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Breast cancer stem cells (BCSCs) are key players in carcinogenesis and development. Small nucleolar RNAs (snoRNAs) seem to have a crucial influence on regulating stem cell-like properties in various cancers, but the underlying mechanism in breast cancer has not been determined. In this study, we first found that the expression of SNORA51 might be strongly and positively related to BCSCs-like properties. SNORA51 expression was assessed in breast cancer tissues (n = 158 patients) by in situ hybridization. Colony formation, cell counting kit-8, and sphere formation assays were used to detect cell proliferation and self-renewal, respectively. Wound healing and transwell assays were used to detect cell migration. Coimmunoprecipitation and molecular docking were used to determine the underlying mechanism through which SNORA51 regulates BCSCs-like properties. High SNORA51 expression was associated with a worse prognosis, overall survival, and disease-free survival, in 158 breast cancer patients and was also closely related to lymph node status, ER status, the Ki-67 index, histological grade, and TNM stage. Further analysis proved that SNORA51 could enhance and maintain stem cell-like properties, including cell proliferation, self-renewal, and migration, in breast cancer. Moreover, high SNORA51 expression could reduce nucleolar RPL3 expression, induce changes in the expression of NPM1 in the nucleolus and nucleoplasm, and ultimately increase c-MYC expression. Taken together, our findings demonstrated that SNORA51 could enhance BCSCs-like properties via the RPL3/NPM1/c-MYC pathway both in vitro and in vivo. Therefore, SNORA51 might be a significant biomarker and potential therapeutic target and might even provide a new viewpoint on the regulatory mechanism of snoRNAs in breast cancer or other malignant tumors.
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Neoplasias da Mama , Proliferação de Células , Células-Tronco Neoplásicas , Nucleofosmina , Proteínas Proto-Oncogênicas c-myc , RNA Nucleolar Pequeno , Proteína Ribossômica L3 , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , RNA Nucleolar Pequeno/genética , RNA Nucleolar Pequeno/metabolismo , Transdução de Sinais , Proteína Ribossômica L3/genética , Proteína Ribossômica L3/metabolismoRESUMO
BACKGROUND: Tumor infiltrating lymphocytes (TILs) have been shown to be associated with the prognosis of breast ductal carcinoma in situ (DCIS). In this systematic review and meta-analysis, we investigated the role of TILs and TIL subsets in predicting the recurrence risk of DCIS. METHOD: PubMed, Medline, Web of Science, Embase and Cochrane were searched to identify publications investigating the prognostic role of TILs in DCIS. After study screening, data extraction and risk of bias assessment, a meta-analysis was performed to assess the association between TILs (total TILs, CD4+, CD8+, FOXP3+, PD-L1+ TILs) and the risk of DCIS recurrence. RESULTS: A pooled analysis indicated that dense stromal TILs in DCIS were associated with a higher recurrence risk (HR 2.11 (95% CI 1.35-3.28)). Subgroup analysis showed that touching TILs (HR 4.73 (95% CI 2.28-9.80)) was more precise than the TIL ratio (HR 1.49 (95% CI 1.11-1.99)) in estimating DCIS recurrence risk. Moreover, the prognostic value of TILs seemed more suitable for patients who are diagnosed with DCIS and then undergo surgery (HR 2.77, (95% CI 1.26-6.07)) or surgery accompanied by radiotherapy (HR 2.26, (95% CI 1.29-3.95)), than for patients who receive comprehensive adjuvant therapies (HR 1.16, (95% CI 1.35-3.28)). Among subsets of TILs, dense stromal PD-L1+ TILs were valuable in predicting higher recurrence risk of DCIS. CONCLUSION: This systematic review and meta-analysis suggested a non-favorable prognosis of TILs and stromal PD-L1+ TILs in DCIS and indicated an appropriate assessment method for TILs and an eligible population.
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Carcinoma Intraductal não Infiltrante , Linfócitos do Interstício Tumoral , Antígeno B7-H1 , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Humanos , Linfócitos do Interstício Tumoral/patologia , PrognósticoRESUMO
BACKGROUND: Accumulating evidence implies that autophagy plays a critical role in breast cancer development and progression. It is crucial to screen out autophagy-related encoding genes (ARGs) with prognostic value in breast cancer and reveal their biological properties in the aggressiveness of breast cancer. METHODS: Univariate and multivariate Cox proportional hazards analyses were used to identify a prognostic risk model of ARGs from The Cancer Genome Atlas (TCGA). Kaplan-Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Western blot and immunohistochemistry (IHC) were conducted to assess the expression of VPS35 (one of ARGs in risk model). CCK8, Colony formation assay, Transwell migration/invasion assays and autophagy flux assay were used to confirm biological function of VPS35 in breast cancer. RESULTS: In this study, the prognostic risk model consisting of six ARGs (VPS35, TRIM21, PRKAB2, RUFY4, MAP1LC3A and LARP1) in breast cancer were identified. The risk model was further verified as a novel independent prognostic factor for breast cancer patients. We also clarified that vacuolar protein sorting-associated protein 35 (VPS35), one of ARGs in the risk model, was upregulated in breast cancer samples and cell lines. VPS35 overexpression was correlated with more aggressive phenotype of breast cancer and indicated worse prognosis in both progression-free survival and overall survival analyses. Meanwhile, VPS35 knockdown inhibited breast cancer cell proliferation, migration and invasion, suggesting that VPS35 promoted the progression of breast cancer. VPS35 silence also influenced autophagy process, indicating that VPS35 was essential for autophagy completion. CONCLUSION: Taken together, the six ARGs risk model has a remarkably prognostic value for breast cancer. Among them, VPS35 might exert as a significant oncogenic and prognostic factor for breast cancer and could be a promising autophagy-related therapeutic target in clinical practice.
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BACKGROUND: Long noncoding RNAs (lncRNAs) are emerging as crucial contributors to the development of breast cancer and are involved in the stemness regulation of breast cancer stem cells (BCSCs). LncRNAs are closely associated with the prognosis of breast cancer patients. It is critical to identify BCSC-related lncRNAs with prognostic value in breast cancer. METHODS: A co-expression network of BCSC-related mRNAs-lncRNAs from The Cancer Genome Atlas (TCGA) was constructed. Univariate and multivariate Cox proportional hazards analyses were used to identify a stemness risk model with prognostic value. Kaplan-Meier analysis, univariate and multivariate Cox regression analyses and receiver operating characteristic (ROC) curve analysis were performed to validate the risk model. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) functional annotation were conducted to analyze the risk model. RESULTS: In this study, BCSC-related lncRNAs in breast cancer were identified. We evaluated the prognostic value of these BCSC-related lncRNAs and eventually obtained a prognostic risk model consisting of 12 BCSC-related lncRNAs (Z68871.1, LINC00578, AC097639.1, AP003119.3, AP001207.3, LINC00668, AL122010.1, AC245297.3, LINC01871, AP000851.2, AC022509.2 and SEMA3B-AS1). The risk model was further verified as a novel independent prognostic factor for breast cancer patients based on the calculated risk score. Moreover, based on the risk model, the low- risk and high-risk groups displayed different stemness statuses. CONCLUSIONS: These findings suggested that the 12 BCSC-related lncRNA signature might be a promising prognostic factor for breast cancer and can promote the management of BCSC-related therapy in clinical practice.
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Neoplasias da Mama , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Longo não Codificante/genéticaRESUMO
BACKGROUND: Breast cancer is a highly heterogeneous disease, this poses challenges for classification and management. Long non-coding RNAs play acrucial role in the breast cancersdevelopment and progression, especially in tumor-related immune processes which have become the most rapidly investigated area. Therefore, we aimed at developing an immune-related lncRNA signature to improve the prognosis prediction of breast cancer. METHODS: We obtained breast cancer patient samples and corresponding clinical data from The Cancer Genome Atlas (TCGA) database. Immune-related lncRNAs were screened by co-expression analysis of immune-related genes which were downloaded from the Immunology Database and Analysis Portal (ImmPort). Clinical patient samples were randomly separated into training and testing sets. In the training set, univariate Cox regression analysis and LASSO regression were utilized to build a prognostic immune-related lncRNA signature. The signature was validated in the training set, testing set, and whole cohorts by the Kaplan-Meier log-rank test, time-dependent ROC curve analysis, principal component analysis, univariate andmultivariate Cox regression analyses. RESULTS: A total of 937 immune- related lncRNAs were identified, 15 candidate immune-related lncRNAs were significantly associated with overall survival (OS). Eight of these lncRNAs (OTUD6B-AS1, AL122010.1, AC136475.2, AL161646.1, AC245297.3, LINC00578, LINC01871, AP000442.2) were selected for establishment of the risk prediction model. The OS of patients in the low-risk group was higher than that of patients in the high-risk group (p = 1.215e - 06 in the training set; p = 0.0069 in the validation set; p = 1.233e - 07 in whole cohort). The time-dependent ROC curve analysis revealed that the AUCs for OS in the first, eighth, and tenth year were 0.812, 0.81, and 0.857, respectively, in the training set, 0.615, 0.68, 0.655 in the validation set, and 0.725, 0.742, 0.741 in the total cohort. Multivariate Cox regression analysis indicated the model was a reliable and independent indicator for the prognosis of breast cancer in the training set (HR = 1.432; 95% CI 1.204-1.702, p < 0.001), validation set (HR = 1.162; 95% CI 1.004-1.345, p = 0.044), and whole set (HR = 1.240; 95% CI 1.128-1.362, p < 0.001). GSEA analysis revealed a strong connection between the signature and immune-related biological processes and pathways. CONCLUSIONS: We constructed and verified a robust signature of 8 immune-related lncRNAs for the prediction of breast cancer patient survival.
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Neoplasias da Mama , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Prognóstico , RNA Longo não Codificante/genéticaRESUMO
In traditional medical school curriculum of cancer education in China, there is a very limited amount of teaching about breast cancer. The current situation may result in indifference to breast cancer education among medical students. Case-based learning (CBL) is a popular teaching method based on clinical cases. To date, there are few research reports about the application and research of CBL in breast cancer education. The aim of this study is to explore the teaching effect about CBL combined with lecture-based learning (LBL) in breast cancer education. Questions of breast cancer in National Medical Licensing Examination (NMLE) from 2011 to 2018 were analyzed. The questions about breast cancer were used as the evaluation criteria for this study. In this pilot study, a total of 140 students were randomly divided into a lecture only group (control group) and a lecture plus CBL group (observation group). The students in the observation group had better academic performances and abilities of memory, understanding, and application. They also had higher favorable impressions of the learning experience. In conclusion, more active approaches yield more learning and are viewed more favorably. CBL plus lecture can significantly improve education about breast cancer among medical students, which may be an important message for the evolution of curriculum in Chinese medical schools.
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Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Currículo/tendências , Educação de Graduação em Medicina/métodos , Educação Médica/normas , Aprendizagem Baseada em Problemas/métodos , Adulto , Estudos de Casos e Controles , China , Feminino , Humanos , Masculino , Projetos Piloto , Ensino , Adulto JovemRESUMO
Invasion and migration is the hallmark of malignant tumors as well as the major cause for breast cancer death. The polypyrimidine tract binding, PTB, protein serves as an important model for understanding how RNA binding proteins affect proliferation and invasion and how changes in the expression of these proteins can control complex programs of tumorigenesis. We have investigated some roles of polypyrimidine tract binding protein 1 (PTBP1) in human breast cancer. We found that PTBP1 was upregulated in breast cancer tissues compared with normal tissues and the same result was confirmed in breast cancer cell lines. Knockdown of PTBP1 substantially inhibited tumor cell growth, migration, and invasion. These results suggest that PTBP1 is associated with breast tumorigenesis and appears to be required for tumor cell growth and maintenance of metastasis. We further analyzed the relationship between PTBP1 and clinicopathological parameters and found that PTBP1 was correlated with her-2 expression, lymph node metastasis, and pathological stage. This will be a novel target for her-2(+ ) breast cancer. PTBP1 exerts these effects, in part, by regulating the phosphatase and tensin homolog-phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PTEN-PI3K/Akt) pathway and autophagy, and consequently alters cell growth and contributes to the invasion and metastasis.
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Autofagia/genética , Neoplasias da Mama/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Proteína de Ligação a Regiões Ricas em Polipirimidinas/genética , Proteínas de Ligação a RNA/genética , Animais , Apoptose , Neoplasias da Mama/patologia , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metástase Linfática/patologia , Células MCF-7 , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Proteína Oncogênica v-akt/genética , PTEN Fosfo-Hidrolase/genética , Receptor ErbB-2/genética , Transdução de Sinais/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The biological role and underlying mechanism of action of zinc-finger protein 326 (ZNF326) in malignant tumors, including breast cancer, are still not clear. In this study, we detected high expression of ZNF326 in breast cancer specimens (60/111, 54.1%) and breast cancer cell lines (7/7); the expression level of ZNF326 was inversely associated with advanced pTNM stage (P = 0.002), positive lymph node metastasis (P = 0.004), poor prognosis in patients with breast cancer (P = 0.0097), and ER/PR/Her2 status (P = 0.013). Meanwhile, the ectopic expression of ZNF326 significantly upregulated MMP7, EMT-related proteins (Snail and Slug), and cell cycle-related proteins (cyclinA2 and cyclinB1); downregulated E-cadherin expression; and promoted the proliferation and invasiveness of breast cancer cells both in vivo and in vitro. Mechanistically, co-immunoprecipitation and immunofluorescence assays both demonstrated that ZNF326 interacted with deleted in breast cancer-1 (DBC1) in breast cancer cells. Additionally, DBC1 knockdown eliminated the up-regulation of MMP7, EMT-related proteins, and cell cycle-related proteins as well as the enhanced proliferation and invasiveness induced by ZNF326. Therefore, we concluded that ZNF326 is highly expressed in breast cancer, is associated with poor prognosis, and plays a vital role in promoting the malignant phenotype of breast cancer cells by interacting with DBC1.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias da Mama/patologia , Proteínas de Transporte/metabolismo , Regulação para Cima , Animais , Neoplasias da Mama/metabolismo , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Células MCF-7 , Metaloproteinase 7 da Matriz/metabolismo , Camundongos , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Análise de SobrevidaRESUMO
Chromosome 6 open reading frame 106 (C6orf106) is a newly discovered protein; its expression and clinical pathological significance in human tumors remains unclear. Immunohistochemistry, Western blot, and immunofluorescence were performed to assess C6orf106 expression in non-small cell lung cancer (NSCLC). In addition, the relationships between subcellular localization and clinical pathological factors were analyzed. Through C6orf106 overexpression and repression, respectively, in lung cancer cell lines, we explored the effect of this molecule on NSCLC invasion abilities. C6orf106 was highly expressed in the cytoplasm of lung cancer tissue cells (60.4 %, 75/124), compared with adjacent normal lung tissues (15.2 %, 7/46, p < 0.001). In addition, its expression was positively correlated with differentiation (p = 0.001), TNM stage (p = 0.011), lymph node metastasis (p = 0.018), and poor prognosis (p = 0.006). Furthermore, C6orf106 overexpression enhanced NSCLC cell invasion. Moreover, C6orf106 was shown to increase vimentin expression, while decreasing E-cadherin and P120ctn. C6orf106 is highly expressed in NSCLC and correlates with clinical and pathological factors, as well as poor prognosis. C6orf106 promotes invasion in NSCLC cells. Finally, C6orf106 upregulates vimentin, and downregulates E-cadherin and P120ctn.
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Caderinas/biossíntese , Carcinoma Pulmonar de Células não Pequenas/genética , Cateninas/biossíntese , Proteínas de Neoplasias/genética , Vimentina/biossíntese , Idoso , Caderinas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Cateninas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Fases de Leitura Aberta/genética , Prognóstico , Vimentina/genética , delta CateninaRESUMO
Previous study indicated diversin overexpression in human cancers. However, its expression pattern in human gliomas and the molecular mechanisms of diversin on cancer progression have not been characterized. In the present study, diversin expression was investigated in 105 glioma specimens using immunohistochemistry. Negative staining was observed in normal glial cells, and positive staining was found in 33 out of 105 (31.4 %) glioma specimens. Diversin overexpression correlated with advanced tumor grade (p < 0.05). Small interfering RNA (siRNA) knockdown was performed in U87 and TG905 cell lines with high endogenous diversin expression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assay showed that diversin knockdown inhibited glioma cell growth. Matrigel invasion assay showed that diversin depletion inhibited cell invasion. In addition, messenger RNA (mRNA) and protein levels of matrix metallopeptidase 9 (MMP9) were downregulated after siRNA treatment. In conclusion, diversin is overexpressed in human glioma and regulates glioma cell proliferation and invasion, possibly through MMP9.
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Neoplasias Encefálicas/patologia , Proliferação de Células , Proteínas do Citoesqueleto/fisiologia , Glioma/patologia , Adulto , Idoso , Neoplasias Encefálicas/química , Linhagem Celular Tumoral , Proteínas do Citoesqueleto/análise , Feminino , Glioma/química , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade NeoplásicaRESUMO
Background: Breast cancer is the second most common cause of cancer-related mortality globally. Apolipoprotein L3 (APOL3), a member of the apolipoprotein family, has been implicated in the pathogenesis of cardiovascular diseases. Nevertheless, the functions and underlying mechanisms of APOL3 in breast cancer have yet to be elucidated. Methods: The patient data were sourced from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) assays were used to assess expression of APOL3. Cell proliferation rates were determined by Cell Counting Kit-8 (CCK-8) and colony formation assays. Flow cytometry was used to examine cell cycle distribution. Western blotting was conducted to investigate the expression of cell cycle related proteins. A xenograft model was used to evaluate the effect of APOL3 in vivo. APOL3-binding proteins were identified through mass spectrometry, co-immunoprecipitation (CO-IP) assay and immunofluorescence assay. Results: APOL3 expression was significantly downregulated in breast cancer, and its low expression was correlated with poor prognostic outcomes. Overexpression of APOL3 suppressed breast cancer cell proliferation, induced cell cycle disruption. Conversely, knockdown of APOL3 promoted cell proliferation. In vivo animal experiments demonstrated that APOL3 overexpression can inhibit tumor proliferation. Mass spectrometry, CO-IP and immunofluorescence assay confirmed the interaction between APOL3 and Y-box binding protein 1 (YBX1). Furthermore, YBX1 knockdown following APOL3 knockdown mitigated the enhanced proliferation. These results provide new ideas for clinically targeting APOL3 to inhibit proliferation in breast cancer. Conclusions: Our findings indicate that APOL3 inhibits breast cancer cell proliferation and cell cycle modulating P53 pathway through the interaction of YBX1.
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ETHNOPHARMACOLOGICAL RELEVANCE: Shenze Shugan capsule is a prescription of traditional Chinese medicine for nonalcoholic steatohepatitis treatment. It includes Rhei Radix et Rhizoma (RR), Cassiae Semen (CS) and Alismatis Rhizoma(AR), which widely contains rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. AIM OF THE STUDY: In this study, we aimed to explore the safety of the medicine, and further elucidate the mechanism of apoptosis induction in HK-2 cells by five components, including rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. MATERIALS AND METHODS: We investigated the nephrotoxicity of Shenze Shugan capsule, including RR, CS, AR and mixed herbs given for two months in rats. Superoxide dismutase (SOD) in kidney tissues, urea nitrogen (BUN) and creatinine (CRE) in serum were detected, and renal pathology analysis was performed. In cell experiments, the apoptotic rate and cell cycle distribution of HK-2 cells were tested by flow cytometry. The levels of mitochondrial membrane potential (ΔΨm) and related protein expression in mitochondrial pathway were measured as well. RESULTS: We confirmed that two months of administering high doses(60 times the dose for clinical use in adults) of RR, CS or mixed herbs upregulated the levels of CRE and RUN, inhibited SOD activity, and increased the degree of tubular degeneration and glomerular dilatation, but Shenze Shugan capsule has no significant differences in renal structure or renal function. In addition, we found that five components all concentration-dependently inhibited HK-2 cells proliferation and induced apoptosis, especially aurantio-obtusin as the novel nephrotoxic component. Rhein and emodin significantly induced S/M accumulation, but aurantio-obtusin, alisol A and alisol B 23-monoacetate significantly induced G1/M accumulation in HK-2 cells. Similarly, they could induce Caspase3 activation, loss of mitochondrial membrane potential (ΔΨm), and down-regulation of Bcl-2 and up-regulation of Bax. CONCLUSIONS: Through a two-month subchronic toxicity study in rats, our preliminary determination is that this formulation is safe and reliable for long-term use. Interestingly, the potentially toxic herbs such as RR, CS, AR can reduce toxicity by drug compatibility. When further exploring the mechanism of action of toxic herbs, we found that mitochondrial pathway is involved in the apoptosis of HK -2 cells induced by rhein, emodin, aurantio-obtusin, alisol A and alisol B 23-monoacetate. Our findings provide new ideas for safety studies of Shenze Shugan capsule.
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Emodina , Ratos , Animais , Antraquinonas/toxicidade , Apoptose , Superóxido DismutaseRESUMO
Background and Objective: Breast cancer gene expression signatures are developing rapidly and are expected to better understand the intrinsic features of the tumor, and also to optimize the treatment strategy in clinical practice. This review is to summarize the controversy and consensus in clinical practice of gene expression signatures, and to provide our perspective on these issues as well as recommendation for future direction. Methods: We reviewed English publications in PubMed related to breast cancer gene expression signatures from 2002 to 2022. Key Content and Findings: Five mature commercial gene expression signatures: Oncotype, MammaPrint, Prosigna/PAM50, EndoPredict and Breast Cancer Index (BCI) are available to provide the prognostic and predictive assessment. Although they could help to evaluate the risk of recurrence and to predict the benefits of certain treatments, their applications remain challenging. Treatment decisions should be determined by a combination of related clinical pathological factors in clinical practice. Conclusions: Gene expression signatures could assist in the determination of the adjuvant therapy of early-stage breast cancer. The prospective randomized clinical trials showed that chemotherapy may be exempted in low-risk patients. More sufficient data are expected for the application in radiotherapy, extended endocrine therapy, and neoadjuvant treatment. The treatment cannot be determined by a single factor but by comprehensive assessments of clinicopathological factors, test purpose, and cost-effectiveness. Patients will benefit from personalized treatments with the publication of further evidence.
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Background: Breast cancer is the most prevalent malignancy worldwide and the leading culprit for women's death. Cuproptosis is a novel and promising modality of tumor cell death and the relationship with long non-coding RNAs (lncRNAs) remains shrouded in a veil. Studies in cuproptosis-related lncRNAs can aid in the clinical management of breast cancer and provide a basis for anti-tumor drug development. Methods: RNA-Seq data, somatic mutation data, and clinical information were downloaded from The Cancer Genome Atlas (TCGA). Patients were divided into high- and low-risk groups according to the risk score. Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were used to select prognostic lncRNAs to construct a risk score system. Its' prognostic value was confirmed in the training and validation cohorts subsequently. Functional analysis regarding cuproptosis-related lncRNAs was performed. Results: Eighteen cuproptosis-related lncRNAs were identified and 11 of them including AL023882.1, AC091588.1, AC138028.2, AC027514.1, AL592301.1, LRRC8C-DT, MFF-DT, NIFK-AS1, MECOM-AS1, OTUD6B-AS1 and RNF32-AS1 were selected for risk score system construction. The risk score was confirmed as an independent prognostic factor and patients in the high-risk group had a worse prognosis. A nomogram based on the independent prognostic factors was constructed for clinical decision aids. Further analyses revealed that patients in the high-risk group faced a heavier tumor mutational burden (TMB) and suppressed anti-tumor immunity. Besides, cuproptosis-related lncRNAs were associated with the expression of immune checkpoint inhibitors, N6-adenylate methylation (m6a), and drug sensitivity in breast cancer. Conclusions: A prognostic risk score system with satisfactory predictive accuracy was constructed. Besides, cuproptosis-related lncRNAs can influence the immune microenvironment, TMB, m6a, and drug sensitivity in breast cancer, which may provide a basis for future anti-tumor drug development.
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Biomaterials, when implanted in the human body, can induce a series of cell- and cytokine-related reactions termed foreign body reactions (FBRs). In the progression of FBRs, macrophages regulate inflammation and healing by polarizing to either a pro-inflammatory or pro-healing phenotype and recruit fibroblasts by secreting cytokines. Stimulated by the biomaterials, fibrotic capsule is formed eventually. The implant, along with its newly formed capsule, introduces various mechanical cues that influence cellular functions. Mechanosensing proteins, such as integrins or ion channels, transduce extracellular mechanical signals into cytoplasm biochemical signals in response to mechanical stimuli. Consequently, the morphology, migration mode, function, and polarization state of the cells are affected. Modulated by different intracellular signaling pathways and their crosstalk, the expression of fibrotic genes increases with fibroblast activation and fibroblast to myofibroblast transition under stiff or force stimuli. However, summarized in most current studies, the outcomes of macrophage polarization in the effect of different mechanical cues are inconsistent. The underlying mechanisms should be investigated with more advanced technology and considering more interfering aspects. Further research is needed to determine how to modulate the progression of fibrotic capsule formation in FBR artificially.
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In recent years, the development of bispecific antibodies (bsAbs) has been rapid, with many new structures and target combinations being created. The boom in bsAbs has led to the successive issuance of industry guidance for their development in the US and China. However, there is a high degree of similarity in target selection, which could affect the development of diversity in bsAbs. This review presents a classification of various bsAbs for cancer therapy based on structure and target selection and examines the advantages of bsAbs over monoclonal antibodies (mAbs). Through database research, we have identified the preferences of available bsAbs combinations, suggesting rational target selection options and warning of potential wastage of medical resources. We have also compared the US and Chinese guidelines for bsAbs in order to provide a reference for their development.
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Four kinds of spinel NiAl2O4were synthesized by the polyacrylamide gel method using Al2(SO4)3·18H2O and Al(NO3)3·9H2O as aluminum salts and anhydrous NiSO4and NiSO4·6H2O as nickel salts. The effects of different aluminum salts and nickel salts on the structure, optical and photocatalytic activity of spinel NiAl2O4were confirmed by various characterizations. There is no NiO impurity in the spinel NiAl2O4synthesized with Al2(SO4)3·18H2O as aluminum salt, while NiAl2O4, NiO and C-O functional group coexist in the target product with Al(NO3)3·9H2O as aluminum salt, and C-O functional group and NiO inhibits the photocatalytic activity of the system. Based on photocatalytic experiment, response surface methodology and free radical verification experiment, the influence of experimental parameters including synthesis pathway, initial drug concentration, initialpHand catalyst content on the photocatalytic activity of spinel NiAl2O4and the main active species involved in the reaction were investigated. The degradation percentage of spinel NiAl2O4synthesized with Al2(SO4)3·18H2O as aluminum salt and NiSO4·6H2O as nickel salt was 86.3% at the initial concentration of 50 mg l-1,pH= 5.33 and catalyst content of 1 g l-1. The mechanism investigation confirmed that the C-O functional group plays the dual role of impurity level and electron transfer in the degradation of tetracycline hydrochloride by spinel NiAl2O4.
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Blocking the PD-1/PD-L1 interaction has become an important strategy for tumor therapy, which has shown outstanding therapeutic effects in clinical settings. However, unsatisfactory response rates and immune-related adverse effects limit the use of anti-PD1/PD-L1 antibodies. Here, we report the discovery and identification of S4-1, an innovative small-molecule inhibitor of PD-L1. In vitro, S4-1 effectively altered the PD-L1/PD-1 interaction, induced PD-L1 dimerization and internalization, improved its localization to endoplasmic reticulum, and thus enhanced the cytotoxicity of peripheral blood mononuclear cells toward tumor cells. In vivo, S4-1 significantly inhibited tumor growth in both lung and colorectal cancer models, particularly in colorectal cancer, where it led to complete clearance of a portion of the tumor cells. Furthermore, S4-1 induced T-cell activation and inversed the inhibitory tumor microenvironment, consistent with the PD-L1/PD-1 pathway blockade. These data support the continued evaluation of S4-1 as an alternative ICB therapeutic strategy.
Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Antígeno B7-H1 , Receptor de Morte Celular Programada 1/metabolismo , Leucócitos Mononucleares/metabolismo , Microambiente Tumoral , Linhagem Celular TumoralRESUMO
Most of the news headline generation models that use the sequence-to-sequence model or recurrent network have two shortcomings: the lack of parallel ability of the model and easily repeated generation of words. It is difficult to select the important words in news and reproduce these expressions, resulting in the headline that inaccurately summarizes the news. In this work, we propose a TD-NHG model, which stands for news headline generation based on an improved decoder from the transformer. The TD-NHG uses masked multi-head self-attention to learn the feature information of different representation subspaces of news texts and uses decoding selection strategy of top-k, top-p, and punishment mechanisms (repetition-penalty) in the decoding stage. We conducted a comparative experiment on the LCSTS dataset and CSTS dataset. Rouge-1, Rouge-2, and Rouge-L on the LCSTS dataset and CSTS dataset are 31.28/38.73, 12.68/24.97, and 28.31/37.47, respectively. The experimental results demonstrate that the proposed method can improve the accuracy and diversity of news headlines.
Assuntos
CausalidadeRESUMO
Occurrences of breast cancer and thyroid cancer metachronously or synchronously are common for women, but axillary lymph node metastasis from both cancers is rarely seen. We report a patient who had two metastatic lymph nodes from papillary thyroid carcinoma after axillary lymph node dissection with mastectomy. Papillary thyroid carcinoma diagnosis was ensured after thyroidectomy. A literature review revealed that even the co-occurrence of breast cancer and thyroid cancer is not rare, but the etiology behind this phenomenon is not elucidated well. Genetic disorders, thyroid dysfunction, and hormone receptors may be relevant. Considering the rareness of axillary lymph node metastasis of thyroid cancer, adjuvant therapy and surgery treatment for this kind of case should be considered elaborately.