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Mircea Tampa, Maria-Isabela Sarbu, Madalina-Irina Mitran, Cristina-Iulia Mitran, Clara Matei, Simona-Roxana Georgescu
Psoriasis is a physically, emotionally, and socially invalidating multifactorial disorder, with a significant impact on the patients' quality of life. Stress is one of the leading triggers for psoriasis and has been associated with disease onset and subsequent flare-ups, while the flare-ups by themselves often lead to psychological discomfort. The treatment of psoriasis is individualized, depending on the patients' measurable severity of illness, as well as the impact the skin condition has on patients' quality of life, as assessed by standardized questionnaires...
2018: Disease Markers
Raul-Augustin Mitran, Cristian Matei, Daniela Berger, Laura Băjenaru, Mihaela G Moisescu
Mesoporous silica materials are promising nano-carriers for drug delivery systems. Even though there are many strategies for controlling the drug release kinetics, these must be adapted through trial and error on a case-by-case basis. Here we explore the possibility of tailoring the release kinetics of hydrophilic, water soluble therapeutic agents from mesoporous silica through addition of a hydrophobic excipient, 1-tetradecanol. In vitro drug release experiments performed at 37 °C, in phosphate buffer solution (pH 7...
March 7, 2018: European Journal of Pharmaceutics and Biopharmaceutics
Kristina Westerlund, Mohamed Altai, Bogdan Mitran, Mark Konijnenberg, Maryam Oroujeni, Christina Atterby, Marion de Jong, Anna Orlova, Johanna Mattsson, Patrick Micke, Amelie Eriksson Karlström, Vladimir Tolmachev
Affibody molecules are small proteins engineered using a non-antibody scaffold. Radiolabeled affibody molecules are excellent imaging probes, but their application for radionuclide therapy was so far prevented by high renal reabsorption. The aim of this study was to test the hypothesis that affibody-based peptide nucleic acid (PNA)-mediated pretargeted therapy of HER2-expressing cancer extends survival without accompanying renal toxicity. Methods: Human epidermal growth factor (HER2)-targeting affibody molecule ligated with AGTCGTGATGTAGTC PNA hybridization probe (ZHER2:342-SR-HP1) was used as the primary pretargeting agent...
February 9, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Kenneth Gavina, Sedami Gnidehou, Eliana Arango, Chloe Hamel-Martineau, Catherine Mitran, Olga Agudelo, Carolina Lopez, Aisha Karidio, Shanna Banman, Jaime Carmona-Fonseca, Ali Salanti, Nicaise Ndam, Michael Hawkes, Amanda Maestre, Stephanie K Yanow
BACKGROUND: Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium (P.) falciparum and P. vivax co-circulate. METHODS: A cohort of 187 pregnant women living in Puerto Libertador in Northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, RT-qPCR, and placental histopathology...
January 29, 2018: Infection and Immunity
R Vladareanu, D Mihu, M Mitran, C Mehedintu, A Boiangiu, M Manolache, S Vladareanu
OBJECTIVE: To evaluate activity and tolerability of an oral product containing the specific probiotic strain Lactobacillus plantarum P17630 on vaginal colonization of lactic acid bacteria. PATIENTS AND METHODS: L. plantarum P17630 (5x109 CFU/capsule) or placebo were formulated in capsules and administrated orally to a total of 93 women with a history of recurrent vulvovaginal candidiasis over a period of 3 treatment cycles (15 days/cycle) separated by 15-day wash-out intervals...
January 2018: European Review for Medical and Pharmacological Sciences
K Binzel, A Adelaja, C L Wright, D Scharre, J Zhang, M V Knopp, E J Teoh, D Bottomley, A Scarsbrook, H Payne, A Afaq, J Bomanji, N van As, S Chua, P Hoskin, A Chambers, G J Cook, V S Warbey, A Chau, P Ward, M P Miller, D J Stevens, L Wilson, F V Gleeson, K Scheidhauer, C Seidl, M Autenrieth, F Bruchertseifer, C Apostolidis, F Kurtz, T Horn, C Pfob, M Schwaiger, J Gschwend, C D'Alessandria, A Morgenstern, C Uprimny, A Kroiss, C Decristoforo, E von Guggenberg, B Nilica, W Horninger, I Virgolini, S Rasul, N Poetsch, A Woehrer, M Preusser, M Mitterhauser, W Wadsak, G Widhalm, M Mischkulnig, M Hacker, T Traub-Weidinger, C L Wright, K Binzel, E J Wuthrick, E D Miller, P Maniawski, J Zhang, M V Knopp, Sebastijan Rep, Marko Hocevar, Janja Vaupotic, Urban Zdesar, Katja Zaletel, Luka Lezaic, S Mairinger, Thomas Filip, M Sauberer, S Flunkert, T Wanek, J Stanek, N Okamura, O Langer, C Kuntner, M C Fornito, R Balzano, V Di Martino, S Cacciaguerra, G Russo, D Seifert, M Kleinova, A Cepa, J Ralis, P Hanc, O Lebeda, M Mosa, S Vandenberghe, E Mikhaylova, D Borys, V Viswanath, M Stockhoff, N Efthimiou, P Caribe, R Van Holen, J S Karp, K Binzel, J Zhang, C L Wright, P Maniawski, M V Knopp, P M Haller, C Farhan, E Piackova, B Jäger, P Knoll, A Kiss, B K Podesser, J Wojta, K Huber, S Mirzaei, A Traxl, K Komposch, Elisabeth Glitzner, T Wanek, S Mairinger, M Sibilia, O Langer, M C Fornito, M Russello, G Russo, R Balzano, S Sorko, H J Gallowitsch, S Kohlfuerst, S Matschnig, M Rieser, M Sorschag, P Lind, L Ležaič, S Rep, J Žibert, N Frelih, S Šuštar, K Binzel, A Adelaja, C L Wright, D Scharre, J Zhang, M V Knopp, R P Baum, T Langbein, A Singh, M Shahinfar, C Schuchardt, G F Volk, H R Kulkarni, M C Fornito, S Cacciaguerra, R Balzano, G V Di Martino, G Russo, W H Thomson, M Kudlacek, M Karik, C Farhan, H Rieger, W Pokieser, K Glaser, S Mirzaei, V Petz, C Tugendsam, W Buchinger, B Schmoll-Hauer, I P Schenk, K Rudolph, M Krebs, G Zettinig, V Zoufal, T Wanek, M Krohn, S Mairinger, J Stanek, M Sauberer, T Filip, J Pahnke, O Langer, F Weitzer, B Pernthaler, S Salamon, R Aigner, P Koranda, L Henzlová, M Kamínek, Mo Váchalová, P Bachleda, D Summer, J Garousi, M Oroujeni, B Mitran, K G Andersson, A Vorobyeva, J N Löfblom, A Orlova, V Tolmachev, C Decristoforo, P Kaeopookum, D Summer, T Orasch, B Lechner, M Petrik, Z Novy, C Rangger, H Haas, C Decristoforo
No abstract text is available yet for this article.
January 23, 2018: EJNMMI Research
Dominik Summer, Javad Garousi, Maryam Oroujeni, Bogdan Mitran, Ken G Andersson, Anzhelika Vorobyeva, John Löfblom, Anna Orlova, Vladimir Tolmachev, Clemens Decristoforo
Zirconium-89 is an emerging radionuclide for positron emission tomography (PET) especially for biomolecules with slow pharmacokinetics as due to its longer half-life, in comparison to fluorine-18 and gallium-68, imaging at late time points is feasible. Desferrioxamine B (DFO), a linear bifunctional chelator (BFC) is mostly used for this radionuclide so far but shows limitations regarding stability. Our group recently reported on fusarinine C (FSC) with similar zirconium-89 complexing properties but potentially higher stability related to its cyclic structure...
January 2, 2018: Molecular Pharmaceutics
Yan Feng, Sorin Mitran
A beam element is constructed for microtubules based upon data reduction of the results from atomistic simulation of the carbon backbone chain of αβ-tubulin dimers. The database of mechanical responses to various types of loads from atomistic simulation is reduced to dominant modes. The dominant modes are subsequently used to construct the stiffness matrix of a beam element that captures the anisotropic behavior and deformation mode coupling that arises from a microtubule's spiral structure. In contrast to standard Euler-Bernoulli or Timoshenko beam elements, the link between forces and node displacements results not from hypothesized deformation behavior, but directly from the data obtained by molecular scale simulation...
February 2018: Cytoskeleton
Javad Garousi, Sarah Lindbo, Bogdan Mitran, Jos Buijs, Anzhelika Vorobyeva, Anna Orlova, Vladimir Tolmachev, Sophia Hober
ABD-Derived Affinity Proteins (ADAPTs) is a novel class of engineered scaffold proteins derived from an albumin-binding domain of protein G. The use of ADAPT6 derivatives as targeting moiety have provided excellent preclinical radionuclide imaging of human epidermal growth factor 2 (HER2) tumor xenografts. Previous studies have demonstrated that selection of nuclide and chelator for its conjugation has an appreciable effect on imaging properties of scaffold proteins. In this study we performed a comparative evaluation of the anti-HER2 ADAPT having an aspartate-glutamate-alanine-valine-aspartate-alanine-asparagine-serine (DEAVDANS) N-terminal sequence and labeled at C-terminus with99m Tc using a cysteine-containing peptide based chelator, glycine-serine-serine-cysteine (GSSC), and a similar variant labeled with111 In using a maleimido derivative of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator...
November 7, 2017: Scientific Reports
Bogdan Mitran, Helge Thisgaard, Ulrika Rosenström, Johan Hygum Dam, Mats Larhed, Vladimir Tolmachev, Anna Orlova
High gastrin releasing peptide receptor (GRPR) expression is associated with numerous cancers including prostate and breast cancer. The aim of the current study was to develop a (55)Co-labeled PET agent based on GRPR antagonist RM26 for visualization of GRPR-expressing tumors. Labeling with (57)Co and (55)Co, stability, binding specificity, and in vitro and in vivo characteristics of (57)Co-NOTA-PEG2-RM26 were studied. NOTA-PEG2-RM26 was successfully radiolabeled with (57)Co and (55)Co with high yields and demonstrated high stability...
2017: Contrast Media & Molecular Imaging
Maria Rosestedt, Ken G Andersson, Bogdan Mitran, Sara S Rinne, Vladimir Tolmachev, John Löfblom, Anna Orlova, Stefan Ståhl
The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated...
October 11, 2017: International Journal of Oncology
Sarah Lindbo, Javad Garousi, Bogdan Mitran, Mohamed Altai, Jos Buijs, Anna Orlova, Sophia Hober, Vladimir Tolmachev
Visualization of cancer-associated alterations of molecular phenotype using radionuclide imaging is a noninvasive approach to stratifying patients for targeted therapies. The engineered albumin-binding domain-derived affinity protein (ADAPT) is a promising tracer for radionuclide molecular imaging because of its small size (6.5 kDa), which satisfies the precondition for efficient tumor penetration and rapid clearance. Previous studies demonstrated that the human epidermal growth factor receptor type 2 (HER2)-targeting ADAPT6 labeled with radiometals at the N terminus is able to image HER2 expression in xenografts a few hours after injection...
January 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Mohamed Altai, Kristina Westerlund, Justin Velletta, Bogdan Mitran, Hadis Honarvar, Amelie Eriksson Karlström
INTRODUCTION: We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide (177)Lu. We also studied the biodistribution profile of (177)Lu-HP2 in mice, and evaluated pretargeting with (177)Lu-HP2 in vitro and in vivo. METHODS: The biodistribution profile of (177)Lu-HP2 was evaluated in NMRI mice and compared to the previously studied (111)In-HP2...
July 12, 2017: Nuclear Medicine and Biology
Javad Garousi, Ken G Andersson, Johan H Dam, Birgitte B Olsen, Bogdan Mitran, Anna Orlova, Jos Buijs, Stefan Ståhl, John Löfblom, Helge Thisgaard, Vladimir Tolmachev
Several anti-cancer therapies target the epidermal growth factor receptor (EGFR). Radionuclide imaging of EGFR expression in tumours may aid in selection of optimal cancer therapy. The (111)In-labelled DOTA-conjugated ZEGFR:2377 Affibody molecule was successfully used for imaging of EGFR-expressing xenografts in mice. An optimal combination of radionuclide, chelator and targeting protein may further improve the contrast of radionuclide imaging. The aim of this study was to evaluate the targeting properties of radiocobalt-labelled DOTA-ZEGFR:2377...
July 20, 2017: Scientific Reports
Andreea Lili Barbulescu, Paulina Lucia Ciurea, Carmen Mitran, Beatrice Andreea Chisalau, Cristina Dorina Parvanescu, Sineta Cristina Firulescu, Maria Balasoiu, Mihail Virgil Boldeanu, Horatiu Popoviciu, Florentin Ananu Vreju
AIM: Accurate diagnosis and early treatment in rheumatoid arthritis (RA) can lead to a good outcome and a correct management of the disease. We aimed toinvestigate the prognostic value of anti-RA33 antibodies, by evaluating the relationship with ultrasonographic (US) findings in patients with early RA. MATERIAL AND METHODS: We performed a prospective study which included 29 patients, diagnosed with early RA according to the ACR/EULAR 2010 criteria and 21 sex and age-matched control subjects...
April 22, 2017: Medical Ultrasonography
Ilinca Nicolae, Cristina Iulia Mitran, Madalina Irina Mitran, Corina Daniela Ene, Mircea Tampa, Simona Roxana Georgescu
OBJECTIVES: Recent studies have highlighted the role of oxidative stress in the pathogenesis of lichen planus (LP). In the present study, the interest of the authors is focused on the investigation of ascorbic acid status in patients with LP and identification of parameters that might influence the level of this vitamin. MATERIAL AND METHOD: We analyzed the level of urinary ascorbic acid (reflectometric method) in 77 patients with LP (cutaneous LP (CLP)-49 cases; oral LP (OLP)-28 cases) and 50 control subjects...
2017: Journal of Immunoassay & Immunochemistry
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
Marc Y Stevens, Shiao Y Chow, Sergio Estrada, Jonas Eriksson, Veronika Asplund, Anna Orlova, Bogdan Mitran, Gunnar Antoni, Mats Larhed, Ola Åberg, Luke R Odell
We describe the development of a new methodology focusing on (11)C-labeling of sulfonyl carbamates in a multicomponent reaction comprised of a sulfonyl azide, an alkyl alcohol, and [(11)C]CO. A number of (11)C-labeled sulfonyl carbamates were synthesized and isolated, and the developed methodology was then applied in the preparation of a biologically active molecule. The target compound was obtained in 24±10 % isolated radiochemical yield and was evaluated for binding properties in a tumor cell assay; in vivo biodistribution and imaging studies were also performed...
December 2016: ChemistryOpen
Richard Furie, Margaret Mitrane, Enxu Zhao, Maya Das, Daner Li, Patrice M Becker
OBJECTIVE: To evaluate the efficacy of a prolonged-release formulation of a porcine adrenocorticotropic hormone analogue (repository corticotropin injection (RCI)) added to standard of care in patients requiring moderate-dose corticosteroids for symptomatic SLE. METHODS: This prospective, randomised, double-blind, phase 4, pilot study (NCT01753401) enrolled 38 patients with persistently active SLE involving skin and/or joints. Enrolled patients received RCI, 40 U daily or 80 U every other day, or volume-matched placebo gel, for 8 weeks, with dose tapering to twice weekly during weeks 5-8...
2016: Lupus Science & Medicine
Ken G Andersson, Maryam Oroujeni, Javad Garousi, Bogdan Mitran, Stefan Ståhl, Anna Orlova, John Löfblom, Vladimir Tolmachev
The epidermal growth factor receptor (EGFR) is overexpressed in a number of malignant tumors and is a molecular target for several specific anticancer antibodies and tyrosine kinase inhibitors. The overexpression of EGFR is a predictive biomarker for response to several therapy regimens. Radionuclide molecular imaging might enable detection of EGFR overexpression by a non-invasive procedure and could be used repeatedly. Affibody molecules are engineered scaffold proteins, which could be selected to have a high affinity and selectivity to predetermined targets...
December 2016: International Journal of Oncology
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