1,721,074 research outputs found
Genotossicità
No full textÈ ormai riconosciuto che l’esposizione a particolari agenti chimici od a miscele complesse può portare allo sviluppo di cancro. Più recentemente, è stato postulato che composti in grado di indurre modificazioni ereditarie nell’uomo possano causare lo sviluppo di patologie nella progenie. Tali modificazioni hanno origine in seguito a danno al DNA e risultano in mutazioni. Queste consistono in alterazioni più o meno grandi del materiale genetico, che possono portare alla sospensione del prodotto genico, alla diminuzione o all’aumento della sua attività, alla perdita delle sue capacità funzionali oppure non avere conseguenze. Il principale obiettivo della Tossicologia Genetica è l’identificazione di quegli agenti che sono in grado di interagire con gli acidi nucleici e che inducono alterazioni nelle componenti genetiche. Nell’industria, tale informazione è di fondamentale importanza per limitare od eliminare l’esposizione individuale a composti mutageni e, nel caso di farmaci, per procedere lungo la complessa strada dello sviluppo, una volta accertato che i benefici derivanti dall’impiego della molecola siano nettamente superiori ai rischi
Flow cytometric analysis of genetic damage, effect on cell cycle progression, and apoptosis by thiophanate-methyl in human lymphocytes
No full textFlow cytometric technique was used to study the effects of the fungicide Thiophanate-methyl on cell proliferation, micronucleus induction, and apoptosis in human peripheral blood lymphocytes treated in vitro. In particular, a combined approach of flow cytometry and fluorescence in situ hybridization (FISH) with a pancentromeric α-satellite probe was used to evaluate the mechanism of micronucleus induction by Thiophanate-methyl. Flow sorted micronuclei (MN) induced in human lymphocytes by Thiophanate-methyl were analyzed by FISH and the results were compared with results from FISH analysis on MN in binucleated cells. It could be shown that most MN induced by Thiophanatemethyl did not reveal any centromeric signal, thus demonstrating clastogenic action of this fungicide. Moreover, it was found that as a function of the concentration of Thiophanate-methyl, cellular proliferation was delayed and the frequency of apoptotic cells was increased. Environ. Mol. Mutagen
Overview of the Anticancer Potential of the "King of Spices" Piper nigrum and Its Main Constituent Piperine
Full text linkThe main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient's quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents-not limited to the well-known piperine-whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients
COMPOSTI ISOTIOCIANATI E ISOSELENCIANATI
No full textLa presente invenzione attiene una nuova famiglia di composti isotiocianati e isoselencianati idonei ad essere utilizzati come:
- farmaci innovativi con spiccato profilo di efficacia terapeutica, tali da consentire un miglior approccio alla patologia tumorale rispetto ai farmaci attuali,
- teranostici per la contemporanea diagnosi e cura della patologia oncologica;
- sonde fluorescenti per l'osservazione diretta di specifici organuli cellulari in applicazioni biomediche
Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects
Full text linkAngiogenesis and metastasis represent two challenging targets to combat cancer development in the later stages of its progression. Numerous studies have indicated the important role of natural products in blocking tumor angiogenesis signaling pathways in several advanced tumors. In recent years, the marine polysaccharides fucoidans emerged as promising anticancer compounds showing potent antitumor activity in both in vitro and in vivo models of different types of cancers. The objective of this review is to focus on the antiangiogenic and antimetastatic activities of fucoidans with special emphasis on preclinical studies. Independently from their source, fucoidans inhibit several angiogenic regulators, primarily vascular endothelial growth factor (VEGF). A glance towards fucoidans' ongoing clinical trials and pharmacokinetic profile is provided to present the main challenges that still need to be addressed for their bench-to-bedside translation
Overview of the Anticancer Profile of Avenanthramides from Oat
Full text linkCancer represents one of the leading causes of death worldwide. Progresses in treatment of cancer have continued at a rapid pace. However, undesirable side effects and drug resistance remain major challenges for therapeutic success. Natural products represent a valuable starting point to develop new anticancer strategies. Polyphenols, well-known as antioxidant, exert anticancer effects through the modulation of multiple pathways and mechanisms. Oat (Avena sativa L., Poaceae) is a unique source of avenanthramides (AVAs), a group of polyphenolic alkaloids, considered as its signature compounds. The present review aims to offer a comprehensive and critical perspective on the chemopreventive and chemotherapeutic potential of AVAs. AVAs prevent cancer mainly by blocking reactive species. Moreover, they exhibit potential therapeutic activity through the modulation of different pathways including the activation of apoptosis and senescence, the block of cell proliferation, and the inhibition of epithelial mesenchymal transition and metastatization. AVAs are promising chemopreventive and anticancer phytochemicals, which need further clinical trials and toxicological studies to define their efficacy in preventing and reducing the burden of cancer diseases
Janus kinase inhibitors and coronavirus disease (Covid)‐19: Rationale, clinical evidence and safety issues
Full text linkWe are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID‐19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID‐19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti‐inflammatory and anti‐viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID‐19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID‐19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID‐19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered
Marine anthraquinones: Pharmacological and toxicological issues
Full text linkThe marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncount-able kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the an-ticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area
Anticancer potential of allicin: A review
Full text linkPhytochemicals have attracted attention in the oncological field because they are biologically friendly and have relevant pharmacological activities. Thanks to the intense and unique spicy aroma, garlic is one of the most used plants for cooking. Its consumption is correlated to health beneficial effects towards several chronic diseases, such as cancer, mainly attributable to allicin, a bioactive sulfur compound stored in different plant parts in a precursor form. The objective of this review is to present and critically discuss the chemistry and biosynthesis of allicin, its pharmacokinetic profile, its anticancer mechanisms and molecular targets, and its selectivity towards tumor cells. The research carried out so far revealed that allicin suppresses the growth of different types of tumors. In particular, it targets many signaling pathways associated with cancer development. Future research directions are also outlined to further characterize this promising natural product
Sulforaphane Potentiates Anticancer Effects of Doxorubicin and Cisplatin and Mitigates Their Toxic Effects
Full text linkThe success of cancer therapy is often compromised by the narrow therapeutic index of many anticancer drugs and the occurrence of drug resistance. The association of anticancer therapies with natural compounds is an emerging strategy to improve the pharmaco-toxicological profile of cancer chemotherapy. Sulforaphane, a phytochemical found in cruciferous vegetables, targets multiple pathways involved in cancer development, as recorded in different cancers such as breast, brain, blood, colon, lung, prostate, and so forth. As examples to make the potentialities of the association chemotherapy raise, here we highlight and critically analyze the information available for two associations, each composed by a paradigmatic anticancer drug (cisplatin or doxorubicin) and sulforaphane
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