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In prior investigations, a correlation was established between patient outcomes in locally advanced non-small cell lung cancer (LA-NSCLC) following thoracic irradiation and parameters, such as pre/post-treatment neutrophil-to-lymphocyte ratio (NLR) and NLR change (ΔNLR). However, these parameters could potentially be influenced by radiation-related variables, such as gross tumor volume (GTV). The primary aim of this study was to elucidate the factors impacting post-treatment NLR and ΔNLR and to further assess their prognostic relevance. In this retrospective study, a cohort of 188 LA-NSCLC patients who underwent thoracic radiation between 2012 and 2017 was assessed. The calculation of pre/post-treatment NLR involved the use of absolute neutrophil and lymphocyte counts. ΔNLR was defined as the difference between post- and pre-treatment NLR values. To assess the relationships between various variables and overall survival (OS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS), the Kaplan-Meier technique and Cox proportional hazards regression were employed. Additionally, Spearman's rank correlation analysis was carried out to investigate correlations between the variables. The analysis revealed that both post-treatment NLR (r = 0.315, P < 0.001) and ΔNLR (r = 0.156, P = 0.032) were associated with GTV. However, OS, LPFS, and DMFS were not independently correlated with pre/post-treatment NLR. ΔNLR, on the other hand, exhibited independent associations with OS and DMFS (HR = 1.054, P = 0.020, and P = 0.046, respectively). Elevated ΔNLR values were linked to poorer OS (P = 0.023) and DMFS (P = 0.018) in the Kaplan-Meier analysis. Furthermore, when stratifying by GTV, a higher ΔNLR remained to be associated with worse OS and DMFS (P = 0.047 and P = 0.035, respectively) in the GTV ≤ 67.41 cm3 group, and in the GTV > 67.41 cm3 group (P = 0.028 and P = 0.042, respectively), highlighting ΔNLR as the sole independent predictive factor for survival and metastasis, irrespective of GTV.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfocitos , Neutrófilos , Humanos , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/sangre , Femenino , Masculino , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/sangre , Linfocitos/patología , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Anciano de 80 o más Años , Adulto , Recuento de Linfocitos , Estimación de Kaplan-MeierRESUMEN
OBJECTIVE: Brachytherapy has been indicated as an alternative option for treating cystic craniopharyngiomas (CPs). The potential benefits of brachytherapy for CPs have not yet been clarified. The purpose of this work was to conduct a meta-analysis to analyze the long-term efficacy and adverse reactions profile of brachytherapy for CPs. MATERIALS AND METHODS: The relevant databases were searched to collect the clinical trials on brachytherapy in patients with CPs. Included studies were limited to publications in full manuscript form with at least 5-year median follow-up, and adequate reporting of treatment outcomes and adverse reactions data. Stata 12.0 was used for data analysis. RESULTS: According to the inclusion and exclusion criteria, a total of 6 clinical trials involving 266 patients with CPs were included in this meta-analysis. The minimum average follow-up was 5 years. The results of the meta-analysis showed that 1-year, 2-3 years and 5 years progression free survival rates (PFS) are 75% (95%CI: 66-84%), 62% (95%CI: 52-72%) and 57% (95%CI: 22-92%), respectively. At the last follow-up, less than 16% of patients with visual outcomes worser than baseline in all included studies. While, for endocrine outcomes, less than 32% of patients worser than baseline level. CONCLUSION: In general, based on the above results, brachytherapy should be considered as a good choice for the treatment of CP.
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Braquiterapia , Craneofaringioma , Neoplasias Hipofisarias , Humanos , Braquiterapia/métodos , Braquiterapia/efectos adversos , Craneofaringioma/radioterapia , Estudios de Seguimiento , Neoplasias Hipofisarias/radioterapia , Supervivencia sin Progresión , Resultado del TratamientoRESUMEN
OBJECTIVE: The objective of this study was to investigate the safety and effectiveness of high-dose-rate brachytherapy as a treatment modality for recurrent or residual neck metastatic lymph nodes following external radiotherapy. METHODS: 38 patients with 52 metastatic lymph nodes recurring or residual after previous external radiotherapy was completed to metastatic lymph nodes in the neck were collected from January 2019 to February 2022. High-dose-rate brachytherapy with 192Ir was performed with a prescribed dose of 20-30 Gy/1f (effective biological dose of 60-120 Gy), and imaging was performed at 1, 3, and 6 months after treatment to assess the local control rate and adverse effects of treatment. RESULTS: All 38 patients received completed treatment, and they were followed up for 6 months. 52 patients with neck lymph node metastases had an objective response rate. (Complete response, CR + Partial response, PR) of 76.9%, which comprised 89.5% (34/38) for lymph nodes ≤ 3 cm and 42.9% (4/14) for > 3 cm, P = 0.028. P > 0.05 for CR + PR versus stable disease, SD + progressive disease, PD for lymph nodes between different subdivisions of the neck. Using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scoring System, there were 6 cases of acute radioskin injuries of degree I and 4 cases of degree II with a 60% symptomatic relief rate. CONCLUSIONS: High-dose-rate brachytherapy serves as a safe and effective method in treating recurrent residual neck metastatic lymph nodes in the field after external radiotherapy, exerting tolerable adverse effects.
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Objective: Prostate cancer (PCa) is one of the most common cancers in the world. The potential benefits of intensity modulated radiation therapy (IMRT) over three-dimensional conformal radiation therapy (3D-CRT) for PCa primary radiation therapy treatment have not yet been clarified. Therefore, this meta-analysis was conducted to assess whether IMRT could improve clinical outcomes in comparison with 3D-CRT in patients diagnosed with PCa. Materials and methods: Relevant studies were identified through searching related databases till December, 2022. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results: The incidence of grade 2 or worse acute adverse gastrointestinal (GI) event was analyzed and the pooled data revealed a clear decreasing trend in the IMRT compared with 3D-CRT (RR=0.62, 95% CI: 0.45-0.84, p=0.002). IMRT slightly increased the grade ≥ 2 acute genitourinary (GU) adverse event in comparison with the 3D-CRT (RR=1.10, 95% CI: 1.02-1.19, p=0.015). The IMRT and the 3D-CRT of patients showed no substantial differences in grade ≥ 2 late GI adverse event (RR =0.62, 95% CI: 0.36-1.09, p=0.1). In those included studies, there was no significant difference between IMRT and 3D-CRT in grade 2-4 late GU adverse event (RR =1.08, 95% CI: 0.77-1.51, p=0.65). There was a significant difference in biochemical control favoring IMRT (RR =1.13, 95% CI: 1.05-1.22, p=0.002). IMRT showed modest increase in biochemical control in comparison with 3D-CRT. Conclusion: In general, based on the above results, IMRT should be considered as a better choice for the treatment of PCa. More randomized controlled trials are needed to determine the subset of patients diagnosed with PCa.
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Objective: To investigate the use of 3D printing technology to customize individualized precise radiotherapy head masks for cranial radiotherapy patients. Through the comparison with thermoplastic head film, evaluate the effect of this material on deep dose attenuation and body surface dose, and evaluate its positioning accuracy and repeatability for clinical application. Methods: Thirty patients with head and neck radiotherapy were divided into the control group and the experimental group. The control group used the traditional thermoplastic head film fixation technique for body position fixation, and the experimental group used the 3D printing head film fixation technique. The patient setup was verified by kV-CBCT scanning to obtain the translational setup error and rotational setup error in the X, Y, and Z directions. Results: At a depth of 5 cm, both materials have a radiation attenuation rate of <1%. At the surface location, the body surface dose of control group increased by approximately 27%. With a 3D printing head film, the body surface dose increased by approximately 18%. The positioning of two groups of patients was verified by the kV-CBCT, and a total of 232 data sets were obtained. The average translation positioning errors in the X, Y, and Z direction of control group and experimental group were 1.29 mm, 1.42 mm, 1.38 mm and 1.16 mm, 1.24 mm, 1.16 mm, respectively. The average rotation positioning error in the X, Y, and Z direction of control group and experimental group were 1.29°, 1.02°, 1.01° and 1.08°, 0.96°, 1.00°, respectively. The translational setup errors in the Y and Z directions and rotational setup errors in the X direction significantly differed between the control and experimental groups (all p<0.05), but no statistical significance was found in the other directions (all p>0. 05). Conclusion: Compared to the traditional thermoplastic head membranes, 3D printing head membranes has shown a reliable and reproducible interactional positioning accuracy. Of course, further investigations are needed before the new technology can be used on a regular basis.
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BACKGROUNDS: It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD. METHODS: The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan-Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed. RESULTS: In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression. CONCLUSIONS: Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes.
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Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Proteína Potenciadora del Homólogo Zeste 2/genética , Pronóstico , Proteínas Proto-Oncogénicas p21(ras) , Ciclo Celular , Adenocarcinoma del Pulmón/genética , Neoplasias Pulmonares/genética , BiomarcadoresRESUMEN
The present study aims to investigate the therapeutic value of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with cranial radiotherapy (RT) in patients with EGFR-positive non-small cell lung cancer (NSCLC) and brain metastases (BMs). Methodology: This is a retrospective study that involved 213 patients with EGFR-NSCLC and BMs, with the patients divided into two groups: the upfront cranial RT (ucRT) group (n = 96) and the non-ucRT group (n = 117). All patients were administered with osimertinib, and those in the ucRT group also underwent RT. The overall survival (OS), progression-free survival (PFS) and intracranial PFS (IPFS) of the two groups were compared. Results: The ucRT group manifested a markedly higher IPFS than the non-ucRT group (29.65 months vs 21.8 months; P < 0.0001). The subgroup analysis revealed that patients with oligometastases (OLOGO-BMs; 1-3 BMs) demonstrated a notably longer OS (44.5 months vs 37.3 months; P < 0.0001), PFS (32.3 months vs 20.8 months; P = 0.6884) and IPFS (37.8 months vs 22.1 months; P < 0.0001) in the ucRT group than in the non-ucRT group. However, for patients with multiple BMs, there was no significant difference in OS (27.3 months vs 34.4 months; P = 0.0710) and PFS (13.7 months vs 13.2 months; P = 0.0516) between the ucRT group and the non-ucRT group; the ucRT group exhibited a higher IPFS (26.4 months vs 21.35 months; P = 0.0028). Cox's multivariate analysis of patients with OLOGO-BM indicated that the use of ucRT was linked to a better OS (heart rate [HR] = 0.392; 95% confidence interval [CI]: 0.178-0.863; P = 0.020) and PFS (HR = 0.558; 95% CI: 0.316-0.986; P = 0.044). Conclusion: Upfront cerebral cranial stereotactic radiosurgery can improve outcomes in EGFR-positive patients with NSCLC and OLOGO-BM. However, for patients with multiple BMs, the preferable strategy may be pre-treatment with EGFR-TKIs.
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Mesothelioma lies one of the most malignant tumors, in which the identification of the corresponding biomarkers is extremely critical. This study aims to investigate the prognostic value of enhancer homolog 2 (EZH2) mRNA expression in mesothelioma patients accompanied with its immune infiltration analysis. Gene expression, clinical information and enrichment analysis were obtained based on the Cancer Genome Atlas (TCGA), the immune infiltration analysis and bioinformatics analysis were performed. Clinical information and gene expression were obtained from 86 patients with mesothelioma based on TCGA database. Survival analysis, GSEA enrichment analysis, and immune infiltration analysis of EZH2 expression were carried out using R (version 3.6.3) (statistical analysis and visualization). The correlation of EZH2 expression with immune cell infiltration in mesothelioma was analyzed according to the TIMER database (Fig. https://cistrome.shinyapps.io/timer/ ). A univariate and multivariate analysis of general data obtained from the TCGA database was performed, involving age, gender, stage, pathological type, and whether they had received radiotherapy, the results indicated the association of high expression of EZH2 with poor prognosis in mesothelioma patients, with the worse prognosis in the High group (HR = 2.75, 95% CI 1.68-4.52, P < 0.010). Moreover, ROC curves showed that EZH2 expression predicted 1-year survival with an AUC of 0.740, 2-year survival with an AUC of 0.756, and 3-year survival with an AUC of 0.692, suggesting a robust predictive effect of EZH2 expression on prognosis. KEGG pathway analysis indicated five pathways showing the strongest positive correlation with EZH2 expression: cell cycle, DNA replication, Cell adhesion molecules cams, Primary immuno deficiency, Tsate transduction, and five pathways showing the strongest negative correlation with EZH2 expression: Glycolysis gluconeogenesis, Drug metabolism, cytochrome P450, retinol metabolism, fatty acid metabolism ribosome. We investigated the correlation between EZH2 expression and the level of immune infiltration in mesothelioma tissues. The results indicated that EZH2 expression played a critical role in immune infiltration, of which the high expression was correlated with the reduced number of NK cells, Mast cells, and Th17 cells. Moreover, mesothelioma patients with high EZH2 expression differ from those with low EZH2 expression in their tumor immune microenvironment. EZH2, as a new prognostic biomarker for mesothelioma, contributes to elucidating how changes in the immune environment promote the development of mesothelioma. Further analysis, EZH2 may serve as a biological test to predict the prognosis of mesothelioma.
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Mesotelioma Maligno , Mesotelioma , Biomarcadores de Tumor/metabolismo , Proteína Potenciadora del Homólogo Zeste 2/metabolismo , Ácidos Grasos , Humanos , Mesotelioma/genética , Pronóstico , ARN Mensajero/genética , Microambiente Tumoral , Vitamina ARESUMEN
This paper proposes a joint model by combining the time-varying coefficient susceptible-infected-removal model with the hierarchical Bayesian vector autoregression model. This model establishes the relationship between several critical macroeconomic variables and pandemic transmission states and performs economic predictions under two predefined pandemic scenarios. The empirical part of the model predicts the economic recovery of several countries severely affected by COVID-19 (e.g., the United States and India, among others). Under the proposed pandemic scenarios, economies tend to recover rather than fall into prolonged recessions. The economy recovers faster in the scenario where the COVID-19 pandemic is controlled.
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Background: Ginsenoside Rg1, a major bioactive ingredient of Panax notoginseng, has been shown to reduce gut inflammation and ameliorate experimental colitis in mice. However, it is not yet known whether it affects the intestinal barrier injury of colitis. Methods: This study explored the effect of ginsenoside Rg1 on intestinal barrier injury in dextran sulfate sodium (DSS)-induced colitis mice through an ultrastructure observation of the colonic mucosa and analysis of the expression of colonic cytoplasmatic zonula occludens-1 (ZO-1) protein. Results: Treatment with ginsenoside Rg1, especially high-dose use, significantly ameliorated colonic histopathologic features and the severity of the colitis and reduced colonic tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) levels and increase IL-4 levels in a mouse model of DSS-induced colitis. Its observed efficacy was comparable to that of 5-Aminosalicylic acid (5-ASA), a first-line therapeutic agent for ulcerative colitis. Notably, ginsenoside Rg1 administration was shown to up-regulate the expression of colonic ZO-1 protein, and it repaired the intestinal barrier structure in DSS-induced colitis mice. Conclusions: Taken together, our findings demonstrated that ginsenoside Rg1 treatment can significantly ameliorate the severity of DSS-induced colitis in mice, which involves intestinal barrier structure remodeling through lowering the levels of the colonic pro-inflammatory cytokines TNF-α and IFN-γ and increasing the anti-inflammatory cytokine IL-4. These results suggest the potential therapeutic use of ginsenoside Rg1 as a promising approach for the treatment of inflammatory bowel disease (IBD).
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Tumor microenvironment (TME) can serve as the 'soil' for the growth and survival of tumor cells and function synergically with tumor cells to mediate tumor progression and therapeutic resistance. Reactive oxygen species (ROS) is somewhat of a doubleedged sword for tumors. Accumulating evidence has reported that regulating ROS levels can serve an antitumor role in the TME, including the promotion of cancer cell apoptosis, inhibition of angiogenesis, preventing immune escape, manipulating tumor metabolic reorganization and improving drug resistance. In the present review, the potential role of ROS in antitumor therapy was summarized, including the possibility of directly or indirectly targeting the TME.
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Neoplasias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Microambiente Tumoral , HumanosRESUMEN
BACKGROUND AND PURPOSE: In previous studies, the estimated dose of radiation to immune cells (EDRIC) showed a correlation with overall survival (OS) of patients with locally advanced non-small cell lung cancer (LA-NSCLC) who received thoracic radiotherapy. However, several factors such as gross tumor volume (GTV) and lymph node (N) stage may impact EDRIC. The purpose of this study was to identify the factors influencing EDRIC and to further assess the prognostic relevance of EDRIC. MATERIALS AND METHODS: We retrospectively analyzed 201 patients with LA-NSCLC who received radiotherapy between 2012 and 2017. EDRIC was calculated based on the model developed by Jin et al. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the correlation of potential factors with OS, local progression-free survival (LPFS), and distant metastasis-free survival (DMFS). Spearman's rank correlation was used to assess the correlation between variables. RESULTS: Both GTV and N stage showed a positive correlation with EDRIC (r = 0.347, P < 0.001 and r = 0.249, P < 0.001, respectively). EDRIC was independently associated with DMFS (HR 1.185, P < 0.001). GTV was associated with OS (HR 1.006, P < 0.001), LPFS (HR 1.003, P = 0.017), and DMFS (HR 1.003, P = 0.032). While using GTV as a stratification factor in Kaplan-Meier analysis, EDRIC showed a trend of negative correlation with OS in GTV ≤ 66.6 cm3 group (P = 0.061). CONCLUSION: EDRIC was an independent prognostic factor for metastasis and it was affected by GTV and N stage. However, the effect of EDRIC on OS was influenced by GTV.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Pronóstico , Dosificación Radioterapéutica , Estudios RetrospectivosRESUMEN
This paper describes a novel approach to measure individual investor sentiment using text-based analysis of millions of posts extracted from Chinese financial online forums. We describe how we built a database of more than 200 million stock posts from online financial forums, created GubaLex, a sentiment dictionary consisting of 48,878 words to allow sentiment analysis, and how we developed GubaSenti, an individual investor sentiment index for the stock market in China. This allowed (1) the first systemic measurement of individual investor sentiment in China; (2) an approach to text-based analysis that reflects investor sentiment about millions of posts about stocks listed in Guba; (3) a way to flexibly measure investor sentiment of a single stock, a sector or an industry and the whole market; and (4) made this possible for daily, weekly, monthly, quarterly, and yearly time periods. We also examine the relationship of the sentiment proxy and stock returns and compare it with two typical BW metrics in China. Empirical results show that GubaSenti correlates better with market performance than BW metrics in China and can be used to predict market changes in the short term.
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Deep squat, bench press and hard pull are important ways for people to improve their strength. The use of sensors to measure force is rare. Measuring strength with sensors is extremely valuable for people to master the intensity of exercise to scientifically effective exercise. To this end, in this paper, we used a real-time wireless motion capture and mechanical evaluation system of the wearable sensor to measure the dynamic characteristics of 30 young men performing deep squat, bench press and hard pull maneuvers. The data of tibia were simulated with AnyBody 5.2 and ANSYS 19.2 to verify the authenticity. The result demonstrated that the appropriate force of the deep squat elbow joint, the hip joint and the knee joint is 40% 1RM, the appropriate force of the bench press is 40% 1RM and the appropriate force of the hard pull is 80% 1RM. The external force is the main factor of bone change. The mechanical characteristics of knee joint can be simulated after the Finite Element Analysis and the simulation of AnyBody model are verified.
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Análisis de Elementos Finitos , Entrenamiento de Fuerza , Aceleración , Ejercicio Físico , Humanos , Masculino , Fuerza Muscular , Músculo Esquelético , Levantamiento de PesoRESUMEN
We investigate the impact of COVID-19 on Chinese stock market by an event study and examine the effect of individual investor sentiment on returns. The pandemic has an overall negative effect on stock market during the post-event window, which can't be explained by real losses. Results show a stronger positive correlation between individual investor sentiment and stock returns than usual. The impact on individual investor sentiment on stock returns is more significant for enterprises with high PB, PE and CMV, low net asset, and low institutional shareholding. Only 7 industries related to pharmacy, digitalization, and agriculture are boosted.
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C-X-C motif chemokine ligand 14 (CXCL14) has antitumor effect. Kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is activated in various tumors. The relationship between CXCL14 and Akt/mTOR pathway in hepatocellular carcinoma (HCC) remained elusive. Therefore, this paper aimed to examine their interaction in HCC. First, CXCL14 expression was determined to be low-expressed in HCC tissues and cells (SNU-423, SNU-182, SNU-387, PLC/PRF/5, HuH7, and HCCLM3). Then, CXCL14 was overexpressed in HuH7 cells and inhibited in HCCLM3 cells to help investigate the function of CXCL14 on cell viability, growth and apoptosis. Akt activator (SC79) and inhibitor (AZD5363) were used to examine the involvement of Akt pathway in hepatocellular carcinoma. Overexpressed CXCL14 suppressed cell viability and growth, but promoted the apoptosis by upregulated Bax and cleaved(C) caspase-3, donwregulated Bcl-2 and the inhibition of Akt and mTOR phosphorylation. Meanwhile, knockdown of CXCL14 imposed an opposite effect to overexpressed CXCL14. SC79 partially mitigated the functions of overexpressed CXCL14, while AZD5363 mitigated the functions of CXCL14 knockdown. To conclude, CXCL14 inhibited growth but promoted apoptosis of HCC cells via suppressing Akt/mTOR pathway, thus, CXCL14 might be a potential target for HCC treatment in clinical practice.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Quimiocinas CXC/metabolismo , Regulación Neoplásica de la Expresión Génica , Fosfatidilinositol 3-Quinasas/química , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferación Celular , Quimiocinas CXC/genética , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Células Tumorales CultivadasRESUMEN
BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with 18 F-FDG PET/CT imaging. METHODS: The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of 18 F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction. RESULTS: CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of 18 F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression. CONCLUSIONS: Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of 18 F-FDG PET/CT imaging for targeted therapeutic efficacy.
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Adenocarcinoma del Pulmón/patología , Basigina/metabolismo , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Neoplasias Pulmonares/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Adenocarcinoma del Pulmón/diagnóstico por imagen , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/cirugía , Animales , Apoptosis , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Femenino , Glucólisis , Humanos , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirugía , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. METHODS: Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. RESULTS: The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93-1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42-3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76-1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12-2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61-0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89-1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86-1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. CONCLUSION: Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.
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Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/radioterapia , Hipofraccionamiento de la Dosis de Radiación , Ensayos Clínicos Controlados Aleatorios como Asunto , Tracto Gastrointestinal/efectos de la radiación , Humanos , Masculino , Neoplasias de la Próstata/etnología , Traumatismos por Radiación/etiología , Tasa de Supervivencia , Resultado del Tratamiento , Sistema Urogenital/efectos de la radiación , Población BlancaRESUMEN
OBJECTIVES: Emerging studies have demonstrated that microRNAs (miRNAs) play crucial roles in carcinogenesis of many developing human tumours. However, the functions and mechanisms of miR-297 in lung cancer have, up to now, been largely undefined. MATERIALS AND METHODS: Here, miR-297 expression was measured in lung adenocarcinoma tissues and cell lines, using qRT-PCR. Lung adenocarcinoma cell line was treated with an miR-297 mimic. MTT and colony analysis were performed to detect cell proliferation and colony formation. The direct target gene of miR-297 was assessed by qRT-PCR, Western blotting and luciferase assays. RESULTS: We demonstrated that miR-297 expression was upregulated in lung adenocarcinomas compared to adjacent normal tissues. Expression of miR-297 was also upregulated in tested lung adenocarcinoma cell lines. Ectopic expression of miR-297 enhanced lung adenocarcinoma cell proliferation and colony formation. Furthermore, overexpression of miR-297 promoted cell migration and invasion. In addition, we identified Glypican-5 (GPC5) as a direct target gene of miR-297 in lung adenocarcinoma cells. Expression of GPC5 was downregulated in both lung adenocarcinoma tissues and cell lines. Moreover, expression of GPC5 was inversely associated with expression of miR-297 in lung adenocarcinoma tissues. CONCLUSIONS: These results suggest that miR-297 acted as an oncogenic miRNA, partly by targeting GPC5, adenocarcinoma of the lung.
Asunto(s)
Adenocarcinoma/genética , Regulación Neoplásica de la Expresión Génica , Glipicanos/genética , Neoplasias Pulmonares/genética , Pulmón/patología , MicroARNs/genética , Adenocarcinoma/patología , Adenocarcinoma del Pulmón , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación hacia Abajo , Humanos , Pulmón/metabolismo , Neoplasias Pulmonares/patología , Oncogenes , Regulación hacia ArribaRESUMEN
Smartphone based activity recognition has recently received remarkable attention in various applications of mobile health such as safety monitoring, fitness tracking, and disease prediction. To achieve more accurate and simplified medical monitoring, this paper proposes a self-learning scheme for patients' activity recognition, in which a patient only needs to carry an ordinary smartphone that contains common motion sensors. After the real-time data collection though this smartphone, we preprocess the data using coordinate system transformation to eliminate phone orientation influence. A set of robust and effective features are then extracted from the preprocessed data. Because a patient may inevitably perform various unpredictable activities that have no apriori knowledge in the training dataset, we propose a self-learning activity recognition scheme. The scheme determines whether there are apriori training samples and labeled categories in training pools that well match with unpredictable activity data. If not, it automatically assembles these unpredictable samples into different clusters and gives them new category labels. These clustered samples combined with the acquired new category labels are then merged into the training dataset to reinforce recognition ability of the self-learning model. In experiments, we evaluate our scheme using the data collected from two postoperative patient volunteers, including six labeled daily activities as the initial apriori categories in the training pool. Experimental results demonstrate that the proposed self-learning scheme for activity recognition works very well for most cases. When there exist several types of unseen activities without any apriori information, the accuracy reaches above 80 % after the self-learning process converges.