RESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most common cancers with high morbidity and mortality worldwide. Long non-coding RNAs (lncRNAs) serve as tumor promoters or suppressors in the development of various human malignancies, including LUAD. Although long intergenic non-protein coding RNA 1089 (LINC01089) suppresses the progression of breast cancer, its mechanism in LUAD requires further exploration. Thus, we aimed to investigate the underlying function and mechanism of LINC01089 in LUAD. METHODS: The expression of LINC01089 in LUAD and normal cell lines was detected. Functional assays were applied to measure cell proliferation, apoptosis and migration. Besides, mechanism experiments were employed for assessing the interplay among LINC01089, miR-301b-3p and StAR related lipid transfer domain containing 13 (STARD13). Data achieved in this study was statistically analyzed with Student's t test or one-way analysis of variance. RESULTS: LINC01089 expression was significantly down-regulated in LUAD tissues and cells and its overexpression could reduce cell proliferation and migration. Moreover, LINC01089 could regulate STARD13 expression through competitively binding to miR-301b-3p in LUAD. Additionally, rescue assays uncovered that STARD13 depletion or miR-301b-3p overexpression could countervail the restraining effect of LINC01089 knockdown on the phenotypes of LUAD cells. CONCLUSION: LINC01089 served as a tumor-inhibitor in LUAD by targeting miR-301b-3p/STARD13 axis, providing an innovative insight into LUAD therapies. Trial registration Not applicable.
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Adenocarcinoma del Pulmón/etiología , Proteínas Activadoras de GTPasa/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Proteínas Supresoras de Tumor/genética , Adenocarcinoma del Pulmón/patología , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular/genética , Proteínas Activadoras de GTPasa/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Objectives: To analyze the effects of deep hyperthermia combined with intraperitoneal chemotherapy on liver-kidney function, immune function, and long-term survival in patients with abdominal metastases. Methods: A total of 88 patients with abdominal metastases confirmed in the hospital were enrolled as the research objects between August 2018 and August 2021. They were randomly divided into control group (n = 44) and observation group (n = 44). The control group was treated with intraperitoneal chemotherapy, while observation group was additionally treated with deep hyperthermia. The general clinical data of patients were recorded. The short-term and long-term curative effects were evaluated. The occurrence of side effects in both groups was recorded. Before and after treatment, levels of alanine transaminase (ALT) and aspartate transaminase (AST) were detected by full-automatic biochemical analyzer. The level of blood urea nitrogen (BUN) was detected by the urease electrode method. The level of serum creatinine (Scr) was detected by the picric acid method. The levels of CD3 +, CD4 +, CD8 +, and NK cells were detected by BD FACSCalibur flow cytometer. Results: There was no significant difference in clinical data between the two groups (P > 0.05). In the observation group, ORR was significantly higher than that in the control group (54.55% vs 29.55%) (P < 0.05), OS was significantly longer than that in the control group (P < 0.05), and median survival time and mPFS were longer than those in the control group. After treatment, the levels of ALT, AST, BUN, and Scr were significantly increased in the control group (P < 0.05), but there was no significant difference in peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio or count of NK cells before and after treatment (P > 0.05). Before and after treatment, there was no significant difference in the levels of ALT, AST, BUN, and Scr in the observation group (P > 0.05). After treatment, peripheral blood CD3 +, CD4 +, and CD4 +/CD8 + ratio and count of NK cells were all increased in the observation group, significantly higher than those in the control group (P < 0.05). The incidence of chemotherapy side effects in the observation group was significantly lower than that in the control group (P < 0.05). Conclusion: The short-term and long-term curative effects of deep hyperthermia combined with intraperitoneal chemotherapy are good on patients with intraperitoneal metastases, with less damage to liver-kidney function. It is beneficial to enhance immune function of patients, with mild side effects.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) are standard therapies for patients with advanced lung adenocarcinoma and significantly improve treatment outcomes. The effect of tobacco smoking on the response of immune checkpoint inhibitors is somewhat diverging. Here, we assessed the impact of tobacco exposure on the tumor microenvironment and developed a feasible tool for predicting prognosis. METHODS: Whole exon sequence data and the corresponding clinical information were downloaded from the Cancer Genome Atlas. The signature was developed by the Random Forest algorithm. CIBERSORTx online tool was used to estimate immune infiltration. Functional assays were performed to assess the roles of tobacco exposure in cancer cells. Immunohistochemistry (IHC) was performed to identify and validate the immune activation status. RESULTS: The TMB of lifelong non-smoker, current reformed smoker for over 15 years, current reformed smoker<15 years and current smoker had a significantly increasing trend in LUAD patients. In vitro tobacco exposure promoted the expression of PD-L1 and malignant phenotype of LUAD cells. In addition, patients with high Random Forest score (RFscore) had a poorer prognosis than those with low RFscore. The ROC curve analysis of RFscore revealed a promising prognostic capability. Memory activated CD4 + T cells, CD8 + t cells and memory B cells were noticeably enriched in the high RFscore group and PDCD1 appreciably upregulated in the high RFscore group as well. Furthermore, IHC results suggested that patients with high RFscore remained an immune activation status, indicating a positive correlation between RFscore and patient's immune status. CONCLUSION: Our analysis provides further insight into the profound impacts of tobacco exposure on tumor immune microenvironment and envisions integrative predictive models of RFscore, predicting the prognosis of smoking lung adenocarcinoma, which might help to understand the potential mechanism of smoking exposure on tumor immune microenvironment.
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Adenocarcinoma/inmunología , Subgrupos de Linfocitos B/inmunología , Neoplasias Pulmonares/inmunología , Linfocitos T/inmunología , Fumar Tabaco/efectos adversos , Células A549 , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidad , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Biología Computacional , Conjuntos de Datos como Asunto , Regulación Neoplásica de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Memoria Inmunológica , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/mortalidad , Modelos Estadísticos , Pronóstico , Proteómica , Análisis de Supervivencia , Microambiente TumoralRESUMEN
The molecular mechanism responsible for Helicobacter pylori infection-mediated gastritis and carcinogenesis is not yet clear. Increased evidence suggests that chronic gastritis and elevated gastric epithelial cell (GEC) apoptosis are crucial events during stomach carcinoma transformation. PUMA is a potent proapoptotic Bcl-2 protein and mediates acute tissue injury. In this study, we aimed to investigate the role of PUMA in GEC apoptosis and inflammation induced by H. pylori infection. As a result, we found that PUMA expression was elevated in gastritis tissues compared with uninvolved tissues, and it was correlated with the severity of apoptosis and gastritis. In mice, PUMA mRNA and protein were markedly induced in GECs upon induction of gastritis by H. pylori. PUMA-deficient mice were highly resistant to apoptosis and gastritis induced by H. pylori. Furthermore, the transcription factor NF-κB p65 binds to PUMA promoter to activate PUMA transcription after H. pylori infection. In addition, NF-κB inhibitor could rescue H. pylori-induced apoptosis and gastritis. Finally, H. pylori-induced activation of p-p65 and PUMA was mediated via Toll-like receptor 2 (TLR2) and blocked in TLR2 knockout mice. Taken together, these results verified the pro-inflammatory effect of PUMA in H. pylori-infected gastric tissue. Moreover, TLR2/NF-κB-mediated transcriptional regulation of PUMA contributes to the pathogenesis of H. pylori-infected gastritis.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis , Células Epiteliales/metabolismo , Mucosa Gástrica/metabolismo , Gastritis/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/patogenicidad , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/deficiencia , Proteínas Reguladoras de la Apoptosis/genética , Línea Celular Tumoral , Modelos Animales de Enfermedad , Células Epiteliales/microbiología , Células Epiteliales/patología , Mucosa Gástrica/microbiología , Mucosa Gástrica/patología , Gastritis/genética , Gastritis/microbiología , Gastritis/patología , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Humanos , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Transducción de Señal , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/metabolismo , Proteínas Supresoras de Tumor/deficiencia , Proteínas Supresoras de Tumor/genéticaRESUMEN
Inhibition of immune checkpoint proteins (checkpoints) has become a promising anti-esophageal cancer strategy. We here tested expressions of immune checkpoints in human esophageal cancers. Our results showed the expressions of many immune checkpoints, including CD28, CD27, CD137L, programmed death 1 (PD-1), T cell immunoglobulin mucin-3 (TIM-3), T cell Ig and ITIM domain (TIGIT), CD160, cytotoxic T lymphocyte antigen 4 (CTLA-4), CD200, CD137 and CD158, were dysregulated in peripheral T cells of esophageal cancer patients. Further, the expressions of PD-1, TIM-3 and TIGIT were upregulated in tumor infiltrating lymphocytes (TILs), which might be associated with TILs exhaustion. Meanwhile, the expressions of PD-1 and TIM-3 on CD4+ T cells were closely associated with clinic pathological features of esophageal cancer patients. These results indicate that co-inhibitory receptors PD-1, TIM-3 and TIGIT may be potential therapeutic oncotargets for esophageal cancer.
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Neoplasias Esofágicas/inmunología , Sistema Inmunológico/fisiología , Linfocitos T/inmunología , Anciano , Linfocitos T CD8-positivos/inmunología , Antígeno CTLA-4/metabolismo , Estudios de Casos y Controles , Puntos de Control del Ciclo Celular , Neoplasias Esofágicas/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Humanos , Inmunoterapia , Activación de Linfocitos , Linfocitos Infiltrantes de Tumor/inmunología , Masculino , Persona de Mediana Edad , Receptor de Muerte Celular Programada 1/metabolismo , Receptores Inmunológicos/metabolismo , Regulación hacia ArribaRESUMEN
The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76.67%, respectively, all of which were significantly higher than those in the tissues adjacent to the tumor. The expression of these proteins represents the local invasion and stage. AR, MMP-2 and MMP-9 expression levels in HCC tissues have the potential to be employed as predictors of the progression of local cancer invasion and the tumor stage.