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https://www.readbyqxmd.com/read/28619753/inhibition-of-hsp90-suppresses-pi3k-akt-mtor-signaling-and-has-antitumor-activity-in-burkitt-lymphoma
#1
Lisa Giulino-Roth, Herman J Van Besien, Tanner Dalton, Jennifer E Totonchy, Anna Rodina, Tony Taldone, Alexander Bolaender, Hediye Erdjument-Bromage, Jouliana Sadek, Amy Chadburn, Matthew J Barth, Filemon S Dela Cruz, Allison Rainey, Andrew L Kung, Gabriela Chiosis, Ethel Cesarman
Heat shock protein 90 (Hsp90) is a molecular chaperone that protects proteins, including oncogenic signaling complexes, from proteolytic degradation.  PU-H71 is a next-generation Hsp90 inhibitor that preferentially targets the functionally distinct pool of Hsp90 present in tumor cells.  Tumors that are driven by the MYC oncoprotein may be particularly sensitive to PU-H71 due to the essential role of Hsp90 in the epichaperome which maintains the malignant phenotype in the setting of MYC.  Burkitt lymphoma (BL) is an aggressive B-cell lymphoma characterized by MYC dysregulation...
June 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28524204/correction-metabolomic-profiling-and-biochemical-evaluation-of-the-follicular-fluid-of-endometriosis-patients
#2
Marianna Santonastaso, Alessia Pucciarelli, Susan Costantini, Francesca Caprio, Angela Sorice, Francesca Capone, Antonella Natella, Patrizia Iardino, Nicola Colacurci, Emilio Chiosi
Correction for 'Metabolomic profiling and biochemical evaluation of the follicular fluid of endometriosis patients' by Marianna Santonastaso et al., Mol. BioSyst., 2017, DOI: 10.1039/c7mb00181a.
May 19, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28475193/metabolomic-profiling-and-biochemical-evaluation-of-the-follicular-fluid-of-endometriosis-patients
#3
Santonastaso Marianna, Pucciarelli Alessia, Costantini Susan, Caprio Francesca, Sorice Angela, Capone Francesca, Natella Antonella, Iardino Patrizia, Colacurci Nicola, Chiosi Emilio
Diseases are complex systems that can be studied through the integration of data derived from different disciplines to obtain a global and reliable picture of the biological phenomenon under investigation. Based on the recent observations that the metabolomics profiling of follicular fluids reflects the ovarian microenvironment of women and that endometriosis represents an example of complex diseases, clearly diagnosed by laparoscopy, we thought that the follicular fluids of endometriosis patients can represent a study model to evaluate the possibility of integrating data obtained by different approaches...
June 1, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28114285/hsp90-stabilizes-b-cell-receptor-kinases-in-a-multi-client-interactome-pu-h71-induces-cll-apoptosis-in-a-cytoprotective-microenvironment
#4
A Guo, P Lu, J Lee, C Zhen, G Chiosis, Y L Wang
Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of B cells in the hematopoietic system and lymphoid tissues. Although inhibitors targeting the B-cell receptor (BCR) pathway have been successful in the treatment of the disease, the underlying mechanisms leading to BCR over-activity in CLL are not fully understood. In this study, we found that HSP90, a highly conserved molecular chaperone, is overexpressed in CLL compared with resting B cells. HSP90 overexpression is accompanied by the overexpression of several BCR kinases including LYN, spleen tyrosine kinase, Bruton tyrosine kinase and AKT...
June 15, 2017: Oncogene
https://www.readbyqxmd.com/read/27982689/the-effect-of-laurus-nobilis-on-the-blood-and-lenses-antioxidant-activity-in-rabbit-under-fat-enriched-diet
#5
D Casamassima, F Chiosi, F Vizzarri, M Palazzo, C Costagliola
Fat-enriched diet is strongly associated with cataract development. Laurus nobilis shows antioxidant activity. Herein we evaluated the effect of Laurus nobilis oral administration on the blood and lenses antioxidant activity in rabbits under fat-enriched diet. Sixty rabbits divided into 4 groups were used. One group represented the control (N-CTR). The second group (P-CTR) fed a diet supplemented with 2.5 % of pig fat; the third group (EXP1) received a diet supplemented with 2.5 % of pig fat and 1 g/kg of dried-bay leaves; the fourth group (EXP2) was treated with dried-bay leaves at the rate of 1 g/kg of feed...
May 4, 2017: Physiological Research
https://www.readbyqxmd.com/read/27741183/guillain-barr%C3%A3-syndrome-in-pregnancy
#6
REVIEW
Luis D Pacheco, Antonio F Saad, Gary D V Hankins, Giuseppe Chiosi, George Saade
Guillain-Barré syndrome has been reported in pregnancy and is a potentially lethal condition. It affects the nervous system with acute onset of symmetric ascending weakness and may result in frank respiratory failure and autonomic dysfunction. Most patients recall symptoms of a respiratory or gastrointestinal illness in the weeks preceding the onset of weakness. Recent evidence suggests a potential role of the Zika virus as a trigger for the syndrome. The diagnosis of Guillain-Barré is clinical. Supportive measures include venous thromboembolism prophylaxis, aggressive physical therapy, pressure ulcer prevention, enteral nutrition, and respiratory support...
November 2016: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/27739063/the-natural-camp-elevating-compound-forskolin-in-cancer-therapy-is-it-time
#7
REVIEW
Luigi Sapio, Monica Gallo, Michela Illiano, Emilio Chiosi, Daniele Naviglio, Annamaria Spina, Silvio Naviglio
Cancer is a major public health problem and the second leading cause of mortality around the world. Although continuous advances in the science of oncology and cancer research are now leading to improved outcomes for many cancer patients, novel cancer treatment options are strongly demanded. Naturally occurring compounds from a variety of vegetables, fruits, and medicinal plants have been shown to exhibit various anticancer properties in a number of in vitro and in vivo studies and represent an attractive research area for the development of new therapeutic strategies to fight cancer...
May 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27729772/resolvins-and-aliamides-lipid-autacoids-in-ophthalmology-what-promise-do-they-hold
#8
REVIEW
Jan M Keppel Hesselink, Flavia Chiosi, Ciro Costagliola
Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives - RX-10045...
2016: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/27706135/the-epichaperome-is-an-integrated-chaperome-network-that-facilitates-tumour-survival
#9
Anna Rodina, Tai Wang, Pengrong Yan, Erica DaGama Gomes, Mark P S Dunphy, Nagavarakishore Pillarsetty, John Koren, John F Gerecitano, Tony Taldone, Hongliang Zong, Eloisi Caldas-Lopes, Mary Alpaugh, Adriana Corben, Matthew Riolo, Brad Beattie, Christina Pressl, Radu I Peter, Chao Xu, Robert Trondl, Hardik J Patel, Fumiko Shimizu, Alexander Bolaender, Chenghua Yang, Palak Panchal, Mohammad F Farooq, Sarah Kishinevsky, Shanu Modi, Oscar Lin, Feixia Chu, Sujata Patil, Hediye Erdjument-Bromage, Pat Zanzonico, Clifford Hudis, Lorenz Studer, Gail J Roboz, Ethel Cesarman, Leandro Cerchietti, Ross Levine, Ari Melnick, Steven M Larson, Jason S Lewis, Monica L Guzman, Gabriela Chiosis
Transient, multi-protein complexes are important facilitators of cellular functions. This includes the chaperome, an abundant protein family comprising chaperones, co-chaperones, adaptors, and folding enzymes-dynamic complexes of which regulate cellular homeostasis together with the protein degradation machinery. Numerous studies have addressed the role of chaperome members in isolation, yet little is known about their relationships regarding how they interact and function together in malignancy. As function is probably highly dependent on endogenous conditions found in native tumours, chaperomes have resisted investigation, mainly due to the limitations of methods needed to disrupt or engineer the cellular environment to facilitate analysis...
October 20, 2016: Nature
https://www.readbyqxmd.com/read/27680013/reduced-fluence-verteporfin-photodynamic-therapy-plus-ranibizumab-for-choroidal-neovascularization-in-pathologic-myopia
#10
M Rinaldi, F Semeraro, F Chiosi, A Russo, M R Romano, M C Savastano, R dell'Omo, C Costagliola
BACKGROUND: To demonstrate the efficacy of intravitreal ranibizumab (IVR) in combination with reduced-fluence photodynamic therapy (RF-PDT) in patients with choroidal neovascularization (CNV) secondary to pathologic myopia. METHODS: Sixty patients affected by myopic CNV (mCNV) were randomized to receive either ranibizumab 0.5 mg monotherapy (RM; n = 20), standard fluence PDT (SF-PDT, n = 20) or RF-PDT combination therapy (n = 20). Subsequently, IVR was injected as needed...
March 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27669096/rnai-screening-of-the-glucose-regulated-chaperones-in-cancer-with-self-assembled-sirna-nanostructures
#11
Mayurbhai R Patel, Stephen D Kozuch, Christopher N Cultrara, Reeta Yadav, Suiying Huang, Uri Samuni, John Koren, Gabriela Chiosis, David Sabatino
The emerging field of RNA nanotechnology has been used to design well-programmed, self-assembled nanostructures for applications in chemistry, biology, and medicine. At the forefront of its utility in cancer is the unrestricted ability to self-assemble multiple siRNAs within a single nanostructure formulation for the RNAi screening of a wide range of oncogenes while potentiating the gene therapy of malignant tumors. In our RNAi nanotechnology approach, V- and Y-shape RNA templates were designed and constructed for the self-assembly of discrete, higher-ordered siRNA nanostructures targeting the oncogenic glucose regulated chaperones...
October 3, 2016: Nano Letters
https://www.readbyqxmd.com/read/27549859/editorial-thematic-issue-heat-shock-proteins-in-disease-from-molecular-mechanisms-to-therapeutics
#12
EDITORIAL
Gabriela Chiosis
No abstract text is available yet for this article.
2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27142687/editorial-heat-shock-protein-in-disease-from-molecular-mechanisms-to-therapeutics
#13
Gabriela Chiosis
No abstract text is available yet for this article.
May 3, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27072698/clients-and-oncogenic-roles-of-molecular-chaperone-gp96-grp94
#14
REVIEW
Ephraim A Ansa-Addo, Jessica Thaxton, Feng Hong, Bill X Wu, Yongliang Zhang, Caroline W Fugle, Alessandra Metelli, Brian Riesenberg, Katelyn Williams, Daniel T Gewirth, Gabriela Chiosis, Bei Liu, Zihai Li
As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt coreceptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF)...
2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/26933742/chemical-tools-to-investigate-mechanisms-associated-with-hsp90-and-hsp70-in-disease
#15
REVIEW
Liza Shrestha, Hardik J Patel, Gabriela Chiosis
The chaperome is a large and diverse protein machinery composed of chaperone proteins and a variety of helpers, such as the co-chaperones, folding enzymes, and scaffolding and adapter proteins. Heat shock protein 90s and 70s (HSP90s and HSP70s), the most abundant chaperome members in human cells, are also the most complex. As we have learned to appreciate, their functions are context dependent and manifested through a variety of conformations that each recruit a subset of co-chaperone, scaffolding, and folding proteins and which are further diversified by the posttranslational modifications each carry, making their study through classic genetic and biochemical techniques quite a challenge...
January 21, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/26806023/radiosynthesis-of-the-iodine-124-labeled-hsp90-inhibitor-pu-h71
#16
Tony Taldone, Danuta Zatorska, Stefan O Ochiana, Peter Smith-Jones, Jacek Koziorowski, Mark P Dunphy, Pat Zanzonico, Alexander Bolaender, Jason S Lewis, Steven M Larson, Gabriela Chiosis, Naga Vara Kishore Pillarsetty
Heat shock protein 90 (Hsp90) is an ATP dependent molecular chaperone protein whose function is critical for maintaining several key proteins involved in survival and proliferation of cancer cells. PU-H71 (1), is a potent purine-scaffold based ATP pocket binding Hsp90 inhibitor which has been shown to have potent activity in a broad range of in vivo cancer models and is currently in Phase I clinical trials in patients with advanced solid malignancies, lymphomas, and myeloproliferative neoplasms. In this report, we describe the radiosynthesis of [(124)I]-PU-H71(5); this was synthesized from the corresponding Boc-protected stannane precursor 3 by iododestannylation with [(124)I]-NaI using chloramine-T as an oxidant for 2 min, followed by Boc deprotection with 6 N HCl at 50 °C for 30 min to yield the final compound...
March 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/26628369/a-hyperactive-signalosome-in-acute-myeloid-leukemia-drives-addiction-to-a-tumor-specific-hsp90-species
#17
Hongliang Zong, Alexander Gozman, Eloisi Caldas-Lopes, Tony Taldone, Eric Sturgill, Sarah Brennan, Stefan O Ochiana, Erica M Gomes-DaGama, Siddhartha Sen, Anna Rodina, John Koren, Michael W Becker, Charles M Rudin, Ari Melnick, Ross L Levine, Gail J Roboz, Stephen D Nimer, Gabriela Chiosis, Monica L Guzman
Acute myeloid leukemia (AML) is a heterogeneous and fatal disease with an urgent need for improved therapeutic regimens given that most patients die from relapsed disease. Irrespective of mutation status, the development of aggressive leukemias is enabled by increasing dependence on signaling networks. We demonstrate that a hyperactive signalosome drives addiction of AML cells to a tumor-specific Hsp90 species (teHsp90). Through genetic, environmental, and pharmacologic perturbations, we demonstrate a direct and quantitative link between hyperactivated signaling pathways and apoptotic sensitivity of AML to teHsp90 inhibition...
December 15, 2015: Cell Reports
https://www.readbyqxmd.com/read/26603836/combinatorial-targeting-of-nuclear-export-and-translation-of-rna-inhibits-aggressive-b-cell-lymphomas
#18
Biljana Culjkovic-Kraljacic, Tharu M Fernando, Rossella Marullo, Nieves Calvo-Vidal, Akanksha Verma, ShaoNing Yang, Fabrizio Tabbò, Marcello Gaudiano, Hiba Zahreddine, Rebecca L Goldstein, Jayeshkumar Patel, Tony Taldone, Gabriela Chiosis, Marco Ladetto, Paola Ghione, Rodolfo Machiorlatti, Olivier Elemento, Giorgio Inghirami, Ari Melnick, Katherine L B Borden, Leandro Cerchietti
Aggressive double- and triple-hit (DH/TH) diffuse large B-cell lymphomas (DLBCLs) feature activation of Hsp90 stress pathways. Herein, we show that Hsp90 controls posttranscriptional dynamics of key messenger RNA (mRNA) species including those encoding BCL6, MYC, and BCL2. Using a proteomics approach, we found that Hsp90 binds to and maintains activity of eIF4E. eIF4E drives nuclear export and translation of BCL6, MYC, and BCL2 mRNA. eIF4E RNA-immunoprecipitation sequencing in DLBCL suggests that nuclear eIF4E controls an extended program that includes B-cell receptor signaling, cellular metabolism, and epigenetic regulation...
February 18, 2016: Blood
https://www.readbyqxmd.com/read/26540670/multifunctional-mri-pet-nanobeacons-derived-from-the-in-situ-self-assembly-of-translational-polymers-and-clinical-cargo-through-coalescent-intermolecular-forces
#19
Charalambos Kaittanis, Travis M Shaffer, Alexander Bolaender, Zachary Appelbaum, Jeremy Appelbaum, Gabriela Chiosis, Jan Grimm
Novel multifunctional platforms are needed for oncology in order to assist physicians during surgery and chemotherapy. In the present study, we show that polymeric nanobeacons, consisting of the glucose-based polymer dextran, can be used to guide surgery and improve drug delivery. For imaging, the nanobeacons stably retained the positron emitter 89-zirconium and the MRI contrast agent gadolinium, without the need of a chelator. In addition to using them for PET imaging, the (89)Zr-nanobeacons guided the surgical resection of sentinel lymph nodes, utilizing their inherent Cerenkov luminescence...
December 9, 2015: Nano Letters
https://www.readbyqxmd.com/read/26529251/pharmacoproteomics-identifies-combinatorial-therapy-targets-for-diffuse-large-b-cell-lymphoma
#20
Rebecca L Goldstein, Shao Ning Yang, Tony Taldone, Betty Chang, John Gerecitano, Kojo Elenitoba-Johnson, Rita Shaknovich, Wayne Tam, John P Leonard, Gabriela Chiosis, Leandro Cerchietti, Ari Melnick
Rationally designed combinations of targeted therapies for refractory cancers, such as activated B cell-like diffuse large B cell lymphoma (ABC DLBCL), are likely required to achieve potent, durable responses. Here, we used a pharmacoproteomics approach to map the interactome of a tumor-enriched isoform of HSP90 (teHSP90). Specifically, we chemically precipitated teHSP90-client complexes from DLBCL cell lines with the small molecule PU-H71 and found that components of the proximal B cell receptor (BCR) signalosome were enriched within teHSP90 complexes...
November 3, 2015: Journal of Clinical Investigation
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