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https://www.readbyqxmd.com/read/28420143/biotinylated-chlorin-and-its-zinc-and-indium-complexes-synthesis-and-in-vitro-biological-evaluation-for-photodynamic-therapy
#1
Meden F Isaac-Lam, Dewana M Hammonds
The synthesis and characterization of biotinylated chlorin photosensitizer and the corresponding zinc and indium complexes are described for potential applications in photodynamic therapy (PDT) for cancer. Phototoxicity of the biotin-chlorin conjugate and the metallated complexes was determined in colon carcinoma CT26 cell lines known to overexpress biotin (Vit B₇) receptors. Cell survival assay indicated that the biotinylated chlorin and indium complex showed increased cell growth inhibition than the zinc complex and the starting chlorin (methyl pheophorbide)...
April 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28420127/glycosaminoglycan-binding-and-non-endocytic-membrane-translocation-of-cell-permeable-octaarginine-monitored-by-real-time-in-cell-nmr-spectroscopy
#2
Yuki Takechi-Haraya, Kenzo Aki, Yumi Tohyama, Yuichi Harano, Toru Kawakami, Hiroyuki Saito, Emiko Okamura
Glycosaminoglycans (GAGs), which are covalently-linked membrane proteins at the cell surface have recently been suggested to involve in not only endocytic cellular uptake but also non-endocytic direct cell membrane translocation of arginine-rich cell-penetrating peptides (CPPs). However, in-situ comprehensive observation and the quantitative analysis of the direct membrane translocation processes are challenging, and the mechanism therefore remains still unresolved. In this work, real-time in-cell NMR spectroscopy was applied to investigate the direct membrane translocation of octaarginine (R8) into living cells...
April 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28398261/novel-proteasome-inhibitors-and-histone-deacetylase-inhibitors-progress-in-myeloma-therapeutics
#3
REVIEW
Saurabh Chhabra
The unfolded protein response is responsible for the detection of misfolded proteins and the coordination of their disposal and is necessary to maintain the cellular homoeostasis. Multiple myeloma cells secrete large amounts of immunoglobulins, proteins that need to be correctly folded by the chaperone system. If this process fails, the misfolded proteins have to be eliminated by the two main garbage-disposal systems of the cell: proteasome and aggresome. The blockade of either of these systems will result in accumulation of immunoglobulins and other toxic proteins in the cytoplasm and cell death...
April 11, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28379203/role-of-trpm7-in-cancer-potential-as-molecular-biomarker-and-therapeutic-target
#4
REVIEW
Nelson S Yee
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed ion channel with intrinsic kinase activity. Molecular and electrophysiological analyses of the structure and activity of TRPM7 have revealed functional coupling of its channel and kinase activity. Studies have indicated the important roles of TRPM7 channel-kinase in fundamental cellular processes, physiological responses, and embryonic development. Accumulating evidence has shown that TRPM7 is aberrantly expressed and/or activated in human diseases including cancer...
April 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28368296/systematic-analysis-of-pharmaceutical-preparations-of-chondroitin-sulfate-combined-with-glucosamine
#5
Gustavo R C Santos, Adriana A Piquet, Bianca F Glauser, Ana M F Tovar, Mariana S Pereira, Eduardo Vilanova, Paulo A S Mourão
Glycosaminoglycans are carbohydrate-based compounds widely employed as nutraceuticals or prescribed drugs. Oral formulations of chondroitin sulfate combined with glucosamine sulfate have been increasingly used to treat the symptoms of osteoarthritis and osteoarthrosis. The chondroitin sulfate of these combinations can be obtained from shark or bovine cartilages and hence presents differences regarding the proportions of 4- and 6-sulfated N-acetyl β-d-galactosamine units. Herein, we proposed a systematic protocol to assess pharmaceutical batches of this combination drug...
April 1, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28358322/development-of-trpm8-antagonists-to-treat-chronic-pain-and-migraine
#6
REVIEW
Andy D Weyer, Sonya G Lehto
A review. Development of pharmaceutical antagonists of transient receptor potential melastatin 8 (TRPM8) have been pursued for the treatment of chronic pain and migraine. This review focuses on the current state of this progress.
March 30, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28353658/development-of-a-glycosaminoglycan-derived-selectin-targeting-anti-adhesive-coating-to-treat-endothelial-cell-dysfunction
#7
James R Wodicka, Andrea M Chambers, Gurneet S Sangha, Craig J Goergen, Alyssa Panitch
Endothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state...
March 29, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28346371/modulation-of-trp-channel-activity-by-hydroxylation-and-its-therapeutic-potential
#8
REVIEW
Yagnesh Nagarajan, Grigori Y Rychkov, Daniel J Peet
Two transient receptor potential (TRP) channels-TRPA1 and TRPV3-are post-translationally hydroxylated, resulting in oxygen-dependent regulation of channel activity. The enzymes responsible are the HIF prolyl hydroxylases (PHDs) and the asparaginyl hydroxylase factor inhibiting HIF (FIH). The PHDs and FIH are well characterized for their hydroxylation of the hypoxic inducible transcription factors (HIFs), mediating their hypoxic regulation. Consequently, these hydroxylases are currently being targeted therapeutically to modulate HIF activity in anemia, inflammation, and ischemic disease...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28346368/pathophysiological-significance-of-dermatan-sulfate-proteoglycans-revealed-by-human-genetic-disorders
#9
REVIEW
Shuji Mizumoto, Tomoki Kosho, Shuhei Yamada, Kazuyuki Sugahara
The indispensable roles of dermatan sulfate-proteoglycans (DS-PGs) have been demonstrated in various biological events including construction of the extracellular matrix and cell signaling through interactions with collagen and transforming growth factor-β, respectively. Defects in the core proteins of DS-PGs such as decorin and biglycan cause congenital stromal dystrophy of the cornea, spondyloepimetaphyseal dysplasia, and Meester-Loeys syndrome. Furthermore, mutations in human genes encoding the glycosyltransferases, epimerases, and sulfotransferases responsible for the biosynthesis of DS chains cause connective tissue disorders including Ehlers-Danlos syndrome and spondyloepimetaphyseal dysplasia with joint laxity characterized by skin hyperextensibility, joint hypermobility, and tissue fragility, and by severe skeletal disorders such as kyphoscoliosis, short trunk, dislocation, and joint laxity...
March 27, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28333082/an-updated-view-on-an-emerging-target-selected-papers-from-the-8th-international-conference-on-protein-kinase-ck2
#10
EDITORIAL
Joachim Jose, Marc Le-Borgne, Lorenzo A Pinna, Mathias Montenarh
n/a.
March 23, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28300791/anacardic-acid-constituents-from-cashew-nut-shell-liquid-nmr-characterization-and-the-effect-of-unsaturation-on-its-biological-activities
#11
Selene M Morais, Katherine A Silva, Halisson Araujo, Icaro G P Vieira, Daniela R Alves, Raquel O S Fontenelle, Artur M S Silva
Anacardic acids are the main constituents of natural cashew nut shell liquid (CNSL), obtained via the extraction of cashew shells with hexane at room temperature. This raw material presents high technological potential due to its various biological properties. The main components of CNSL are the anacardic acids, salicylic acid derivatives presenting a side chain of fifteen carbon atoms with different degrees of unsaturation (monoene-15:1, diene-15:2, and triene-15:3). Each constituent was isolated by column chromatography using silica gel impregnated with silver nitrate...
March 16, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28300769/aptamers-biomedical-interest-and-applications
#12
EDITORIAL
Cristina Romero-López, Alfredo Berzal-Herranz
Aptamers are short DNA or RNA oligonucleotides specialized in the specific and efficient binding to a target molecule. They are obtained by in vitro selection or evolution processes. It was in 1990 that two independent research groups described the bases of a new in vitro technology for the identification of RNA molecules able to specifically bind to a target [1,2]. Tuerk and Gold established the principals of the in vitro selection process that was named SELEX (Systematic Evolution of Ligands by Exponential enrichment), which is based on iterative cycles of binding, partitioning, and amplification of oligonucleotides from a pool of variant sequences [2]...
March 16, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28295000/current-status-of-radiopharmaceuticals-for-the-theranostics-of-neuroendocrine-neoplasms
#13
REVIEW
Melpomeni Fani, Petra Kolenc Peitl, Irina Velikyan
Nuclear medicine plays a pivotal role in the management of patients affected by neuroendocrine neoplasms (NENs). Radiolabeled somatostatin receptor analogs are by far the most advanced radiopharmaceuticals for diagnosis and therapy (radiotheranostics) of NENs. Their clinical success emerged receptor-targeted radiolabeled peptides as an important class of radiopharmaceuticals and it paved the way for the investigation of other radioligand-receptor systems. Besides the somatostatin receptors (sstr), other receptors have also been linked to NENs and quite a number of potential radiolabeled peptides have been derived from them...
March 15, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28287433/theranostic-value-of-multimers-lessons-learned-from-trimerization-of-neurotensin-receptor-ligands-and-other-targeting-vectors
#14
Simone Maschauer, Jürgen Einsiedel, Dominik Reich, Harald Hübner, Peter Gmeiner, Hans-Jürgen Wester, Olaf Prante, Johannes Notni
Neurotensin receptor 1 (NTS1) is overexpressed on a variety of cancer entities; for example, prostate cancer, ductal pancreatic adenocarcinoma, and breast cancer. Therefore, it represents an interesting target for the diagnosis of these cancers types by positron emission tomography (PET) [...].
March 10, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28287430/targeted-drugs-as-maintenance-therapy-after-autologous-stem-cell-transplantation-in-patients-with-mantle-cell-lymphoma
#15
REVIEW
Fengting Yan, Ajay K Gopal, Solomon A Graf
The treatment landscape for mantle cell lymphoma (MCL) is rapidly evolving toward the incorporation of novel and biologically targeted pharmaceuticals with improved disease activity and gentler toxicity profiles compared with conventional chemotherapeutics. Upfront intensive treatment of MCL includes autologous stem cell transplantation (SCT) consolidation aimed at deepening and lengthening disease remission, but subsequent relapse occurs. Maintenance therapy after autologous SCT in patients with MCL in remission features lower-intensity treatments given over extended periods to improve disease outcomes...
March 10, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28273877/protein-kinase-ck2-intricate-relationships-within-regulatory-cellular-networks
#16
REVIEW
Teresa Nuñez de Villavicencio-Diaz, Adam J Rabalski, David W Litchfield
Protein kinase CK2 is a small family of protein kinases that has been implicated in an expanding array of biological processes. While it is widely accepted that CK2 is a regulatory participant in a multitude of fundamental cellular processes, CK2 is often considered to be a constitutively active enzyme which raises questions about how it can be a regulatory participant in intricately controlled cellular processes. To resolve this apparent paradox, we have performed a systematic analysis of the published literature using text mining as well as mining of proteomic databases together with computational assembly of networks that involve CK2...
March 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230733/ck2-molecular-targeting-tumor-cell-specific-delivery-of-rnai-in-various-models-of-cancer
#17
REVIEW
Janeen H Trembley, Betsy T Kren, Md Joynal Abedin, Rachel I Vogel, Claire M Cannon, Gretchen M Unger, Khalil Ahmed
Protein kinase CK2 demonstrates increased protein expression relative to non-transformed cells in the majority of cancers that have been examined. The elevated levels of CK2 are involved in promoting not only continued proliferation of cancer cells but also their resistance to cell death; thus, CK2 has emerged as a plausible target for cancer therapy. Our focus has been to target CK2 catalytic subunits at the molecular level using RNA interference (RNAi) strategies to achieve their downregulation. The delivery of oligonucleotide therapeutic agents warrants that they are protected and are delivered specifically to cancer cells...
February 21, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28230762/the-development-of-ck2-inhibitors-from-traditional-pharmacology-to-in-silico-rational-drug-design
#18
REVIEW
Giorgio Cozza
Casein kinase II (CK2) is an ubiquitous and pleiotropic serine/threonine protein kinase able to phosphorylate hundreds of substrates. Being implicated in several human diseases, from neurodegeneration to cancer, the biological roles of CK2 have been intensively studied. Upregulation of CK2 has been shown to be critical to tumor progression, making this kinase an attractive target for cancer therapy. Several CK2 inhibitors have been developed so far, the first being discovered by "trial and error testing". In the last decade, the development of in silico rational drug design has prompted the discovery, de novo design and optimization of several CK2 inhibitors, active in the low nanomolar range...
February 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28208677/targeting-protein-kinase-ck2-evaluating-cx-4945-potential-for-gl261-glioblastoma-therapy-in-immunocompetent-mice
#19
Laura Ferrer-Font, Lucia Villamañan, Nuria Arias-Ramos, Jordi Vilardell, Maria Plana, Maria Ruzzene, Lorenzo A Pinna, Emilio Itarte, Carles Arús, Ana Paula Candiota
Glioblastoma (GBM) causes poor survival in patients even with aggressive treatment. Temozolomide (TMZ) is the standard chemotherapeutic choice for GBM treatment but resistance always ensues. Protein kinase CK2 (CK2) contributes to tumour development and proliferation in cancer, and it is overexpressed in human GBM. Accordingly, targeting CK2 in GBM may benefit patients. Our goal has been to evaluate whether CK2 inhibitors (iCK2s) could increase survival in an immunocompetent preclinical GBM model. Cultured GL261 cells were treated with different iCK2s including CX-4945, and target effects evaluated in vitro...
February 12, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28208634/rna-eluting-surfaces-for-the-modulation-of-gene-expression-as-a-novel-stent-concept
#20
Olivia Koenig, Diane Zengerle, Nadja Perle, Susanne Hossfeld, Bernd Neumann, Andreas Behring, Meltem Avci-Adali, Tobias Walker, Christian Schlensak, Hans Peter Wendel, Andrea Nolte
Presently, a new era of drug-eluting stents is continuing to improve late adverse effects such as thrombosis after coronary stent implantation in atherosclerotic vessels. The application of gene expression-modulating stents releasing specific small interfering RNAs (siRNAs) or messenger RNAs (mRNAs) to the vascular wall might have the potential to improve the regeneration of the vessel wall and to inhibit adverse effects as a new promising therapeutic strategy. Different poly (lactic-co-glycolic acid) (PLGA) resomers for their ability as an siRNA delivery carrier against intercellular adhesion molecule (ICAM)-1 with a depot effect were tested...
February 10, 2017: Pharmaceuticals
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