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Predicting the binding poses of docking with an accurate estimation of binding energies is highly important but very challenging in computational drug design. A quantum mechanics (QM) calculation-based docking approach considering multiple conformations and orientations of the ligand is introduced here to tackle the problem. This QM docking consists of three steps: generating an ensemble of binding poses with a conventional docking simulation, computing the binding energies with self-consistent charge density functional theory tightly binding with dispersion correction (DFTB-D) to selecting the 10 top binding modes, and optimizing the selected binding mode structures using the ONIOM(DFTB:PM7) technique to determine the binding poses. The ONIOM(DFTB-D:PM6) docking approach is tested on 121 ligand-receptor biocomplexes with the crystal structures obtained from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB). The result shows that the new method is highly satisfactory for the accurate prediction of the binding poses. The new docking method should be beneficial to structure-based drug design.
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Simulação de Acoplamento Molecular , Teoria Quântica , Ligantes , Proteínas/química , Proteínas/metabolismo , Sítios de Ligação , Ligação Proteica , Bases de Dados de Proteínas , Termodinâmica , Teoria da Densidade FuncionalRESUMO
Metal-organic frameworks (MOFs) are porous materials with potential in biomedical applications such as sensing, drug delivery, and radiosensitization. However, how to tune the properties of the MOFs for such applications remains challenging. Herein, we synthesized two MOFs, Zr-PEB and Hf-PEB. Zr-PEB can be classified as porous interpenetrated zirconium frameworks (PIZOFs) and Hf-PEB is its analogue. We controlled their sizes while maintaining their crystal structure by employing a coordination modulation strategy. They were designed to serve as sensitizer for X-ray therapy and as potential drug carriers. Comprehensive characterizations of the MOFs' properties have been conducted, and the in vitro biological impacts have been studied. Since viability assay showed that Hf-PEB was more biocompatible compared to Zr-PEB, the cellular uptake of Hf-PEB by cells was evaluated using both fluorescence microscopy and soft X-ray tomography (SXT), and the three-dimensional structure of Hf-PEB in cells was observed. The results revealed the potential of Zr-PEB and Hf-PEB as nanomaterials for biomedical applications and demonstrated that SXT is an effective tool to assist the development of such materials.
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Estruturas Metalorgânicas , Zircônio , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/síntese química , Zircônio/química , Humanos , Tomografia por Raios X , Porosidade , Sobrevivência Celular/efeitos dos fármacos , Háfnio/química , Tamanho da Partícula , Propriedades de Superfície , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/farmacologiaRESUMO
OBJECTIVE: To developed a magnetic resonance imaging (MRI) radiomics nomogram to identify adenocarcinoma at the cervix-corpus junction originating from the endometrium or cervix in order to better guide clinical treatment. METHODS: Between February 2011 and September 2021, the clinicopathological data and MRI in 143 patients with histopathologically confirmed cervical adenocarcinoma (CAC, n = 86) and endometrioid adenocarcinoma (EAC, n = 57) were retrospectively analyzed at the cervix-corpus junction. Radiomics features were extracted from fat-suppressed T2-weighted imaging (FS-T2WI), diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, and delayed phase contrast-enhanced T1-weighted imaging (CE-T1WI) sequences. A radiomics nomogram was developed integrating radscore with independent clinical risk factors. The area under the curve (AUC) was used to evaluate the diagnostic efficacy of the radscore, nomogram and two different experienced radiologists in differentiating CAC from EAC at the cervix-corpus junction, and Delong test was applied to compare the differences of their diagnostic performance. RESULTS: In the training cohort, the AUC was 0.93 for radscore; 0.97 for radiomics nomograms; 0.85 and 0.86 for radiologists 1 and 2, respectively. Delong test showed that the differential efficacy of nomogram was significant better than those of radiologists in the training cohort (both P < 0.05). CONCLUSIONS: The nomogram based on radscore and clinical risk factors could better differentiate CAC from EAC at the cervix-corpus junction than radiologists, and preoperatively and non-invasively identify the origin of adenocarcinoma at the cervix-corpus junction, which facilitates clinicians to make individualized treatment decision.
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Adenocarcinoma , Carcinoma Endometrioide , Neoplasias do Endométrio , Imageamento por Ressonância Magnética Multiparamétrica , Nomogramas , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Carcinoma Endometrioide/diagnóstico por imagem , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Adulto , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Idoso , Diagnóstico Diferencial , Colo do Útero/diagnóstico por imagem , Colo do Útero/patologia , Meios de Contraste , RadiômicaRESUMO
This study investigated the effects of semaglutide (Sema) on the gut microbiota of obese mice induced with high-fat diet (HFD). Male C57BL/6 J mice aged 6 weeks were enrolled and randomly distributed to four groups, which were provided with a normal control diet (NCD,NCD + Sema) and a 60% proportion of a high-fat diet (HFD,HFD + Sema), respectively. HFD was given for 10 weeks to develop an obesity model and the intervention was lasted for 18 days. The results showed semaglutide significantly reduced body weight gain, areas under the curve (AUC) of glucose tolerance test and insulin resistance test, as well as adipose tissue weight in mice. Semaglutide effectively reduced lipid deposition and lipid droplet formation in the liver of obese mice, and regulated the expression of genes related to abnormal blood glucose regulation. Additionally, semaglutide influenced the composition of gut microbiota, mitigating the microbial dysbiosis induced by a high-fat diet by impacting the diversity of the gut microbiota. After the high-fat diet intervention, certain strains such as Akkermansia, Faecalibaculum, and Allobaculum were significantly decreased, while Lachnospiraceae and Bacteroides were significantly increased. However, the application of semaglutide restored the lost flora and suppressed excessive bacterial abundance. Moreover, semaglutide increased the content of tight junction proteins and repaired the damage to intestinal barrier function caused by the high-fat diet intervention. Furthermore, correlation analysis revealed inverse relationship among Akkermansia levels and weight gain, blood glucose levels, and various obesity indicators. Correlation analysis also showed that Akkermansia level was negatively correlated with weight gain, blood glucose levels and a range of obesity indicators. This phenomenon may explain the anti-obesity effect of semaglutide, which is linked to alterations in gut microbiota, specifically an increase in the abundance of Akkermansia. In summary, our findings indicate that semaglutide has the potential to alleviate gut microbiota dysbiosis, and the gut microbiota may contribute to the obesity-related effects of this drug.
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Microbioma Gastrointestinal , Peptídeos Semelhantes ao Glucagon , Doenças não Transmissíveis , Masculino , Camundongos , Animais , Dieta Hiperlipídica/efeitos adversos , Glicemia/análise , Disbiose/metabolismo , Camundongos Obesos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/microbiologia , Aumento de PesoRESUMO
PURPOSE: The effectiveness of iodine-131(131I) therapy in patients with papillary thyroid cancer (PTC) of various stage is controversial. This study aimed to use prognostic risk groups to guide 131I therapy in patients with PTC after radical thyroidectomy. METHODS: Data of 53,484 patients with PTC after radical thyroidectomy were collected from the Epidemiology and End Results (SEER) database. Patients were divided into subgroups according to MACIS system and regional lymph node involvement. The prognostic role of 131I therapy was investigated by comparing Kaplan-Meier survival analysis and Cox proportional hazard models in different subgroups. RESULTS: Sex, age, tumor size, invasion, regional lymph node involvement, and distant metastasis was related to the survival of patients with PTC. If MACIS < 7, 131I treatment didn't affect the cancer-specific survival (CSS) rate. If MACIS ≥ 7, 131I therapy didn't work on CSS rate for patients with N0 or N1a < 5 status; 131I therapy had improved CSS rate for patients in the N1a ≥ 5 or N1b status. If patients with distant metastasis, invasion, or large tumor, 131I therapy didn't improve CSS rate for patients in N0 or N1a < 5 stage. CONCLUSION: After radical thyroidectomy, if MACIS < 7, patients with PTC could avoid 131I therapy. If MACIS ≥ 7, patients in the N0 or N1a < 5 could avoid 131I therapy; those in the N1a ≥ 5 or N1b stage should be given 131I therapy. Among them, all patients with distant metastasis should be given 131I therapy.
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Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/radioterapia , Câncer Papilífero da Tireoide/cirurgia , Prognóstico , Radioisótopos do Iodo/uso terapêutico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Carcinoma Papilar/radioterapia , Carcinoma Papilar/cirurgia , Metástase Linfática , Estudos Retrospectivos , Tireoidectomia/métodosRESUMO
Introduction: It is unclear whether admission-blood-glucose-to-albumin ratio (AAR) predicts adverse clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) who are treated with percutaneous coronary intervention (PCI). Here, we performed a observational study to explore the predictive value of AAR on clinical outcomes. Methods: Patients diagnosed with STEMI who underwent PCI between January 2010 and February 2020 were enrolled in the study. The patients were classified into three groups according to AAR tertile. The primary outcome was in-hospital all-cause mortality, and the secondary outcomes were in-hospital major adverse cardiac events (MACEs), as well as all-cause mortality and MACEs during follow-up. Logistic regression, Kaplan-Meier analysis, and Cox proportional hazard regression were the primary analyses used to estimate outcomes. Results: Among the 3,224 enrolled patients, there were 130 cases of in-hospital all-cause mortality (3.9%) and 181 patients (5.4%) experienced MACEs. After adjustment for covariates, multivariate analysis demonstrated that an increase in AAR was associated with an increased risk of in-hospital all-cause mortality [adjusted odds ratio (OR): 2.72, 95% CI: 1.47-5.03, P = 0.001] and MACEs (adjusted OR: 1.91, 95% CI: 1.18-3.10, P = 0.009), as well as long-term all-cause mortality [adjusted hazard ratio (HR): 1.64, 95% CI: 1.19-2.28, P = 0.003] and MACEs (adjusted HR: 1.58, 95% CI: 1.16-2.14, P = 0.003). Receiver operating characteristic (ROC) curve analysis indicated that AAR was an accurate predictor of in-hospital all-cause mortality (AUC = 0.718, 95% CI: 0.675-0.761) and MACEs (AUC = 0.672, 95% CI: 0.631-0.712). Discussion: AAR is a novel and convenient independent predictor of all-cause mortality and MACEs, both in-hospital and long-term, for STEMI patients receiving PCI.
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OBJECTIVES: Preoperative identification of POLE mutation status would help tailor the surgical procedure and adjuvant treatment strategy. This study aimed to explore the feasibility of developing a radiomics model to pre-operatively predict the pathogenic POLE mutation status in patients with EC. METHODS: The retrospective study involved 138 patients with histopathologically confirmed EC (35 POLE-mutant vs 103 non-POLE-mutant). After selecting relevant features with a series of steps, three radiomics signatures were built based on axial fat-saturation T2WI, DWI, and CE-T1WI images, respectively. Then, two radiomics models which integrated features from T2WI + DWI and T2WI + DWI+CE-T1WI were further developed using multivariate logistic regression. The performance of the radiomics model was evaluated from discrimination, calibration, and clinical utility aspects. RESULTS: Among all the models, radiomics model2 (RM2), which integrated features from all three sequences, showed the best performance, with AUCs of 0.885 (95%CI: 0.828-0.942) and 0.810 (95%CI: 0.653-0.967) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) analyses indicated that RM2 had improvement in predicting POLE mutation status when compared with the single-sequence-based signatures and the radiomics model1 (RM1). The calibration curve, decision curve analysis, and clinical impact curve suggested favourable calibration and clinical utility of RM2. CONCLUSIONS: The RM2, fusing features from three sequences, could be a potential tool for the non-invasive preoperative identification of patients with POLE-mutant EC, which is helpful for developing individualized therapeutic strategies. ADVANCES IN KNOWLEDGE: This study developed a potential surrogate of POLE sequencing, which is cost-efficient and non-invasive.
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Neoplasias do Endométrio , Humanos , Feminino , Estudos Retrospectivos , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/genética , Área Sob a Curva , Imageamento por Ressonância Magnética , MutaçãoRESUMO
Background: Connexin 43 (Cx43) has been closely linked to the occurrence and progression of breast cancer. Distant metastasis of breast cancer is aided by the epithelial-mesenchymal transition of circulating tumor cells (CTCs). However, the impact of Cx43 expression on CTCs and the extent of its role in the disease remain unclear. Methods: We determined CTCs in 156 patients, who had breast cancer with a disease course of two or more years. We also measured the expression of Cx43 in the CTCs. The CTCs were detected in the blood of 139 of these patients. These 139 patients were divided into two groups: the Cx43 group and the non-Cx43 group based on their Cx43 expression. Results: Overall, Cx43 expression was found in 83 of the 139 patients (59.7%, 83/139 cases). The two groups significantly differed in terms of the number of mixed biphenotypic type CTCs and the total number of CTCs (P < 0.05). There were significant correlations between Cx43 expression and Ki67 expression, tumor size, lymph node metastasis, and TNM stage (P < 0.05 for all). The data suggested that patients with Cx43 expression had a higher risk of distant metastasis and had later-stage disease. The difference in Cx43 expression between patients with and without epidermal growth factor receptor 2 (Her2) overexpression was statistically significant (P < 0.05). The difference in disease-free survival (DFS) between the two groups was statistically significant (P = 0.03), and the Cx43 group had a shorter duration of DFS. Univariate Cox regression analysis revealed that Cx43 expression, Her2 expression, and tumor size were significantly correlated with DFS (P = 0.03, 0.0023, and 0.01, respectively). Conclusion: Cx43 expression in the CTCs of patients with breast cancer is a cancer-promoting factor.
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Communications between tumor cells and surrounding immune cells help shape the tumor immunity continuum. Recent breakthroughs in high-throughput technologies as well as computational algorithms had reported many important tumor-immune cell (TIC) communications, which were scattered in thousands of published studies and impeded systematical characterization of the TIC communications across cancer. Here, a comprehensive database, TICCom, was developed to model TIC communications, containing 739 experimentally-validated or manually-curated interactions collected from more than 3,000 literatures as well as 4,537,709 predicted interactions inferred via six computational algorithms by reanalyzing 32 scRNA-seq datasets and bulk RNA-seq data across 25 cancer types. The communications between tumor cells and 14 types of immune cells were characterized, and the involved ligand-receptor interactions were further integrated. 14190 human and 3650 mouse integrated ligand-receptor interactions with supplemented corresponding function information were also stored in the TICCom database. Our database would serve as a valuable resource for investigating TIC communications.
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Sistema Imunitário , Neoplasias , Animais , Humanos , Camundongos , Algoritmos , Comunicação Celular , Bases de Dados Factuais , LigantesRESUMO
OBJECTIVES: To develop a fusion model based on clinicopathological factors and MRI radiomics features for the prediction of recurrence risk in patients with endometrial cancer (EC). METHODS: A total of 421 patients with histopathologically proved EC (101 recurrence vs. 320 non-recurrence EC) from four medical centers were included in this retrospective study, and were divided into the training (n = 235), internal validation (n = 102), and external validation (n = 84) cohorts. In total, 1702 radiomics features were respectively extracted from areas with different extensions for each patient. The extreme gradient boosting (XGBoost) classifier was applied to establish the clinicopathological model (CM), radiomics model (RM), and fusion model (FM). The performance of the established models was assessed by the discrimination, calibration, and clinical utility. Kaplan-Meier analysis was conducted to further determine the prognostic value of the models by evaluating the differences in recurrence-free survival (RFS) between the high- and low-risk patients of recurrence. RESULTS: The FMs showed better performance compared with the models based on clinicopathological or radiomics features alone but with a reduced tendency when the peritumoral area (PA) was extended. The FM based on intratumoral area (IA) [FM (IA)] had the optimal performance in predicting the recurrence risk in terms of the ROC, calibration curve, and decision curve analysis. Kaplan-Meier survival curves showed that high-risk patients of recurrence defined by FM (IA) had a worse RFS than low-risk ones of recurrence. CONCLUSIONS: The FM integrating intratumoral radiomics features and clinicopathological factors could be a valuable predictor for the recurrence risk of EC patients. CLINICAL RELEVANCE STATEMENT: An accurate prediction based on our developed FM (IA) for the recurrence risk of EC could facilitate making an individualized therapeutic decision and help avoid under- or over-treatment, therefore improving the prognosis of patients. KEY POINTS: ⢠The fusion model combined clinicopathological factors and radiomics features exhibits the highest performance compared with the clinicopathological model and radiomics model. ⢠Although higher values of area under the curve were observed for all fusion models, the performance tended to decrease with the extension of the peritumoral region. ⢠Identifying patients with different risks of recurrence, the developed models can be used to facilitate individualized management.
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Neoplasias do Endométrio , Imageamento por Ressonância Magnética , Humanos , Feminino , Estudos Retrospectivos , Prognóstico , Estimativa de Kaplan-Meier , Neoplasias do Endométrio/diagnóstico por imagemRESUMO
Although the perovskite (Nd,Sr)CoO3 (NSC113)/Ruddlesden-Popper (R-P) oxide (Nd,Sr)2CoO4 (NSC214) heterostructure is reported to improve the oxygen reduction reaction (ORR) activity by 2-3 orders of magnitude, the enhancement mechanism remains unclear. For the first time, we conclude that there are two main factors that can enhance the ORR activity: (1) Oxygen adsorbed on such heterostructures would gain more electrons, promoting the oxygen adsorption. (2) The more distant rock-salt layers on the heterointerfaces can facilitate the insertion of interstitial oxygen and form a high-speed transport channel of interstitial oxygen. Moreover, the perovskite/double-layered R-P oxide heterostructure, which has not been reported yet, is predicted to have better ORR performance than the perovskite/single-layered R-P oxide heterostructure. Our work elucidates the ORR enhancement mechanism on perovskite/R-P oxide heterostructures from the atomic level, which is demonstrated by experiments and, thus, is very meaningful for the development of high-performance electrochemical devices.
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Blockade of indoleamine 2,3-dioxygenase (IDO) has been shown to alleviate lipopolysaccharide (LPS)-induced endotoxic shock and reduce sepsis mortality, but its effect on LPS-induced kidney damage has not been reported. Herein, we established a mouse kidney injury model by intraperitoneal injection of 10 mg/kg LPS and established an in vitro renal tubular epithelial cell injury model by stimulating TCMK-1 cells with 10 mg/L LPS. We found that pretreatment with 1-methyl tryptophan (1-MT), an IDO inhibitor, significantly improved LPS-induced mouse survival, and IDO knockout (KO) mice also had higher survival rates after LPS exposure than wild-type mice. At the same time, IDO KO or pretreatment with 1-MT not only reduced serum creatinine, blood urea nitrogen, renal tubular injury pathological score, but also inflammatory factors and oxidative stress status in serum or kidney of LPS-exposed mice. In vitro, blockade of IDO with 1-MT significantly inhibited LPS-induced apoptosis, inflammation and oxidative stress in TCMK-1 cells. In addition, blockade of IDO significantly inhibited LPS-activated TLR4/NF-κB signaling pathway in kidney of mice or in TCMK-1 cells. In conclusion, our results suggested that blockade of IDO attenuated kidney inflammation, apoptosis and oxidative stress to protect against LPS-induced septic kidney injury via inhibiting the TLR4/NF-κB signaling pathway.
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Injúria Renal Aguda , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais , Rim , Inflamação/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/prevenção & controleRESUMO
Background: Our study aimed to evaluate the safety and immunogenicity of the third (booster) dose of the COVID-19 vaccine for patients with endocrine-related cancers. Methods: This observational study involved 94 breast cancer patients, 92 thyroid cancer patients, and 123 healthy individuals who had received the third (booster) dose of the COVID-19 vaccine. Data on the adverse effects, serum anti-receptor binding domain (RBD)-immunoglobulin (Ig) G, and neutralizing antibodies (NAbs) were collected prospectively. Results: The serum anti-RBD-IgG and NAb titers were significantly lower for the patients with endocrine-related malignancies than for the healthy controls (3.01 [IQR: 1.11-6.70] vs. 4.19 [1.95-9.11], p = 0.001; 0.23 [0.11-0.52] vs. 0.41 [0.22-0.78], p = 0.001), and the seroconversion rates of anti-RBD-IgG and NAbs showed similar results. The serum antibody titers and seroconversion rates were significantly lower for patients aged ≥65 years with endocrine-related cancers, but there were no significant differences related to gender, vaccine type, or cancer type. Subgroup analysis showed that the antibody titers and seroconversion rates were significantly lower for patients with intermediate to advanced breast cancer, HR-/Her2+ breast cancer, and breast cancer undergoing treatment than for healthy controls. In contrast, breast cancer patients who completed their treatment and those who received endocrine therapy after completing their treatment were not significantly different from healthy controls. The NAbs titers and seroconversion rates were significantly lower for patients with primary thyroid cancer (0.19 [IQR: 0.10-0.46] vs. 0.41 [0.22-0.78], p = 0.003; 55.9 vs. 84.9%, p < 0.001); the seroconversion rates were significantly higher for the patients with combined Hashimoto's thyroiditis than for those without it. Multiple linear regression showed that patients aged ≥65 years who were receiving treatment were at risk of having lower antibody levels. Conclusion: The third (booster) dose of the COVID-19 vaccine is safe and well-tolerated. Our data support a third (booster) dose of the SARS-CoV-2 vaccine for breast and thyroid cancer patients. Breast cancer patients aged ≥65 years who are receiving treatment should be more protected, while thyroid cancer and breast cancer patients who have completed their treatment can be vaccinated like the general population.
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Neoplasias da Mama , COVID-19 , Neoplasias da Glândula Tireoide , Humanos , Feminino , Vacinas contra COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Imunoglobulina GRESUMO
PURPOSE: To develop and validate an MRI-based radiomics nomogram for the preoperative prediction of miliary changes in the small bowel mesentery (MCSBM) in advanced high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and twenty-eight patients with pathologically proved advanced HGSOC (training cohort: n = 91; validation cohort: n = 37) were retrospectively included. All patients were initially evaluated as MCSBM-negative by preoperative imaging modalities but were finally confirmed by surgery and histopathology (MCSBM-positive: n = 53; MCSBM-negative: n = 75). Five radiomics signatures were built based on the features from multisequence magnetic resonance images. Independent clinicoradiological factors and radiomics-fusion signature were further integrated to construct a radiomics nomogram. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves and clinical utility. RESULTS: Radiomics signatures, ascites, and tumor size were independent predictors of MCSBM. A nomogram integrating radiomics features and clinicoradiological factors demonstrated satisfactory predictive performance with areas under the curves (AUCs) of 0.871 (95% CI 0.801-0.941) and 0.858 (95% CI 0.739-0.976) in the training and validation cohorts, respectively. The net reclassification index (NRI) and integrated discrimination improvement (IDI) revealed that the nomogram had a significantly improved ability compared with the clinical model in the training cohort (NRI = 0.343, p = 0.002; IDI = 0.299, p < 0.001) and validation cohort (NRI = 0.409, p = 0.015; IDI = 0.283, p = 0.001). CONCLUSION: Our proposed nomogram has the potential to serve as a noninvasive tool for the prediction of MCSBM, which is helpful for the individualized assessment of advanced HGSOC patients.
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Nomogramas , Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , MesentérioRESUMO
Background: Microsatellite instability (MSI) status is an important indicator for screening patients with endometrial cancer (EC) who have potential Lynch syndrome (LS) and may benefit from immunotherapy. This study aimed to develop a magnetic resonance imaging (MRI)-based radiomics nomogram for the prediction of MSI status in EC. Methods: A total of 296 patients with histopathologically diagnosed EC were enrolled, and their MSI status was determined using immunohistochemical (IHC) analysis. Patients were randomly divided into the training cohort (n=236) and the validation cohort (n=60) at a ratio of 8:2. To predict the MSI status in EC, the tumor radiomics features were extracted from T2-weighted images and contrast-enhanced T1-weighted images, which in turn were selected using one-way analysis of variance (ANOVA) and the least absolute shrinkage and selection operator (LASSO) algorithm to build the radiomics signature (radiomics score; radscore) model. Five clinicopathologic characteristics were used to construct a clinicopathologic model. Finally, the nomogram model combining radscore and clinicopathologic characteristics was constructed. The performance of the three models was evaluated using receiver operating characteristic (ROC), calibration, and decision curve analyses (DCA). Results: Totals of 21 radiomics features and five clinicopathologic characteristics were selected to develop the radscore and clinicopathological models. The radscore and clinicopathologic models achieved an area under the curve (AUC) of 0.752 and 0.600, respectively, in the training cohort; and of 0.723 and 0.615, respectively, in the validation cohort. The radiomics nomogram model showed improved discrimination efficiency compared with the radscore and clinicopathologic models, with an AUC of 0.773 and 0.740 in the training and validation cohorts, respectively. The calibration curve analysis and DCA showed favorable calibration and clinical utility of the nomogram model. Conclusions: The nomogram incorporating MRI-based radiomics features and clinicopathologic characteristics could be a potential tool for the prediction of MSI status in EC.
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BACKGROUND: Preoperative assessment of whether a successful primary debulking surgery (PDS) can be performed in patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains a challenge. A reliable model to precisely predict resectability is highly demanded. PURPOSE: To investigate the value of diffusion-weighted MRI (DW-MRI) combined with morphological characteristics to predict the PDS outcome in advanced HGSOC patients. STUDY TYPE: Prospective. SUBJECTS: A total of 95 consecutive patients with histopathologically confirmed advanced HGSOC (ranged from 39 to 77 years). FIELDS STRENGTH/SEQUENCE: A 3.0 T, readout-segmented echo-planar DWI. ASSESSMENT: The MRI morphological characteristics of the primary ovarian tumor, a peritoneal carcinomatosis index (PCI) derived from DWI (DWI-PCI) and histogram analysis of the primary ovarian tumor and the largest peritoneal carcinomatosis were assessed by three radiologists. Three different models were developed to predict the resectability, including a clinicoradiologic model combing MRI morphological characteristic with ascites and CA125 level; DWI-PCI alone; and a fusion model combining the clinical-morphological information and DWI-PCI. STATISTICAL TESTS: Multivariate logistic regression analyses, receiver operating characteristic (ROC) curve, net reclassification index (NRI) and integrated discrimination improvement (IDI) were used. A P < 0.05 was considered to be statistically significant. RESULTS: Sixty-seven cases appeared as a definite mass, whereas 28 cases as an infiltrative mass. The morphological characteristics and DWI-PCI were independent factors for predicting the resectability, with an AUC of 0.724 and 0.824, respectively. The multivariable predictive model consisted of morphological characteristics, CA-125, and the amount of ascites, with an incremental AUC of 0.818. Combining the application of a clinicoradiologic model and DWI-PCI showed significantly higher AUC of 0.863 than the ones of each of them implemented alone, with a positive NRI and IDI. DATA CONCLUSIONS: The combination of two clinical factors, MRI morphological characteristics and DWI-PCI provide a reliable and valuable paradigm for the noninvasive prediction of the outcome of PDS. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.
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Neoplasias Ovarianas , Neoplasias Peritoneais , Feminino , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Ascite , Procedimentos Cirúrgicos de Citorredução , Estudos Prospectivos , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
Subsequently to the publication of the above article, the authors have contacted the Editorial Office to explain that Fig. 7 was published containing an erroneously placed data panel. Specifically, the center panel of the images selected for the invasion assay experiments portrayed in Fig. 7A (i.e., the miR382 experiment) was chosen incorrectly, and the authors have requested that this panel be replaced by the panel containing the data that was actually used for the statistical analysis shown in part (B). The revised version of Fig. 7, showing the correct data panel for the miR382 experiment in the invasion assay images in part (A), is shown on the next page. The authors can confirm that the change made to this figure does not affect the overall conclusions reported in the study, and all the authors agree to the publication of this corrigendum. The authors are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this additional Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [International Journal of Oncology 61: 126, 2022; DOI: 10.3892/ijo.2022.5416].
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Background: Estrogen and progesterone receptor status can predict breast cancer patient prognosis and treatment sensitivity, but research on low ER and PR levels and expression balance remains limited. Methods: From January 2010 to October 2016, 283 ER+/PR+/HER2-breast cancer patients who met the inclusion criteria were enrolled and divided into the H group (ER > 10%, N = 261) and the L group (1% ≤ ER ≤ 10%, N = 22). Groups were further divided into the HH group (ER > 10%/PR > 20%, N = 201), the HL group (ER > 10%/ER 1% ≤ PR ≤ 20% PR, N = 60), the LH group (1% ≤ ER ≤ 10%/PR > 20%, N = 5), and the LL group (1% ≤ ER ≤ 10%/1% ≤ PR ≤ 20%, N = 17). The LH group was excluded due to its small size, leaving the clinical and prognostic characteristics of 2 large groups and 3 subgroups to be analyzed. Results: L group patients had significantly more stage N2 axillary lymph nodes than H group patients (31.8% vs. 9.2%, P = 0.007). Age (P = 0.011), menopause status (P = 0.001), and tumor size (P = 0.024) were significantly different in the HL vs. HH and LL groups. Five-year DFS (94.6% vs. 77.0%, P < 0.001) and 5-year OS (97.2% vs. 85.8%, P = 0.001) rates significantly differed between HH and HL. No significant differences in 5-year DFS (77.0% vs. 81.9%, P = 0.564) or 5-year OS (85.8% vs. 87.8%, P = 0.729) rates were observed between HL and LL; the OS rates of HL and LL were similar. Conclusion: In the group of ER+/PR+/HER2-patients, there was no significant prognostic difference between ER-low positive and ER-high positive groups, but low PR expression was significantly associated with a worse prognosis. The role of ER and PR balance in breast cancer progression and individualized treatment requires further investigation.
Assuntos
Neoplasias da Mama , Receptores de Progesterona , Feminino , Humanos , Receptores de Progesterona/metabolismo , Neoplasias da Mama/patologia , Estudos Retrospectivos , Receptores de Estrogênio/metabolismo , Receptor ErbB-2/metabolismo , Prognóstico , Estrogênios/uso terapêutico , Biomarcadores TumoraisRESUMO
Macrophages are principal immune cells with a high plasticity in the human body that can differentiate under different conditions in the tumor microenvironment to adopt two polarized phenotypes with opposite functions. Therefore, converting macrophages from the immunosuppressive phenotype (M2) to the inflammatory phenotype (M1) is considered a promising therapeutic strategy for cancer. However, the molecular mechanisms underlying this conversion process have not yet been completely elucidated. In recent years, microRNAs (miRNAs or miRs) have been shown to play key roles in regulating macrophage polarization through their ability to modulate gene expression. In the present study, it was found that miR382 expression was significantly downregulated in tumorassociated macrophages (TAMs) and M2polarized macrophages in breast cancer. In vitro, macrophage polarization toward the M2 phenotype and M2type cytokine release were inhibited by transfection with miR382overexpressing lentivirus. Similarly, the overexpression of miR382 inhibited the ability of TAMs to promote the malignant behaviors of breast cancer cells. In addition, peroxisome proliferatoractivated receptor γ coactivator1α (PGC1α) was identified as the downstream target of miR382 and it was found that PGC1α affected macrophage polarization by altering the metabolic status. The ectopic expression of PGC1α restored the phenotype and cytokine secretion of miR382overexpressing macrophages. Furthermore, PGC1α expression reversed the miR382induced changes in the metabolic state of TAMs and the effects of TAMs on breast cancer cells. Of note, the in vivo growth and metastasis of 4T1 cells were inhibited by miR382overexpressing TAMs. Taken together, the results of the present study suggest that miR382 may alter the metabolic status of macrophages by targeting PGC1α, thereby decreasing the proportion of TAMs with the M2 phenotype, and inhibiting the progression and metastasis of breast cancer.