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BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.
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Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/epidemiologia , Carga Global da Doença , China/epidemiologia , Efeitos Psicossociais da Doença , Análise por Conglomerados , IncidênciaRESUMO
Genetically engineered T cells expressing a chimeric antigen receptor (CAR) have rapidly developed into a powerful and innovative therapeutic modality for cancer patients. However, the problem of dose-dependent systemic toxicity cannot be ignored. In this study, exosomes derived from mesothelin (MSLN)-targeted CAR-T cells were isolated, and we found that they maintain most characteristics of the parental T cells, including surface expression of the CARs and CD3. Furthermore, CAR-carrying exosomes significantly inhibited the growth of both endogenous and exogenous MSLN-positive triple-negative breast cancer (TNBC) cells. The expression of the effector molecules perforin and granzyme B may be a mechanism of tumor killing. More importantly, a highly effective tumor inhibition rate without obvious side effects was observed with the administration of CAR-T cell exosomes in vivo. Thus, the use of CAR-T cell exosomes has great therapeutic potential against MSLN-expressing TNBC.
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Exossomos/metabolismo , Proteínas Ligadas por GPI/metabolismo , Imunoterapia Adotiva/métodos , Animais , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Exossomos/imunologia , Feminino , Proteínas Ligadas por GPI/efeitos dos fármacos , Humanos , Imunoterapia/métodos , Masculino , Mesotelina , Camundongos , Camundongos Endogâmicos NOD , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/imunologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Background: Dendritic cells (DCs) play an essential role in the induction and regulation of immune responses, including the activation of effector T lymphocytes for the eradication of cancers. However, the tumor microenvironment (TME) often leads to DCs dysfunction due to their immature state. MicroRNA-155 (miR-155) has emerged as a typical multifunctional gene regulator associated with immune system development and immune cell activation and differentiation.Methods: In this study, a three-dimensional TME model that closely mimics the microenvironment of breast cancer was prepared. MiR-155 overexpression and control vectors were constructed using lentivirus. The relative expression of miR-155 was determined by qRT-PCR. Cell viability, antigen uptake and cell surface marker expression were analyzed by live-dead staining and flow cytometry. The migration ability of bone marrow-derived DCs (BMDCs) was qualified by transwell assay. A mixed lymphocyte culture assay was used to assess T cell-specific proliferation. Cytokine levels were determined by ELISA.Results: We found that the expression of miR-155 in DCs was inhibited by the TME. Furthermore, upregulation of miR-155 enhanced the migration ability, uptake of antigen and elevated the expression of the mature DCs markers CD80 and MHCII. More importantly, overexpression of miR-155 in DCs significantly induced T cell proliferation and IFN-γ and IL-2 secretion.Conclusion: MiR-155 is a potential molecular regulator that may improve the efficacy of DCs-based tumor immunotherapy.
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Neoplasias da Mama , MicroRNAs , Neoplasias da Mama/genética , Células Cultivadas , Células Dendríticas , Feminino , Humanos , MicroRNAs/genética , Microambiente Tumoral , Regulação para CimaRESUMO
BACKGROUND: Some evidence has revealed that marital status is an important predictor of breast cancer (BC) prognosis. However, what role marital quality plays in the effect of marital status on BC prognosis remains unclear. METHODS: We conducted a prospective cohort study of women aged 20-50 years with stage I-III BC treated in accordance with a standard treatment protocol. The following three categories of marital quality were assessed: marital satisfaction, sexual relationship, and couple communication. The log-rank test was used to compare survival. Cox proportional hazards models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) for recurrence and metastasis, BC-specific mortality, and overall mortality, adjusting for clinical variables. RESULTS: A total of 1,043 married women were initially recruited in the study. Forty-five (4.3%) patients refused to participate in this study and 141 (13.5%) were excluded from the analysis. Among 857 participants, there were 59 deaths, including 57 from BC. Multivariate Cox regression analysis showed that patients with poor marital satisfaction had significantly higher risks of recurrence and metastasis (HR 3.942, 95% CI: 1.903-8.167), BC-specific mortality (HR 3.931, 95% CI: 1.896-8.150), and overall mortality (HR 3.916, 95% CI: 1.936-7.924). Those with poor sexual relationship had significantly higher risks of recurrence and metastasis (HR 5.763, 95% CI: 3.012-11.027), BC-specific mortality (HR 5.724, 95% CI: 2.992-10.949), and overall mortality (HR 5.653, 95% CI: 2.993-10.680). CONCLUSIONS: Our results identified a subset of BC patients who have a poor prognosis, namely, those with poor marital quality. Early screening for marital quality and applying necessary social support interventions are helpful in improving the prognosis of patients with poor marital quality.
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Neoplasias da Mama , Feminino , Humanos , População do Leste Asiático , Seguimentos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
Long non-coding RNAs (lncRNA) have been reported as key regulators in the progression and metastasis of breast cancer. In this study, we found that the lncRNA myocardial infarction associated transcript (MIAT) expression was upregulated in breast cancer in The Cancer Genome Atlas (TCGA) data sets. We validated that MIAT was higher in breast cancer cell lines and advanced breast tumors than in normal controls. And MIAT overexpression associated with TNM stage and lymphnode metastasis. Knockdown MIAT inhibited breast cancer cell proliferation and promoted apoptosis. Also MIAT downregulation suppressed epithelial-mesenchymal transition (EMT) and decreased migration and invasion in MDA-MB-231 and MCF-7 breast cancer cell lines. More importantly, knockdown MIAT inhibited tumor growth in vivo. Our results suggested that MIAT acted as a competing endogenous RNA (ceRNA) to regulate the expression of dual specificity phosphatase 7 (DUSP7) by taking up miR-155-5p in breast cancer. There were positive correlation between MIAT and DUSP7 expression in breast cancer patients. We conclude that MIAT promotes breast cancer progression and functions as ceRNA to regulate DUSP7 expression by sponging miR-155-5p in breast cancer.
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The transcription factor PU.1 was previously identified as an oncogene or a tumor suppressor in different types of leukemia. The aim of the present study was to investigate the expression of PU.1 in breast cancer and to analyze its association with clinical features and prognosis. Immunohistochemistry was used to determine PU.1 expression in breast cancer tissue microarrays and paraffin-embedded sections. The association between PU.1 expression and clinicopathological factors was assessed by using chi-square test. The survival analysis of patients was conducted by using Kaplan-Meier analysis and log-rank tests. Cox regression was utilized for univariate and multivariate analyses of prognostic factors. The results indicated that the expression level of PU.1 protein in breast cancer samples was significantly higher compared with normal breast tissues (P=2.63×10-8). Furthermore, the level of PU.1 expression was detected to be positively associated with androgen receptor (P=0.027) and human epidermal growth factor receptor 2 status (P=2.03×10-21) as well as molecular subtype (P=3.51×10-11). Furthermore, patients with negative PU.1 expression had longer OR compared with those with positive PU.1 expression (P=3.67×10-4). Multivariate Cox regression analysis revealed that PU.1 expression level and tumor-node-metastasis stage were independent prognostic factors for overall survival (P=0.034 and P=0.018, respectively). Therefore, PU.1 protein expression may contribute to breast cancer progression and may be a valuable molecular marker to predict the prognosis of patients with breast cancer.