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191.
Ersilia Nigro Aurora Daniele Alessia Salzillo Angela Ragone Silvio Naviglio Luigi Sapio 《International journal of molecular sciences》2021,22(11)
The high mortality rate together with an ever-growing number of annual cases have defined neoplastic disorders as “the real 21st-century disease”. Its dubious distinction also results from conventional therapy failure, which has made cancer an orphan disease. Therefore, innovative and alternative therapeutic strategies are mandatory. The ability to leverage human naturally occurring anti-tumor defenses has always represented a fascinating perspective, and the immuno blockage approval in cancer treatment represents in timeline the latest success. As a multifunctional organ, adipose tissue releases a large amount of adipokines having both carcinogenic and antitumor properties. The negative correlation between serum levels and risk for developing malignancies, as well as the huge number of existing preclinical studies, have identified adiponectin as a potential anticancer adipokine. Nevertheless, its usage in clinical has constantly clashed with the inability to reproduce a mimic synthetic compound. Between 2011 and 2013, two distinct adiponectin receptor agonists were recognized, opening new scenarios even in cancer. Here, we review the first orally active adiponectin receptor agonists AdipoRon, from the discovery to the anticancer evidence. Including our latest findings in osteosarcoma models, we summarize AdipoRon and other existing agonists state-of-art, questioning about the feasibility assessment of this strategy in cancer treatment. 相似文献
192.
Andrea Marchetti Matteo Rosellini Veronica Mollica Alessandro Rizzo Elisa Tassinari Giacomo Nuvola Alessia Cimadamore Matteo Santoni Michelangelo Fiorentino Rodolfo Montironi Francesco Massari 《International journal of molecular sciences》2021,22(12)
Non-clear cell renal cell carcinomas are a miscellaneous group of tumors that include different histological subtypes, each one characterized by peculiarity in terms of genetic alteration, clinical behavior, prognosis, and treatment response. Because of their low incidence and poor enrollment in clinical trials, alongside their heterogeneity, additional efforts are required to better unveil the pathogenetic mechanisms and, consequently, to improve the treatment algorithm. Nowadays, tyrosine kinase inhibitors, mTOR and MET inhibitors, and even cisplatin-based chemotherapy and immunotherapy are potential weapons that are still under evaluation in this setting. Various biomarkers have been evaluated for detecting progression and monitoring renal cell carcinoma, but more studies are necessary to improve this field. In this review, we provide an overview on the molecular characteristics of this group of tumors and the recently published trials, giving an insight into what might become the future therapeutic standard in this complex world of non-clear cell kidney cancers. 相似文献
193.
Alessia Cimadamore Liang Cheng Francesco Massari Matteo Santoni Laura Pepi Carmine Franzese Marina Scarpelli Antonio Lopez-Beltran Andrea Benedetto Galosi Rodolfo Montironi 《International journal of molecular sciences》2021,22(11)
Approximately 23% of metastatic castration-resistant prostate cancers (mCRPC) harbor deleterious aberrations in DNA repair genes. Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) therapy has shown improvements in overall survival in patients with mCRPC who harbor somatic and/or germline alterations of homology recombination repair (HRR) genes. Peripheral blood samples are typically used for the germline mutation analysis test using the DNA extracted from peripheral blood leucocytes. Somatic alterations can be assessed by extracting DNA from a tumor tissue sample or using circulating tumor DNA (ctDNA) extracted from a plasma sample. Each of these genetic tests has its own benefits and limitations. The main advantages compared to the tissue test are that liquid biopsy is a non-invasive and easily repeatable test with the value of better representing tumor heterogeneity than primary biopsy and of capturing changes and/or resistance mutations in the genetic tumor profile during disease progression. Furthermore, ctDNA can inform about mutation status and guide treatment options in patients with mCRPC. Clinical validation and test implementation into routine clinical practice are currently very limited. In this review, we discuss the state of the art of the ctDNA test in prostate cancer compared to blood and tissue testing. We also illustrate the ctDNA testing workflow, the available techniques for ctDNA extraction, sequencing, and analysis, describing advantages and limits of each techniques. 相似文献
194.
Silvia Rivara Prof. Federica Vacondio Dr. Alessandro Fioni Dr. Claudia Silva Prof. Caterina Carmi Dr. Marco Mor Prof. Valeria Lucini Dr. Marilou Pannacci Dr. Alessia Caronno Dr. Francesco Scaglione Prof. Gabriella Gobbi Prof. Gilberto Spadoni Prof. Annalida Bedini Dr. Pierfrancesco Orlando Dr. Simone Lucarini Dr. Giorgio Tarzia Prof. 《ChemMedChem》2009,4(10):1746-1755
The class of N‐(anilinoethyl)amides includes melatonin receptor ligands with varied subtype selectivity and intrinsic activity. One of these ligands, the MT2‐selective partial agonist UCM765 (N‐{2‐[(3‐methoxyphenyl)phenylamino]ethyl}acetamide), had evidenced hypnotic effects in rodents at doses ≥40 mg kg?1 (s.c.), in spite of its sub‐nanomolar affinity for human melatonin receptors. Supposing that its low in vivo potency could be due, at least in part, to metabolic liability in rat liver, UCM765 was incubated with rat liver S9 fraction and rat, mouse, or human microsomes, and the major metabolites were identified by LC–MS, synthesized, and in vitro tested for their affinity toward MT1 and MT2 receptors. The obtained information was exploited to design novel analogues of UCM765 that are more resistant to in vitro oxidative degradation, while maintaining a similar binding profile. The analogue UCM924 (N‐{2‐[(3‐bromophenyl)‐(4‐fluorophenyl)amino]ethyl}acetamide) displayed a binding profile similar to that of UCM765 on cloned human receptors (MT2‐selective partial agonist) and a significantly longer half‐life in the presence of rat liver S9 fraction. 相似文献
195.
Aurelio Salerno Maria Oliviero Ernesto Di Maio Paolo A. Netti Cristina Rofani Alessia Colosimo Valentina Guida Bruno Dallapiccola Paolo Palma Emidio Procaccini Anna C. Berardi Francesco Velardi Anna Teti Salvatore Iannace 《Journal of materials science. Materials in medicine》2010,21(9):2569-2581
The design of bioactive scaffold materials able to guide cellular processes involved in new-tissue genesis is key determinant in bone tissue engineering. The aim of this study was the design and characterization of novel multi-phase biomaterials to be processed for the fabrication of 3D porous scaffolds able to provide a temporary biocompatible substrate for mesenchymal stem cells (MSCs) adhesion, proliferation and osteogenic differentiation. The biomaterials were prepared by blending poly(ε-caprolactone) (PCL) with thermoplastic zein (TZ), a thermoplastic material obtained by de novo thermoplasticization of zein. Furthermore, to bioactivate the scaffolds, microparticles of osteoconductive hydroxyapatite (HA) were dispersed within the organic phases. Results demonstrated that materials and formulations strongly affected the micro-structural properties and hydrophilicity of the scaffolds and, therefore, had a pivotal role in guiding cell/scaffold interaction. In particular, if compared to neat PCL, PCL–HA composite and PCL/TZ blend, the three-phase PCL/TZ–HA showed improved MSCs adhesion, proliferation and osteogenic differentiation capability, thus demonstrating potential for bone regeneration. 相似文献
196.
Silicon nanowires (Si NWs) are the emerging nanostructures for future nanodevices. In this work we have prepared them by electron beam evaporation (EBE) through the vapor-liquid-solid (VLS) mechanism. We discuss the growth of epitaxial NWs by EBE and the possibility to control their orientation and length by changing the experimental conditions. Moreover, the effects of the surface contamination and of the Au cluster preparation on the NWs structural properties and density will be discussed. We demonstrate that any O contamination has to be avoided since just a very thin native SiO2 layer stops ad-atom diffusion on the surface and inhibits the NWs growth. Au cluster preparation has a determinant role too: by varying the procedure for their formation, it is possible to change NWs density and length. In particular, we observed that by evaporating Au on the heated substrate, the droplets active to promote NW growth are immediately formed and a faster growth process starts. The growth rate is about a factor of 4 times higher than in the sample where the Au is evaporated at room temperature and the cluster formed after a subsequent thermal annealing. On the contrary, the slower process allows the atom arrangement and ordering in an epitaxial manner, and a precise control of NW orientation can be achieved. 相似文献
197.
Giovanni Smaldone Daniela Caruso Annamaria Sandomenico Emanuela Iaccarino Annalia Foc Alessia Ruggiero Menotti Ruvo Luigi Vitagliano 《International journal of molecular sciences》2021,22(19)
The three members (GADD45α, GADD45β, and GADD45γ) of the growth arrest and DNA damage-inducible 45 (GADD45) protein family are involved in a myriad of diversified cellular functions. With the aim of unravelling analogies and differences, we performed comparative biochemical and biophysical analyses on the three proteins. The characterization and quantification of their binding to the MKK7 kinase, a validated functional partner of GADD45β, indicate that GADD45α and GADD45γ are strong interactors of the kinase. Despite their remarkable sequence similarity, the three proteins present rather distinct biophysical properties. Indeed, while GADD45β and GADD45γ are marginally stable at physiological temperatures, GADD45α presents the Tm value expected for a protein isolated from a mesophilic organism. Surprisingly, GADD45α and GADD45β, when heated, form high-molecular weight species that exhibit features (ThT binding and intrinsic label-free UV/visible fluorescence) proper of amyloid-like aggregates. Cell viability studies demonstrate that they are endowed with a remarkable toxicity against SHSY-5Y and HepG2 cells. The very uncommon property of GADD45β to form cytotoxic species in near-physiological conditions represents a puzzling finding with potential functional implications. Finally, the low stability and/or the propensity to form toxic species of GADD45 proteins constitute important features that should be considered in interpreting their many functions. 相似文献
198.
Protein biosynthesis is a central process in cell life. Although the ribosome provides the machinery for biosynthesis, successful translation of the information contained in mRNA also relies on a number of protein factors that transiently associate with this giant ribonucleic complex. Among them, the elongation factors EF-Tu (bacteria) and EFIA (eukarya and archaea), which carry the aa-tRNA to the ribosome, have earned a special consideration. Here we present an excursus of structural information collected in the last decade on these enzymes. A significant advance in this field has been the recent crystallographic characterization of the complex between ribosome and EF-Tu. These findings, along with structural studies performed on EF-Tu complexes with small molecules and proteins, have provided a picture of the interactions of these proteins with a differentiate variety of biological partners. In contrast to EF-Tu, t he structural characterization of the states assumed by archaeal and eukaryal EFIA is largely incomplete. Here we also review solution and computational studies that have been successfully applied to integrate and complement crystallographic data. Analogies and differences between EFs isolated from different organisms will be highlighted. The new challenges of this research area, including the structural interpretation of the role of these proteins in other biological processes, are also addressed. 相似文献
199.
Sonia Trombino Roberta Cassano Teresa Ferrarelli Alessia Cilea Rita Muzzalupo Erika Cione Picci Nevio 《应用聚合物科学杂志》2009,114(5):3177-3183
Novel antioxidant biopolymers composed by broom or cotton fibers, and trans‐ferulic acid, α‐lipoic acid, and α‐tocopherol, were prepared. The acids were directly linked to fibers microfibrils hydroxylic groups using N,N‐dimethylacetamide/lithium chloride (DMAc/LiCl) as solvent with dicyclohexylcarbodiimide (DCC) and N,N‐dimethylaminopyridine (DMAP). Broom or cotton tocopherulate were prepared in the same conditions by using carboxylated fibers. Ester linkages were confirmed by using Fourier transformed infrared spectroscopy; biopolymers substitution degrees (DS) were determined by volumetric analysis. Antioxidant activity in inhibiting lipid peroxidation, in rat‐liver microsomal membranes, induced in vitro by two different sources of free radicals, 2,2′‐azobis (2‐amidinopropane) (AAPH) and tert‐butyl hydroperoxide (tert‐BOOH), was evaluated. Finally, biocompatibility of these biomaterials was also tested by controlling glutathione‐S‐transferase (GST) basal concentrations. Our results strongly suggested that the better derivatives were the ferulate ones. However, all obtained biomaterials, showing excellent antioxidant properties and biocompatibility, could be successfully applied in biomedical and in packaging areas. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009 相似文献
200.
Alessia Battigelli Julie Tzu‐Wen Wang Julie Russier Tatiana Da Ros Kostas Kostarelos Khuloud T. Al‐Jamal Maurizio Prato Alberto Bianco 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(21):3610-3619
A series of multi‐walled carbon nanotube (MWCNT) conjugates is described, functionalized with different dendrons bearing positive charges at their termini (i.e. ammonium or guanidinium groups). The dendrimeric units are anchored to the nanotube scaffolds using two orthogonal synthetic approaches, amidation and click reactions. The final nanohybrids are characterized by complementary analytical techniques, while their ability to interact with siRNA is investigated by means of agarose gel electrophoresis. The demonstration of the cell uptake capacity, the low cytotoxicity, and the ability of these cationic conjugates to silence cytotoxic genes suggests them to be promising carriers for genetic material. 相似文献