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1.
Comput Biol Med ; 177: 108666, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820773

RESUMO

BACKGROUND: α-1,3-mannosyltransferase (ALG3) holds significance as a key member within the mannosyltransferase family. Nevertheless, the exact function of ALG3 in cancer remains ambiguous. Consequently, the current research aimed to examine the function and potential mechanisms of ALG3 in various types of cancer. METHODS: Deep pan-cancer analyses were conducted to investigate the expression patterns, prognostic value, genetic variations, single-cell omics, immunology, and drug responses associated with ALG3. Subsequently, in vitro experiments were executed to ascertain the biological role of ALG3 in breast cancer. Moreover, the link between ALG3 and CD8+ T cells was verified using immunofluorescence. Lastly, the association between ALG3 and chemokines was assessed using qRT-PCR and ELISA. RESULTS: Deep pan-cancer analysis demonstrated a heightened expression of ALG3 in the majority of tumors based on multi-omics evidence. ALG3 emerges as a diagnostic and prognostic biomarker across diverse cancer types. In addition, ALG3 participates in regulating the tumor immune microenvironment. Elevated levels of ALG3 were closely linked to the infiltration of bone marrow-derived suppressor cells (MDSC) and CD8+ T cells. According to in vitro experiments, ALG3 promotes proliferation and migration of breast cancer cells. Moreover, ALG3 inhibited CD8+ T cell infiltration by suppressing chemokine secretion. Finally, the inhibition of ALG3 enhanced the responsiveness of breast cancer cells to 5-fluorouracil treatment. CONCLUSION: ALG3 shows potential as both a prognostic indicator and immune infiltration biomarker across various types of cancer. Inhibition of ALG3 may represent a promising therapeutic strategy for tumor treatment.


Assuntos
Linfócitos T CD8-Positivos , Fluoruracila , Humanos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Fluoruracila/farmacologia , Quimiocinas/metabolismo , Quimiocinas/genética , Feminino , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/genética , Neoplasias/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Multiômica
2.
Artigo em Inglês | MEDLINE | ID: mdl-38476642

RESUMO

Background: Breast cancer (BC) is increasingly becoming the primary reason for death in women, which sounded the alarm. Thus, finding a novel management target for BC is imminent. Materials and Methods: The data on gene expression and clinicopathological characteristics were downloaded from The Cancer Genome Atlas (TCGA). The expression of GNPNAT1 in 40 paired breast cancer and adjacent tissues was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Univariate and Multivariate logistic regression methodology was applied to analyze the prognostic factors for lymph node metastasis (LNM). Based on the status of breast cancer-relative receptors, patients were distributed into six groups, and then the Kaplan-Meier survival analysis with a Log rank test was applied to investigate the involvement among the expression of GNPNAT1 and overall survival (OS). Results: We found higher expression of GNPNAT1 was connected with poor survival in breast cancer by COX regulation analysis. GO, KEGG, and GSEA analysis prompted that GNPNAT1 was connected with the defense mechanism of cells, cell proliferation, and division. Immunization infiltration analysis showed that high GNPNAT1 was negatively connected with 16 immunization infiltration cell types and positively connected with four immunization infiltration cell types. Conclusion: As a whole, our results indicated that GNPNAT1 might be a probable biomarker for diagnosis and prognosis in breast cancer.

3.
Curr Med Chem ; 31(15): 2073-2089, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37282654

RESUMO

BACKGROUND: To create effective medicines, researchers must first identify the common or unique genes that drive oncogenic processes in human cancers. Serine protease 27 (PRSS27) has been recently defined as a possible driver gene in esophageal squamous cell carcinoma. However, no thorough pan-cancer study has been performed to date, including breast cancer. METHODS: Using the TCGA (The Cancer Genome Atlas), the GEO (Gene Expression Omnibus) dataset, and multiple bioinformatic tools, we investigated the function of PRSS27 in 33 tumor types. In addition, prognosis analysis of PRSS27 in breast cancer was carried out, as well as in vitro experiments to verify its role as an oncogene. We first explored the expression of PRSS27 in over 10 tumors and then we looked into PRSS27 genomic mutations. RESULTS: We discovered that PRSS27 has prognostic significance in breast cancer and other cancers' survival, and we developed a breast cancer prognostic prediction model by combining a defined set of clinical factors. Besides, we confirmed PRSS27 as an oncogene in breast cancer using some primary in vitro experiments. CONCLUSION: Our pan-cancer survey has comprehensively reviewed the oncogenic function of PRSS27 in various human malignancies, suggesting that it may be a promising prognostic biomarker and tumor therapeutic target in breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Feminino , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Prognóstico , Endopeptidases , Serina Proteases/genética , Biomarcadores , Serina Endopeptidases/genética
4.
Clin Med Insights Oncol ; 17: 11795549231199920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37744427

RESUMO

Background: Thyroid nodules, although mostly benign and symptomless, have a small chance of being cancerous, necessitating accurate diagnosis. This study aims to develop and validate a nomogram for differentiating malignant and non-malignant thyroid nodules in individuals with type 2 diabetes. Methods: The study included 484 patients with both thyroid nodules and type 2 diabetes who underwent thyroid gland lobectomy at Wenzhou Medical University Hospital. Optimal cutoff values for continuous variables were determined using ROC curve analysis. Significant factors identified in univariable analysis were used to construct the nomogram. The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) was visualized through a histogram and scatter diagram. Discriminatory power was assessed using ROC analysis, and calibration curves ensured consistency. Decision curve analysis (DCA) evaluated clinical benefits. Results: The cohort was divided into a training group (70%) and an internal validation group (30%). The scatter diagram revealed a correlation between MHR levels and the proportion of goiter cases, with higher MHR levels associated with increased goiter incidence. The histogram showed higher average MHR levels in goiter patients compared to those with papillary thyroid carcinoma (PTC) in both groups. Multivariate logistic regression identified age, total cholesterol (TC), triglyceride (TG), fasting blood sugar (FSG), fibrinogen, lymphocyte-to-monocyte ratio (LMR), and MHR as independent predictive factors for malignancy in thyroid nodules with type 2 diabetes. The nomogram achieved high discrimination, with C-index values of 0.901 (training data set) and 0.760 (internal validation data set). Calibration curves displayed good agreement, and DCA demonstrated significant net clinical benefits. Conclusions: MHR is associated with sex, serum cholesterol levels, and peripheral blood cell counts, making it a potential novel biomarker for differentiating between PTC and goiter in type 2 diabetes patients.

5.
Neoplasia ; 43: 100913, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37348428

RESUMO

Human epidermal growth factor receptor 2 (HER2) plays a critical role in breast cancer progression in patients with HER2 overexpression, thereby driving the development of targeted drugs and advancing therapy strategies targeting this gene. Pyrotinib is a novel irreversible pan-ErbB kinase inhibitor, primarily suppresses the downstream MAPK and PI3K/AKT pathways. Alpelisib, a selective PI3K p110α inhibitor, has been approved for clinical application in HR+, HER2-, PIK3CA mutated breast cancers and is also being developed for use in other breast cancer subtypes. In this study, we hypothesised that combining pyrotinib with alpelisib would yield superior results compared to single-drug treatment. Our data demonstrated that the combination of alpelisib and pyrotinib exhibited a synergistic effect in HER2+ breast cancer both in vitro and in vivo. This combination led to decreased cell proliferation and migration, G0-G1 cell cycle arrest, and increased apoptosis rates. Additionally, the deactivation of ErbB receptors and sustained activation of PI3K/AKT pathway by upstream compensatory pathways induced acquired pyrotinib resistant cells resistant to pyrotinib treatment, thus alpelisib combined with pyrotinib showed a tremendous synergistic effect and reverse pyrotinib resistance in acquired pyrotinib resistant cells by suppressing the activated PI3K/AKT pathway. Our results revealed a combination of pyrotinib and alpelisib as an effective therapeutic strategy in treating HER2+ breast cancer, whether sensitive or resistant to pyrotinib treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor ErbB-2/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Classe I de Fosfatidilinositol 3-Quinases
6.
Curr Med Chem ; 2023 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-37221682

RESUMO

BACKGROUND: Thyroid cancer (TC), the most common endocrine malignant tumor, is increasingly causing a huge threat to our health nowadays. METHODS: To explore the tumorigenesis mechanism of thyroid cancer, we identified that long intergenic non-coding RNA-00891 (LINC00891) was upregulated in TC using the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and local databases. LINC00891 expression correlated with histological type and lymph node metastasis (LNM). The high expression of LINC00891 could serve as a diagnostic marker for TC and its LNM. In vitro experiments demonstrated that LINC00891 knockdown could inhibit cell proliferation, migration, invasion apoptosis, and of TC cells. We also investigated the related mechanisms of LINC00891 promoting TC progression using RNA sequencing, Gene Set Enrichment Analysis, and Western blotting. RESULTS: Our experiments demonstrated that LINC00891 promoted TC progression via the EZH2-SMAD2/3 signaling axis. In addition, overexpression of EZH2 could reverse the suppressive epithelial-to-mesenchymal transition (EMT) caused by LINC00891 knockdown. CONCLUSION: In conclusion, the LINC00891/EZH2/SMAD2/3 regulatory axis participated in tumorigenesis and metastasis of thyroid cancer, which may provide a novel target for treatment.

7.
Phytomedicine ; 114: 154769, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36940580

RESUMO

BACKGOUND: Triple negative breast cancer (TNBC) is an extremely aggressive and rapidly progressing cancer, wherein existing therapies provide little benefit to patients. ß, ß-Dimethylacrylshikonin (DMAS), an active naphthoquinone derived from comfrey root, has potent anticancer activity. However, the antitumor function of DMAS against TNBC remains to be proved. PURPOSE: Explore effects of DMAS on TNBC and clarify the mechanism. STUDY DESIGN: Network pharmacology, transcriptomics and various cell functional experiments were applied to TNBC cells to explore the effects of DMAS on TNBC. The conclusions were further validated in xenograft animal models. METHODS: MTT, EdU, transwell, scratch tests, flow cytometry, immunofluorescence, and immunoblot were utilized to assess the activity of DMAS on three TNBC cell lines. The anti-TNBC mechanism of DMAS was clarified by overexpression and knockdown of STAT3 in BT-549 cells. In vivo efficacy of DMAS was analysed using a xenograft mouse model. RESULTS: In vitro analysis revealed that DMAS inhibited the G2/M phase transition and suppressed TNBC proliferation. Additionally, DMAS triggered mitochondrial-dependent apoptosis and reduced cell migration by antagonizing epithelial-mesenchymal transition. Mechanistically, DMAS exerted its antitumour effects by inhibiting STAT3Y705 phosphorylation. STAT3 overexpression abolished the inhibitory effect of DMAS. Further studies showed that treatment with DMAS inhibited TNBC growth in a xenograft model. Notably, DMAS potentiated the sensitivity of TNBC to paclitaxel and inhibited immune evasion by downregulating the immune checkpoint PD-L1. CONCLUSIONS: For the first time, our study revealed that DMAS potentiates paclitaxel activity, suppresses immune evasion and TNBC progression by inhibiting STAT3 pathway. It has the potential as a promising agent for TNBC.


Assuntos
Paclitaxel , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Paclitaxel/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Evasão da Resposta Imune , Fosforilação , Farmacologia em Rede , Transcriptoma , Proliferação de Células , Apoptose , Linhagem Celular Tumoral
8.
Environ Toxicol ; 38(5): 1100-1117, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36757015

RESUMO

In this study, we first comprehensively investigated the expression profile, mutation status, and survival analysis of FAM72A as well as the correlation between FAM72A and DNA damage repair, methylation, and cell stemness analysis using bioinformatics techniques. In addition, we also analyzed the relationship between FAM72A and immune cell infiltration and pathway enrichment. The role of FAM72A in breast cancer (BC) was so conspicuous that we analyzed the prognostic significance and clinicopathological parameter's relevance of FAM72A in BC. We also validated biological functions by applying in vitro experiments. FAM72A was highly expressed in 26 types of a total of 31 cancers, while it expressed low levels in only five cancers. FAM72A expression was relative to clinical stages in nine cancers and has a significant difference in disease-free survival among 31 kinds of cancers. In addition, FAM72A has negatively correlated with cancer-associated fibroblast and endothelial cells in BC but positively correlated with follicular helper T cells. Univariate and multivariate cox regression analyses identified T, N, M, age, and FAM72A expression as independent influences on BC prognosis, so we created a nomogram to predict patient survival benefits. In in vitro experiments, we verified that downregulation of FAM72A not only inhibited cell proliferation, colony formation, cell migration, cell invasion, and G2/M cell cycle transition but also promoted apoptosis of breast invasive carcinoma cells. Our study discovered FAM72A as a clinically meaningful biomarker for prognostic predicting and a guiding target for immune treatment in BC.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Feminino , Humanos , Apoptose/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Células Endoteliais/metabolismo , Imunoterapia , Prognóstico
9.
Front Genet ; 13: 897538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072666

RESUMO

Breast cancer (BC) accounts for the highest proportion of the all cancers among women, and necroptosis is recognized as a form of caspase-independent programmed cell death. We created prognostic signatures using univariate survival analysis, and lasso regression, to assess immune microenvironments between subgroups. We then used network pharmacology to bind our drugs to target differentially expressed genes (DEGs). A signature comprising a set of necroptosis-related genes was established to predict patient outcomes based on median risk scores. Those above and below the median were classified as high-risk group (HRG) and low-risk group (LRG), respectively. Patients at high risk had lower overall survival, and poorer predicted tumor, nodes, and metastases stages (TNM). The novel prognostic signature can effectively predict the prognosis of breast cancer patients docking of ß,ß-dimethyl acryloyl shikonin (DMAS) to possible targets to cure breast cancer. We found that all current prognostic models do not offer suitable treatment options. In additional, by docking drugs DMAS that have been initially validated in our laboratory to treat breast cancer. We hope that this novel approach could contribute to cancer research.

11.
J Cancer ; 12(22): 6851-6860, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659573

RESUMO

Background: Thyroid malignancy is the most frequent endocrine malignant tumor whose incidence is still increasing. Mechanisms genomic variations play a major part in the pathogenesis of many types of malignancy. Synaptotagmin 12 (SYT12) is a member gene of the synaptotagmins family and SYT12's variants were shown to be associated with some malignancies. Nevertheless, SYT12's specific function and probable clinical value in papillary cancer were still unknown. Methods: We conducted complete genome sequence of 39 pairs PTC malignant neoplasm and matched non-neoplastic tissues. We found that SYT12 was significantly overexpressed in thyroid malignancy. Next, we investigated the expression level of SYT12 and the relation between clinical information and SYT12 expression in thyroid cancer in the Cancer Genome Atlas (TCGA). QRt-PCR of else 40 pairs local verified cohort was performed to confirm the sequencing data and TCGA cohort. Then, we used small interfering RNA (si-RNA) to knock down the expression of SYT12 in PTC cells. Finally, proliferation, cell colony formation, migration, invasion, and apoptosis assays were done to demonstrate the function of SYT12. Results: SYT12 is significantly overexpressed and higher expression of SYT12 upsurges the risk of lymph node metastatic and incidence rate of primary neoplasm multivariate focus type and classical histological type for PTC patients in TCGA cohort. In vitro experiments, the results of functional assays presented that knock-down of SYT12 inhibited the cell proliferation, cell colony formation, trans-well migration, and trans-well invasion and promoted cell apoptotic in PTC cell lines. Conclusion: SYT12 was a novel oncogene that promotes thyroid carcinoma progression and metastasis potential and a potential biomarker for diagnosis and treatment in PTC.

12.
Sci Rep ; 11(1): 20492, 2021 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650125

RESUMO

Recently some evidence has demonstrated the significance of PSMB8 in various malignancies. Nevertheless, PSMB8 (proteasome subunit beta 8), more familiar in the field of immunology contributing to the process of antigen presentation, is indeterminate in the role as a survival predictor of human pan-cancer. Besides, how PSMB8 interacts with immune cell infiltration in the tumor microenvironment requires further research. We then penetrated into the analysis of the PSMB8 expression profile among 33 types of cancer in the TCGA database. The results show that overexpression of PSMB8 was associated with poor clinical outcomes in overall survival (Sartorius et al. in Oncogene 35(22):2881-2892, 2016), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) in most cancer varieties. In addition, there existed distinctly positive correlations between PSMB8 and immunity, reflected straightforwardly in the form of immune scores, tumor-infiltrating immune cells (TIICs) abundance, microsatellite instability, tumor mutation burden, and neoantigen level. Notably, specific markers of dendrite cells exhibited the tightest association with PSMB8 expression in terms of tumor-related immune infiltration patterns. Moreover, gene enrichment analysis showed that elevated PSMB8 expression was related to multiple immune-related pathways. We finally validated the PSMB8 expression in our local breast samples via quantitative PCR assays and concluded that PSMB8 appeared to perform well in predicting the survival outcome of BRCA patients. These findings elucidate the pivotal role of the antigen presentation-related gene PSMB8, which could potentially serve as a robust biomarker for prognosis determination in multiple cancers.


Assuntos
Neoplasias/diagnóstico , Neoplasias/imunologia , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Instabilidade de Microssatélites , Oncogenes , Prognóstico , Complexo de Endopeptidases do Proteassoma/metabolismo , Análise de Sobrevida , Microambiente Tumoral
13.
Front Cell Dev Biol ; 9: 698388, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490250

RESUMO

Given the relatively poor understanding of the expression and functional effects of the N6-methyladenosine (m6A) RNA methylation on colorectal cancer (CRC), we attempted to measure its prognostic value and clinical significance. We comprehensively screened 37 m6A-related prognostic long non-coding RNAs (lncRNAs) with significant differences in expression based on 21 acknowledged regulators of m6A modification and data on 473 colorectal cancer tissues and 41 para-cancer tissues obtained from the TCGA database. Accordingly, we classified 473 CRC patients into two clusters by consensus clustering on the basis of significantly different survival outcomes. We also found a potential correlation between m6A-related prognostic lncRNAs and BRAF-KRAS expression, as well as immune cell infiltration. Then, we established a prognostic model by selecting 16 m6A-related prognostic lncRNAs via LASSO Cox analysis and grouped the CRC patients into low- and high-risk groups to calculate risk scores. Then, we performed stratified sampling to validate and confirm our model by categorising the 473 samples into a training group (N = 208) and a testing group (N = 205) in a 1:1 ratio. The survival curve showed a distinct clinical outcome in the low- and high-risk subgroups. We reconfirmed the reliability and independence of the prognostic model through various measures: risk curve, heat map and univariate and multivariate Cox analyses. To ensure that the outcomes were applicable to clinical settings, we performed stratified analyses on different clinical features, such as age, lymph node status and clinical stage. CRC patients with downregulated m6A-related gene expression, lower immune score, distant metastasis, lymph node metastasis or more advanced clinical staging had higher risk scores, indicating less-desirable outcomes. Moreover, we explored the immunology of colorectal cancer cells. The risk score showed positive correlations with eosinophils, M2 macrophages and neutrophils. In summary, our effort revealed the significance of m6A RNA methylation regulators in colorectal cancer, and the prognostic model we constructed may be used as an essential reference for predicting the outcome of CRC patients.

14.
Anesth Analg ; 133(4): 1048-1059, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34524989

RESUMO

BACKGROUND: Cardiotoxicity can be induced by the commonly used amide local anesthetic, bupivacaine. Bupivacaine can inhibit protein kinase B (AKT) phosphorylation and activated adenosine monophosphate-activated protein kinase alpha (AMPKα). It can decouple mitochondrial oxidative phosphorylation and enhance reactive oxygen species (ROS) production. Apelin enhances the phosphatidylinositol 3-kinase (PI3K)/AKT and AMPK/acetyl-CoA carboxylase (ACC) pathways, promotes the complete fatty acid oxidation in the heart, and reduces the release of ROS. In this study, we examined whether exogenous (Pyr1) apelin-13 could reverse bupivacaine-induced cardiotoxicity. METHODS: We used the bupivacaine-induced inhibition model in adult male Sprague Dawley (SD) rats (n = 48) and H9c2 cardiomyocyte cell cultures to explore the role of apelin-13 in the reversal of bupivacaine cardiotoxicity, and its possible mechanism of action. AMPKα, ACC, carnitine palmitoyl transferase (CPT), PI3K, AKT, superoxide dismutase 1 (SOD1), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p47-phox) were quantified. Changes in mitochondrial ultrastructure were examined, and mitochondrial DNA, cell viability, ROS release, oxygen consumption rate (OCR) were determined. RESULTS: Apelin-13 reduced bupivacaine-induced mitochondrial DNA lesions in SD rats (P < .001), while increasing the expression of AMPKα (P = .007) and PI3K (P = .002). Furthermore, apelin-13 blocked bupivacaine-induced depolarization of the mitochondrial membrane potential (P = .019) and the bupivacaine-induced increases in ROS (P = .001). Also, the AMPK pathway was activated by bupivacaine as well as apelin-13 (P = .002) in H9c2 cardiomyocytes. Additionally, the reduction in the PI3K expression by bupivacaine was mitigated by apelin-13 in H9c2 cardiomyocytes (P = .001). While the aforementioned changes induced by bupivacaine were not abated by apelin-13 after pretreatment with AMPK inhibitor compound C; the bupivacaine-induced changes were still mitigated by apelin-13, even when pretreated with PI3K inhibitor-LY294002. CONCLUSIONS: Apelin-13 treatment reduced bupivacaine-induced oxidative stress, attenuated mitochondrial morphological changes and mitochondrial DNA damage, enhanced mitochondrial energy metabolism, and ultimately reversed bupivacaine-induced cardiotoxicity. Our results suggest a role for the AMPK in apelin-13 reversal of bupivacaine-induced cardiotoxicity.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiopatias/prevenção & controle , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Animais , Bupivacaína , Cardiotoxicidade , Linhagem Celular , Dano ao DNA , Modelos Animais de Doenças , Cardiopatias/induzido quimicamente , Cardiopatias/enzimologia , Cardiopatias/patologia , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/enzimologia , Mitocôndrias Cardíacas/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Estresse Oxidativo , Fosfatidilinositol 3-Quinase/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais
15.
J Cancer ; 12(18): 5413-5422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34405004

RESUMO

Background: The morbidity of thyroid cancer is gradually increasing, meanwhile, the average age of the morbidity population also becomes younger. Mechanisms genomic variations serve an important function for the pathogenesis of many cancer types. Pleckstrin and sec7 domain-containing 3 (PSD3), also known as EFA6R, was shown to be associated with some cancers such as acute myeloid leukemia, breast cancer metastasis, and astrocytoma. But it was unknown that whether PSD3 took effect and how did it work in thyroid cancer. Methods: We guessed that PSD3 might play an important role in thyroid cancer by consulting previous literature. Then, we analyzed the level of PSD3 expression in thyroid malignancy and the connection with clinical manifestation in The Cancer Genome Atlas (TCGA). And RNA extraction, reverse transcription, and real-time quantitative polymerase chain reaction (qRt-PCR) of 40 pairs of local samples were done to verify the result of TCGA. Then, PSD3 was knocked down by small interfering RNA (siRNA) for flowing functional experiments. Results: Bioinformatics and qRt-PCR analysis shown PSD3 was overexpressed in papillary thyroid cancer (PTC) and connected with the histological type (P=0.009) and risk of lymph node metastasis (P=0.016). In vitro assays, we confirmed that down-regulation PSD3 could not only suppress the cell proliferation, colony formation, cell migration, cell invasion, and G1/S cell cycle transition but also promote apoptosis in PTC cells. Conclusion: PSD3 promotes proliferation, migration, invasion, and G1/S transition while inhibits apoptotic in PTC and a possible biomarker in PTC.

16.
Am J Transl Res ; 13(7): 7695-7704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377246

RESUMO

BACKGROUND: It is necessary to identify patients at risk of developing lymph node metastasis prior to papillary thyroid carcinoma (PTC) surgery. This can be challenging due to limiting factors, and an artificial intelligence algorithm may be a viable option. OBJECTIVE: In this study, we aimed to evaluate whether combining an artificial intelligence algorithm (support vector machine and probabilistic neural network) and clinico-pathologic data can preoperatively predict lymph node metastasis of papillary thyroid carcinoma (PTC). METHODS: We retrospectively examined 251 PTCs with lymph node metastasis and 194 PTCs without lymph node metastasis. The artificial intelligence algorithm included the support vector machine (SVM) and the probabilistic neural network (PNN). RESULTS: The ACR TI-RADS (Thyroid Imaging, Reporting and Data System), number of tumours, no well-defined margin, lymph node status and rim calcification on ultrasonography (US), age, sex, tumour size, and presence of Hashimoto's thyroiditis were significantly more frequent among PTCs with central lymph node metastasis than those without metastasis (P<0.05). The PNN classifier revealed an F1 score of 0.88 on the central lymph node metastasis test set. The SVM classifier revealed an F1 score of 0.93 on the lateral lymph node metastasis test set. Our study demonstrates that combining artificial intelligence algorithms and clinico-pathologic data can effectively predict the lymph node metastasis of papillary thyroid carcinoma prior to surgery.

17.
Aging (Albany NY) ; 13(14): 18360-18375, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34282052

RESUMO

Recent publications have presented research showing that WD repeat domain 4 (WDR4) plays a significant role in various kinds of malignant tumours. However, the expression profile of WDR4 is still unspecified, as is its significance in the analysis of human pan-cancer. We conducted an in-depth analysis of three aspects of WDR4 expression patterns from 33 types of cancer and determined the value of WDR4 for prognostic prediction and carcinoma drug resistance prediction. WDR4 was expressed in different cancer cell lines at inconsistent levels. Aberrant expression of WDR4 has been observed in various malignant cancers and is significantly implicated in overall survival outcomes. The expression level of WDR4 is also strongly associated with tumour immunity, such as immune scores and tumour-infiltrating immune cells. The level of WDR4 is related to microsatellite instability and tumour mutation burden in several types of malignancy, and validation studies implied that WDR4-associated terms and pathways are involved in malignancy. We explored the expression level of WDR4 across 33 types of cancer and showed that WDR4 plays a significant role during cancer development. More crucially, WDR4 is associated with immune infiltration, which suggests that WDR4 could be an immunotherapy target in cancers. In summary, our research showed that WDR4 plays a vital role in tumorigenesis and has the potential for to be targeted with treatments.


Assuntos
Biomarcadores Tumorais , Proteínas de Ligação ao GTP/genética , Imunidade , Neoplasias/genética , Neoplasias/imunologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Humanos , Imunomodulação , Instabilidade de Microssatélites , Mutação , Neoplasias/patologia , Prognóstico , Análise de Sobrevida , Microambiente Tumoral
18.
Am J Transl Res ; 13(4): 2399-2409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017398

RESUMO

INTRODUCTION: Endometriosis is an illness caused by the presence of foci of endometrial implants outside the uterine cavity. Laparoscopy (minimally invasive surgical method) is considered as the definitive treatment for Endometriosis. METHOD: Clinical data from January 2014 till December 2018, between the ages of 20 and 40 years were collected. A total of 175 women with pelvic Endometriosis complicated with infertility, underwent laparoscopy in our hospital, were followed up to assess fertility outcome. We analyzed using univariate logistic regression analysis as well as multivariate logistic analysis. RESULTS: We analyzed the relationship between them by logistic regression analysis. Univariate logistic regression analysis indicated that the significant factors for influencing pregnancy were the following factors: age, infertility types: primary or secondary infertility, treatment with Gonadotrophin Releasing Hormone-agonist, r-AFS grade, operative method: excision or ablation. And multivariate logistic regression using all the factors also revealed that age, infertility types: primary or secondary, treatment with GnRH-a, revised- American Fertility Society grading and operative method: excision or ablation were positively correlated and were the significant factors to influence pregnancy outcome. While the other factors such as Body Mass Index, and endometriosis along with other gynecological pathology were not statistically significant. CONCLUSIONS: In this study, we found out that age, infertility type, treatment with Laparoscopy surgery, use of GnRH-a after the operation, grading of the disease, and different types of operative methods were found to be significant and were found to be the factors which influenced the pregnancy outcome.

19.
Aging (Albany NY) ; 13(8): 11860-11876, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893247

RESUMO

Considerable efforts have been devoted to exploring the breast cancer mutational landscape to understand its genetic complexity. However, no studies have yet comprehensively elucidated the molecular characterization of breast tumors in Chinese women. This study aimed to determine the potential clinical utility of peripheral blood assessment for circulating tumor-derived DNA (ctDNA) and comprehensively characterize the female Chinese population's genetic mutational spectrum. We used Omi-Seq to create cancer profiles of 273 patients enrolled at The First Affiliated Hospital of Wenzhou Medical University. The gene landscape results indicate PIK3CA and TP53 as the most frequently detected genes, followed by ERBB2, in Chinese breast cancer patients. The accuracy of ERBB2 copy number variations in tissue/formalin-fixed and paraffin-embedded samples was 95% with 86% sensitivity and 99% specificity. Moreover, mutation numbers varied between different molecular cell-free DNA subtypes, with the basal-like patients harboring a higher number of variants than the luminal patients. Furthermore, ratio changes in the max ctDNA allele fraction highly correlated with clinical response measurements, including cancer relapse and metastasis. Our data demonstrate that ctDNA characterization using the Omi-Seq platform can extend the capacity of personalized clinical cancer management.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , DNA Tumoral Circulante/genética , Recidiva Local de Neoplasia/epidemiologia , Povo Asiático/genética , Biomarcadores Tumorais/sangue , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , China/epidemiologia , DNA Tumoral Circulante/sangue , Classe I de Fosfatidilinositol 3-Quinases/genética , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Feminino , Seguimentos , Humanos , Biópsia Líquida , Mastectomia , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico , Receptor ErbB-2/genética , Medição de Risco , Proteína Supressora de Tumor p53/genética
20.
Hum Cell ; 34(3): 901-917, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33665786

RESUMO

Breast cancer (BC) threatened the life health of a tremendous amount of the population, and the estimated number of death is still rising nowadays. We found that stress-induced phosphoprotein 1 (STIP1) is overexpressed in BC tissues compared to non-tumorous breast tissues. Our study is to validate the prognostic value of STIP1 and investigate its biological role in BC. We verified the upregulation of STIP1 in multiple databases, proved that STIP1 is upregulated in BC tissues and cell lines using real-time quantitative PCR (qRT-PCR). We used small interfering RNA to examine the function of STIP1 in BC cell lines (BT-549, MDA-MB-231, Hs-578 T) and explored the mechanism of function of STIP1 in BC cells using Western blotting and qRT-PCR. Analyses of multiple databases indicated that high STIP1 expression is a marker that effectively distinguishes BC patients from healthy control and predicts worse clinical outcomes in BC. The loss-of-function experiments showed that STIP1 silencing results in inhibition of cell proliferation and migration, inducing cell apoptosis, and S-phase arrest in vitro. Our study also showed that STIP1 downregulation inhibited the JAK2/STAT3 pathway and epithelial-mesenchymal transition process. Rescue experiments demonstrated that the oncogenic effect of STIP1 is partially dependent on mediating JAK2 expression. This study verified that STIP1 is an oncogenic gene that promotes BC progression and serves as a valuable diagnostic and outcome-related marker of BC.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica/genética , Proteínas de Choque Térmico/fisiologia , Apoproteínas/genética , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Feminino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Janus Quinase 2/metabolismo , Prognóstico , Fase S/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
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