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Andrea Bolognesi is Full Professor of General Pathology at the Department of Experimental, Diagnostic and Specialty Medicine (DIMES) of the University of Bologna and is Chair of the Faculty-Student Joint Committee of the Medical School. His current fields of investigation include identification, purification and characterization of plant toxic polynucleotide:adenine glycosylases, also named ribosome-inactivating proteins, and their use as the toxic component of immunoconjugates mainly developed for the targeted therapy of malignancies. Professor Bolognesi is responsible for the production, possession and use for research purposes of ricin, a substance included in table 1 by the Organization for the Prohibition of Chemical Weapons, with authorization from the Ministry of Economic Development - Chemical Weapons Office. His laboratory is the reference center of the Ministry of Health and the Ministry of Agriculture for the analysis of ricin in commercial products and environmental pollutants.
Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies. Among them, antibody-based therapies have been the most studied. Immunoconjugates consist of a carrier portion, frequently represented by an antibody, linked to a toxic moiety, i.e., a drug, toxin, or radionuclide. While the efficacy of immunoconjugates is well demonstrated in the therapy of hematological tumors and more recently also of epithelial ones, their potential as therapeutic agents against sarcomas is still not completely explored. In this paper, we summarize the results obtained with immunoconjugates targeting sarcoma surface antigens, considering both preclinical and clinical studies. To date, the encouraging results obtained in preclinical studies allowed nine immunoconjugates to enter clinical trials, demonstrating the validity of immunotherapy as a promising pharmacological tool also for sarcoma therapy.
Letizia Polito; Giulia Calafato; Massimo Bortolotti; Cecilia Chiarelli Olivari; Stefania Maiello; Andrea Bolognesi. Antibody Conjugates for Sarcoma Therapy: How Far along Are We? Biomedicines 2021, 9, 978 .
AMA StyleLetizia Polito, Giulia Calafato, Massimo Bortolotti, Cecilia Chiarelli Olivari, Stefania Maiello, Andrea Bolognesi. Antibody Conjugates for Sarcoma Therapy: How Far along Are We? Biomedicines. 2021; 9 (8):978.
Chicago/Turabian StyleLetizia Polito; Giulia Calafato; Massimo Bortolotti; Cecilia Chiarelli Olivari; Stefania Maiello; Andrea Bolognesi. 2021. "Antibody Conjugates for Sarcoma Therapy: How Far along Are We?" Biomedicines 9, no. 8: 978.
Human xanthine oxidoreductase (XOR) is a multiple-level regulated enzyme, resulting from a complicated evolutionary process that assigned it many physiological roles. The main XOR activities are: (i) xanthine dehydrogenase (XDH) activity that performs the last two steps of purine catabolism, from hypoxanthine to uric acid; (ii) xanthine oxidase (XO) activity that, besides purine catabolism, produces reactive oxygen species (ROS); (iii) nitrite reductase activity that generates nitric oxide, contributing to vasodilation and regulation of blood pressure; (iv) NADH oxidase activity that produces ROS. All these XOR activities contribute also to metabolize various endogenous and exogenous compounds, including some drugs. About XOR products, it should be considered that (i) uric acid is not only a proinflammatory agent, but also a fundamental antioxidant molecule in serum and (ii) XOR-derived ROS are essential to the inflammatory defensive response. Although XOR has been the object of a large number of studies, most of them were focused on the pathological consequences of its activity and there is not a clear and schematic picture of XOR physiological roles. In this review, we try to fill this gap, reporting and graphically schematizing the main roles of XOR and its products.
Massimo Bortolotti; Letizia Polito; Maria Giulia Battelli; Andrea Bolognesi. Xanthine oxidoreductase: One enzyme for multiple physiological tasks. Redox Biology 2021, 41, 101882 .
AMA StyleMassimo Bortolotti, Letizia Polito, Maria Giulia Battelli, Andrea Bolognesi. Xanthine oxidoreductase: One enzyme for multiple physiological tasks. Redox Biology. 2021; 41 ():101882.
Chicago/Turabian StyleMassimo Bortolotti; Letizia Polito; Maria Giulia Battelli; Andrea Bolognesi. 2021. "Xanthine oxidoreductase: One enzyme for multiple physiological tasks." Redox Biology 41, no. : 101882.
Ribosome-inactivating proteins (RIPs) are plant toxins that irreversibly damage ribosomes and other substrates, thus causing cell death. RIPs are classified in type 1 RIPs, single-chain enzymatic proteins, and type 2 RIPs, consisting of active A chains, similar to type 1 RIPs, linked to lectin B chains, which enable the rapid internalization of the toxin into the cell. For this reason, many type 2 RIPs are very cytotoxic, ricin, volkensin and stenodactylin being the most toxic ones. From the caudex of Adenia kirkii (Mast.) Engl., a new type 2 RIP, named kirkiin, was purified by affinity chromatography on acid-treated Sepharose CL-6B and gel filtration. The lectin, with molecular weight of about 58 kDa, agglutinated erythrocytes and inhibited protein synthesis in a cell-free system at very low concentrations. Moreover, kirkiin was able to depurinate mammalian and yeast ribosomes, but it showed little or no activity on other nucleotide substrates. In neuroblastoma cells, kirkiin inhibited protein synthesis and induced apoptosis at doses in the pM range. The biological characteristics of kirkiin make this protein a potential candidate for several experimental pharmacological applications both alone for local treatments and as component of immunoconjugates for systemic targeting in neurodegenerative studies and cancer therapy.
Massimo Bortolotti; Stefania Maiello; José Ferreras; Rosario Iglesias; Letizia Polito; Andrea Bolognesi. Kirkiin: A New Toxic Type 2 Ribosome-Inactivating Protein from the Caudex of Adenia kirkii. Toxins 2021, 13, 81 .
AMA StyleMassimo Bortolotti, Stefania Maiello, José Ferreras, Rosario Iglesias, Letizia Polito, Andrea Bolognesi. Kirkiin: A New Toxic Type 2 Ribosome-Inactivating Protein from the Caudex of Adenia kirkii. Toxins. 2021; 13 (2):81.
Chicago/Turabian StyleMassimo Bortolotti; Stefania Maiello; José Ferreras; Rosario Iglesias; Letizia Polito; Andrea Bolognesi. 2021. "Kirkiin: A New Toxic Type 2 Ribosome-Inactivating Protein from the Caudex of Adenia kirkii." Toxins 13, no. 2: 81.
The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.
Maria Giulia Battelli; Massimo Bortolotti; Andrea Bolognesi; Letizia Polito. Pro-Aging Effects of Xanthine Oxidoreductase Products. Antioxidants 2020, 9, 839 .
AMA StyleMaria Giulia Battelli, Massimo Bortolotti, Andrea Bolognesi, Letizia Polito. Pro-Aging Effects of Xanthine Oxidoreductase Products. Antioxidants. 2020; 9 (9):839.
Chicago/Turabian StyleMaria Giulia Battelli; Massimo Bortolotti; Andrea Bolognesi; Letizia Polito. 2020. "Pro-Aging Effects of Xanthine Oxidoreductase Products." Antioxidants 9, no. 9: 839.
Stenodactylin is one of the most potent type 2 ribosome-inactivating proteins (RIPs); its high toxicity has been demonstrated in several models both in vitro and in vivo. Due to its peculiarities, stenodactylin could have several medical and biotechnological applications in neuroscience and cancer treatment. In this work, we report the complete amino acid sequence of stenodactylin and 3D structure prediction. The comparison between the primary sequence of stenodactylin and other RIPs allowed us to identify homologies/differences and the amino acids involved in RIP toxic activity. Stenodactylin RNA was isolated from plant caudex, reverse transcribed through PCR and the cDNA was amplificated and cloned into a plasmid vector and further analyzed by sequencing. Nucleotide sequence analysis showed that stenodactylin A and B chains contain 251 and 258 amino acids, respectively. The key amino acids of the active site described for ricin and most other RIPs are also conserved in the stenodactylin A chain. Stenodactylin amino acid sequence shows a high identity degree with volkensin (81.7% for A chain, 90.3% for B chain), whilst when compared with other type 2 RIPs the identity degree ranges from 27.7 to 33.0% for the A chain and from 42.1 to 47.7% for the B chain.
Rosario Iglesias; Letizia Polito; Massimo Bortolotti; Manuela Pedrazzi; Lucía Citores; José M. Ferreras; Andrea Bolognesi. Primary Sequence and 3D Structure Prediction of the Plant Toxin Stenodactylin. Toxins 2020, 12, 538 .
AMA StyleRosario Iglesias, Letizia Polito, Massimo Bortolotti, Manuela Pedrazzi, Lucía Citores, José M. Ferreras, Andrea Bolognesi. Primary Sequence and 3D Structure Prediction of the Plant Toxin Stenodactylin. Toxins. 2020; 12 (9):538.
Chicago/Turabian StyleRosario Iglesias; Letizia Polito; Massimo Bortolotti; Manuela Pedrazzi; Lucía Citores; José M. Ferreras; Andrea Bolognesi. 2020. "Primary Sequence and 3D Structure Prediction of the Plant Toxin Stenodactylin." Toxins 12, no. 9: 538.
The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation.
Letizia Polito; Massimo Bortolotti; Maria Battelli; Giulia Calafato; Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. Toxins 2019, 11, 324 .
AMA StyleLetizia Polito, Massimo Bortolotti, Maria Battelli, Giulia Calafato, Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. Toxins. 2019; 11 (6):324.
Chicago/Turabian StyleLetizia Polito; Massimo Bortolotti; Maria Battelli; Giulia Calafato; Andrea Bolognesi. 2019. "Ricin: An Ancient Story for a Timeless Plant Toxin." Toxins 11, no. 6: 324.
The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for several biocrimes. This manuscript intends to give the reader an overview of ricin, focusing on the historical path to the current knowledge on this protein. The main steps of ricin research are here reported, with particular regard to its enzymatic activity, structure, and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation between bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been used to develop immunotoxins for the elimination of unwanted cells, mainly cancer cells; some of these immunoconjugates gave promising results in clinical trials but also showed critical limitation.
Letizia Polito; Massimo Bortolotti; Maria Giulia Battelli; Giulia Calafato; Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. Toxins 2019, 11, 1 .
AMA StyleLetizia Polito, Massimo Bortolotti, Maria Giulia Battelli, Giulia Calafato, Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. Toxins. 2019; 11 (6):1.
Chicago/Turabian StyleLetizia Polito; Massimo Bortolotti; Maria Giulia Battelli; Giulia Calafato; Andrea Bolognesi. 2019. "Ricin: An Ancient Story for a Timeless Plant Toxin." Toxins 11, no. 6: 1.
The castor plant (Ricinus communis L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide. Castor bean has been mainly recommended as anti-inflammatory, anthelmintic, anti-bacterial, laxative, abortifacient, for wounds, ulcers, and many other indications. Many cases of human intoxication occurred accidentally or voluntarily with the ingestion of castor seeds or derivatives. Ricinus toxicity depends on several molecules, among them the most important is ricin, a protein belonging to the family of ribosome-inactivating proteins. Ricin is the most studied of this category of proteins and it is also known to the general public, having been used for biocrimes in several cases. Here, the main steps of ricin research are reported with particular regards to its enzymatic activity, structure and cytotoxicity. Moreover, we discuss ricin toxicity for animals and humans, as well as the relation amongst bioterrorism and ricin and its impact on environmental toxicity. Ricin has also been of great utility to develop a number of immunotoxins specific for the elimination of unwanted cells, mainly cancer cells; some of these immunotoxins gave promising results also in clinical trials.
Letizia Polito; Massimo Bortolotti; Maria Giulia Battelli; Giulia Calafato; Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. 2019, 1 .
AMA StyleLetizia Polito, Massimo Bortolotti, Maria Giulia Battelli, Giulia Calafato, Andrea Bolognesi. Ricin: An Ancient Story for a Timeless Plant Toxin. . 2019; ():1.
Chicago/Turabian StyleLetizia Polito; Massimo Bortolotti; Maria Giulia Battelli; Giulia Calafato; Andrea Bolognesi. 2019. "Ricin: An Ancient Story for a Timeless Plant Toxin." , no. : 1.
Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional monounsaturated fatty acid (MUFA) isomers are under development. Furthermore, sapienic acid can bring to the de novo synthesis of the n-10 polyunsaturated fatty acid (PUFA) sebaleic acid (5cis,8cis-18:2), but such transformations in cancer cells are not known. The model of Caco-2 cell line was used to monitor sapienic acid supplementation (150 and 300 μM) and provide evidence of the formation of n-10 fatty acids as well as their incorporation at levels of membrane phospholipids and triglycerides. Comparison with palmitoleic and palmitic acids evidenced that lipid remodelling was influenced by the type of fatty acid and positional isomer, with an increase of 8cis-18:1, n-10 PUFA and a decrease of saturated fats in case of sapienic acid. Cholesteryl esters were formed only in cases with sapienic acid. Sapienic acid was the less toxic among the tested fatty acids, showing the highest EC50s and inducing death only in 75% of cells at the highest concentration tested. Two-photon fluorescent microscopy with Laurdan as a fluorescent dye provided information on membrane fluidity, highlighting that sapienic acid increases the distribution of fluid regions, probably connected with the formation of 8cis-18:1 and the n-10 PUFA in cell lipidome. Our results bring evidence for MUFA positional isomers and de novo PUFA synthesis for developing lipidomic analysis and cancer research.
Roberta Scanferlato; Massimo Bortolotti; Anna Sansone; Chryssostomos Chatgilialoglu; Letizia Polito; Marco De Spirito; Giuseppe Maulucci; Andrea Bolognesi; Carla Ferreri. Hexadecenoic Fatty Acid Positional Isomers and De Novo PUFA Synthesis in Colon Cancer Cells. International Journal of Molecular Sciences 2019, 20, 832 .
AMA StyleRoberta Scanferlato, Massimo Bortolotti, Anna Sansone, Chryssostomos Chatgilialoglu, Letizia Polito, Marco De Spirito, Giuseppe Maulucci, Andrea Bolognesi, Carla Ferreri. Hexadecenoic Fatty Acid Positional Isomers and De Novo PUFA Synthesis in Colon Cancer Cells. International Journal of Molecular Sciences. 2019; 20 (4):832.
Chicago/Turabian StyleRoberta Scanferlato; Massimo Bortolotti; Anna Sansone; Chryssostomos Chatgilialoglu; Letizia Polito; Marco De Spirito; Giuseppe Maulucci; Andrea Bolognesi; Carla Ferreri. 2019. "Hexadecenoic Fatty Acid Positional Isomers and De Novo PUFA Synthesis in Colon Cancer Cells." International Journal of Molecular Sciences 20, no. 4: 832.
Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9cis-16:1; n-7 series) and sapienic acid (6cis-16:1; n-10 series), respectively. The corresponding biological consequences and lipidomic research on these positional MUFA isomers are under development. Furthermore, sapienic acid can bring to the de novo synthesis of the n-10 polyunsaturated fatty acid (PUFA) sebaleic acid (5cis,8cis-18:2), but such transformations in cancer cells are not known. The model of Caco-2 cell line was used to monitor sapienic acid supplementation (150 and 300 μM) and evidence the formation of n-10 fatty acids as well as their incorporation at levels of membrane phospholipids and triglycerides. Comparison with palmitoleic and palmitic acids evidenced that lipid remodeling was influenced by the type of fatty acid and positional isomer, with increase of 8cis-18:1, n-10 PUFA and decrease of saturated fats in case of sapienic acid. Cholesteryl esters were formed only in case of sapienic acid. EC50 of sapienic acid (232.3 μM at 96 hrs) was the highest found among the tested fatty acids, thus influencing cell viability that was only reduced at 25% at 300 μM, whereas palmitoleic acid induced cell death. Two-photon fluorescent microscopy with Laurdan as a fluorescent dye provided information on membrane fluidity, highlighting that sapienic acid increases the distribution of fluid regions, probably connected with the formation of 8cis-18:1 and the n-10 PUFA in cell lipidome. Our results bring evidence for MUFA positional isomers and de novo PUFA synthesis for developing lipidomic analysis and cancer research.
Roberta Scanferlato; Massimo Bortolotti; Anna Sansone; Chryssostomos Chatgilialoglu; Letizia Polito; Marco De Spirito; Giuseppe Maulucci; Andrea Bolognesi; Carla Ferreri. Hexadecenoic Fatty Acid Positional Isomers and de Novo PUFA Synthesis in Colon Cancer Cells. 2019, 1 .
AMA StyleRoberta Scanferlato, Massimo Bortolotti, Anna Sansone, Chryssostomos Chatgilialoglu, Letizia Polito, Marco De Spirito, Giuseppe Maulucci, Andrea Bolognesi, Carla Ferreri. Hexadecenoic Fatty Acid Positional Isomers and de Novo PUFA Synthesis in Colon Cancer Cells. . 2019; ():1.
Chicago/Turabian StyleRoberta Scanferlato; Massimo Bortolotti; Anna Sansone; Chryssostomos Chatgilialoglu; Letizia Polito; Marco De Spirito; Giuseppe Maulucci; Andrea Bolognesi; Carla Ferreri. 2019. "Hexadecenoic Fatty Acid Positional Isomers and de Novo PUFA Synthesis in Colon Cancer Cells." , no. : 1.
Obesity and related pathologies such as diabetes and metabolic syndrome are associated with chronic inflammation and cancer. The serum level of xanthine oxidoreductase (XOR) is correlated to obesity-associated metabolic disorders. XOR can play a role in the pathogenesis of both metabolic syndrome and cancer through the inflammatory response and the oxidative stress elicited by the products of its activity. The reactive oxygen and nitrogen species and the uric acid derived from XOR concur to the development of hypertension, dyslipidemia and insulin resistance and participate in both cell transformation and proliferation, as well as in the progression and metastasis process. Despite the availability of different drugs to inhibit in vivo XOR activity, the complexity of XOR inhibition effects should be carefully considered before clinical application, save in the case of symptomatic hyperuricemia.
Maria Giulia Battelli; Massimo Bortolotti; Letizia Polito; Andrea Bolognesi. Metabolic syndrome and cancer risk: The role of xanthine oxidoreductase. Redox Biology 2018, 21, 101070 .
AMA StyleMaria Giulia Battelli, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi. Metabolic syndrome and cancer risk: The role of xanthine oxidoreductase. Redox Biology. 2018; 21 ():101070.
Chicago/Turabian StyleMaria Giulia Battelli; Massimo Bortolotti; Letizia Polito; Andrea Bolognesi. 2018. "Metabolic syndrome and cancer risk: The role of xanthine oxidoreductase." Redox Biology 21, no. : 101070.
Bougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that, bouganin has some peculiarities, such as a higher activity on DNA with respect to ribosomal RNA, low systemic toxicity, and immunological properties quite different than other RIPs. The sequencing of bouganin and the knowledge of its three-dimensional structure allowed to obtain a not immunogenic mutant of bouganin. These features make bouganin a very attractive tool as a component of immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier molecule. Bouganin-containing ITs showed very promising results in the experimental treatment of both hematological and solid tumors, and one bouganin-containing IT has entered Phase I clinical trial. In this review, we summarize the milestones of the research on bouganin such as bouganin chemico-physical characteristics, the structural properties and de-immunization studies. In addition, the in vitro and in vivo results obtained with bouganin-containing ITs are summarized.
Massimo Bortolotti; Andrea Bolognesi; Letizia Polito. Bouganin, an Attractive Weapon for Immunotoxins. Toxins 2018, 10, 323 .
AMA StyleMassimo Bortolotti, Andrea Bolognesi, Letizia Polito. Bouganin, an Attractive Weapon for Immunotoxins. Toxins. 2018; 10 (8):323.
Chicago/Turabian StyleMassimo Bortolotti; Andrea Bolognesi; Letizia Polito. 2018. "Bouganin, an Attractive Weapon for Immunotoxins." Toxins 10, no. 8: 323.
Xanthine oxidoreductase (XOR) could contribute to the pathogenesis of metabolic syndrome through the oxidative stress and the inflammatory response induced by XOR-derived reactive oxygen species and uric acid. Hyperuricemia is strongly linked to hypertension, insulin resistance, obesity and hypertriglyceridemia. The serum level of XOR is correlated to triglyceride/high density lipoprotein cholesterol ratio, fasting glycemia, fasting insulinemia and insulin resistance index. Increased activity of endothelium-linked XOR may promote hypertension. In addition, XOR is implicated in pre-adipocyte differentiation and adipogenesis. XOR and uric acid play a role in cell transformation and proliferation as well as in the progression and metastatic process. Collected evidences confirm the contribution of XOR and uric acid in metabolic syndrome. However, in some circumstances XOR and uric acid may have anti-oxidant protective outcomes. The dual-face role of both XOR and uric acid explains the contradictory results obtained with XOR inhibitors and suggests caution in their therapeutic use.
Maria Giulia Battelli; Massimo Bortolotti; Letizia Polito; Andrea Bolognesi. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 2018, 1864, 2557 -2565.
AMA StyleMaria Giulia Battelli, Massimo Bortolotti, Letizia Polito, Andrea Bolognesi. The role of xanthine oxidoreductase and uric acid in metabolic syndrome. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2018; 1864 (8):2557-2565.
Chicago/Turabian StyleMaria Giulia Battelli; Massimo Bortolotti; Letizia Polito; Andrea Bolognesi. 2018. "The role of xanthine oxidoreductase and uric acid in metabolic syndrome." Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1864, no. 8: 2557-2565.
Osteosarcoma (OS) is an aggressive osteoid-producing tumor of mesenchymal origin, which represents the most common primary bone malignancy. It is characterized by a complex and frequently uncertain etiology. The current standard care for high-grade OS treatment is neoadjuvant chemotherapy, followed by surgery and post-operative chemotherapy. In order to ameliorate survival rates of patients, new therapeutic approaches have been evaluated, mainly immunotherapy with antibody-drug conjugates or immunoconjugates. These molecules consist of a carrier (frequently an antibody) joined by a linker to a toxic moiety (drug, radionuclide, or toxin). Although several clinical trials with immunoconjugates have been conducted, mainly in hematological tumors, their potential as therapeutic agents is relatively under-explored in many types of cancer. In this review, we report the immunoconjugates directed against OS surface antigens, considering the in vitro and in vivo studies. To date, several attempts have been made in preclinical settings, reporting encouraging results and demonstrating the validity of the idea. The clinical experience with glembatumumab vedotin may provide new insights into the real efficacy of antibody-drug conjugates for OS therapy, possibly giving more information about patient selection. Moreover, new opportunities could arise from the ongoing clinical trials in OS patients with unconjugated antibodies that could represent future candidates as carrier moieties of immunoconjugates.
Daniele Mercatelli; Massimo Bortolotti; Alberto Bazzocchi; Andrea Bolognesi; Letizia Polito. Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives. Biomedicines 2018, 6, 19 .
AMA StyleDaniele Mercatelli, Massimo Bortolotti, Alberto Bazzocchi, Andrea Bolognesi, Letizia Polito. Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives. Biomedicines. 2018; 6 (1):19.
Chicago/Turabian StyleDaniele Mercatelli; Massimo Bortolotti; Alberto Bazzocchi; Andrea Bolognesi; Letizia Polito. 2018. "Immunoconjugates for Osteosarcoma Therapy: Preclinical Experiences and Future Perspectives." Biomedicines 6, no. 1: 19.
Immunotoxins (ITs) are hybrid proteins combining the binding specificity of antibodies with the cytocidal properties of toxins. They represent a promising approach to lymphoma therapy. The cytotoxicity of two immunotoxins obtained by chemical conjugation of the plant toxin saporin-S6 with the anti-CD20 chimeric antibody rituximab and the anti-CD22 murine antibody OM124 were evaluated on the CD20-/CD22-positive cell line Raji. Both ITs showed strong cytotoxicity for Raji cells, but the anti-CD22 IT was two logs more efficient in killing, probably because of its faster internalization. The anti-CD22 IT gave slower but greater caspase activation than the anti-CD20 IT. The cytotoxic effect of both immunotoxins can be partially prevented by either the pan-caspase inhibitor Z-VAD or the necroptosis inhibitor necrostatin-1. Oxidative stress seems to be involved in the cell killing activity of anti-CD20 IT, as demonstrated by the protective role of the H2O2 scavenger catalase, but not in that of anti-CD22 IT. Moreover, the IT toxicity can be augmented by the contemporary administration of other chemotherapeutic drugs, such as PS-341, MG-132, and fludarabine. These results contribute to the understanding of the immunotoxin mechanism of action that is required for their clinical use, either alone or in combination with other drugs.
Letizia Polito; Daniele Mercatelli; Massimo Bortolotti; Stefania Maiello; Alice Djemil; Maria Giulia Battelli; Andrea Bolognesi. Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells. Toxins 2017, 9, 182 .
AMA StyleLetizia Polito, Daniele Mercatelli, Massimo Bortolotti, Stefania Maiello, Alice Djemil, Maria Giulia Battelli, Andrea Bolognesi. Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells. Toxins. 2017; 9 (6):182.
Chicago/Turabian StyleLetizia Polito; Daniele Mercatelli; Massimo Bortolotti; Stefania Maiello; Alice Djemil; Maria Giulia Battelli; Andrea Bolognesi. 2017. "Two Saporin-Containing Immunotoxins Specific for CD20 and CD22 Show Different Behavior in Killing Lymphoma Cells." Toxins 9, no. 6: 182.
The enzymes called ribosome‐inactivating proteins (RIPs) that are able to depurinate nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline research field, mostly because of their promising medical applications. The contributions of Stirpe to the development of these studies has been one of the most relevant. After a short biographical introduction, an overview is offered of the main results obtained by his investigations during last 55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs.
Andrea Bolognesi; Massimo Bortolotti; Maria Giulia Battelli; Letizia Polito. Hyperuricaemia, Xanthine Oxidoreductase and Ribosome‐Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research. Molecules 2017, 22, 206 .
AMA StyleAndrea Bolognesi, Massimo Bortolotti, Maria Giulia Battelli, Letizia Polito. Hyperuricaemia, Xanthine Oxidoreductase and Ribosome‐Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research. Molecules. 2017; 22 (2):206.
Chicago/Turabian StyleAndrea Bolognesi; Massimo Bortolotti; Maria Giulia Battelli; Letizia Polito. 2017. "Hyperuricaemia, Xanthine Oxidoreductase and Ribosome‐Inactivating Proteins from Plants: The Contributions of Fiorenzo Stirpe to Frontline Research." Molecules 22, no. 2: 206.
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery. Studies on RIP/cell interactions were able to detail the endocytosis and intracellular routing of ricin, thus increasing our knowledge of how cells handle exogenous proteins. The identification of new RIPs and the finding that most RIPs are single-chain polypeptides, together with their genetic sequencing, has aided in the development of new phylogenetic theories. Overall, the biological properties of these proteins, including their abortifacient, anticancer, antiviral and neurotoxic activities, suggest that RIPs could be utilized in agriculture and in many biomedical fields, including clinical drug development.
Andrea Bolognesi; Massimo Bortolotti; Stefania Maiello; Maria Giulia Battelli; Letizia Polito. Ribosome-Inactivating Proteins from Plants: A Historical Overview. Molecules 2016, 21, 1627 .
AMA StyleAndrea Bolognesi, Massimo Bortolotti, Stefania Maiello, Maria Giulia Battelli, Letizia Polito. Ribosome-Inactivating Proteins from Plants: A Historical Overview. Molecules. 2016; 21 (12):1627.
Chicago/Turabian StyleAndrea Bolognesi; Massimo Bortolotti; Stefania Maiello; Maria Giulia Battelli; Letizia Polito. 2016. "Ribosome-Inactivating Proteins from Plants: A Historical Overview." Molecules 21, no. 12: 1627.
Paolo Trevisi; Bevis Miller; Dilip Patel; Andrea Bolognesi; Massimo Bortolotti; Paolo Bosi. Two differentin vitrotests confirm the blocking activity ofd-galactose lectins on the adhesion ofEscherichia coliF4 to pig brush border receptors. Italian Journal of Animal Science 2016, 16, 101 -107.
AMA StylePaolo Trevisi, Bevis Miller, Dilip Patel, Andrea Bolognesi, Massimo Bortolotti, Paolo Bosi. Two differentin vitrotests confirm the blocking activity ofd-galactose lectins on the adhesion ofEscherichia coliF4 to pig brush border receptors. Italian Journal of Animal Science. 2016; 16 (1):101-107.
Chicago/Turabian StylePaolo Trevisi; Bevis Miller; Dilip Patel; Andrea Bolognesi; Massimo Bortolotti; Paolo Bosi. 2016. "Two differentin vitrotests confirm the blocking activity ofd-galactose lectins on the adhesion ofEscherichia coliF4 to pig brush border receptors." Italian Journal of Animal Science 16, no. 1: 101-107.
Ribosome-inactivating proteins (RIPs) are enzymes that deadenylate nucleic acids and are broadly distributed in the plant kingdom. Many plants that contain RIPs are listed in the pharmacopoeias of folk medicine all over the world, mostly because of their toxicity. This review analyses the position occupied in traditional medicine by plants from which RIPs have been isolated. The overview starts from the antique age of the Mediterranean area with ancient Egypt, followed by the Greek and Roman classic period. Then, the ancient oriental civilizations of China and India are evaluated. More recently, Unani medicine and European folk medicine are examined. Finally, the African and American folk medicines are taken into consideration. In conclusion, a list of RIP-expressing plants, which have been used in folk medicine, is provided with the geographical distribution and the prescriptions that are recommended by traditional healers. Some final considerations are provided on the present utilization of such herbal treatments, both in developing and developed countries, often in the absence of scientific validation. The most promising prospect for the medicinal use of RIP-expressing plants is the conjugation of purified RIPs to antibodies that recognise tumour antigens for cancer therapy.
Letizia Polito; Massimo Bortolotti; Stefania Maiello; Maria Giulia Battelli; Andrea Bolognesi. Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine. Molecules 2016, 21, 1560 .
AMA StyleLetizia Polito, Massimo Bortolotti, Stefania Maiello, Maria Giulia Battelli, Andrea Bolognesi. Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine. Molecules. 2016; 21 (11):1560.
Chicago/Turabian StyleLetizia Polito; Massimo Bortolotti; Stefania Maiello; Maria Giulia Battelli; Andrea Bolognesi. 2016. "Plants Producing Ribosome-Inactivating Proteins in Traditional Medicine." Molecules 21, no. 11: 1560.
The enzyme xanthine oxidoreductase (XOR) catalyzes the last two steps of purine catabolism in the highest uricotelic primates. XOR is an enzyme with dehydrogenase activity that, in mammals, may be converted into oxidase activity under a variety of pathophysiologic conditions. XOR activity is highly regulated at the transcriptional and post-translational levels and may generate reactive oxygen and nitrogen species, which trigger different consequences, ranging from cytotoxicity to inflammation. The low specificity for substrates allows XOR to metabolize a number of endogenous metabolites and a variety of exogenous compounds, including drugs. The present review focuses on the role of XOR as a drug-metabolizing enzyme, specifically for drugs with anticancer, antimicrobial, antiviral, immunosuppressive or vasodilator activities, as well as drugs acting on metabolism or inducing XOR expression. XOR has an activating role that is essential to the pharmacological action of quinone drugs, cyadox, antiviral nucleoside analogues, allopurinol, nitrate and nitrite. XOR activity has a degradation function toward thiopurine nucleotides, pyrazinoic acid, methylxanthines and tolbutamide, whose half-life may be prolonged by the use of XOR inhibitors. In conclusion, to avoid potential drug interaction risks, such as a toxic excess of drug bioavailability or a loss of drug efficacy, caution is suggested in the use of XOR inhibitors, as in the case of hyperuricemic patients affected by gout or tumor lysis syndrome, when it is necessary to simultaneously administer therapeutic substances that are activated or degraded by the drug-metabolizing activity of XOR.
Maria Giulia Battelli; Letizia Polito; Massimo Bortolotti; Andrea Bolognesi. Xanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme. Current Medicinal Chemistry 2016, 23, 4027 -4036.
AMA StyleMaria Giulia Battelli, Letizia Polito, Massimo Bortolotti, Andrea Bolognesi. Xanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme. Current Medicinal Chemistry. 2016; 23 (35):4027-4036.
Chicago/Turabian StyleMaria Giulia Battelli; Letizia Polito; Massimo Bortolotti; Andrea Bolognesi. 2016. "Xanthine Oxidoreductase in Drug Metabolism: Beyond a Role as a Detoxifying Enzyme." Current Medicinal Chemistry 23, no. 35: 4027-4036.