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Keyword mnemonics and retrieval practice are two learning strategies that facilitate foreign language vocabulary learning. This study examined the combination of these strategies for learning English L2 vocabulary with a limited retrieval time. We recruited 110 Chinese college students studying English as a foreign language to investigate the effects of four learning strategies on the retention of English-Chinese word pairs: restudy, retrieval practice, imposed keyword mnemonic combined with retrieval practice, and induced keyword mnemonic combined with retrieval practice. The results revealed that when retrieval practice was constrained to two times, the final performance of the retrieval practice group did not exceed that of the restudy group; however, the combined keyword-retrieval group outperformed the restudy group, regardless of whether the keyword was imposed or induced. Furthermore, there was no significant difference in memory retention performance between the induced and imposed keyword-retrieval combinations. The findings suggest that when retrieval practice is constrained to two times, the keyword-retrieval strategy combination significantly enhances English L2 vocabulary learning compared to restudy or retrieval practice alone, and both the imposed and induced keyword mnemonics can strengthen its efficiency.
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Circadian rhythm genes were reported to be strongly associated with the development and prognosis of circadian rhythm disorders related to stomach adenocarcinoma (STAD), which is one of the most prevalent cancers. This study aimed to identify a circadian rhythm-related gene signature that could help predict STAD outcome. Using bioinformatics analysis approaches, 105 genes were examined in 350 patients with STAD. Overall, six hub-type circadian rhythm-associated genes (GNA11, PER1, SOX14, EZH2, MAGED1, and NR1D1) were identified using univariate and multivariate Cox regression analyses. These genes were then used to build a genetic predictive model, which was further validated using a publicly available dataset (GSE26899). Overall, genes associated with the circadian rhythm were found to be substantially correlated with the characteristics of the STAD patients (grade, sex, and M stage). In addition, the circadian rhythm-related gene signature was significantly associated with the MAPK and Notch signaling pathways, which are known risk factors for poorer STAD outcome. Taken together, these findings suggest that the herein proposed prognostic model based on six circadian rhythm-associated genes may have predictive value and potential application for clinical decision-making and for personalized treatment of STAD.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Prognóstico , Ritmo Circadiano/genética , Adenocarcinoma/genética , Neoplasias Gástricas/genética , Fatores de Transcrição SOXB2RESUMO
Colorectal cancer (CRC) is the most common and fatal tumor in the gastrointestinal system. Its incidence and mortality rate have increased in recent years. Hypoxia, a persistent physiological tumor feature, plays a vital role in CRC tumorigenesis, metastasis, and tumor microenvironment (TME). Therefore, we constructed a hypoxia-related gene (HRG) nomogram to predict overall survival (OS) and explored the role of HRGs in the CRC TME. The Cancer Genome Atlas (TCGA) dataset was used as the training set, and two Gene Expression Omnibus datasets (GSE39582 and GSE103479) were used as the testing sets. HRGs were identified using the Gene Set Enrichment Analysis (GSEA) database. An HRG prognostic model was constructed in the training set using the least absolute shrinkage and selection operator regression algorithm and validated in the testing sets. Then, we analyzed tumor-infiltrating cells (TICs) using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Furthermore, single-cell next-generation RNA sequencing (RNA-seq) was used to investigate HRG expression in different TICs in the GSE139555 dataset. Finally, reverse transcription polymerase chain reactions (RT-PCR) were used to validate HRG mRNA expression in ten pairs of CRC normal and cancer tissue samples. A six HRG prognostic signature was constructed, with a superior OS prediction ability in CRC patients (area under the receiver operating characteristic curve (AUC) at one year: 0.693, AUC at three years: 0.712, and AUC at five years: 0.780). GSEA enrichment analysis identified six pathways enriched in the high-risk group. The TIC analysis indicated that the high-risk group had lower T-cell expression and higher neutrophil expression than the low-risk group. Furthermore, immune-related genes had an inseparable relationship with the HRG prognostic signature. Based on single-cell RNA-seq data, we found elevated hexokinase 1 (HK1) and glucose-6-phosphate isomerase (GPI) gene expression in natural killer (NK) and CD8+ T cells. RT-PCR in ten CRC normal-tumor tissue pairs showed that expression of the signature's six HRGs varied differently in cancerous and paracancerous tissues. The constructed HRG signature successfully predicted the OS of whole-stage CRC patients. In addition, we showed that the signature's six HRGs were closely associated with the TME in CRC, where hypoxia inhibits the antitumor function of T cells.
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Linfócitos T CD8-Positivos , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/genética , Hipóxia/genética , Prognóstico , Análise da Expressão Gênica de Célula Única , Microambiente Tumoral/genéticaRESUMO
BACKGROUND: Current clinical guidelines recommend the removal of at least 12 lymph nodes (LNs) in resectable colorectal cancer (CRC). With advancements in lymphadenectomy technologies, the number of retrieved lymph nodes (rLNs) has markedly increased. This study aimed to investigate the lowest number of rLNs in node-negative patients. MATERIALS AND METHODS: A total of 1103 N0 and 208 N1a stage patients were enrolled in our cohort, while 8503 N0 and 1276 N1a patients from the Surveillance, Epidemiology, and End Results CRC database were included. Propensity score matching and multivariate Cox regression analyses were performed to mitigate the influence of selection bias and control for potential confounding variables. RESULTS: The median number of rLNs in N0 patients increased from 13.5 (interquartile range [IQR]: 9-18) in 2013 to 17 (IQR: 15-20) in 2019. The restrictive cubic spline illustrated a nonlinear relationship between rLNs and prognosis (nonlinearity, P =0.009), with a threshold ( N =16) influencing clinical outcomes. Patients at either N0 or N1a stage with sufficient rLNs (≥16) demonstrated superior prognoses to those with a limited rLNs (<16). After adjusting for clinical confounders, similar prognoses were observed in N0 limited and N1a adequate populations. Furthermore, Kaplan-Meier curves revealed that N0 limited patients who received chemotherapy exhibited better outcomes than those who did not. CONCLUSIONS: Among patients with node-negative CRC, it is crucial to remove 16 or more LNs effectively. Fewer than 16 rLNs should be regarded as an independent risk factor, implying the need for adjuvant chemotherapy.
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Neoplasias Colorretais , Linfonodos , Humanos , Estadiamento de Neoplasias , Estudos Retrospectivos , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo , Prognóstico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologiaRESUMO
The IGF1 signal pathway is highly activated in some subtype of gastric cancer(GC) that exhibits poor survival and chemotherapy resistance. Although the results of clinical trials of anti-IGF1R monoclonal antibodies and IGF-1R inhibitors have been mostly disappointing in unselected cancer patients, some patients benefit from anti-IGF1R therapy in these failed studies. Therefore, it is necessary to characterize the complex IGF signaling in GC and help refine the strategies targeting the IGF1 pathway. We found that GC cell lines exhibit differential responses to the specific IGF1R inhibitor OSI906. According to the phosphorylation status of Akt upon the OSI906 treatment, we divided the GC cell lines into IGF1R-dependent and IGF1R-independent cells. Both in vitro and in vivo experiments indicate that Dox-induced knockdown of NEDD4 significantly suppresses tumor growth of IGF1R-dependent GC cells and NEDD4 overexpression promotes tumor growth of IGF1R-dependent GC cells. In contrast, the proliferation of IGF1R-independent GC cells is not affected by NEDD4 silencing and overexpression. The rescue experiments show that a PTEN-IRS1 axis is required for NEDD4-mediated regulation of Akt activation and tumor growth in GC cells. Clinically, NEDD4 is expressed higher in IGF1-high GC tissues compared with IGF1-low GC tissues and normal tissues, and the co-high expression of NEDD4 and IGF1 predicts a worse prognosis in GC patients. Taken together, our study demonstrated that NEDD4 specifically promotes proliferation of GC cells dependent on IGF1/IGF1R signaling by antagonizing the protein phosphatase activity of PTEN to IRS1, and targeting NEDD4 may be a promising therapeutic strategy for IGF1 signal pathway-driven gastric cancer.
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Neoplasias Gástricas , Ubiquitina-Proteína Ligases , Humanos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor IGF Tipo 1/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transdução de Sinais , Fosforilação , Linhagem Celular TumoralRESUMO
Fork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.