, and papain. This scaffold was investigated at four positions, T1, T2, T3, and T3', with various targeted substitutions to understand the structure-activity relationships. Inhibitor synthesis was accomplished by first obtaining the appropriate dipeptide precursors with common structural components. The pyrrolidine moiety introduced interesting rotamers in a number of synthesized molecules, which was confirmed using high-temperature (1)H NMR spectroscopy. Among the synthesized compounds, 61, 62, and 66 inhibited falcipain-2 activity with inhibition constants (Ki) of 1.8 ± 1.1, 0.2 ± 0.1 and 7.0 ± 2.3 μM, respectively. A group of molecules with a pyrrolidine moiety at the T2 position (68, 70, 71, 72, and 73) also potently inhibited falcipain-2 activity (Ki=0.4 ± 0.1, 2.5 ± 0.5, 3.3 ± 1.1, 7.5 ± 1.9, and 4.6 ± 0.7 μM, respectively). Overall, compound 74 exhibited potent anti-parasitic activity (IC₅₀=0.9 ± 0.1 μM), corresponding with its inhibitory activity against falcipain-2, with a Ki of 1.1 ± 0.1 μM. Compounds 62 and 67 inhibited the growth of the drug resistant parasite Dd2 with better efficacy, and compound 74 exhibited a 7- to 12-fold higher potency against Dd2 and MCamp isolates, than the laboratory strain (3D7). These data suggest that this novel series of compounds should be further investigated as potential antimalarial agents. PMID:25840796

  7. Whole-Genome Sequence of Pseudomonas graminis Strain UASWS1507, a Potential Biological Control Agent and Biofertilizer Isolated in Switzerland

    PubMed Central

    Crovadore, Julien; Calmin, Gautier; Chablais, Romain; Cochard, Bastien; Schulz, Torsten

    2016-01-01

    We report here the whole-genome shotgun sequence of the strain UASWS1507 of the species Pseudomonas graminis, isolated in Switzerland from an apple tree. This is the first genome registered for this species, which is considered as a potential and valuable resource of biological control agents and biofertilizers for agriculture. PMID:27795260

  8. Potential biological control agents for management of cogongrass [Imperata cylindrica 15 (Cyperales: Poaceae)] in the southeastern USA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cogongrass, Imperata cylindrica (L.) Palisot de Beauvois (Cyperales: Poaceae), is a noxious invasive weed in the southeastern USA. Surveys for potential biological control agents of cogongrass were conducted in Asia and East Africa from 2013 to 2016. Several insect herbivores were found that may hav...

  9. Multifunctional Fe3O4-TiO2 nanocomposites for magnetic resonance imaging and potential photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Zeng, Leyong; Ren, Wenzhi; Xiang, Lingchao; Zheng, Jianjun; Chen, Bin; Wu, Aiguo

    2013-02-01

    Multifunctional Fe3O4-TiO2 nanocomposites with Janus structure for magnetic resonance imaging (MRI) and potential photodynamic therapy (PDT) were synthesized, in which Fe3O4 was used as a MRI contrast agent and TiO2 as an inorganic photosensitizer for PDT. Their morphology, structure, and MRI and PDT performance were characterized, respectively. Moreover, the location of Fe3O4-TiO2 nanocomposites in MCF-7 cells was also investigated by the staining of Prussian blue and alizarin red, respectively. The results showed that the as-prepared Fe3O4-TiO2 nanocomposites had good T2-weighted MRI performance, and the MCF-7 cells incubated with nanocomposites could be killed under the irradiation of UV light. Compared with traditional organic photosensitizers, TiO2 inorganic photosensitizers could have more stable PDT performance due to their nanoscale size and anti-photodegradable stability. Therefore, the as-prepared Fe3O4-TiO2 nanocomposites could have potential applications as a new kind of multifunctional agent for both MRI and PDT.

  10. Cabozantinib in the treatment of advanced renal cell carcinoma: design, development, and potential place in the therapy

    PubMed Central

    Grassi, Paolo; Verzoni, Elena; Ratta, Raffaele; Mennitto, Alessia; de Braud, Filippo; Procopio, Giuseppe

    2016-01-01

    The treatment of metastatic renal cell carcinoma (mRCC) has markedly improved over the