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Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.
Assuntos
Nanomedicina , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Compreensão , Recidiva Local de Neoplasia , Transdução de Sinais , Inflamação/tratamento farmacológicoRESUMO
Head and neck squamous cell carcinoma (HNSCC) is among the most common cancer worldwide, accounting for hundreds thousands deaths annually. Unfortunately, most patients are diagnosed in an advanced stage and only a percentage respond favorably to therapies. To help fill this gap, we hereby propose a retrospective in silico study to shed light on gene-miRNA interactions driving the development of HNSCC. Moreover, to identify topological biomarkers as a source for designing new drugs. To achieve this, gene and miRNA profiles from patients and controls are holistically reevaluated using protein-protein interaction (PPI) and bipartite miRNA-target networks. Cytoskeletal remodeling, extracellular matrix (ECM), immune system, proteolysis, and energy metabolism have emerged as major functional modules involved in the pathogenesis of HNSCC. Of note, the landscape of our findings depicts a concerted molecular action in activating genes promoting cell cycle and proliferation, and inactivating those suppressive. In this scenario, genes, including VEGFA, EMP1, PPL, KRAS, MET, TP53, MMPs and HOXs, and miRNAs, including mir-6728 and mir-99a, emerge as key players in the molecular interactions driving HNSCC tumorigenesis. Despite the heterogeneity characterizing these HNSCC subtypes, and the limitations of a study pointing to relationships that could be context dependent, the overlap with previously published studies is encouraging. Hence, it supports further investigation for key molecules, both those already and not correlated to HNSCC.
RESUMO
In silico docking studies serve as a swift and efficient means to sift through a vast array of natural and synthetic small molecules, aiding in the identification of potential inhibitors for cancer biomarkers. One such biomarker, ceruloplasmin (CP), has been implicated in various tumor types due to its overexpression, earning it recognition as a marker of aggressive tumors. This study focused on pinpointing inhibitors for the CP -Myeloperoxidase (MPO) interaction site, a complex formation known to impede HOCl production, a crucial process for inducing apoptotic cell death in tumor cells. The initial phase of our investigation involved in silico docking studies, which screened a diverse library of phytochemicals and marine compounds. Through this process, we identified several promising drug candidates based on their binding affinities. Subsequently, these candidates underwent rigorous filtration based on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties. Finally, we subjected the selected compounds to molecular dynamics (MDs) simulation to further assess their viability. Lycoperoside F, a steroidal alkaloid glycoside derived from tomatoes (Lycopersicon esculentum), stood out with notable interactions at the binding site. Another noteworthy compound was Xyloglucan (XG) oligosaccharides, predominantly found in the primary cell walls of higher plants. During the subsequent MDs simulations, these interactions were accompanied by highly stable root mean square deviation (RMSD) plots, signifying the consistency and robustness of the observed MDs behavior. XG oligosaccharides demonstrated the highest binding affinity with CP, reaffirming their potential as strong candidates. Additionally, Ardimerin digallate, known as a retroviral ribonuclease H inhibitor for HIV-1 and HIV-2, displayed favorable interactions at the MPO interaction site. Given that promising drug candidates must meet stringent criteria, including non-toxicity, effectiveness, specificity, stability and potency, these phytochemicals have the potential to progress to in vitro studies as CP inhibitors. Ultimately, this could contribute to the suppression of tumor growth, marking a significant step in cancer treatment research.Communicated by Ramaswamy H. Sarma.
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Quercetin is a naturally occurring bioactive flavonoid abundant in many plants and fruits. Quercetin and its derivatives have shown an array of pharmacological activities in preclinical tests against various illnesses and ailments. Owing to its protective role against oxidative stress and neuroinflammation, quercetin is a possible therapeutic choice for the treatment of neurological disorders. Quercetin and its derivatives can modulate a variety of signal transductions, including neuroreceptor, neuroinflammatory receptor, and redox signaling events. The research on quercetin and its derivatives in neurology-related illnesses mainly focused on the targets, such as redox stress, neuroinflammation, and signaling pathways; however, the function of quercetin and its derivatives on specific molecular targets, such as nuclear receptors and proinflammatory mediators are yet to be explored. Findings showed that various molecular targets of quercetin and its derivatives have therapeutic potential against psychological and neurodegenerative disorders.
Assuntos
Transtornos Mentais , Doenças Neurodegenerativas , Humanos , Quercetina/farmacologia , Quercetina/uso terapêutico , Doenças Neuroinflamatórias , Antioxidantes , Transtornos Mentais/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológicoRESUMO
Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases.
Assuntos
Pneumopatias , Nanopartículas , Humanos , Nanomedicina/métodos , Sistemas de Liberação de Medicamentos/métodos , Nanotecnologia/métodos , Preparações Farmacêuticas , Pulmão , Pneumopatias/tratamento farmacológicoRESUMO
Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro- and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer.