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https://www.readbyqxmd.com/read/29141866/prostate-specific-membrane-antigen-cleavage-of-vitamin-b9-stimulates-oncogenic-signaling-through-metabotropic-glutamate-receptors
#1
Charalambos Kaittanis, Chrysafis Andreou, Haley Hieronymus, Ninghui Mao, Catherine A Foss, Matthias Eiber, Gregor Weirich, Palak Panchal, Anuradha Gopalan, Juan Zurita, Samuel Achilefu, Gabriela Chiosis, Vladimir Ponomarev, Markus Schwaiger, Brett S Carver, Martin G Pomper, Jan Grimm
Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer. Its expression correlates inversely with survival and increases with tumor grade. However, the biological role of PSMA has not been explored, and its role in prostate cancer remained elusive. Filling this gap, we demonstrate that in prostate cancer, PSMA initiates signaling upstream of PI3K through G protein-coupled receptors, specifically via the metabotropic glutamate receptor (mGluR). PSMA's carboxypeptidase activity releases glutamate from vitamin B9 and other glutamated substrates, which activate mGluR I...
November 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29100402/stk33-participates-to-hsp90-supported-angiogenic-program-in-hypoxic-tumors-by-regulating-hif-1%C3%AE-vegf-signaling-pathway
#2
Yang Liu, Konrad Steinestel, Arefeh Rouhi, Milena Armacki, Kristina Diepold, Gabriela Chiosis, Thomas Simmet, Thomas Seufferlein, Ninel Azoitei
Lately, the HSP90 client serine/threonine kinase STK33 emerged to be required by cancer cells for their viability and proliferation. However, its mechanistic contribution to carcinogenesis is not clearly understood. Here we report that elevated STK33 expression correlates with advanced stages of human pancreatic and colorectal carcinomas. Impaired proliferation and augmented apoptosis associated with genetic abrogation of STK33 were paralleled by decreased vascularization in tumor xenografts. In line with this, ectopic STK33 not only promoted tumor growth after pharmacologic inhibition of HSP90 using structurally divergent small molecules currently in clinical development, but also restored blood vessel formation in vivo...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29090356/ilm-peeling-in-nontractional-diabetic-macular-edema-review-and-metanalysis
#3
REVIEW
M Rinaldi, R dell'Omo, F Morescalchi, F Semeraro, E Gambicorti, F Cacciatore, F Chiosi, C Costagliola
PURPOSE: To evaluate the effect of internal limiting membrane (ILM) peeling during vitrectomy for nontractional diabetic macular edema. METHODS: PUBMED, MEDLINE and CENTRAL were reviewed using the following terms (or combination of terms): diabetic macular edema, nontractional diabetic macular edema, internal limiting membrane peeling, vitrectomy, Müller cells. Randomized and nonrandomized studies were included. The eligible studies compared anatomical and functional outcomes of vitrectomy with or without ILM peeling for tractional and nontractional diabetic macular edema...
October 31, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28990809/proteomic-interrogation-of-hsp90-and-insights-for-medical-research
#4
Lorenz Weidenauer, Tai Wang, Suhasini Joshi, Gabriela Chiosis, Manfredo R Quadroni
Heat shock protein 90 (HSP90) regulates protein homeostasis in eukaryotes. As a "professional interactor", HSP90 binds to and chaperones many proteins and has both housekeeping and disease-related functions but its regulation remains in part elusive. HSP90 complexes are a target for therapy, notably against cancer, and several inhibitors are currently in clinical trials. Proteomic studies have revealed the vast interaction network of HSP90 and, in doing so, the extent of cellular processes the chaperone takes part in, especially in yeast and human cells...
October 9, 2017: Expert Review of Proteomics
https://www.readbyqxmd.com/read/28619753/inhibition-of-hsp90-suppresses-pi3k-akt-mtor-signaling-and-has-antitumor-activity-in-burkitt-lymphoma
#5
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
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...
September 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28524204/correction-metabolomic-profiling-and-biochemical-evaluation-of-the-follicular-fluid-of-endometriosis-patients
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
RANDOMIZED CONTROLLED TRIAL
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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