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The diagnosis of thyroid cancer (TC) has increased dramatically in recent years. Papillary TC is the most frequent type and has shown a good prognosis. Conventional treatments for TC are surgery, hormonal therapy, radioactive iodine, chemotherapy, and targeted therapy. However, resistance to treatments is well documented in almost 20% of all cases. Genomic sequencing has provided valuable information to help identify variants that hinder the success of chemotherapy as well as to determine which of those represent potentially druggable targets. There is a plethora of targeted therapies for cancer, most of them directed toward point mutations; however, chromosomal rearrangements that generate fusion genes are becoming relevant in cancer but have been less explored in TC. Therefore, it is relevant to identify new potential inhibitors for genes that are recurrent in the formation of gene fusions. In this review, we focus on describing potentially druggable variants and propose both point variants and fusion genes as targets for drug repositioning in TC.
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Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and has the worst prognosis. In patients with TNBC tumors, the tumor cells have been reported to have mesenchymal features, which help them migrate and invade. Various studies on cancer have revealed the importance of microRNAs (miRNAs) in different biological processes of the cell in that aberrations, in their expression, lead to alterations and deregulations in said processes, giving rise to tumor progression and aggression. In the present work, we determined the miRNAs that are deregulated in the epithelial-mesenchymal transition process in breast cancer. We discovered that 25 miRNAs that regulate mesenchymal genes are overexpressed in patients with TNBC. We found that miRNA targets modulate different processes and pathways, such as apoptosis, FoxO signaling pathways, and Hippo. We also found that the expression level of miR-934 is specific to the molecular subtype of the triple-negative breast cancer and modulates a set of related epithelial-mesenchymal genes. We determined that miR-934 inhibition in TNBC cell lines inhibits the migratory abilities of tumor cells.
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MicroARNs , Neoplasias de la Mama Triple Negativas , Humanos , Línea Celular Tumoral , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Transducción de Señal , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patologíaRESUMEN
Breast cancer is the most common cancer in women. Despite advances in diagnosis and prognosis, distal metastases occur in these patients in up to 15% of cases within 3 years of diagnosis. The main organs in which BC metastasises are the bones, lungs, liver, and brain. Unfortunately, 90% of metastatic patients will die, making this an incurable disease. Researchers are therefore seeking biomarkers for diagnosis and metastasis in different organs. Optimally, such biomarkers should be easy to detect using, preferably, non-invasive methods, such as using miRNA molecules, which are small molecules of about 22 nt that have as their main function the post-transcriptional regulation of genes. Furthermore, due to their uncomplicated detection and reproducibility in the laboratory, they are a tool of complementary interest for diagnosis, prognosis, and treatment. With this in mind, in this review, we focus on describing the most current studies that propose using miRNA independently as a potential biomarker for the diagnosis and prediction of brain, lung, liver, and bone metastases, as well as to open a window of opportunity to deepen this area of study to eventually use miRNAs molecules in clinical practice for the benefit of BC patients.
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Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , Neoplasias de la Mama/patología , Reproducibilidad de los Resultados , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Because cancer is a multifactorial disease, it is difficult to identify the specific agents responsible for the disease's progression and development, but lifestyle and diet have been shown to play a significant role. Diverse natural compounds are demonstrating efficacy in the development of novel cancer therapies, including sulforaphane (1-isothiocyanate-4-(methylsulfinyl)butane), a compound found in broccoli and other cruciferous vegetables that promotes key biological processes such as apoptosis, cell cycle arrest, autophagy, and suppression of key signalling pathways such as the PI3K/AKT/mTOR pathway in breast cancer cells. However, one of the primary challenges with sulforaphane treatment is its low solubility in water and oral bioavailability. As a consequence, several investigations were conducted using this component complexed in nanoparticles, which resulted in superior outcomes when combined with chemotherapy drugs. In this study, we discuss the properties and benefits of sulforaphane in cancer therapy, as well as its ability to form complexes with nanomolecules and chemotherapeutic agents that synergize the antitumour response in breast cancer cells.
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Anticarcinógenos , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt , Fosfatidilinositol 3-Quinasas , Nanomedicina , Tiocianatos , Isotiocianatos/farmacología , Isotiocianatos/uso terapéutico , Serina-Treonina Quinasas TOR , Butanos , AguaRESUMEN
Resveratrol and quercetin are natural compounds contained in many foods and beverages. Reports indicate implications for the health of the general population; on the other hand the use of both compounds has interesting results for the treatment of many diseases as cardiovascular affections, diabetes, Alzheimer's disease, viral and bacterial infections among others. Based on their capacities described as anti-inflammatory, antioxidant, and anti-aging, resveratrol and quercetin showed antiproliferative and anticancer activity specifically in maligned cells. These molecular characteristics trigger the pharmacological repurposing of both compounds and improved its research for treating different cancer types with interesting results at in vitro, in vivo, and clinical trial studies. Meanwhile, the development of different systems of drug release in specific sites as nanomaterials and specifically the nanoparticles, potentiates the personal treatment perspective in conjunct with the actual cancer therapies; regularly invasive and aggressive, the perspective of nanomedicine as higher effective and lower invasive has gained popularity. Knowledge of molecular interactions of resveratrol and quercetin in diseases confirms the evidence of multiple benefits, while the multiple analyses suggested a positive response for the treatment and diagnostics of cancer in different stages, including at metastatic stage. The present work reviews the reports related to the impact of resveratrol and quercetin in cancer treatment and its effects when the antioxidants are encapsulated in different nanoparticle systems, which improve the prospects of cancer treatment.
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Carbon nanotubes (CNTs) are used as carriers in medicine due to their ability to be functionalized with chemical substances. However, cytotoxicity analysis is required prior to use for in vivo models. The aim of this study was to evaluate the cytotoxic effect of CNTs functionalized with a 46 kDa surface protein from Entamoeba histolytica (P46-CNTs) on J774A macrophages. With this purpose, CNTs were synthesized by spray pyrolysis and purified (P-CNTs) using sonication for 48 h. A 46 kDa protein, with a 4.6-5.4 pI range, was isolated from E. histolytica HM1:IMSS strain trophozoites using an OFFGEL system. The P-CNTs were functionalized with the purified 46 kDa protein, classified according to their degree of functionalization, and characterized by Raman and Infrared spectroscopy. In vitro cytotoxicity was evaluated by MTT, apoptosis, and morphological assays. The results demonstrated that P46-CNTs exhibited cytotoxicity dependent upon the functionalized grade. Contrary to what was expected, P46-CNTs with a high grade of functionalization were more toxic to J774 macrophages than P46-CNTs with a low grade of functionalization, than P-CNTs, and had a similar level of toxicity as UP-CNT. This suggests that the nature of the functionalized protein plays a key role in the cytotoxicity of these nanoparticles.