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1.
Gland Surg ; 13(5): 640-653, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38845837

RESUMO

Background: Breast-conserving surgery (BCS) stands as the favored modality for treating early-stage breast cancer. Accurately forecasting the feasibility of BCS preoperatively can aid in surgical planning and reduce the rate of switching of surgical methods and reoperation. The objective of this study is to identify the radiomics features and preoperative breast magnetic resonance imaging (MRI) characteristics that are linked with positive margins following BCS in patients with breast cancer, with the ultimate aim of creating a predictive model for the feasibility of BCS. Methods: This study included a cohort of 221 pretreatment MRI images obtained from patients with breast cancer. A total of seven MRI semantic features and 1,561 radiomics features of lesions were extracted. The feature subset was determined by eliminating redundancy and correlation based on the features of the training set. The least absolute shrinkage and selection operator (LASSO) logistic regression was then trained with this subset to classify the final BCS positive and negative margins and subsequently validated using the test set. Results: Seven features were significant in the discrimination of cases achieving positive and negative margins. The radiomics signature achieved area under the curve (AUC), accuracy, sensitivity, and specificity of 0.760 [95% confidence interval (CI): 0.630, 0.891], 0.712 (95% CI: 0.569, 0.829), 0.882 (95% CI: 0.623, 0.979) and 0.629 (95% CI: 0.449, 0.780) in the test set, respectively. The combined model of radiomics signature and background parenchymal enhancement (BPE) demonstrated an AUC, accuracy, sensitivity, and specificity of 0.759 (95% CI: 0.628, 0.890), 0.654 (95% CI: 0.509, 0.780), 0.679 (95% CI: 0.476, 0.834) and 0.625 (95% CI: 0.408, 0.804). Conclusions: The combination of preoperative MRI radiomics features can well predict the success of breast conserving surgery.

2.
Acta Pharm Sin B ; 14(5): 2263-2280, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799639

RESUMO

Chemotherapeutics can induce immunogenic cell death (ICD) in tumor cells, offering new possibilities for cancer therapy. However, the efficiency of the immune response generated is insufficient due to the inhibitory nature of the tumor microenvironment (TME). Here, we developed a pH/reactive oxygen species (ROS) dual-response system to enhance chemoimmunotherapy for melanoma. The system productively accumulated in tumors by specific binding of phenylboronic acid (PBA) to sialic acids (SA). The nanoparticles (NPs) rapidly swelled and released quercetin (QUE) and doxorubicin (DOX) upon the stimulation of tumor microenvironment (TME). The in vitro and in vivo results consistently demonstrated that the NPs improved anti-tumor efficacy and prolonged survival of mice, significantly enhancing the effects of the combination. Our study revealed DOX was an ICD inducer, stimulating immune responses and promoting maturation of dendritic cells (DCs). Additionally, QUE served as a TME regulator by inhibiting the cyclooxygenase-2 (COX2)-prostaglandin E2 (PGE2) axis, which influenced various immune cells, including increasing cytotoxic T cells (CLTs) infiltration, promoting M1 macrophage polarization, and reducing regulatory T cells (Tregs) infiltration. The combination synergistically facilitated chemoimmunotherapy efficacy by remodeling the immunosuppressive microenvironment. This work presents a promising strategy to increase anti-tumor efficiency of chemotherapeutic agents.

3.
Toxicology ; 505: 153844, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801937

RESUMO

Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.


Assuntos
Dano ao DNA , Exossomos , Compostos de Trialquitina , Humanos , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Compostos de Trialquitina/toxicidade , Células MCF-7 , Dano ao DNA/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Sobrevivência Celular/efeitos dos fármacos
5.
Toxicology ; 504: 153795, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574842

RESUMO

The mechanistic target of rapamycin (RAPA) complex 1 (mTORC1) - transcription factor EB (TFEB) pathway plays a crucial role in response to nutritional status, energy and environmental stress for maintaining cellular homeostasis. But there is few reports on its role in the toxic effects of arsenic exposure and the related mechanisms. Here, we show that the exposure of bronchial epithelial cells (BEAS-2B) to sodium arsenite promoted the activation of mTORC1 (p-mTORC1) and the inactivation of TFEB (p-TFEB), the number and activity of lysosomes decreased, the content of reduced glutathione (GSH) and superoxide dismutase (SOD) decreased, the content of malondialdehyde (MDA) increased, the DNA and chromosome damage elevated. Further, when mTORC1 was inhibited with RAPA, p-mTORC1 and p-TFEB down-regulated, GSH and SOD increased, MDA decreased, the DNA and chromosome damage reduced significantly, as compared with the control group. Our data revealed for the first time that mTORC1 - TFEB pathway was involved in sodium arsenite induced lysosomal alteration, oxidative stress and genetic damage in BEAS-2B cells, and it may be a potential intervention target for the toxic effects of arsenic.


Assuntos
Arsenitos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Dano ao DNA , Lisossomos , Alvo Mecanístico do Complexo 1 de Rapamicina , Estresse Oxidativo , Compostos de Sódio , Arsenitos/toxicidade , Compostos de Sódio/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Linhagem Celular , Dano ao DNA/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Brônquios/citologia , Brônquios/patologia , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Complexos Multiproteicos/metabolismo , Malondialdeído/metabolismo
6.
Heliyon ; 10(7): e28496, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601520

RESUMO

Background: The prognostic effects of different treatment modalities on patients with hypopharyngeal squamous cell carcinoma (HPSCC) remain unclear. Methods: HPSCC patients diagnosed and treated at either West China Hospital or Sichuan Cancer Hospital between January 1, 2009, and December 31, 2019, were enrolled in this retrospective, real-world study. Survival rates were presented using Kaplan-Meier curves and compared using log-rank tests. Univariable and multivariable Cox proportional hazards regression models were used to identify the predictors of overall survival (OS). Subgroup analyses were conducted for patients with advanced-stage HPSCC (stages III and IV and category T4). Results: A total of 527 patients with HPSCC were included. Patients receiving SRC (surgery, radiotherapy [RT], and chemotherapy) showed the best OS (p < 0.0001). In comparison with RT alone, both surgery alone (all cases: hazard ratio [HR] = 0.39, p = 0.0018; stage IV cases: HR = 0.38, p = 0.0085) and surgery-based multimodality treatment (SBMT; all cases: HR = 0.27, p < 0.0001; stage IV cases: HR = 0.30, p = 0.00025) showed prognostic benefits, while SBMT also showed survival priority over chemoradiotherapy (CRT; all cases: HR = 0.52, p < 0.0001; stage IV cases: HR = 0.59, p = 0.0033). Moreover, patients who underwent surgery alone had comparable OS to those who underwent SBMT (all patients: p = 0.13; stage IV cases: p = 0.34), while CRT yielded similar prognostic outcomes as RT alone (all patients: p = 0.054; stage IV cases: p = 0.11). Conclusions: Surgery alone was comparable to SBMT and superior to RT/CRT in terms of OS in patients with HPSCC. We suggest that surgery should be encouraged for the treatment of HPSCC, even in patients with advanced-stage disease.

7.
Environ Toxicol ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38480676

RESUMO

Ovarian cancer (OC), known for its pronounced heterogeneity, has long evaded a unified classification system despite extensive research efforts. This study integrated five distinct multi-omics datasets from eight multicentric cohorts, applying a combination of ten clustering algorithms and ninety-nine machine learning models. This methodology has enabled us to refine the molecular subtyping of OC, leading to the development of a novel Consensus Machine Learning-driven Signature (CMLS). Our analysis delineated two prognostically significant cancer subtypes (CS), each marked by unique genetic and immunological signatures. Notably, CS1 is associated with an adverse prognosis. Leveraging a subtype classifier, we identified five key genes (CTHRC1, SPEF1, SCGB3A1, FOXJ1, and C1orf194) instrumental in constructing the CMLS. Patients classified within the high CMLS group exhibited a poorer prognosis and were characterized by a "cold tumor" phenotype, indicative of an immunosuppressive microenvironment rich in MDSCs, CAFs, and Tregs. Intriguingly, this group also presented higher levels of tumor mutation burden (TMB) and tumor neoantigen burden (TNB), factors that correlated with a more favorable response to immunotherapy compared to their low CMLS counterparts. In contrast, the low CMLS group, despite also displaying a "cold tumor" phenotype, showed a favorable prognosis and a heightened responsiveness to chemotherapy. This study's findings underscore the potential of targeting immune-suppressive cells, particularly in patients with high CMLS, as a strategic approach to enhance OC prognosis. Furthermore, the redefined molecular subtypes and risk stratification, achieved through sophisticated multi-omics analysis, provide a framework for the selection of therapeutic agents.

8.
Nano Lett ; 24(2): 607-616, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38095305

RESUMO

In recent years, live-cell-based drug delivery systems have gained considerable attention. However, shear stress, which accompanies blood flow, may cause cell death and weaken the delivery performance. In this study, we found that reducing cholesterol in macrophage plasma membranes enhanced their tumor targeting ability by more than 2-fold. Our study demonstrates that the reduced cholesterol level deactivated the mammalian target of rapamycin (mTOR) and consequently promoted the nuclear translocation of transcription factor EB (TFEB), which in turn enhanced the expression of superoxide dismutase (SOD) to reduce reactive oxygen species (ROS) induced by shear stress. A proof-of-concept system using low cholesterol macrophages attached to MXene (e.g., l-RX) was fabricated. In a melanoma mouse model, l-RX and laser irradiation treatments eliminated tumors with no recurrences observed in mice. Therefore, cholesterol reduction is a simple and effective way to enhance the targeting performance of macrophage-based drug delivery systems.


Assuntos
Macrófagos , Superóxido Dismutase , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Macrófagos/metabolismo , Sistemas de Liberação de Medicamentos , Colesterol/metabolismo , Mamíferos/metabolismo
9.
Int Wound J ; 21(1): e14384, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37697692

RESUMO

Pathological scarring resulting from traumas and wounds, such as hypertrophic scars and keloids, pose significant aesthetic, functional and psychological challenges. This study provides a comprehensive transcriptomic analysis of these conditions, aiming to illuminate underlying molecular mechanisms and potential therapeutic targets. We employed a co-expression and module analysis tool to identify significant gene clusters associated with distinct pathophysiological processes and mechanisms, notably lipid metabolism, sebum production, cellular energy metabolism and skin barrier function. This examination yielded critical insights into several skin conditions including folliculitis, skin fibrosis, fibrosarcoma and congenital ichthyosis. Particular attention was paid to Module Cluster (MCluster) 3, encompassing genes like BLK, TRPV1 and GABRD, all displaying high expression and potential implications in immune modulation. Preliminary immunohistochemistry validation supported these findings, showing elevated expression of these genes in non-fibrotic samples rich in immune activity. The complex interplay of different cell types in scar formation, such as fibroblasts, myofibroblasts, keratinocytes and mast cells, was also explored, revealing promising therapeutic strategies. This study underscores the promise of targeted gene therapy for pathological scars, paving the way for more personalised therapeutic approaches. The results necessitate further research to fully ascertain the roles of these identified genes and pathways in skin disease pathogenesis and potential therapeutics. Nonetheless, our work forms a strong foundation for a new era of personalised medicine for patients suffering from pathological scarring.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Cicatriz Hipertrófica/genética , Cicatriz Hipertrófica/terapia , Cicatriz Hipertrófica/metabolismo , Queloide/genética , Queloide/terapia , Queratinócitos/metabolismo , Fibroblastos/metabolismo , Miofibroblastos/metabolismo
10.
J Hazard Mater ; 465: 133263, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38118200

RESUMO

Lead (Pb) and cadmium (Cd) are common heavy metal pollutants that are often found in the soil in soybean agricultural production, adversely impacting symbiotic nitrogen fixation in soybean nodules. In this study, the exposure of soybean nodules to Pb and Cd stress was found to reduce nitrogenase activity. Shifts in the RNA methylation profiles of nodules were subsequently examined by profiling the differential expression of genes responsible for regulating m6A modifications and conducting transcriptome-wide analyses of m6A methylation profiles under Pb and Cd stress condition. Differentially methylated genes (DMGs) that were differentially expressed were closely related to reactive oxygen species activity and integral membrane components. Overall, 19 differentially expressed DMGs were ultimately determined to be responsive to both Pb and Cd stress, including Glyma.20G082450, which encodes GmAMT1;1 and was confirmed to be a positive regulator of nodules tolerance to Pb and Cd. Together, these results are the first published data corresponding to transcriptome-wide m6A methylation patterns in soybean nodules exposed to Cd and Pb stress, and provide novel molecular insight into the regulation of Pb and Cd stress responses in nodules, highlighting promising candidate genes related to heavy metal tolerance, that may also be amenable to application in agricultural production. ENVIRONMENTAL IMPLICATIONS: Lead (Pb) and cadmium (Cd) are prevalent heavy metal pollutants in soil, and pose a major threat to crop production, food security and human health. Here, MeRIP-seq approach was employed to analyze the regulatory network activated in soybean nodules under Pb and Cd stress, ultimately leading to the identification of 19 shared differentially expressed DMGs. When overexpressed, GmATM1;1 was found to enhance the Pb and Cd tolerance of soybean nodules. These results provide a theoretical basis for studies on tolerance to heavy metals in symbiotic nitrogen fixation, and provide an approach to enhancing Pb and Cd tolerance in soybean production.


Assuntos
Poluentes Ambientais , Metais Pesados , Poluentes do Solo , Humanos , Cádmio/metabolismo , Transcriptoma , Glycine max , Chumbo , Metais Pesados/metabolismo , Metilação , Solo , Poluentes do Solo/metabolismo
11.
BMC Cancer ; 23(1): 1106, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957566

RESUMO

BACKGROUND: Researches have manifested that the disorder of iron metabolism is participated in Gastric cancer (GC), but whether iron metabolism-relevant genes (IMRGs) is related to the survival outcome of GC remain unknown. METHODS: Eleven tumor as well as nine adjacent normal tissues from GC patients were underwent mRNA sequencing, and the The Cancer Genome Atlas Stomach Cancer (TCGA-STAD) datasets were acquired from the TCGA database. Cox analyses and least absolute shrinkage and selection operator (LASSO) regression were applied to build a IMRGs signature. The relationship between signature genes and the infiltration profiling of 24 immune cells were investigated using single-sample GSEA (ssGSEA). Meanwhile, the potential biological significance, genes that act synergistically with signature genes, and the upstream regulatory targets were predicted. Finally, the abundance of the signature genes were measured via the quantitative real-time PCR (qRT-PCR). RESULTS: A IMRGs signature was constructed according to the expression and corresponding coefficient of DOHH, P4HA3 and MMP1 (The Schoenfeld individual test showed risk score was not significant with P values = 0.83). The prognostic outcome of patients in the high-risk group was terrible (p < 0.05). Receiver operating characteristic (ROC) curves confirmed that the IMRGs signature presented good efficiency for predicting GC prognosis (AUC > 0.6). The nomogram was performed well for clinical utilize (C-index = 0.60), and the MMP1 expression significantly increased in the cohorts at age > 60 and Stage II-IV (p < 0.05). The positive correlation of P4HA3 and MMP1 expression as well as the negative correlation of DOHH expression with risk score (p < 0.0001) and worse prognosis (p < 0.05) were detected as well. Furthermore, 11 differential immune cells were associated with these signature genes (most p < 0.01). Finally, qRT-PCR revealed that the abundance of DOHH, P4HA3 and MMP1 were high in tumor cases, indicating the complex mechanism between the high expression of DOHH as a protective factor and the high expression of P4HA3 and MMP1 as the risk factors in the development of GC. CONCLUSION: An iron metabolism-related signature was constructed and has significant values for foretelling the OS of GC.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Metaloproteinase 1 da Matriz , Prognóstico , Análise de Sequência de RNA , Ferro , Pró-Colágeno-Prolina Dioxigenase
12.
Parasit Vectors ; 16(1): 285, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587524

RESUMO

BACKGROUND: Clonorchiasis remains a non-negligible global zoonosis, causing serious socioeconomic burdens in endemic areas. Clonorchis sinensis infection typically elicits Th1/Th2 mixed immune responses during the course of biliary injury and periductal fibrosis. However, the molecular mechanism by which C. sinensis juvenile initially infects the host remains poorly understood. METHODS: The BALB/c mouse model was established to study early infection (within 7 days) with C. sinensis juveniles. Liver pathology staining and observation as well as determination of biochemical enzymes, blood routine and cytokines in blood were conducted. Furthermore, analysis of liver transcriptome, proteome and metabolome changes was performed using multi-omics techniques. Statistical analyses were performed using Student's t-test. RESULTS: Histopathological analysis revealed that liver injury, characterized by collagen deposition and inflammatory cell infiltration, occurred as early as 24 h of infection. Blood indicators including ALT, AST, WBC, CRP and IL-6 indicated that both liver injury and systemic inflammation worsened as the infection progressed. Proteomic data showed that apoptosis and junction-related pathways were enriched within 3 days of infection, indicating the occurrence of liver injury. Furthermore, proteomic and transcriptomic analysis jointly verified that the detoxification and antioxidant defense system was activated by enrichment of glutathione metabolism and cytochrome P450-related pathways in response to acute liver injury. Proteomic-based GO analysis demonstrated that biological processes such as cell deformation, proliferation, migration and wound healing occurred in the liver during the early infection. Correspondingly, transcriptomic results showed significant enrichment of cell cycle pathway on day 3 and 7. In addition, the KEGG analysis of multi-omics data demonstrated that numerous pathways related to immunity, inflammation, tumorigenesis and metabolism were enriched in the liver. Besides, metabolomic screening identified several metabolites that could promote inflammation and hepatobiliary periductal fibrosis, such as CA7S. CONCLUSIONS: This study revealed that acute inflammatory injury was rapidly triggered by initial infection by C. sinensis juveniles in the host, accompanied by the enrichment of detoxification, inflammation, fibrosis, tumor and metabolism-related pathways in the liver, which provides a new perspective for the early intervention and therapy of clonorchiasis.


Assuntos
Clonorquíase , Clonorchis sinensis , Animais , Camundongos , Clonorchis sinensis/genética , Proteômica , Fígado , Inflamação
13.
Front Oncol ; 13: 1202650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427127

RESUMO

Background: Immediate breast reconstruction is widely accepted following oncologic mastectomy. This study aimed to build a novel nomogram predicting the survival outcome for Chinese patients undergoing immediate reconstruction following mastectomy for invasive breast cancer. Methods: A retrospective review of all patients undergoing immediate reconstruction following treatment for invasive breast cancer was performed from May 2001 to March 2016. Eligible patients were assigned to a training set or a validation set. Univariate and multivariate Cox proportional hazard regression models were used to select associate variables. Two nomograms were developed based on the training cohort for breast cancer-specific survival (BCSS) and disease-free survival (DFS). Internal and external validations were performed, and the C-index and calibration plots were generated to evaluate the performance (discrimination and accuracy) of the models. Results: The 10-year estimated BCSS and DFS were 90.80% (95% CI: 87.30%-94.40%) and 78.40% (95% CI: 72.50%-84.70%), respectively, in the training cohort. In the validation cohort, they were and 85.60% (95% CI, 75.90%-96.50%) and 84.10% (95% CI, 77.80%-90.90%), respectively. Ten independent factors were used to build a nomogram for prediction of 1-, 5- and 10-year BCSS, while nine were used for DFS. The C-index was 0.841 for BCSS and 0.737 for DFS in internal validation, and the C-index was 0.782 for BCSS and 0.700 for DFS in external validation. The calibration curve for both BCSS and DFS demonstrated acceptable agreement between the predicted and actual observation in the training and the validation cohorts. Conclusion: The nomograms provided valuable visualization of factors predicting BCSS and DFS in invasive breast cancer patients with immediate breast reconstruction. The nomograms may have tremendous potential in guiding individualized decision-making for physicians and patients in choosing the optimized treatment methods.

14.
Nanotechnology ; 34(43)2023 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-37499632

RESUMO

Developing cathode materials with high specific capability and excellent electrochemical performance is crucial for the advancement of aluminum-ion batteries, which leverage the high theoretical energy density of aluminum metal anodes. In this paper, we investigated the interaction ofAlCl4cluster and Al atom with AlN (-100) and (001) monolayer using density functional theory to assess the applicability of AlN as cathode material for aluminum-ion batteries. The results show that the AlN (001) monolayer is the most effective for adsorbing and accommodatingAlCl4clusters. Moreover, the AlN (001) monolayer maintains metallic behavior at different concentrations of theAlCl4cluster, laying the foundation for its battery application. The theoretical storage capacity of theAlCl4cluster is 105.93mAhg-1,which exceeds that of the Al/graphite battery. The formation energy ofAlCl4-intercalated AlN compounds is -2.74 eV, and the intercalant gallery height is moderate. Furthermore, the diffusion barrier of 0.19 eV forAlCl4cluster between the AlN (001) monolayer provides high rate capability. The results indicate that AlN monolayer may be a potential cathode material for aluminum-ion batteries.

15.
Biomol Biomed ; 23(5): 902-913, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37096424

RESUMO

Understanding the clinical features and accurately predicting the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) is important for patient centered decision-making. This study aimed to create a multi-factor nomogram predictive model and a web-based calculator to predict post-therapy survival for patients with LA-HPSCC. A retrospective cohort study analyzing Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for patients diagnosed with LA-HPSCC was conducted and randomly divided into a training and a validation group (7:3 ratio). The external validation cohort included 276 patients from Sichuan Cancer Hospital, China. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was used to identify independent factors associated with overall survival (OS) and cancer-specific survival (CSS), and nomogram models and web-based survival calculators were constructed. Propensity score matching (PSM) was used to compare survival with different treatment options. A total of 2526 patients were included in the prognostic model. The median OS and CSS for the entire cohort were 20 (18.6-21.3) months and 24 (21.7-26.2) months, respectively. Nomogram models integrating the seven factors demonstrated high predictive accuracy for 3-year and 5-year survival. PSM found that patients who received surgery-based curative therapy had better OS and CSS than those who received radiotherapy-based treatment (median survival times: 33 months vs 18 months and 40 months vs 22 months, respectively). The nomogram model accurately predicted patient survival from LA-HPSCC. Surgery with adjuvant therapy yielded significantly better survival than definitive radiotherapy. and should be prioritized over definitive radiotherapy.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Hipofaríngeas , Humanos , Nomogramas , Pontuação de Propensão , Estudos Retrospectivos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Internet
16.
Nat Commun ; 14(1): 1697, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36973263

RESUMO

Advances in membrane technologies are significant for mitigating global climate change because of their low cost and easy operation. Although mixed-matrix membranes (MMMs) obtained via the combination of metal-organic frameworks (MOFs) and a polymer matrix are promising for energy-efficient gas separation, the achievement of a desirable match between polymers and MOFs for the development of advanced MMMs is challenging, especially when emerging highly permeable materials such as polymers of intrinsic microporosity (PIMs) are deployed. Here, we report a molecular soldering strategy featuring multifunctional polyphenols in tailored polymer chains, well-designed hollow MOF structures, and defect-free interfaces. The exceptional adhesion nature of polyphenols results in dense packing and visible stiffness of PIM-1 chains with strengthened selectivity. The architecture of the hollow MOFs leads to free mass transfer and substantially improves permeability. These structural advantages act synergistically to break the permeability-selectivity trade-off limit in MMMs and surpass the conventional upper bound. This polyphenol molecular soldering method has been validated for various polymers, providing a universal pathway to prepare advanced MMMs with desirable performance for diverse applications beyond carbon capture.

17.
Ecotoxicol Environ Saf ; 252: 114563, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36701876

RESUMO

Bisphenol A (BPA), one of the typical environmental endocrine disruptors (EEDs), can promote the proliferation and migration of cancer cells, but the mechanism of which remains largely unclear. Exosome secretion plays an important role in the stress response of cells to environmental stimuli. This study was designed to explore whether exosome secretion was involved in the toxic effect of BPA on the proliferation and migration of MCF-7 cells, and the related mechanism. Our data shows that the IC50 value of MCF-7 exposure to BPA was about 65.82 µM. The exposure of MCF-7 to 10 µM BPA resulted in a decreased miR-26b expression and the activation of miR-26b/Rab-31 pathway, consequently, the number and activity of lysosomes decreased, the secretion of exosomes increased, cell proliferation and migration were enhanced obviously. Interestingly, miR-26b mimic up-regulated the number and activity of lysosomes via miR-26b/miR-31 pathway, exosome secretion was down-regulated, cell proliferation and migration decreased. Further, when GW4869 was used to directly inhibit the exosome secretion of MCF-7 treated with BPA, their proliferation and migration were down-regulated. Herein, we concluded that the stimulating effect of BPA on the proliferation and migration of MCF-7 cells was associated with the lysosome - related exosome secretion via miR-26b / Rab31 pathway.


Assuntos
Exossomos , MicroRNAs , Humanos , Células MCF-7 , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/fisiologia , Lisossomos/metabolismo , Linhagem Celular Tumoral , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo
18.
Cell Mol Biol (Noisy-le-grand) ; 68(7): 90-94, 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36495514

RESUMO

Liver cancer poses a great threat to the life safety of patients, which is a common malignant tumor worldwide. This study aims to explore the effect of miR-144 negatively regulating CCNB1 on the biological behavior of liver cancer cells, including the proliferation, apoptosis and migration of liver cancer cells, so as to provide a sufficient biological basis for the treatment of liver cancer. A 3 armour hospital at the records of 100 patients with liver cancer in 2015-2019 as the research object, and resection of the liver cancer cells and tissue adjacent to carcinoma as the research samples, using polymerase chain reaction (PCR) for the organization of miR-144 gene and detect CCNB1 protein expression level, and by using a technique called RNA interference to silence the CCNB1 gene, and try to transfer by transfection CCNB1 protein, thus all kinds of biological behaviour of hepatocellular carcinoma cells. The liver tissue of miR-144 is low, the level of gene expression CCNB1 protein expression level is higher, the expression level in liver cancer cells directly influences the curative effect of hepatocellular carcinoma patients, the miR-144 gene can negative regulation CCNB1 protein, through this kind of negative adjustment to the biological behavior of liver cancer cells have a profound impact.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Humanos , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias Hepáticas/patologia , Movimento Celular/genética , Ciclina B1/genética , Ciclina B1/metabolismo
19.
Radiother Oncol ; 177: 113-120, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36336111

RESUMO

PURPOSE: To determine the differences in supraclavicular lymph node metastasis between esophageal cancer (EC) and nasopharyngeal cancer (NPC) and explore the feasibility of differential supraclavicular clinical target volume (CTV) contouring between these two diseases based on the involvement of different fascial spaces. MATERIALS AND METHODS: One hundred patients with supraclavicular nodes positive for EC or NPC were enrolled, and their pre-treatment images were reviewed. The distribution patterns of nodes between the two diseases were compared in the context of node levels defined by the 2017 Japanese Esophageal Society and 2013 International Consensus on Cervical Lymph Node Level Classification. Grouping supraclavicular nodes based on sub-compartments formed by the cervical fascia was discussed, and the feasibility of differential CTV contouring based on the differences in the involvement of these sub-compartments between EC and NPC was explored. RESULTS: The 2013 Consensus on cervical node levels and 2017 Japanese Esophageal Society node station could not practically guide supraclavicular CTV contouring. We divided the supraclavicular space into six sub-compartments: the para-esophageal space (PES), carotid sheath space (CSS), sub-thyroid pre-trachea space (STPTS), pre-vascular space (PVS), and vascular lateral space (VLS) I and II. EC mainly spread to the PES, STPTS, CSS, and VLS I, whereas NPC tended to spread to the CSS, VLS I, and VLS II. These combinations of sub-compartments may help constitute the supraclavicular CTVs for EC and NPC. CONCLUSIONS: The fascia anatomy-based sub-compartments sufficiently distinguished metastasis to the supraclavicular space between EC and NPC, thus facilitating differential CTV contouring between these two diseases.


Assuntos
Neoplasias Esofágicas , Neoplasias Nasofaríngeas , Humanos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Esofágicas/patologia , Metástase Linfática/patologia , Carcinoma Nasofaríngeo/patologia , Linfonodos/patologia , Fáscia/patologia , Drenagem
20.
Nat Biotechnol ; 40(12): 1794-1806, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36203011

RESUMO

Resolving the spatial distribution of RNA and protein in tissues at subcellular resolution is a challenge in the field of spatial biology. We describe spatial molecular imaging, a system that measures RNAs and proteins in intact biological samples at subcellular resolution by performing multiple cycles of nucleic acid hybridization of fluorescent molecular barcodes. We demonstrate that spatial molecular imaging has high sensitivity (one or two copies per cell) and very low error rate (0.0092 false calls per cell) and background (~0.04 counts per cell). The imaging system generates three-dimensional, super-resolution localization of analytes at ~2 million cells per sample. Cell segmentation is morphology based using antibodies, compatible with formalin-fixed, paraffin-embedded samples. We measured multiomic data (980 RNAs and 108 proteins) at subcellular resolution in formalin-fixed, paraffin-embedded tissues (nonsmall cell lung and breast cancer) and identified >18 distinct cell types, ten unique tumor microenvironments and 100 pairwise ligand-receptor interactions. Data on >800,000 single cells and ~260 million transcripts can be accessed at http://nanostring.com/CosMx-dataset .


Assuntos
Proteínas , RNA , Humanos , Inclusão em Parafina , RNA/genética , Imagem Molecular , Formaldeído
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