Lonsway D.R.,Centers for Disease Control and Prevention |
Urich S.K.,Centers for Disease Control and Prevention |
Heine H.S.,U.S. Army |
Heine H.S.,Ordway Research Institute Inc. |
And 4 more authors.
Journal of Clinical Microbiology | Year: 2011
The utility of Etest for antimicrobial susceptibility testing of Yersinia pestis was evaluated in comparison with broth microdilution and disk diffusion for eight agents. Four laboratories tested 26 diverse strains and found Etest to be reliable for testing antimicrobial agents used to treat Y. pestis, except for chloramphenicol and trimethoprim-sulfamethoxazole. Disk diffusion testing is not recommended. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Mousa S.A.,Albany College of Pharmacy and Health Sciences |
Mousa S.A.,King Saud University |
Yalcin M.,Albany College of Pharmacy and Health Sciences |
Yalcin M.,Uludag University |
And 7 more authors.
Lung Cancer | Year: 2012
Thyroid hormone stimulates cell proliferation of several types of cancers and stimulates cancer-relevant angiogenesis. In the present study, we investigated the proliferative effect of thyroid hormone and the anti-proliferative and anti-angiogenic action of its nano-derivative, tetrac-NP, on human non-small cell lung cancer (NSCLC) H1299 cells in vitro and in xenografts. The anti-proliferative activity of unmodified tetrac and tetrac-NP against human H1299 cells was determined in three models: (a) cultured H1299 cells in vitro, (b) tumor cell implants in the fertilized chick chorioallantoic membrane (CAM) system and (c) xenografts in the nude mouse. An integrin αvβ3 antibody inhibited thyroid hormone-induced cell proliferation in vitro, as did unmodified tetrac and tetrac-NP. Pharmacologic inhibition of the mitogen-activated protein kinase pathway also blocked NSCLC cell proliferation in response to thyroid hormone. Tetrac and tetrac-NP arrested tumor growth and tumor-related angiogenesis in H1299 cells grown in the CAM model and both agents prevented chick embryo mortality. Xenografts of H1299 cells were established in nude mice (n=8, treatment and control groups) and when tumor volumes reached 250-300mm 3, tetrac (1mg/kg) or tetrac-NP (1mg tetrac as the nanoparticle/kg) were administered intraperitoneally every 2 days. Tetrac and tetrac-NP significantly suppressed tumor growth and angiogenesis. Thus, both tetrac and tetrac-NP effectively arrest human NSCLC tumor cell proliferation in vitro and in the CAM assay and in murine xenograft models. © 2011 Elsevier Ireland Ltd.
Mousa S.S.,Albany College of Pharmacy and Health Sciences |
Davis F.B.,Ordway Research Institute Inc. |
Davis P.J.,Albany College of Pharmacy and Health Sciences |
Davis P.J.,Ordway Research Institute Inc. |
And 2 more authors.
Clinical and Applied Thrombosis/Hemostasis | Year: 2010
The endogenous thyroid hormones L-thyroxine (T 4) and 3,5,3g2-triiodo-L-thyronine (T 3) induce angiogenesis via an endothelial cell iodothyronine receptor on integrin ±Vβ3. This receptor also exists on platelets. Diiodothyropropionic acid (DITPA) and GC-1, a noniodinated thyroid hormone analog, also induce angiogenesis. Here we examined the effects of iodothyronines (L-T 4 vs L-T 3) and analogs DITPA and GC-1 on human platelet function. Subthreshold aggregation of platelets obtained from healthy human donors was induced with collagen. Platelet activation (proaggregation) and adenosine triphosphate (ATP) secretion (degranulation) induced by L-T 4, L-T 4-agarose, L-T 3, DITPA, or GC-1 were determined simultaneously. Platelet aggregation and ATP secretion induced by a subthreshold level of collagen were enhanced 3-fold by either L-T 4 or L-T 4-agarose (0.01 1/4mol/L) as compared to control, whereas, L-T 3, DITPA, or GC-1 had no effect under the same conditions. The platelet proaggregatory and degranulation effects of L-T 4 were blocked by the ±vβ3 antagonist XT199 (0.1 1/4mol/ L) and by tetraiodothyroacetic acid (tetrac; 0.1 1/4mol/L). Tetrac inhibits binding of thyroid hormone analogs to the receptor on ±vβ3 and lacks thyromimetic activity at this site; thus, the proaggregatory action of L-T 4 likely involves the cell surface receptor on integrin ±vβ3. The thyroid hormone receptor (TR) on human platelets but not endothelial cells distinguishes among iodothyronines, reflecting quantitative differences in integrin sites on endothelial cells and platelets or qualitative differences in the phospholipids/protein microenvironment of endothelial and platelet membranes that can affect integrin function. Additional studies in different populations with larger sample sizes are warranted to determine the impact of the current findings on clinical interventions. © 2010 The Author(s).
Yalcin M.,Pharmaceutical Research Institute |
Yalcin M.,Uludag University |
Bharali D.J.,Pharmaceutical Research Institute |
Dyskin E.,Pharmaceutical Research Institute |
And 7 more authors.
Thyroid | Year: 2010
Background: Tetraiodothyroacetic acid (tetrac) is a deaminated analogue of L-thyroxine that blocks the actions of L-thyroxine and 3,5,3'-triiodo-L- thyronine at the cell surface receptor for thyroid hormone on integrin αvβ3. Tetrac blocks the proliferative effects of thyroid hormone on tumor cells and the proangiogenesis actions of the hormone. In the absence of thyroid hormone, tetrac also blocks angiogenesis induced by various growth factors. Covalently linked to poly(lactide-co-glycolide), tetrac nanoparticles (tetrac NP) do not gain access to the cell interior and act exclusively at the integrin receptor. Here, the activity of tetrac and tetrac NP against follicular thyroid carcinoma (FTC)-236 cells was studied in two models: (1) tumor cell implants in the chick chorioallantoic membrane (CAM) system and (2) xenografts in the nude mouse. Methods: FTC-236 cells (106) were implanted in the CAM (n=8 each for control, and for tetrac and tetrac NP, both at 1 μg/CAM) and the actions of tetrac and tetrac NP were determined after 8 days on tumor-related angiogenesis and tumor growth. Xenografts of 107 FTC-236 cells were implanted in nude mice (n=8 per group). Tetrac or tetrac NP was administered intraperitoneal (1mg=kg and 1mg tetrac equivalent=kg, respectively) every other day for 32 days beginning on day 10, when tumor volume was 200-250mm3. Animals were monitored after discontinuation of treatment up to day 40. Results: In the CAM paradigm, tetrac and tetrac NP arrested tumor-related angiogenesis and tumor growth. In the xenograft model, tetrac and tetrac NP promptly and progressively reduced tumor volume ( p<0.01) over 32 days. There was some regrowth of tumor after interruption of tetrac treatment, but at day 40, tumor volume and tumor weight at sacrifice were 45-55% below those of controls ( p<0.01). Animal weight gain was comparable in the control and treatment groups of animals. Conclusions: Tetrac and tetrac NP effectively arrest FTC-236 cell tumor growth in the CAM and xenograft models, suggesting its potential utility against FTC. Copyright 2010, Mary Ann Liebert, Inc.
Ordway Research Institute Inc., Albany College of Pharmacy and Health Sciences | Date: 2011-06-22
Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric form of thyroid hormone, or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.
Ordway Research Institute Inc., Albany College of Pharmacy and Health Sciences | Date: 2013-11-13
Disclosed are methods of increasing the chemosensitivity of normal and/or chemoresistant tumor or cancer cells using thyroid hormone antagonists and/or nanoparticulate or polymeric forms thereof. Also disclosed are methods of increasing radiosensitivity of normal and/or radioresistant tumor or cancer cells using thyroid hormone antagonists and/or nanoparticulate or polymeric forms thereof.
De Vito P.,University of Rome Tor Vergata |
Incerpi S.,Third University of Rome |
Pedersen J.Z.,University of Rome Tor Vergata |
Luly P.,University of Rome Tor Vergata |
And 2 more authors.
Thyroid | Year: 2011
Background: Increasing evidence suggests that thyroid hormones, L-thyroxine (T 4) and 3,3′,5-triiodo-L-thyronine (T 3), are modulators of the immune response. In monocytes, macrophages, leukocytes, natural killer cells, and lymphocytes, a wide range of immune functions such as chemotaxis, phagocytosis, generation of reactive oxygen species (ROS), and cytokine synthesis and release are altered under hypo- and hyperthyroid conditions. Summary: Hyperthyroidism decreases the proinflammatory activities of monocytes and macrophages, whereas enhancement of phagocytosis and increased levels of ROS may occur during hypothyroidism. The expression of proinflammatory molecules such as macrophage inflammatory protein-1α and interleukin-1β increases in hypothyroidism. However, in Kupffer cells, proinflammatory activities such as the respiratory burst, nitric oxide synthase activity, and tumor necrosis factor-α expression may result from increased T 3 levels. Thyroid hormones also affect natural killer cell activity and cell-mediated immune responses. Still, for many immune cells no clear correlation has been found so far between abnormally high or low T 3 or T 4 levels and the effects observed on the immune responses. Conclusions: In this review we outline the contributions of thyroid hormones to different aspects of innate and adaptive immune responses. The relationship between thyroid hormones and immune cells is complex and T 3 and T 4 may modulate immune responses through both genomic and nongenomic mechanisms. Future studies of the molecular signaling mechanisms involved in this cross-talk between thyroid hormones and the immune system may support development of new strategies to improve clinical immune responses. © Copyright 2011, Mary Ann Liebert, Inc.
PubMed | Ordway Research Institute Inc.
Type: Journal Article | Journal: Physiology & behavior | Year: 2010
Thyroid hormone has been shown experimentally to affect cellular ion fluxes. For example, thyroid hormone-induced modulation has been described of cellular sodium current (I(Na)), inward rectifying potassium current (IKir) and sodium pump (Na, K-ATPase) and of calcium pump (Ca(2+)-ATPase) activities. Certain of these actions appear to reflect nongenomic mechanisms of hormone action that are initiated at the plasma membrane receptor for iodothyronines described on integrin alphavbeta3. One such action is the recent demonstration of enhancement by the hormone of I(Na) in neurons. Nongenomic actions of thyroid hormone initiated at the plasma membrane may be specifically inhibited by tetraiodothyroacetic acid (tetrac), a deaminated thyroid hormone analogue. Important behavioral changes are associated with clinical states of excessive or deficient thyroid function. The molecular basis for these changes has not been established. It is proposed that nongenomic actions of thyroid hormone in neurons-such as that on sodium current-underlie certain of these behaviors. The contribution of such nongenomic actions of the hormone to animal behavioral paradigms possibly relevant to thyroid hormone actions in human subjects may be tested in vivo with tetrac.
PubMed | Ordway Research Institute Inc.
Type: Journal Article | Journal: Current cardiology reviews | Year: 2010
A series of reports in the past decade have ascribed pro-angiogenic activity to several thyroid hormone analogues, including L-thyroxine (T(4)), 3,5,3-triiodo-L-thyronine (T(3)) and diiodothyropropionic acid (DITPA). Model systems of angiogenesis have demonstrated that thyroid hormone-induced neovascularization is initiated at a cell surface receptor for the hormone on an integrin. The hormone signal is transduced within the cell by extracellular regulated kinase 1/2 (ERK1/2) into secretion of basic fibroblast growth factor (bFGF) and other vascular growth factors and consequent angiogenesis. Intact animal studies have shown that endogenous thyroid hormone supports blood vessel density in heart and brain and that thyroid hormone administration can induce angiogenesis in ischemic limbs.