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Biomarkers, including proteins, nucleic acids, antibodies, and peptides, are essential for identifying diseases such as cancer and differentiating between healthy and abnormal cells in patients. To date, studies have shown that cancer stem cells have DNA repair mechanisms that deter the effects of medicinal treatment. Experiments with cell cultures and chemotherapy treatments of these cultures have revealed the presence of small cells, with a small amount of cytoplasm that can be intensively stained with azure eosin, called microcells. Microcells develop during sporosis from a damaged tumor macrocell. After anticancer therapy in tumor cells, a defective macrocell may produce one or more microcells. This study aims to characterize microcell morphology in melanoma cell lines. In this investigation, we characterized the population of cancer cell microcells after applying paclitaxel treatment to a Sk-Mel-28 melanoma cell line using immunocytochemical cell marker detection and fluorescent microscopy. Paclitaxel-treated cancer cells show stronger expression of stem-associated ALDH2, SOX2, and Nanog markers than untreated cells. The proliferation of nuclear antigens in cells and the synthesis of RNA in microcells indicate cell self-defense, promoting resistance to applied therapy. These findings improve our understanding of microcell behavior in melanoma, potentially informing future strategies to counteract drug resistance in cancer treatment.
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The aim of the study was to clarify correlations between body mass index (BMI), blood pressure (BP), and serum levels of cytokines in female migraine patients. A total of 14 migraineurs with aura, and 12 without aura during their interictal period were compared with 25 controls. Interleukin-8 (IL-8), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), matrix metalloproteinase-9 (MMP-9), interferon gamma (IFN-γ), monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), and plasminogen activator inhibitor-1 (PAI-1) were measured. Migraineurs have elevated levels of IL-8, but decreased serum levels of PAI-1 and sICAM-1 during the interictal period, regardless of aura. BMI correlates with BP, and also with IFN-γ and MMP-9 only in patients with aura. There are three correlations in migraine patients with aura that are absent in patients without aura: between IL-8 and PAI-1; MMP-9 and IL-8; and IL-8 and sICAM-1. Migraineurs without aura, on the other hand, have correlations that patients with aura do not have (between PAI-1 and MCP-1, sICAM-1; between MMP-9 and sICAM-1, MCP-1; between TGF-α and PAI-1, MMP-9, sICAM-1; between sICAM-1 and MMP-9, PAI-1, MCP-1; as well as between sVCAM-1 and MCP-1). PAI-1, TGF, and MMP-9 could be used as biomarkers to distinguish migraineurs from healthy individuals.
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BACKGROUND: Cancer remains one of the leading causes of death worldwide, despite the possibilities to detect early onset of the most common cancer types. The search for the optimal therapy is complicated by the cancer diversity within tumors and the unsynchronized development of cancerous cells. Therefore, it is necessary to characterize cancer cell populations after treatment has been applied, because cancer recurrence is not rare. In our research, we concentrated on small cancer cell subpopulation (microcells) that has a potential to be cancer resistance source. Previously made experiments has shown that these cells in small numbers form in specific circumstances after anticancer treatment. METHODS: In experiments described in this research, the anticancer agents' paclitaxel and doxorubicin were used to stimulate the induction of microcells in fibroblast, cervix adenocarcinoma, and melanoma cell lines. Mainly for the formation of microcells in melanoma cells. The drug-stimulated cells were then characterized in terms of their formation efficiency, morphology, and metabolic activity. RESULTS: We observed the development of cancer microcells and green fluorescent protein (GFP) transfection efficiency after stress. In the time-lapse experiment, we observed microcell formation through a renewal process and GFP expression in the microcells. Additionally, the microcells were viable after anticancer treatment, as indicated by the nicotinamide adenine dinucleotide hydrogen phosphate (NADPH) enzyme activity assay results. Taken together, these findings indicate that cancer microcells are viable and capable of resisting the stress induced by anticancer drugs, and these cells are prone to chemical substance uptake from the environment. CONCLUSION: Microcells are not only common to a specific cancer type, but can be found in any tumor type. This study could help to understand cancer emergence and recurrence. The appearance of microcells in the studied cancer cell population could be an indicator of the individual anticancer therapy effectiveness and patient survival.
Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Recuento de Células , Línea Celular Tumoral , Núcleo Celular/ultraestructura , Autorrenovación de las Células , Supervivencia Celular/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Doxorrubicina/farmacología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Femenino , Fibroblastos/efectos de los fármacos , Proteínas Fluorescentes Verdes/metabolismo , Células HeLa , Humanos , Indicadores y Reactivos/farmacocinética , Melanoma/metabolismo , Melanoma/patología , Microscopía Electrónica , NADP/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Neoplasias/metabolismo , Neoplasias/ultraestructura , Rojo Neutro/farmacocinética , Paclitaxel/farmacología , Estrés Fisiológico , Imagen de Lapso de Tiempo , Factores de Transcripción/metabolismo , Transfección , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: There are many pathophysiological mechanisms underlying reciprocal relationships between changes in cytokines and insulin resistance in metabolic and cardiovascular disorders. The aim of this study was to evaluate alterations in soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), matrix metalloproteinase-9 (MMP-9), plasminogen activator inhibitor-1 (PAI-1), and myeloperoxidase (MPO) levels, and their relation to insulin resistance in coronary artery disease (CAD) patients with stable and unstable angina (SAP, UAP). METHODS: Non-diabetic CAD patients were classified into two groups: 22 patients with SAP and 22 patients with UAP. 22 healthy subjects were selected as controls. The study groups were matched for age and sex. Insulin resistance was evaluated by HOMA-IR method. Serum levels of sICAM-1, sVCAM-1, sE-selectin PAI-1(total), MPO and MMP-9 were quantified by xMAP technology (Luminex-200 analyzer). RESULTS: Both patient groups demonstrated significantly elevated serum levels of sICAM-1, sE-selectin, PAI-1(total), MPO and MMP-9 (p<0.05) as well as higher IR-HOMA values (p<0.05) than those of healthy controls. The elevation was more pronounced in the UAP group (p<0.01). HOMA-IR was correlated with sICAM-1, PAI-1(total), and MMP-9 (p<0.01). CONCLUSION: Our findings show that CAD patients have elevated HOMA-IR values. Furthermore, CAD patients with UAP have higher levels of sICAM-1, sVCAM-1, sE-selectin, MMP-9, PAI-1(total), and MPO than patients with SAP, and there are relationships between three of the above biomarkers: sICAM-1, PAI-1(total), MMP-9 and HOMA-IR.
Asunto(s)
Angina de Pecho/sangre , Moléculas de Adhesión Celular/sangre , Enfermedad de la Arteria Coronaria/sangre , Metaloproteinasa 9 de la Matriz/sangre , Peroxidasa/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Anciano , Angina de Pecho/complicaciones , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither. METHODS: CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology. RESULTS: Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01). CONCLUSION: Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.