RESUMO
BACKGROUND: Breast cancer (BC) is the most prevalent cancer in women, with increasing incidence and death rates in recent years. Disruptions of different signaling pathways partially cause breast cancer. Hence, different genes through particular pathways are involved in BC tumorigenesis. METHODS: In this study, we evaluated the expression level of GLIS2 and CCND1 genes in 50 patients. Also, in-silico analyses were used to enrich related signaling pathways involving the mentioned genes. RESULTS: The results showed an increased expression level of Cyclin D1 and decreased expression level of GLIS2 in BC patients. Moreover, a relationship between aberrant expression levels of GLIS2 and CCND1 and BC development was determined. CONCLUSION: These observations could help uncover new therapeutic targets for treating patients with BC in the progressive stage.
Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Ciclina D1/genética , Ciclina D1/metabolismo , Amplificação de GenesRESUMO
Background and Objectives: Phytotherapeutically, various herbal remedies, such as St. John's wort oil, have been introduced as wound care options. Recently, Neem oil has been considered a herbal option for the management of superficial wounds. Wound care is a complex process that involves several factors including the patient, caregiver, and medications. Herbal combinations could be an alternative to the chemical counterparts in the wound care area. This report includes an investigation of the possible supportive impacts of the St. John's wort and Neem oil containing ointment (W Cura G Plus ®) in the management of pressure ulcers (PUs) in three intensive care unit (ICU) patients. Materials and Methods: The ointment was administered to individuals once daily for 42 consecutive days. The status of individuals was macroscopically monitored by measuring the PU area and histopathological assessment of the tissue sections taken on the first and last days of wound treatment. Results: The outcomes of the macroscopic and histopathological techniques exhibited that St. John's wort and Neem oil containing ointment provided a remarkable supportive impact on the patients that suffered from PUs in the ICUs. Conclusions: The combination of St. John's wort and Neem oil could be suggested as an efficient active phytoconstituent for the management of PUs. The herbal ointments may be suggested as an alternative for the patients that have PUs in the ICUs.
Assuntos
Hypericum , Úlcera por Pressão , Humanos , Úlcera por Pressão/tratamento farmacológico , Pomadas/uso terapêutico , Unidades de Terapia Intensiva , Supuração/tratamento farmacológico , Extratos Vegetais/uso terapêuticoRESUMO
Nervous system disorders are one of the common problems that affect many people around the world every year. Regarding the beneficial effects of the probiotics on the gut and the gut-brain axis, their application along with current medications has been the subject of intense interest. Psychobiotics are a probiotic strain capable to affect the gut-brain axis. The effective role of Psychobiotics in several neurological disorders is documented. Consumption of the Psychobiotics containing nutrients has positive effects on the improvement of microbiota as well as alleviation of some symptoms of central nervous system (CNS) disorders. In the present study, the effects of probiotic strains on some CNS disorders in terms of controlling the disease symptoms were reviewed. Finding suggests that Psychobiotics can efficiently alleviate the symptoms of several CNS disorders such as autism spectrum disorders, Parkinson's disease, multiple sclerosis, insomnia, depression, diabetic neuropathy, and anorexia nervosa. It can be concluded that functional foods containing psychotropic strains can help to improve mental health.
Assuntos
Doenças do Sistema Nervoso Central , Microbioma Gastrointestinal , Microbiota , Probióticos , Encéfalo , Eixo Encéfalo-Intestino , Humanos , Microbiota/fisiologia , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
ß-Arrestins (ßArrs) are intracellular signal regulating proteins. Their expression level varies in some cancers and they have a significant impact on cancer cell function. In general, the significance of ßArrs in cancer research comes from studies examining GPCR signalling. Given the diversity of different GPCR signals in cancer cell regulation, contradictory results are inevitable regarding the role of ßArrs. Our approach examines the direct influence of ßArrs on cellular function and gene expression profiles by changing their expression levels in breast cancer cells, MDA-MB-231 and MDA-MB-468. Reducing expression of ßArr1 or ßArr2 tended to increase cell proliferation and invasion whereas increasing their expression levels inhibited them. The overexpression of ßArrs caused cell cycle S-phase arrest and differential expression of cell cycle genes, CDC45, BUB1, CCNB1, CCNB2, CDKN2C and reduced HER3, IGF-1R, and Snail. Regarding to the clinical relevance of our results, low expression levels of ßArr1 were inversely correlated with CDC45, BUB1, CCNB1, and CCNB2 genes compared to normal tissue samples while positively correlated with poorer prognosis in breast tumours. These results indicate that ßArr1 and ßArr2 are significantly involved in cell cycle and anticancer signalling pathways through their influence on cell cycle genes and HER3, IGF-1R, and Snail in TNBC cells.
Assuntos
Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , beta-Arrestinas/genética , Arrestinas/genética , Arrestinas/metabolismo , Ciclo Celular/genética , Pontos de Checagem do Ciclo Celular , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Transdução de Sinais , beta-Arrestinas/metabolismoRESUMO
Cetuximab is a monoclonal antibody developed to inhibit the binding of growth factors and the subsequent activation of epidermal growth factor receptor (EGFR). Triplenegative breast cancer (TNBC) is resistant to cetuximab treatment. The aim of the present study was to examine the partial agonistic properties of cetuximab, which not only blocks ligand binding, but also partially triggers EGFR activation, which may lead to cetuximab resistance in TNBC. The phosphorylation of growth factor receptors and their signalling pathways were evaluated by determining the phosphorylation of EGFR, insulinlike growth factor receptor (IGF1R), vascular endothelial growth factor receptor (VEGFR)2, Src kinase, phosphoinositide3kinase (PI3K), extracellular signalregulated kinase (ERK1/2) and serine/threoninespecific protein kinase (Akt) and the degradation of EGFR, and by assessing the morphology and proliferation of MDAMB231 and MDAMB468 cells. Cetuximab treatment led to the phosphorylation of EGFR, VEGFR2, IGF1R and downstream signalling molecules, Src kinase and PI3K in these cells, as well as Akt in the MDAMB231 cells. The cetuximabmediated phosphorylation of IGF1R, VEGFR2 and Akt was inhibited by the EGFR kinase inhibitor, AG1478, and the Src kinase inhibitor, PP2. Cetuximab treatment led to the degradation of EGFR. The cetuximabinduced phosphorylation and EGFR degradation were less prominent compared with those induced by EGF. Cetuximab partially inhibited EGFmediated responses. Cetuximab, similar with EGF, altered cellular morphology in a serumfree medium. In both cell lines, the Src kinase inhibitor enhanced the cetuximabinduced antiproliferative response. These results indicate that cetuximab exerts a partial agonistic effect on EGFR, which activates Src kinase and subsequently transactivates IGF1R and VEGFR2. This partial agonistic property is likely one of the mechanisms underlying the resistance of TNBC to cetuximab.
Assuntos
Cetuximab/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Mama Triplo Negativas/metabolismo , Quinases da Família src/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB/agonistas , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fosforilação/efeitos dos fármacos , Receptor IGF Tipo 1 , Receptores de Somatomedina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Triple negative breast cancer cell lines express high levels of ß2-adrenergic receptor, which have a significant influence on the activity of extracellular signalregulated kinase (ERK)1/2. Therefore, it is important to understand the link between ß2adrenergic receptor signaling and ERK1/2 activity in terms of cancer cell regulation and cancer progression. Although the molecular mechanisms are not completely clarified, ß2adrenergic receptor stimulation appears to reduce the basal levels of phosphorylated (p)ERK1/2 in MDAMB231 breast cancer cells. The aim of the current study was to determine the mechanism of ß2adrenergic receptormediated ERK1/2 dephosphorylation by investigating the role of dualspecificity phosphatase (DUSP)1/6 and protein phosphatase (PP)1/2, which are established regulators of ERK1/2 phosphorylation, in MDAMB231 and MDAMB468 breast cancer cell lines. (E)2benzylidene3(cyclohexylâamino)2,3 dihydro1Hinden1one (BCI) and calyculin A were employed as DUSP1/6 and PP1/PP2 inhibitors, respectively. Subsequently, the protein levels of DUSP1, PP1, pPP1, ERK1/2 and pERK1/2 were measured by western blot analysis. Cells were transfected with DUSP1 small interfering (si)RNA or PP1 siRNA to inhibit their expression. The results demonstrated that ß2adrenergic receptor agonists led to the dephosphorylation of basal pERK1/2 in MDAMB231 and MDAMB468 cells. The DUSP1/6 inhibitor, BCI, and the PP1/PP2 inhibitor, calyculin A, antagonized the ß2adrenergic receptormediated dephosphorylation of ERK1/2. Furthermore, ß2adrenergic receptor stimulation increased the protein expression level of DUSP1, with no effects on DUSP6, PP1 and PP2 expression, and enhanced the expression of the active form of PP1. Downregulation of the expression of DUSP1 or PP1 led to a decline in the ß2adrenergic receptormediated dephosphorylation of ERK1/2. The results of the present study indicate that ß2adrenergic receptormediated dephosphorylation of ERK1/2 may be associated with the activity of DUSP1 and PP1 in MDAMB231 and MDAMB468 triple negative breast cancer cell lines. The clinical importance of ß2adrenergic receptormediated inactivation of ERK1/2 as well as the activation of DUSP1 and PP1 should be carefully evaluated in future studies, particularly when ß2adrenergic blockers are used in patients with triple negative breast cancer.