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Female cancers, especially breast, ovarian, cervical, and endometrial cancers, constitute a major threat to women's health worldwide. In view of the complex genetic background of cancers cannot be fully explained with current genetic information, we used a bidirectional two-sample mendelian randomization approach to explore the causal associations between serum metabolites and four major female cancers-breast, ovarian, cervical, and endometrial cancers. We analyzed the metabolites dataset from the Canadian Longitudinal Study of Aging and cancer datasets from the 10th round of the Finngen project. Replication analyses was performed with Cancer Association Consortium and Leo's studies. Instrumental variables were analyzed using methods including the Wald ratio, inverse-variance weighted, MR-Egger, and weighted median. To ensure robustness, sensitivity analyses were performed using Cochrane's Q, Egger's intercept, MR-PRESSO, and leave-one-out methods. After meticulous analysis, we obtained levels of 3-hydroxyoleoylcarnitine, hexadecanedioate, tetradecanedioate, and carnitine C14 with robust causal associations with breast cancer, levels of 5alpha-androstan-3alpha,17beta-diol monosulfate (1), androstenediol (3beta,17beta) monosulfate (1), androsterone sulfate, and 5alpha-androstan-3beta,17beta-diol disulfate causal associations with endometrial cancer. The reverse analysis showed that breast, ovarian, and endometrial cancer and survival of breast and ovarian cancer were found to have causal relationships with 8, 5, 2, 6, and 3 metabolites, respectively. These insights underscore the potential roles of specific metabolites in the etiology of female cancers, providing new biomarkers for early detection, risk stratification, and disease progression monitoring. Further research could elucidate how these metabolites influence specific pathways in cancer development, offering theoretical foundations for prevention and treatment strategies.
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Análisis de la Aleatorización Mendeliana , Humanos , Femenino , Neoplasias de la Mama/sangre , Neoplasias de la Mama/genética , Neoplasias Ováricas/sangre , Neoplasias Ováricas/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Canadá/epidemiología , Neoplasias Endometriales/sangre , Neoplasias Endometriales/genéticaRESUMEN
Over-expression of glutathione S-transferase (GST) can promote Cisplatin resistance in hepatocellular carcinoma (HCC) treatment. Hence, inhibiting GST is an attractive strategy to improve Cisplatin sensitivity in HCC therapy. Although several synthesized GST inhibitors have been developed, the side effects and narrow spectrum for anticancer seriously limit their clinical application. Considering the abundance of natural compounds with anticancer activity, this study developed a rapid fluorescence technique to screen "green" natural GST inhibitors with high specificity. The fluorescence assay demonstrated that schisanlactone B (hereafter abbreviated as C1) isolated from Xue tong significantly down-regulated GST levels in Cisplatin-resistant HCC cells in vitro and in vivo. Importantly, C1 can selectively kill HCC cells from normal liver cells, effectively improving the therapeutic effect of Cisplatin on HCC mice by down-regulating GST expression. Considering the high GST levels in HCC patients, this compound demonstrated the high potential for sensitizing HCC therapy in clinical practice by down-regulating GST levels.
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Objective: Hormone receptor (HR)-low/HER2-negative breast cancers (BCs) are more likely to be basal-like BCs, with similar molecular features and gene expression profiles to HR-negative (estrogen receptor <1% or negative and progesterone receptor <1% or negative) BCs. Recently, with the clinical application of adjuvant intensive therapy for triple-negative breast cancer (TNBC), the prognosis of TNBC patients without pathological complete response (pCR) has significantly improved. Therefore, it is necessary to reanalyse the prognostic characteristics of clinically high-risk HR-low/HER2-negative BC. Methods: According to the inclusion and exclusion standards, 288 patients with HR-low/HER2-negative BC and TNBC who received NAC and were followed up between 2015 and 2022 at three breast centres in Hunan Province, China, were enrolled. Inverse probability of treatment weighting (IPTW) was utilized to mitigate imbalances in baseline characteristics between the HR-low/HER2-negative BC group and TNBC group regarding event-free survival (EFS) and overall survival (OS). The primary clinical endpoints were pCR and EFS, while the secondary endpoints included OS, objective response rate (ORR), and clinical benefit rate (CBR). Results: The pCR rate (27.1% vs. 28.0%, P = 1.000), ORR rate (76.9% vs. 78.3%, P = 0.827) and CBR rate (89.7% vs. 96.5%, P = 0.113) after NAC were similar between the HR-low/HER2-negative BC and the TNBC group. EFS in patients with non-pCR from the 2 groups was significantly inferior in comparison to patients with pCR (P = 0.001), and the 3-year EFS was 94.74% (95% CI = 85.21% to 100.00%) and 57.39% (95% CI =43.81% to 75.19%) in patients with pCR and non-pCR from the HR-low/HER2-negative BC group, respectively, and 89.70% (95% CI = 82.20% to 97.90%) and 69.73% (95% CI = 62.51% to 77.77%) in the TNBC patients with pCR and non-pCR, respectively. Conclusions: In the real world, the therapeutic effects of NAC for HR-low/HER2-negative BCs and TNBCs were similar. EFS of patients with non-pCR in the HR-low/HER2-negative BC group was inferior to that of the TNBC group with non-pCR, suggesting that it is necessary to explore new adjuvant intensive therapy strategies for these patients.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Terapia Neoadyuvante , Pronóstico , Estudios de Cohortes , ChinaRESUMEN
BACKGROUND: Suture knotting is the basis of surgical skills. In the process of surgical skills learning, the surrounding environment, especially the light, will affect the efficiency of learning. This study investigated the effect of optical environment on the learning of stitching and knotting skills. METHODS: A total of 44 medical students were randomly divided into four groups and participated in the study of suture knotting in four different optical environments. During the process, we assess objective pressure level by testing salivary amylase activity Likert scale and objective structured clinical examination (OSCE) was used to estimate the subjective psychological state and overall skill mastery in surgical suturing respectively. RESULTS: Under high illumination conditions (700 lx), the salivary amylase activity of the high color temperature group (6000 K) was significantly higher than that of the low color temperature group (4000 K) (p < 0.0001). Similarly, under low illumination (300 lx), the salivary amylase activity of the high color temperature group was also significantly higher than that of the low color temperature group (p < 0.05). The student under high illumination conditions (700 lx) and the low color temperature (6000 K) have an autonomy score between 37-45, which is significantly higher compared to the other three groups (p < 0.0001). Group 2 has an average OSCE score of 95.09, which were significantly higher than those of the other three groups (p < 0.05). CONCLUSION: High illumination combined with low color temperature is considered as the optimal training conditions, promoting trainees' optimism, reducing stress levels, and enhancing learning efficiency. These results highlight the pivotal role of light environment in improving the quality and efficiency of surgical skills training.
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Aprendizaje , Examen Físico , Humanos , Amilasas , Competencia Clínica , Técnicas de Sutura/educaciónRESUMEN
Purpose: Meigs' syndrome is a rare gynecological disease characterized by the triad of benign ovarian tumor, ascites, and pleural effusion. Ovarian malignancies should be highly suspected in a postmenopausal woman with a pelvic mass, ascites, hydrothorax, and an elevated carbohydrate antigen 125 (CA125) level. It can be challenging to make a preoperative diagnosis of Meigs' syndrome. In this report, we present a case of Meigs' syndrome caused by an ovarian fibrothecoma and review the relevant literature to raise awareness and avoid misdiagnosis. Case Presentation: An 82-year-old woman with a 2-week history of abdominal distension was admitted to the Department of Gynecology. Ultrasound and thoracoabdominal computed tomography scans showed a left-sided hypoechoic mass in the pelvic cavity with bilateral pleural effusion and massive ascites. The CA125 concentration was 1040 U/mL (normal, 0-35 U/mL). With a working diagnosis of ovarian malignancy, the patient underwent ultrasound-guided fine-needle puncture of the pelvic mass and paracentesis to drain the ascites. The fine-needle puncture and paracentesis fluid analysis results revealed that the ascites did not contain any tumor cells, and the pelvic mass was identified as a spindle cell tumor. Immunohistochemistry confirmed that it was a sex-cord stromal tumor. Total abdominal hysterectomy and bilateral adnexectomy were performed under general anesthesia. The pathology results confirmed the mass to have been an ovarian fibrothecoma. At the 2-month postoperative follow-up, the ascites and hydrothorax had resolved and not recurred, and the CA125 level was normal. Conclusion: Despite the high suspicion of ovarian carcinoma in postmenopausal women presenting with pelvic mass, ascites, pleural effusion, and elevated CA125, Meigs' syndrome should be considered.
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OBJECTIVE: Promoting angiogenesis is crucial for tissue repair. Adipose-derived mesenchymal stem cells (ADSCs) are endowed with the ability of paracrine secretion of various angiogenic cytokines and the differentiation potential into endothelium-like cells to directly participate in angiogenesis. ADSCs are key seed cells for promoting angiogenesis in regenerative medicine and tissue engineering. This study aimed to explore the role and mechanism of C9orf106 (LINC02913) in the angiogenesis of ADSCs. METHODS: The microarray dataset GSE12884 was analyzed to identify the differentially expressed lncRNAs in ADSCs under normoxia and hypoxia. The expression of the key genes was detected using qRT-PCR, western blot assay (western blot), and immunofluorescence (IF) staining. The adipogenic ability and tube formation ability of ADSCs was detected using oil red O staining and tube formation assay, respectively. The regulatory relationship between hypoxia-inducible factor-1alpha (HIF1A) and LINC02913 was verified using chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay. A skin wound healing nude mice model was established. Hematoxylin and eosin (H&E) staining was applied to detect pathological skin damage. Immunohistochemistry (IHC) staining was used to determine the level of CD31 in skin tissues. RESULTS: LINC02913 expression was decreased in ADSCs under hypoxia; LINC02913 overexpression inhibited the proliferation, adipogenic ability, endothelial differentiation ability, and tube formation ability of ADSCs. ChIP assay and dual-luciferase reporter gene assay results showed that HIF1A could directly bind to the LINC02913 promoter region to inhibit its transcription. Through RNAact prediction and analysis of the correlation with LINC02913 expression, it was found that IGF1R may directly interact with LINCO02913. The HIF1A/LINC02913/IGF1R axis could activate the PI3K/AKT pathway to promote the biological function of ADSCs. Hypoxia-ADSCs significantly promoted vascularization in the wounded skin. The regulatory effect of LINC02913/IGF1R axis on hypoxia-ADSCs treated skin wound healing were verified. CONCLUSION: The HIF1A/LINC02913/IGF1R axis promoted the proliferation, adipogenic ability, and tube formation ability of ADSCs under hypoxia via activating the PI3K/AKT pathway.
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Subunidad alfa del Factor 1 Inducible por Hipoxia , Hipoxia , Células Madre Mesenquimatosas , ARN Largo no Codificante , Receptor IGF Tipo 1 , Animales , Humanos , Ratones , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Luciferasas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones Desnudos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Metabolic reprogramming is a hallmark of cancer. Several studies have shown that inactivation of Krebs cycle enzymes, such as citrate synthase (CS) and fumarate hydratase (FH), facilitates aerobic glycolysis and cancer progression. MAEL has been shown to play an oncogenic role in bladder, liver, colon, and gastric cancers, but its role in breast cancer and metabolism is still unknown. Here, we demonstrated that MAEL promoted malignant behaviours and aerobic glycolysis in breast cancer cells. Mechanistically, MAEL interacted with CS/FH and HSAP8 via its MAEL domain and HMG domain, respectively, and then enhanced the binding affinity of CS/FH with HSPA8, facilitating the transport of CS/FH to the lysosome for degradation. MAEL-induced degradation of CS and FH could be suppressed by the lysosome inhibitors leupeptin and NH4 Cl, but not by the macroautophagy inhibitor 3-MA or the proteasome inhibitor MG132. These results suggested that MAEL promoted the degradation of CS and FH via chaperone-mediated autophagy (CMA). Further studies showed that the expression of MAEL was significantly and negatively correlated with CS and FH in breast cancer. Moreover, overexpression of CS or/and FH could reverse the oncogenic effects of MAEL. Taken together, MAEL promotes a metabolic shift from oxidative phosphorylation to glycolysis by inducing CMA-dependent degradation of CS and FH, thereby promoting breast cancer progression. These findings have elucidated a novel molecular mechanism of MAEL in cancer.
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Neoplasias de la Mama , Autofagia Mediada por Chaperones , Humanos , Femenino , Neoplasias de la Mama/genética , Fumarato Hidratasa/genética , Fumarato Hidratasa/metabolismo , Citrato (si)-Sintasa/metabolismo , Ciclo del Ácido Cítrico , AutofagiaRESUMEN
Although combined photodynamic/photothermal therapy (PDT/PTT) has been used for cancer theranostics recently, their therapeutic efficacy has been compromised by the low O2 partial pressure and high concentration of GSH in the tumor microenvironment (TME). Thus, the construction of intelligent TME-responsive nanocomplexes is a powerful strategy for addressing the above issues. In this study, MnO2-coated Prussian blue nanocomplexes (PM NPs) were designed as O2 suppliers and GSH depletion agents to reprogram the TME. Subsequently, tumor-targeting peptide (RGD)-modified erythrocyte membrane vesicles loaded with photosensitizer (Ce6) were used to camouflage PM NPs (PMRCR NPs). Importantly, the prepared PMRCR NPs exhibited excellent photothermal performance with a photothermal conversion efficiency of 44.9%. Moreover, the in vitro PDT/PTT was enhanced, by which the cell viability was reduced to 21.4%, which is lower than the 55.6% (PDT) and 66.7% (PTT) of PMRCR NPs with a single laser treatment. By modeling 4T1 tumor-bearing mice, the combined PDT/PTT of PMRCR NPs greatly inhibited tumor growth, and after 20 days, a tumor inhibition rate of 92.9% was achieved. This work provides a promising strategy by developing TME-reprogrammed multifunctional nanocomplexes to enhance PDT/PTT antitumor efficacy.
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Fotoquimioterapia , Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Membrana Eritrocítica , Compuestos de Manganeso , Óxidos , Microambiente TumoralRESUMEN
Highly sensitive and reliable detection of multiple myeloma remains a major challenge in liquid biopsy. Herein, for the first time, quantum dot-molecular beacon (QD-MB) functionalized MoS2 (QD-MB @MoS2) fluorescent probes were designed for the dual detection of multiple myeloma (MM)-related miRNA-155 and miRNA-150. The results indicate that the two probes can effectively detect miRNA-155 and miRNA-150 simultaneously with satisfactory recovery rates, and the limit of detections (LODs) of miRNA-155 and miRNA-150 in human serum are low to 7.19 fM and 5.84 fM, respectively. These results indicate that our method is the most sensitive detection so far reported and that the designed fluorescent probes with signal amplification strategies can achieve highly sensitive detection of MM-related miRNAs for MM diagnosis.
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Colorectal cancer (CRC) is one of the most frequently occurring malignancy tumors with a high morbidity additionally, CRC patients may develop liver metastasis, which is the major cause of death. Despite significant advances in diagnostic and therapeutic techniques, the survival rate of colorectal liver metastasis (CRLM) patients remains very low. CRLM, as a complex cascade reaction process involving multiple factors and procedures, has complex and diverse molecular mechanisms. In this review, we summarize the mechanisms/pathophysiology, diagnosis, treatment of CRLM. We also focus on an overview of the recent advances in understanding the molecular basis of CRLM with a special emphasis on tumor microenvironment and promise of newer targeted therapies for CRLM, further improving the prognosis of CRLM patients.
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Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Microambiente Tumoral/genéticaRESUMEN
The role of PTPRT in breast cancer was not comprehensively explored and well analyzed. Our study comprehensively searched available databases to analyze the clinical role of PTPRT in breast cancer. We found PTPRT was an antioncogene and could be used to distinguish different stages, age groups, molecular types, and grades for breast cancer. PTPRT might be primary resistance biomarkers for taxane, anthracycline, and ixabepilone but not be acquired resistance biomarkers. Higher PTPRT expression levels were associated with longer overall survival and recurrence-free survival. PTPRT was negatively associated with Ki67 and CDK4/6 but positively associated with BCL-2. PTPRT might be associated with cell cycle and microtubule, and tumor infiltration in B cell and macrophage cell. PTPRT could predict chemotherapy effectiveness and prognosis for breast cancer patients. PTPRT might inhibit tumor growth via disrupting the microtubule dynamics and cell cycle in breast cancer.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Metilación de ADN , Resistencia a Antineoplásicos , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Regulación hacia Arriba , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Bases de Datos Genéticas , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Regiones Promotoras Genéticas , Análisis de Supervivencia , Adulto JovenRESUMEN
Although drug combination has proved to be an efficient strategy for clinic gastric cancer therapy, how to further improve their bioavailability and reduce the side effects are still challenges due to the low solubility and untargeted ability of drugs. Recently, newly emerging nanotechnology has provided an alternative for constructing new drug delivery systems with high targeting ability and solubility. In this study, a pH-responsive liposome (Liposome-PEO, LP) loaded with apatinib (AP) and cinobufagin (CS-1) was used for combinational therapy against gastric cancer after coating with a hybrid membrane (R/C). The results indicated that the constructed nanocomplex LP-R/C@AC not only efficiently killed tumor cells in vitro by inducing apoptosis, autophagy, and pyroptosis, but also significantly inhibited tumor invasion and metastasis via the VEGFR2/STAT3 pathway. Moreover, it showed stronger anti-tumor activity in gastric cancer-bearing mouse models, as compared to the sole drugs. A naturally-derived hybrid cell membrane coating bestowed nanocomplexes with enhanced biointerfacing including prolonged circulation time and targeting ability.
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Antineoplásicos/farmacología , Liposomas/química , Nanopartículas/química , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Materiales Biocompatibles/química , Bufanólidos/química , Bufanólidos/farmacología , Bufanólidos/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Ratones , Ratones Desnudos , Nanopartículas/metabolismo , Piridinas/química , Piridinas/farmacología , Piridinas/uso terapéutico , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología , Distribución Tisular , Trasplante Heterólogo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
MicroRNAs (miRNAs) are regarded as important biomarkers for disease diagnostics and therapeutics due to their significant regulatory roles in physiologic and pathologic processes. Herein, a versatile nanoprobe based on reduced graphene oxide (rGO) and nucleic acid (DNA) probe was prepared for simultaneously visualize miR-451a and miR-214-3p in living cells. In vitro experiments demonstrated that the nanoprobe exhibits excellent selectivity and outstanding sensitivity as low as 1 nM towards miR-451a and miR-214-3p. Moreover, the detection signals of miRNAs have good linearity in their respective concentration ranges (miR-451a: 1-100 nM, Y1 = 9.3062X1+114.85 (R2 = 0.9965). miR-214-3p: 1-200 nM, Y2 = 1.4424X2+91.312 (R2 = 0.9961)). Finally, simultaneous dual-color imaging of miR-451a and miR-214-3p in human breast cancer cells (MDA-MB-231) was realized by exploiting the P1&P2@rGO nanoprobe. In summary, this simple and effective strategy provides a general sensing platform for highly sensitive detection and simultaneous imaging of dual miRNAs in living cells.
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Grafito , MicroARNs , Biomarcadores , Humanos , MicroARNs/genéticaRESUMEN
Accumulating evidence shows that circular RNA (circRNA) is an important regulator of many diseases, especially cancer. Gastric cancer (GC) is a malignant tumor of the digestive system. The regulatory role and potential mechanism of circRNAs in GC remain unknown. This study aims to explore the function and regulatory mechanism of circRNA-related competitive endogenous RNA (ceRNA) in GC. The circRNA expression profile was downloaded from the Gene Expression Omnibus (GEO) database. The RNA expression profile and clinical data were downloaded from The Cancer Genome Atlas (TCGA) database. Difference analysis was conducted after quality control. Based on CircInteractome, TargetScan, and miRDB databases, a circRNA-related ceRNA network was constructed. R package "clusterProfiler" was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Then, a univariate and multivariate Cox regression was used to construct a prognostic-related gene model to predict survival models. Finally, a gene set enrichment analysis (GSEA) analysis was performed to elucidate the function of genes related to prognosis. Altogether, 23 DEcircRNAs, 319 DEmiRNAs, and 14,541 DEmRNAs were identified. Based on ceRNA trends, the ceRNA network included 15 DEcircRNAs, 25 DEmiRNAs, and 1099 DEmRNAs in GC. Univariate and multivariate Cox proportional hazards regression analysis was used to establish a survival model with 11 prognosis-related genes and its AUC was 0.741, indicating good sensitivity and specificity in the prediction of GC prognosis. Finally, three prognostic-related genes were selected randomly to verify expression levels, which were consistent with the analysis result. The prognostic genes were significantly enriched in cancer-related biological processes, suggesting their roles in the onset and progression of GC. Our study constructs a prognostic model of GC, deepens our understanding of circRNA-related ceRNA networks in GC biology, and provided further implications for the diagnosis and treatment of GC.
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Redes Reguladoras de Genes/genética , ARN Circular/metabolismo , Neoplasias Gástricas/genética , Línea Celular Tumoral , Humanos , Pronóstico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Análisis de SupervivenciaRESUMEN
Breast cancer is one of the most frequent cancers in women and the globally leading cause of cancer-related deaths. Bioinformatics and experimental analyses found that miR-937-5p may play a proto-oncogenic role in breast cancer; however, the specific effects and the molecular mechanism need further investigation. GSEA-KEGG and GSEA-GO suggested that miR-937-5p might be related to cell cycle and DNA replication. The experimental data indicated that miR-937-5p inhibition significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest. Meanwhile, the protein levels of proliferating marker ki-67 and cell cycle regulators Cyclin A2, Cyclin B1, CDK1, and Cyclin D1 were also decreased by miR-937-5p inhibition. miR-937-5p could directly bind to and negatively regulate SOX17. SOX17 overexpression also significantly repressed the proliferation of breast carcinoma cells and elicited S-phase cell cycle arrest and decreased ki-67, ß-catenin, c-Myc, Cyclin A2, Cyclin B1, Cyclin D1, and CDK1 protein contents. More importantly, the effects of miR-937-5p were reversed by SOX17.
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Proliferación Celular , MicroARNs/metabolismo , Puntos de Control de la Fase S del Ciclo Celular , Factores de Transcripción SOXF/metabolismo , Vía de Señalización Wnt , Regiones no Traducidas 3' , Antagomirs/metabolismo , Secuencia de Bases , Neoplasias de la Mama , Proteína Quinasa CDC2/metabolismo , Línea Celular Tumoral , Movimiento Celular , Ciclina A2/metabolismo , Ciclina D1/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Factores de Transcripción SOXF/antagonistas & inhibidores , Factores de Transcripción SOXF/genética , Alineación de SecuenciaRESUMEN
Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) was reported to be a critical regulator of tumorigenesis and is frequently deregulated in several cancer types. However, the exact mechanism by which SNHG1 contributes to breast cancer progression has not been fully elucidated. The identification of the molecular mechanism of SNHG1 is important for understanding the development of breast cancer and for improving the prognosis of the patients with this disease. In the present study, increased expression levels of SNHG1 were noted in breast cancer tumors following analysis of differentially expressed lncRNAs between 1,063 tumor and 102 normal tissues derived from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGABRCA) dataset. This finding was further validated using 50 pairs of normal and tumor tissues that were collected from patients with breast cancer. Notably, SNHG1 expression was significantly correlated with estrogen receptor (ER)/progesterone receptor (PR) negative status (ER/PR) and advanced clinical stage in breast cancer tissues. Knockdown of SNHG1 led to cell growth arrest, cell cycle redistribution and cell migration inhibition of breast cancer cells. The miRDB database predicted that miR573 interacts with SNHG1. RTPCR confirmed the negative regulation of miR573 levels by SNHG1 in breast cancer cells and the Dualluciferase reporter assay confirmed their complementary binding. The repression of miR573 by SNGH1 decreased LIM domain only 4 (LMO4) mRNA and protein expression levels in the breast cancer cell lines tested and induced the expression of cyclin D1 and cyclin E. In vitro experiments indicated that LMO4 overexpression could reverse siSNHG1induced cell growth arrest, cell cycle redistribution and inhibition of cell migration in breast cancer cells. Moreover, the tumor xenograft model indicated that SNHG1 knockdown inhibited MDAMB231 growth in vivo and LMO4 overexpression reversed the tumor growth inhibition induced by SNHG1 knockdown. The present study demonstrated that SNHG1 acts as a novel oncogene in breast cancer via the SNHG/miR573/LMO4 axis and that it could be a promising therapeutic target for patients with breast cancer.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias de la Mama/patología , Proteínas con Dominio LIM/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Regulación hacia Arriba , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Neoplasias de la Mama/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas con Dominio LIM/metabolismo , Células MCF-7 , Ratones , Trasplante de NeoplasiasRESUMEN
OBJECTIVES: As a complication of diabetes mellitus (DM), one of the leading causes for death and disability for DM patients is diabetic foot ulcers (DFUs). Epithelial to mesenchymal transition (EMT) plays a critical role in wound healing of DFUs. miR-203 is specifically enriched in keratinocytes and has been shown to target interleukin 8 (IL-8), which acts as an activator for the EMT process. In this study, we explored the interaction between miR-203 and IL-8 in DFU rat models and human keratinocyte cells, underlying the mechanism of miR-203's function in DFUs progression. METHODS: DFU rat models were used to test gene expression in DFU progression. Diabetic keratinocyte cell lines were used to validate in vitro. Wound healing and Transwell assays were applied to evaluate cell migration and invasion abilities. The EMT process was estimated by testing expression of E-cadherin, Vimentin and Slug. The interaction between miR-203 and IL-8 was determined by Luciferase assay. RESULTS: Our results demonstrated that the wound-healing process had been slowed in DFUs, and the advanced glycation end products (AGEs) and the receptor for advanced glycation end products (RAGEs) in wound tissue were of a higher expression than those in normal rat. miR-203 was increased in skin tissues from DFU rat models, while IL-8 was decreased. Through knock-down of miR-203 in AGE-treated keratinocyte cells, it had been shown that the downregulation of miR-203 could promote cell proliferation and migration, and facilitate the EMT process. Meanwhile, Luciferase assay proved that miR-203 could directly target and inhibit IL-8. The repression of IL-8 could rescue the outcomes brought about by miR-203 inhibition. CONCLUSIONS: The upregulation of miR-203 in DFU tissues impaired wound healing by the repress EMT process. Specific knock-down of miR-203 could promote wound healing through the reactivation of its target gene IL-8 and the downstream IL-8/AKT pathway.
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Pie Diabético/genética , Transición Epitelial-Mesenquimal/genética , Queratinocitos/metabolismo , MicroARNs/genética , Animales , Cadherinas/metabolismo , Línea Celular , Movimiento Celular/genética , Pie Diabético/inmunología , Pie Diabético/metabolismo , Transición Epitelial-Mesenquimal/inmunología , Expresión Génica , Técnicas de Silenciamiento del Gen , Productos Finales de Glicación Avanzada/metabolismo , Humanos , Interleucina-8/inmunología , Interleucina-8/metabolismo , Queratinocitos/inmunología , MicroARNs/inmunología , MicroARNs/metabolismo , Ratas , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Factores de Transcripción de la Familia Snail/metabolismo , Vimentina/metabolismo , Cicatrización de Heridas/genética , Cicatrización de Heridas/inmunologíaRESUMEN
OBJECTIVE: To study the clinical application value of ultrasound-guided fine needle aspiration biopsy (US-FNAB) and contrast-enhanced ultrasound (CEU) in the diagnosis of thyroid imaging reported and data system Grade 4 (TI-RADS 4) nodules.â© Methods: A retrospective analysis of 134 patients with thyroid nodules surgery were selected, and their results of preoperative color Doppler ultrasonography were TI-RADS 4. The data of US-FNAB and CEU before operation and the results of pathological section after operation were collected. The pathological results were taken as the gold standard, and the specimens obtained by US-FNAB puncture were used for HE staining and cytological diagnosis. The sensitivity, specificity, accuracy and the cost were calculated for CEU and US-FNAB, respectively. The diagnostic efficacy of the 2 methods was compared.â© Results: Of 134 thyroid nodules, there were 131 malignant nodules (97.76%) and 3 benign ones (2.24%). The sensitivity of US-FNAB and CEU were 87.02% and 93.89% respectively. The specificity of US-FNAB and CEU were 100.00% and 66.67%. The accuracy of US-FNAB and CEU were 87.31% and 93.28% respectively. Comparisons of the diagnostic accuracy were performed by χ2 test. There was no significant difference in sensitivity between CEU and US-FNAB (P>0.05). However, the sensitivity of US-FNAB and CEU were 87.50% and 100.00%, respectively, when the maximum diameter of nodule was less than 10 mm, and there was statistical significance (P<0.05). The sensitivity of US-FNAB and CEU were 92.73% and 85.45%, respectively, when the maximum diameter of nodule was more than 10 mm, and there was no statistical significance (P>0.05). The cost and risk of US-FNAB was higher than those of CEU.â© Conclusion: The sensitivity of US-FNAB is higher than that of CEU for thyroid nodules with the diameter larger than 10 mm. With high detection rate, good safety and low cost, CEU can still be used for thyroid nodules with the diameter less than 10 mm, which is diagnosed as negative nodules by US-FNAB.
Asunto(s)
Neoplasias de la Tiroides , Nódulo Tiroideo , Biopsia con Aguja Fina , Sistemas de Datos , Humanos , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The role of supraclavicular lymph node dissection (SCLND) in breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLM) remains controversial. So far, there have been no effective imaging methods to precisely judge the feasibility of SCLND and the modes of ISLM. CASE REPORT: We innovatively applied a three-dimensional (3D) reconstruction system to assess the feasibility of SCLND preoperatively for 13 breast cancer patients with ISLM. Based on the 3D reconstruction system and intraoperative findings, we performed lymph node dissection of their lesion areas. Compared to computed tomography or ultrasonography, the 3D reconstruction system found more lymph nodes not only in the ipsilateral supraclavicular area but also in other areas in which metastasis may occur (p < 0.05), and provided visual images pertaining to the relationship between the lymph nodes and major blood vessels, nerves, and muscles. CONCLUSION: The 3D reconstruction system could significantly benefit the precise assessment of the lesion area and facilitate subsequent relevant surgery.
RESUMEN
PURPOSE: To study the predictive value of the DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT in the cervical intraepithelial neoplasia prognosis. METHOD: In the present study, 139 cases were collected and followed up for 24 months. The DNA methylation levels of JAM3, SOX1, SLIT2, C13ORF18, and TERT were tested from their exfoliated cells. One-way ANOVA, receiver operating characteristic (ROC) curve analyses were conducted to analyze the data. RESULTS: The DNA methylation of the five genes was associated with prognosis of CIN. The levels of methylation increased as the progression of lesion for the prognosis. For CIN1, difference between DNA methylation of JAM3, SOX1, SLIT2, and C13ORF18 had significance statistically (P < 0.001). Sensitivity (95.2%) and specificity (93.1%) of JAM3 were the highest compared with other genes for the prognosis of CIN1. In addition, for CIN2/3, DNA methylation of JAM3, SOX1, SLIT2, TERT, and C13ORF18 had difference statistically (P < 0.001). JAM3 were also the highest in sensitivity (95.2%) and specificity (93.1%) compared with other genes for the prognosis of CIN2/3. CONCLUSIONS: Our data suggest for the first time that DNA methylation levels are associated with prognosis of CIN significantly. DNA methylation levels of some genes, especially JAM3, may serve as markers for the prediction of the CIN prognosis, including CIN1 nature prognosis and CIN2/3 after treatment.