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Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high death rate and lacks a targeted therapy plan. The ratio of blood urea nitrogen to albumin, known as BAR, is a valuable method for assessing the outlook of various infectious diseases. The objective of this research was to evaluate the effectiveness of BAR in forecasting the outcome of individuals with SFTS. Four hundred and thirty-seven patients with SFTS from two clinical centers were included in this study according to inclusion and exclusion criteria. Clinical characteristics and test parameters of SFTS patients were analyzed between survival and fatal groups. Least absolute shrinkage and selection operator (LASSO) regression and Cox regression suggested that BAR might serve as a standalone prognostic indicator for patients with SFTS in the initial phase (hazard ratio = 18.669, 95% confidence interval [CI]: 8.558-40.725, p < 0.001). And BAR had a better predictive effectiveness in clinical outcomes in patients with SFTS with an AUC of 0.832 (95% CI: 0.788-0.876, p < 0.001), a cutoff value of 0.19, a sensitivity of 0.812, and a specificity of 0.726 compared to C-reactive protein, procalcitonin, and platelet to lymphocyte ratio via receiver operating characteristic curve. KM (Kaplan Meier) curves demonstrated that high level of BAR was associated with poor survival condition in patients with SFTS. Furthermore, the high level of BAR was associated with long hospital stays and test paraments of kidney, liver, and coagulation function in survival patients. So, BAR could be used as a promising early warning biomarker of adverse outcomes in patients with SFTS.
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Nitrogênio da Ureia Sanguínea , Febre Grave com Síndrome de Trombocitopenia , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Febre Grave com Síndrome de Trombocitopenia/mortalidade , Febre Grave com Síndrome de Trombocitopenia/sangue , Febre Grave com Síndrome de Trombocitopenia/diagnóstico , Febre Grave com Síndrome de Trombocitopenia/virologia , Idoso , Prognóstico , Biomarcadores/sangue , Estudos Retrospectivos , Adulto , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Early diagnosis and treatment are crucial to improve the prognosis of colorectal cancer (CRC). At present, there is a lack of an accurate CRC screening factor. We conducted folate receptor-positive circulating tumor cell analysis (FR + CTC analysis) in distinguishing CRC from benign colorectal diseases to evaluate the diagnostic efficiency. METHODS: Clinical data of patients admitted to The First Affiliated Hospital of Anhui Medical University from January 2021 to July 2022 were retrospectively collected. Levels of FR + CTC and other indicators were analyzed. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic performance of these molecular biomarkers. RESULTS: Data of 103 patients with CRC and 54 patients with benign colorectal diseases were collected. FR + CTC levels were observed significantly higher in CRC patients than in patients with benign colorectal diseases (P < 0.001). FR + CTC level was correlated with tumor diameter, differentiation, T-stage, pathological stage, clinical stage, and intravascular tumor thrombus in patients with CRC (P < 0.05). The optimal cutoff value of FR + CTC level for diagnosing CRC patients was 7.66 FU/3 ml, with a sensitivity of 85.4%, a specificity of 74.1%, and an Area Under Curve (AUC) of 0.855 (95% CI 0.77-0.923). In < 50-years old patients with CRC, the diagnostic efficiency of FR + CTC was excellent, with an AUC of 0.936 (95% CI 0.877-0.995). CONCLUSION: FR + CTC counting has excellent diagnostic efficiency in screening of CRC. FR + CTC count can also predict the tumor stage of CRC patients before surgery, and guide the choice of treatment.
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Neoplasias Colorretais , Células Neoplásicas Circulantes , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Células Neoplásicas Circulantes/patologia , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Ácido FólicoRESUMO
BACKGROUND: Drug resistance is a main factor affecting the chemotherapy efficacy of gastric cancer (GC), in which meiosis plays an important role. Therefore, it is urgent to explore the effect of meiosis related genes on chemotherapy resistance. METHODS: The expression of meiotic nuclear divisions 1 (MND1) in GC was detected by using TCGA and clinical specimens. In vitro and in vivo assays were used to investigate the effects of MND1. The molecular mechanism was determined using luciferase reporter assay, CO-IP and mass spectrometry (MS). RESULTS: Through bioinformatics, we found that MND1 was highly expressed in platinum-resistant samples. In vitro experiments showed that interference of MND1 significantly inhibited the progression of GC and increased the sensitivity to oxaliplatin. MND1 was significantly higher in 159 GC tissues in comparison with the matched adjacent normal tissues. In addition, overexpression of MND1 was associated with worse survival, advanced TNM stage, and lower pathological grade in patients with GC. Further investigation revealed that forkhead box protein A1 (FOXA1) directly binds to the promoter of MND1 to inhibit its transcription. CO-IP and MS assays showed that MND1 was coexpressed with transketolase (TKT). In addition,TKT activated the PI3K/AKT signaling axis and enhanced the glucose uptake and lactate production in GC cells. CONCLUSIONS: Our results confirm that FOXA1 inhibits the expression of MND1, which can directly bind to TKT to promote GC progression and reduce oxaliplatin sensitivity through the PI3K/AKT signaling pathway.
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BACKGROUND: To explore the correlation of tumor necrosis factor-α-induced protein 8-like protein 3 (TIPE3) expressions in colorectal cancer (CRC) with tumor-immune infiltration and patient prognosis. METHODS: Formalin-fixed paraffin-embedded tumor samples from CRC patients (n = 110) were used in this study. Immunohistochemistry staining of TIPE3 and three prognostic immune biomarkers (CD8, CD20, and CD66b) was conducted in the tumor tissues and adjacent normal tissues. A Cox regression analysis of univariate and multivariate variables was performed to assess the correlation between TIPE3 and patient prognosis. RESULT: We found that TIPE3 was mainly expressed in the cytoplasm, with a small amount in the nucleus. The expression of TIPE3 in tumor tissues is significantly higher than in adjacent normal tissues, and it is significantly correlated with the survival rate of patients in tumor tissues (p = 0.0038) and adjacent normal tissues (p<0.0001). Patients with a high TIPE3 expression had a lower survival rate, while patients with a low TIPE3 expression had a higher survival rate. Univariate regression analysis showed that the TIPE3 expression in tumor tissues (p = 0.007), the TIPE3 expression in adjacent normal tissues (p<0.001), the number of CD8+ T cells in tumor tissues (p = 0.020), the number of CD20+ B cells in tumor tissues (p = 0.023), the number of CD20+ B cells in adjacent normal tissues (p = 0.023), the number of CD66b+ neutrophils in tumor tissues (p = 0.005), the number of CD66b+ neutrophils in adjacent normal tissues (p<0.001), lymphatic metastasis (p = 0.010), TNM stage (p = 0.013), and tumor grade (p = 0.027) were significantly correlated with overall survival (OS). These prognostic factors were then subjected to multivariate regression analysis, and the results showed that the expression of TIPE3, the number of CD8+ T cells, and the number of CD66b+ neutrophils were prognostic factors affecting the OS rate of CRC patients. CONCLUSION: We found that the TIPE3 protein is upregulated in CRC cancer tissues and is correlated with survival rate.
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Neoplasias Colorretais , Peptídeos e Proteínas de Sinalização Intracelular , Humanos , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Metástase Linfática , Prognóstico , Fator de Necrose Tumoral alfa , Peptídeos e Proteínas de Sinalização Intracelular/genéticaRESUMO
Recent studies have shown that the high incidence and low cure rate of hepatocellular carcinoma (HCC) have not improved significantly. Surgery and liver transplantation are the mainstays of prolonging the survival of HCC patients. However, the surgical resection rate of HCC patients is very low, and even after radical surgical resection, the recurrence rate at 5 years postoperatively remains high and the prognosis is very poor, so more treatment options are urgently needed. Increasing evidence suggests that cellular senescence is not only related to cancer development but may also be one of its primary driving factors. We aimed to establish a prognostic signature of senescence-associated genes to predict the prognosis and therapeutic response of HCC patients. The aim of this study was to develop a risk model associated with cellular senescence and to search for potential strategies to treat HCC. We divided HCC patients into two clusters and identified differentially expressed genes (DEGs) between clusters. In this study, low-risk patients had a better prognosis, higher levels of immune cell infiltration, and better efficacy to fluorouracil, Paclitaxel and Cytarabine chemotherapy compared to high-risk patients. To further identify potential biomarkers for HCC, we further validated the expression levels of the four signature genes in HCC and neighbouring normal tissues by in vitro experiments. In conclusion, we identified and constructed a relevant prognostic signature, which performed well in predicting the survival and treatment response of HCC patients. This helps to differentiate between low-score and high-risk HCC, and the results may contribute to precise treatment protocols in clinical practice.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Prognóstico , Senescência Celular/genética , CitarabinaRESUMO
BACKGROUND: Solute carrier family 38 member 2 (SLC38A2) has previously been reported to participate in carcinogenesis. However, its expression and function in gastric cancer (GC) remain unclear. The present study aimed to investigate the role of SLC38A2 in GC. METHODS: The prognostic value and expression of SLC38A2 in GC was analyzed by combining bioinformatics and experimental analyses. Colony formation, Cell Counting Kit-8, wound healing, Transwell and tumor formation assays were performed to assess the biological function of SLC38A2. The cBioPortal, GeneMANIA and LinkedOmics databases were mined to determine the underlying regulatory mechanisms of SLC38A2. The role of SLC38A2 in tumor immune infiltration was explored using the TIMER database. RESULTS: Our results demonstrated that SLC38A2 was upregulated and was correlated with a poor prognosis in GC patients. SLC38A2 downregulation significantly inhibited the proliferation, invasion and migration of GC cells. Abnormal genetic alteration and epigenetic regulation may contribute to the upregulation of SLC38A2 expression levels in GC. The results of enrichment analysis demonstrated that SLC38A2 was associated with 'hippo signaling' and 'ubiquitinyl hydrolase activity'. The results also indicated that SLC38A2 may be a key factor in GC immune infiltration and M2 macrophage polarization. CONCLUSION: Overall, these data identified that SLC38A2 may serve as a potential prognostic biomarker and therapeutic target in GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Epigênese Genética , Movimento Celular/genética , Proliferação de Células/genética , Prognóstico , Sistema A de Transporte de Aminoácidos/genética , Sistema A de Transporte de Aminoácidos/metabolismoRESUMO
This article focuses on the specific effects and mechanisms of donepezil (DNPZ) hydrochloride on inflammation and apoptosis in ulcerative colitis (UC). In vivo and in vitro models of UC were established using dextran sodium sulfate (DSS)-induced mice and NCM460 cells, respectively. Following oral administration of DNPZ, body weight, disease activity index (DAI) scores and colon lengths of mice were recorded. Histopathological damage was detected employing hematoxylin and eosin (H&E) staining. Inflammatory factors were tested using enzyme-linked immunosorbent assay and quantitative reverse transcription polymerase chain reaction, respectively. Apoptosis was estimated utilizing terminal deoxynucleotidyl transferase dUTP nick-end labeling and western blot. Low-density lipoprotein receptor-related protein 1 (LRP1)/AMP activated protein kinase (AMPK)/nuclear factor-κB (NF- κB) signaling proteins were detected utilizing western blot. NCM460 cell viability was assessed by cell counting kit (CCK)-8. We found that DNPZ partially restored body weight, reduced DAI scores and attenuated intestinal pathological damage in DSS-induced mice. Additionally, inflammatory factors decreased significantly after DNPZ treatment, accompanied by reduced apoptosis level. Phosphorylation (p)-AMPK increased and p-p65 decreased after DNPZ treatment, whereas LRP1 knockdown showed the opposite effect. Moreover, DNPZ treatment greatly restored NCM460 cell viability after DSS stimulation. DNPZ attenuated DSS-induced inflammation and apoptosis in NCM460 cells, which was reversed by LRP1 knockdown. In summary, DNPZ hydrochloride attenuates inflammation and apoptosis in UC via LRP1/AMPK/NF-κB signaling.
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Colite Ulcerativa , Colite , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Donepezila/efeitos adversos , Donepezila/metabolismo , Colo/patologia , Inflamação/metabolismo , Apoptose , Peso Corporal , Modelos Animais de Doenças , Colite/metabolismo , Colite/patologia , Camundongos Endogâmicos C57BLRESUMO
PURPOSE: To explore the role of HS1-binding protein 3 (HS1BP3) in hepatocellular carcinoma (HCC) and the potential mechanism. METHODS: The effect of HS1BP3 in the prognosis of HCC was analyzed. The influence of HS1BP3 silence on proliferation, migration, cell cycle, and apoptosis of HCC cells (Huh-7 and Sun-449) were evaluated. The upstream transcription factors of HS1BP3 were further explored. RESULTS: The high expression of HS1BP3 in HCC was significantly associated with poor prognosis. The silencing of HS1BP3 inhibited proliferation, invasion, migration, and promoted G1 phase cell cycle arrest and apoptosis of HCC cells. Estrogen receptors 1 (ESR1) inhibited proliferation and improved the prognosis of HCC via fusion with HS1BP3 promoter. CONCLUSION: HS1BP3 may serve as a novel tumor-promoting factor transcriptionally regulated by ESR1.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Apoptose/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologiaRESUMO
BACKGROUND: Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. METHODS: CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). RESULTS: CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CONCLUSIONS: CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.
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MicroRNAs , Neoplasias Gástricas , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Gástricas/patologia , Proteínas rasRESUMO
BACKGROUND: Frailty is emerging as an important determinant for health. Compared with Western countries, research in the field of frailty started at a later stage in China and mainly focused on older community dwellers. Little is known about frailty in Chinese cancer patients, nor the risk factors of frailty. This study aimed at investigating the prevalence of frailty and its risk factors in elderly inpatients with gastric and colorectal cancer. METHODS: This cross-sectional study was conducted at a tertiary hospital in China from Mar. 2020 to Nov. 2020. The study enrolled 265 eligible inpatients aged 60 and older with gastric and colorectal cancer who underwent surgery. Demographic and clinical characteristics, biochemical laboratory parameters, and anthropometric data were collected from all patients. The Groningen Frailty Indicator was applied to assess the frailty status of patients. A multivariate logistic regression model analysis was performed to identify the risk factors of frailty and to estimate their 95% confidence intervals. RESULTS: The prevalence of frailty in elderly inpatients with gastric and colorectal cancer was 43.8%. A multivariate logistic regression analysis showed that older age (OR = 1.065, 95% CI: 1.001-1.132, P = 0.045), low handgrip strength (OR = 4.346, 95% CI: 1.739-10.863, P = 0.002), no regular exercise habit (OR = 3.228, 95% CI: 1.230-8.469, P = 0.017), and low MNA-SF score (OR = 11.090, 95% CI: 5.119-24.024, P < 0.001) were risk factors of frailty. CONCLUSIONS: This study suggested a relatively high prevalence of frailty among elderly inpatients with gastric and colorectal cancer. Older age, low handgrip strength, no regular exercise habit, and low MNA-SF score were identified as risk factors of frailty.
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Neoplasias Colorretais , Fragilidade , Idoso , China/epidemiologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Estudos Transversais , Idoso Fragilizado , Avaliação Geriátrica , Força da Mão , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Gastric cancer (GC) is the most frequent digestive system malignant tumour and the second most common cause of cancer death globally. Cancer stem cell (CSC) is a small percentage of cancer cells in solid tumours that have differentiation, self-renewal and tumorigenic capabilities. They have an active participation in the initiation, development, metastasis, recurrence and resistance of tumours to chemotherapy and radiotherapy. Gastric cancer stem cells (GCSCs) have been shown to be correlated with GC initiation and metastasis. In this study, we found that TAK1 expression level in GC tissues was significantly increased compared to the adjacent non-cancerous tissues by RT-qPCR, Western blot and immunohistochemistry. TAK1 has been identified as a critical molecule that promoted a variety of malignant GC phenotypes both in vivo and in vitro and promoted the self-renewal of GCSCs. Mechanistically, TAK1 was up-regulated by IL-6 and prevented the degradation of yes-associated protein (YAP) in the cytoplasm by binding to YAP. Thus, TAK1 promoted the SOX2 and SOX9 transcription and the self-renewal and oncogenesis of GCSCs. Our findings provide insights into the mechanism of self-renewal and tumorigenesis of TAK1 in GCSCs and have broad implications for clinical therapies.
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Carcinogênese/genética , MAP Quinase Quinase Quinases/genética , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOXB1/genética , Neoplasias Gástricas/genética , Diferenciação Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Autorrenovação Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Interleucina-6/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais/genética , Neoplasias Gástricas/patologia , Fator de Crescimento Transformador beta/genética , Proteínas de Sinalização YAP/genéticaRESUMO
BACKGROUND: Integrin Subunit Alpha 5 (ITGA5), belongs to the integrin alpha chain family, is vital for promoting cancer cell invasion, metastasis. However, the correlation between ITGA5 expression and immune infiltration in gastrointestinal tumors remain unclear. METHODS: The expression level of ITGA5 was detected by Oncomine and Tumor Immune Estimation Resource (TIMER). The association between ITGA5 and prognosis of patients was identified by Kaplan-Meier plotter, Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and PrognoScan. We evaluated the correlation between ITGA5 expression and immune infiltrating level via TIMER. Besides, TIMER, immunohistochemistry (IHC) staining and western blot were used to explore correlations between ITGA5 expression and markers of immune infiltrates cells. Furthermore, we constructed protein-protein interaction (PPI) network and performed functional enrichment by GeneMANIA and Metascape. RESULTS: ITGA5 was generally overexpressed and correlated with worse prognosis in multiple types of gastrointestinal tumors. In addition, ITGA5 expression level was significantly associated with tumor purity and immune infiltration levels of different immune cells in gastrointestinal tumors. Interestingly, immune markers for monocytes, tumor - associated macrophages (TAMs), macrophages 2 (M2) cells and T-helper 2 (Th2) cells were found to be significantly and positively correlated with ITGA5 expression levels in colon and gastric cancer. Results from IHC staining and western blot further proved that markers of Th2 and M2 cell were significantly increased in gastric cancer patients with high ITGA5 expression levels. Lastly, interaction network and function enrichment analysis revealed ITGA5 was mainly involved in "integrin mediated signaling pathway", "leukocyte migration", "cell-substrate adhesion". CONCLUTIONS: Our study demonstrated that ITGA5 may act as an essential regulator of tumor immune cell infiltration and a valuable prognostic biomarker in gastrointestinal tumors. Additional work is needed to fully elucidate the underlying mechanisms behind these observations.
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Biomarcadores Tumorais/metabolismo , Neoplasias Gastrointestinais/mortalidade , Integrinas/metabolismo , Microambiente Tumoral/imunologia , Conjuntos de Dados como Assunto , Neoplasias Gastrointestinais/imunologia , Neoplasias Gastrointestinais/patologia , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , Células Th2/imunologia , Macrófagos Associados a Tumor/imunologiaRESUMO
BACKGROUND: The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. METHODS: The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. RESULTS: Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. CONCLUSION: A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.
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Neoplasias do Colo , Ferroptose , Neoplasias do Colo/genética , Humanos , Estadiamento de Neoplasias , Nomogramas , PrognósticoRESUMO
BACKGROUND: The tumor suppressor role of tissue factor pathway inhibitor 2 (TFPI-2) has been reported in various tumors. The present study aimed to improve the understanding of the oncogenic properties of TFPI-2 in gastric cancer. METHODS: Relative expression of TFPI-2 was determined by a real-time polymerase chain reaction (PCR) and western blotting, respectively. Cell viability was measured via a cell counting kit-8 assay and proliferation was evaluated by a colony formation assay. Cell apoptosis was assessed with a caspase-3 activity kit and invasion was evaluated by a transwell chamber assay. The methylation level of TFPI-2 promoter was assayed by methylation-specific PCR. The regulatory effect of miR-27a-3p on TFPI-2 was analyzed with a luciferase reporter assay. The direct association between miR-27a-3p and TFPI-2 was shown by biotin-labelling pulldown. RESULTS: TFPI-2 was down-regulated in gastric cancer, which associated with an unfavorable prognosis clinically. Ectopic introduction of TFPI-2 greatly compromised cell viability, colony formation and invasive capacity, and also induced cell apoptosis simultaneously. The promoter region of TFPI-2 was extensively methylated in gastric cancer tissues compared to normal tissues, suggesting the epigenetic inhibition of TFPI-2 expression. We further identified that TFPI-2 functioned as sponge RNA against miR-27a-3p. Most importantly, miR-27a-3p-specific inhibitor significantly exerted a tumor suppressor function akin to TFPI-2 itself, and the anti-tumoral activities were completely abolished by TFPI-2 knockdown. CONCLUSIONS: We found that the epigenetically suppressed TFPI-2 compromised sponging effects with respect to miR-27a-3p in gastric cancer, which consequently and mechanistically contributed to the tumor biology of gastric cancer.
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Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Glicoproteínas/metabolismo , MicroRNAs/metabolismo , Neoplasias Gástricas/metabolismo , Regiões 3' não Traduzidas , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Metilação de DNA , Progressão da Doença , Regulação para Baixo , Epigênese Genética , Glicoproteínas/genética , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Prognóstico , Regiões Promotoras Genéticas , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologiaRESUMO
BACKGROUND: The significance of human epidermal growth factor receptor 2 (Her2) and nucleus-associated antigen Ki-67 expression remains controversial in gastric adenocarcinoma (GaC). The aim of this study was to investigate the expression and clinicopathologic and prognostic significance of Her2 and Ki-67 in resected GaC without distant metastasis. METHODS: Malignant tissues and clinicopathologic data were obtained from 195 patients with resected non-metastatic GaC. Immunohistochemistry staining was performed to examine the expression of Her2 and Ki-67; their association with clinicopathologic factors were investigated using logistic regression, and their association with survival was explored using Kaplan-Meier analysis and Cox proportional hazards regression. RESULTS: Her2 was majorly expressed in cell membrane and Ki-67 in cell nucleus in non-metastatic GaC. Stronger Her2 expression was significantly associated with better tumor differentiation, neurovascular invasion, less advanced pathological tumor (pT) stage, and more advanced pathological node (pN) stage; while Ki-67 expression was not significantly associated with any investigated clinicopathologic factors. Patients with both negative Her2 and negative Ki-67 expression had poorer tumor differentiation, and more advanced pT and pathological tumor-node-metastasis (pTNM) stages; the association with pT and pTNM stages were further confirmed by multivariable analyses, especially in node-negative disease. Her2 or Ki-67 alone was not significantly associated with pTNM stage. A strongly positive (+++) Her2 expression was associated with poorer survival in multivariable analysis only (P = 0.047); while Ki-67 or combined expression was not significantly associated with prognosis. CONCLUSIONS: In non-metastatic GaC, Her2 expression and combined expression of Her2 and Ki-67 were associated with several clinicopathologic factors including tumor differentiation and stage, and only a +++ Her2 expression was associated with poorer prognosis in multivariable analysis with marginal significance in this study; while Ki-67 alone had both limited clinicopathologic and prognostic values.
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Adenocarcinoma , Neoplasias Gástricas , Biomarcadores Tumorais , Estudos de Coortes , Humanos , Antígeno Ki-67 , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2RESUMO
BACKGROUND: Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown. METHODS: HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas. RESULTS: We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC. CONCLUSIONS: HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
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Colágeno Tipo V/metabolismo , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/genética , Regulação para Cima/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Metástase Neoplásica/genética , Microambiente Tumoral/genéticaRESUMO
Gastric cancer (GC) is one of malignant tumors with high mortality and morbidity in the world. MicroRNA-122 (miR-122) acts as a tumor suppressor in a variety of cancers and has been found to be dominant in gastric adenocarcinoma. However, the specific biological function of miR-122-5p in GC is not completely clear. In this study, we found that miR-122-5p was low-expressed in GC tissues and cell lines by using qRT-PCR. Overexpression of miR-122-5p inhibited the proliferation, migration, and invasion of GC cells by using CCK-8 and transwell assays. On the contrary, downregulation of miR-122-5p promoted the proliferation, migration, and invasion of GC cells. In addition, we found that the expression of LYN, an Src family tyrosine kinase, was inversely correlated with miR-122-5p expression in GC tissues by using western blot analysis, immunohistochemistry, and qRT-PCR assays. Meanwhile, luciferase assay results indicated that LYN is a direct target of miR-122-5p in GC cells. Moreover, silencing LYN expression by its siRNA inhibited the proliferation, migration, and invasion of GC cells. Importantly, overexpression of LYN restored miR-122-5p-mediated inhibition of the proliferation, migration, and invasion of GC cells. Taken together, our results indicated miR-122-5p inhibited the proliferation, migration, and invasion by targeting LYN in GC.
Assuntos
Movimento Celular/genética , Proliferação de Células/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Invasividade Neoplásica/genética , Neoplasias Gástricas/metabolismo , Quinases da Família src/genética , Quinases da Família src/metabolismo , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Mimetismo Molecular/genética , Mutação , RNA Interferente Pequeno/genética , Neoplasias Gástricas/patologia , TransfecçãoRESUMO
BACKGROUND: The marijuana policy varies greatly worldwide. Marijuana use is illegal in most countries. Nevertheless, the medical potentials of marijuana have been increasingly uncovered, and its use by women is increasing. Objectives: Herein we aimed to share some of our perspectives on the hot important topic: marijuana use for women. Methods: We reviewed publications indexed in PubMed reporting the benefits and harms regarding the medical use of marijuana for women and its impact on offspring. Results: For non-pregnant women with some long-lasting conditions refractory to regular management, marijuana could be prescribed as potential new hope with acceptable safety profile based on current evidence. However, the side-effects especially long-term consequences are cautionary. For instance, for adolescents and young women, cannabis might affect their neuronal development and increase stroke risk. Notably, cannabinoids might promote proliferation of breast cancer cells. The potential harms should be carefully weighed against the benefits associated with cannabis. Cannabis use in pregnant or lactating women increases the risks of offspring exposures, and should be mostly avoided. Prenatal marijuana exposure might affect fetal growth and be teratogenic. The psychoactive cannabinoid tetrahydrocannabinol (THC), a partial agonist of human endocannabinoid system, could cross placental barrier, and adversely affect fetus brain development. THC could also affect the maturation of multiple neurotransmitter systems. The neurobehavioral consequences include impaired arousal and psychomotor functions at birth and disturbed sleep and higher-order executive functions in childhood. For mothers, the short-term and long-term side-effects, withdrawal syndromes, and use disorder associated with use of marijuana especially high-potency cannabis could all adversely affect their ability to care children and thus child development and safety. However, if the disease itself more dramatically tortures maternal behavior which could otherwise be alleviated by marijuana, then the use could somehow be justified. Conclusions: Benefits and risks for both the patient and the offspring especially in the long term regarding marijuana use should be carefully weighed for each specific case. Standardized dosing and duration of treatment need to be determined. Recommendations should be made by physicians with expert training and after careful patient evaluation for fully informed patients, whose preference should be respected. Legislations should encourage more active basic, translational, and clinical studies.
Assuntos
Cannabis , Fumar Maconha , Uso da Maconha , Adolescente , Criança , Feminino , Humanos , Recém-Nascido , Lactação , Placenta , GravidezRESUMO
Venous thromboembolism (VTE), encompassing deep venous thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease. miR-150 is one of important microRNAs which play critical role in various cellular function such as endothelial progenitor cells (EPCs). In this study, we investigate the effect of miR-150 on EPCs function ex vivo and thrombus resolution in vivo. We determined miR-150 expression in EPCs isolated from DVT patients and control subjects by RT-PCR. Potential target of miR-150 was confirmed by bioinformatics analysis and luciferase reporter respectively. The angiogenesis and proliferation were tested by MTT and tube formation assay. A murine model of venous thrombosis was developed as in vivo model. Finally, the effect of miR-150 on EPCs with inferior venous thrombosis were evaluated in vivo. Our data showed that miR-150 was downregulated in EPCs from DVT patients. By using miR-150 agomir and antagomir, we found that miR-150 promoted angiogenesis and proliferation of EPCs. Bioinformatics analysis revealed SRCIN1 as a target of miR-150 and SRCIN1 knockdown inhibited function of EPCs. Forced expression of miR-150 contributed thrombus resolution in a murine model of venous thrombosis. In general, miR-150 was downregulated in EPCs from DVT. Upregulation of miR-150 promoted angiogenesis and proliferation of EPCs by targeting SRCIN1 in vitro and thrombus resolution in vivo.
Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proliferação de Células , Células Progenitoras Endoteliais/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica , Trombose Venosa/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Adolescente , Adulto , Animais , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Células Progenitoras Endoteliais/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Transdução de Sinais , Trombose Venosa/genética , Trombose Venosa/patologia , Trombose Venosa/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Blood counting and the liver function tests, as the routine examinations, can reflect the immune and nutritional status of the body, our aim is to assess the prognostic significance of serum gamma-glutamyltransferase (GGT) levels and AST/ALT in primary hepatic carcinoma. METHODS: Clinico-pathological data of 414 patients with primary hepatic carcinoma in the 1st Affiliated Hospital of Anhui Medical College between January 2007 to January 2014 was analyzed retrospectively in this study. Survival curves were described by Kaplan-Meier method and compared by Log-rank test, univariate and multivariate analysis were used to identify the prognostic factors. RESULTS: GGT was positively correlated with the tumor size(P = 0.000), tumor volume (P = 0.000), tumor volume percent (P = 0.004), TNM stage(P = 0.009), 1-year survival rate (P = 0.000), 3- years survival rate (P = 0.000) and 5-years survival rate(P = 0.000). The serum ALT/AST was significantly correlated with age (P = 0.047), tumor size(P = 0.002), tumor volume (P = 0.010), tumor volume percent (P = 0.005), TNM stage(P = 0.006), liver cirrhosis(P = 0.003), 3- years survival rate (P = 0.032) and 5-years survival rate(P = 0.000). The Kaplan-Meier curves showed that the patients with primary hepatic carcinoma had a longer time in the low GGT group and low AST/ALT group, showing a significant difference (P < 0.05). The univariate and multivariate analyses showed that TNM stage, differentiation grade, tumor volume, GGT and AST/ALT were independent factors for predicting overall survival rate of primary hepatic carcinoma patients. CONCLUSIONS: GGT and AST/ALT were independent factors for predicting overall survival rate of primary hepatic carcinoma patients.