RESUMO
MARCH8, an E3 ubiquitin ligase, plays a crucial role in regulating various cellular processes such as protein degradation and signaling pathways and is implicated in the development and spread of pancreatic cancer. Analysis of pancreatic cancer tissues compared to adjacent normal tissues showed a decrease in miRNA-30d-5p levels and an increase in OIP5-AS1 and MARCH8 levels, as confirmed by qRT-PCR and Western blot analysis. The dual-luciferase reporter assay demonstrated a binding relationship between OIP5-AS1 and miRNA-30d-5p, as well as between miRNA-30d-5p and MARCH8 in PACN-1 cells, derived from a human pancreatic carcinoma specimen. Further investigations utilizing various assays revealed that OIP5-AS1 inhibited apoptosis and promoted cell proliferation, invasion, and migration in PACN-1 cells via the miRNA-30d-5p/MARCH8 axis in vitro. Tumor experiments in nude mice confirmed that OIP5-AS1 enhanced PACN-1 cell growth in vivo through the miRNA-30d-5p/MARCH8 axis. Additionally, OIP5-AS1 was found to activate downstream genes of the JAK-STAT pathway, namely IFNAR2, SOCS3, and JAK1, in PACN-1 cells. Furthermore, OIP5-AS1 increased the IC50 values for doxorubicin, gemcitabine, and cisplatin in PACN-1 cells, as determined by the Cell Counting Kit-8 assay. Overall, OIP5-AS1 was shown to promote aggressive traits and resistance to chemotherapy in PACN-1 cells through the miRNA-30d-5p/MARCH8 axis.
RESUMO
PURPOSE: To investigate the post-radiofrequency ablation (RFA) magnetic resonance imaging (MRI) characteristics in patients with liver metastases from colorectal cancer and to build a predictive model for local tumor progression based on these imaging markers. MATERIALS AND METHODS: A cohort of 73 patients with 110 colorectal cancer liver metastases (CRCLM) who underwent RFA and MRI one month post-ablation was included in image signs analysis and predictive model training. Using a newly developed MRI appearance scoring criteria, MR Image Appearance Scoring at One Month after RFA (MRIAS 1MO), the semi-quantitative analysis of MRI findings within the ablation zone were conducted independently by two radiologists. The intraclass correlation coefficient (ICC) was calculated to evaluate measurement reliability. Differences in MRIAS 1MO scores were compared using Mann-Whitney U test, focusing on local tumor response outcomes. Using local tumor progression (LTP) as the primary end point, MRIAS 1MO scores and other lesion morphological and clinical characteristics were included to establish predictive model. Predication accuracy was subsequently evaluated using calibration curve, time-dependent concordance index (C index) curve, and LTP-free survival (LTPFS) curve. Another cohort comprising 60 patients with 76 CRCLMs provided additional MRIAS 1MO scores and clinical data associated with LTP. We evaluated the performance of the established predictive model using calibration curve, time-dependent C index curve, and LTPFS curve. RESULTS: The MRIAS 1MO criteria exhibited strong measurement reliability. The ICC values of T1S (scores from T1WI), T2S (scores form T2WI) and NCES (scores by adding T1S to T2S) MRIS (the overall scores) were 0.825, 0.779, 0.826 and 0.873, respectively. Lesions with LTP showed significantly higher median values for the overall MRIAS 1MO score (MRIS) compared to lesions without LTP (16 vs. 12, p < 0.001). MRIS and lesion diameter were independent prognostic factors of LTP and were included in predictive model (hazard ratio: MRIS over 13.5:4.275, lesion diameter larger than 30 mm: 2.056). The predictive model demonstrated an overall C index of 0.721 and risk stratification using the predictive model resulted in significantly different LPTFS times. In the validation cohort, the C index were 0.825, 0.794 and 0.764 at six, twelve and twenty-four months, respectively. Patients classified as high-risk in the validation cohort had a median LTPFS time of 10.0 months, while the median LTPFS time was not reached in the low-risk group. CONCLUSIONS: The semi-quantitative MRIAS 1MO criteria, used for post-RFA MRI appearance analysis, exhibited strong measurement reliability. Prediction models established based on overall MRIAS 1MO score (MRIS) and lesion diameter had good predictive performance for LTP in patients undergoing RFA for CRCLM treatment.
Assuntos
Neoplasias Colorretais , Progressão da Doença , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Ablação por Radiofrequência , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Idoso , Ablação por Radiofrequência/métodos , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou maisRESUMO
Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (Râ ) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive Râ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of Râ . At a temperature of 43 °C, the generated Râ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied Râ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.
Assuntos
Carbono , NF-kappa B , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Radicais Livres/química , Radicais Livres/metabolismo , Humanos , Carbono/química , Micelas , DNA/química , DNA/metabolismo , Animais , CamundongosRESUMO
PURPOSE: To create radiomics signatures based on habitat to assess the instant response in lung metastases of colorectal cancer (CRC) after radiofrequency ablation (RFA). METHODS: Between August 2016 and June 2019, we retrospectively included 515 lung metastases in 233 CRC patients who received RFA (412 in the training group and 103 in the test group). Multivariable analysis was performed to identify independent risk factors for developing the clinical model. Tumor and ablation regions of interest (ROI) were split into three spatial habitats through K-means clustering and dilated with 5 mm and 10 mm thicknesses. Radiomics signatures of intratumor, peritumor, and habitat were developed using the features extracted from intraoperative CT data. The performance of these signatures was primarily evaluated using the area under the receiver operating characteristics curve (AUC) via the DeLong test, calibration curves through the Hosmer-Lemeshow test, and decision curve analysis. RESULTS: A total of 412 out of 515 metastases (80%) achieved complete response. Four clinical variables (cancer antigen 19-9, simultaneous systemic treatment, site of lung metastases, and electrode type) were utilized to construct the clinical model. The Habitat signature was combined with the Peri-5 signature, which achieved a higher AUC than the Peri-10 signature in the test set (0.825 vs. 0.816). The Habitat+Peri-5 signature notably surpassed the clinical and intratumor radiomics signatures (AUC: 0.870 in the test set; both, p < 0.05), displaying improved calibration and clinical practicality. CONCLUSIONS: The habitat-based radiomics signature can offer precise predictions and valuable assistance to physicians in developing personalized treatment strategies.
Assuntos
Neoplasias Colorretais , Neoplasias Pulmonares , Ablação por Radiofrequência , Humanos , Radiômica , Estudos RetrospectivosRESUMO
OBJECTIVES: The purpose of this study is to inquire about the potential association between radiomics features and the pathological nature of thyroid nodules (TNs), and to propose an interpretable radiomics-based model for predicting the risk of malignant TN. METHODS: In this retrospective study, computed tomography (CT) imaging and pathological data from 141 patients with TN were collected. The data were randomly stratified into a training group (n = 112) and a validation group (n = 29) at a ratio of 4:1. A total of 1316 radiomics features were extracted by using the pyradiomics tool. The redundant features were removed through correlation testing, and the least absolute shrinkage and selection operator (LASSO) or the minimum redundancy maximum relevance standard was used to select features. Finally, 4 different machine learning models (RF Hybrid Feature, SVM Hybrid Feature, RF, and LASSO) were constructed. The performance of the 4 models was evaluated using the receiver operating characteristic curve. The calibration curve, decision curve analysis, and SHapley Additive exPlanations method were used to evaluate or explain the best radiomics machine learning model. RESULTS: The optimal radiomics model (RF Hybrid Feature model) demonstrated a relatively high degree of discrimination with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI, 0.70-0.97; P < 0.001) for the validation cohort. Compared with the commonly used LASSO model (AUC, 0.78; 95% CI, 0.60-0.91; P < 0.01), there is a significant improvement in AUC in the validation set, net reclassification improvement, 0.79 (95% CI, 0.13-1.46; P < 0.05), and integrated discrimination improvement, 0. 20 (95% CI, 0.10-0.30; P < 0.001). CONCLUSION: The interpretable radiomics model based on CT performs well in predicting benign and malignant TNs by using quantitative radiomics features of the unilateral total thyroid. In addition, the data preprocessing method incorporating different layers of features has achieved excellent experimental results. CLINICAL RELEVANCE STATEMENT: As the detection rate of TNs continues to increase, so does the diagnostic burden on radiologists. This study establishes a noninvasive, interpretable and accurate machine learning model to rapidly identify the nature of TN found in CT.
Assuntos
Bócio Nodular , Nódulo da Glândula Tireoide , Humanos , Radiômica , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagemRESUMO
OBJECTIVE: The role E3 ubiquitin ligase membrane-associated RING-CH 8 (MARCH8) has not been studied in pancreatic cancer. METHOD: Pancreatic cancer cell lines and the normal pancreatic cells were tested in vitro studies and male athymic nude mice were tested in vivo studies. Measuring cell viability by Cell Counting Kit-8 assay (CCK8), 5-ethynyl-2'- deoxyuridine (Edu) staining, and colony formation assay. Wound healing assay was implemented for cell migration and Transwell assay was performed for cell invasion to evaluate the histological status by hematoxylin and eosin staining and to detect the protein ubiquitination by ubiquitination assay. The protein expression was determined by immunohistochemistry staining and western blotting, and mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. RESULT: The expression of MARCH8 was increased whereas PTPN4 was decreased in pancreatic cancer cells. Overexpression of MARCH8 promoted the growth, migration, and invasion of cells, and knockdown of PTPN4 had the similar effects both in vitro and in vivo. MARCH8 promoted PTPN4 protein degradation through ubiquitination. Moreover, PTPN4 suppressed the transcription activities of STAT3 by impairing the level of pSTAT3 (705), while inhibition of PTPN4 activated phosphorylation of STAT3. CONCLUSIONS: MARCH8 promoted pancreatic cancer growth and invasion through mediating the degradation of PTPN4 and activated the phosphorylation of STAT3.
Assuntos
Neoplasias Pancreáticas , Ubiquitina-Proteína Ligases , Animais , Masculino , Camundongos , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Membrana/genética , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Humanos , Fator de Transcrição STAT3/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 4/metabolismoRESUMO
PURPOSE: We investigated the clinical features and prognosis outcomes of pulmonary neuroendocrine neoplasms (PNENs) which were histologically confirmed after percutaneous computed tomography-guided core needle biopsy (PCT-CNB). MATERIALS AND METHODS: We retrospectively investigated 173 patients who had PNENs which were histologically confirmed after PCT-CNB; patients were split into low and intermediate-grade neuroendocrine tumor (LIGNET) (typical carcinoid (TC) and atypical carcinoid (AC)) and high-grade neuroendocrine carcinoma-tumor (HGNEC) groups. In this latter group, patients were further subdivided into large-cell neuroendocrine carcinoma (LCNEC), small-cell lung cancer (SCLC), and high-grade neuroendocrine carcinoma-not otherwise specified (HGNEC-NOS) groups. Complications after biopsy were recorded. We also assessed overall survival (OS) rates using Kaplan-Meier curves, with prognostic factors determined using univariate and multivariate analyses. RESULTS: Complications were mainly pneumothorax (22.5; 39/173 patients), chest tube placement (4.0; 7/173 patients), and pulmonary bleeding (33.5%; 58/173 procedures)-no patient mortality was recorded. Definitive diagnoses were ascribed to 102 SCLC, 10 LCNEC, 43 HGNEC-NOS, 7 TC, and 11 AC patients. The 1- and 3-year OS rates in the LIGNET group were 87.5% and 68.1%, respectively, and 59.2 and 20.9% in the HGNEC group, respectively these data were statistically significant (P = 0.010). For SCLC, 1- and 3-year OS rates were 63.3 and 22.3%, 30.0 and 10.0% for LCNEC, and 53.3% and 20.1% for HGNEC-NOS, respectively (P = 0.031). Independent prognostic factors for OS included disease type and distant metastasis. CONCLUSION: PNENs may be pathologically diagnosed using PCT-CNB. While differential diagnoses between LCNEC and SCLC are problematic in some patients, a HGNEC-NOS diagnosis was ascribed and PCT-CNB samples were shown to predict NEN OS rates.
Assuntos
Tumor Carcinoide , Carcinoma de Células Grandes , Carcinoma Neuroendócrino , Neoplasias Pulmonares , Tumores Neuroendócrinos , Humanos , Estudos Retrospectivos , Biópsia com Agulha de Grande Calibre , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Carcinoma Neuroendócrino/patologia , Prognóstico , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Tumor Carcinoide/patologia , Biópsia Guiada por Imagem , Carcinoma de Células Grandes/patologia , Tomografia Computadorizada por Raios XRESUMO
Introduction: Multimode thermal therapy (MTT) is an innovative interventional therapy developed for the treatment of liver malignancies. When compared to the conventional radiofrequency ablation (RFA), MTT typically offers improved prognosis for patients. However, the effect of MTT on the peripheral immune environment and the mechanisms underlying the enhanced prognosis have yet to be explored. The aim of this study was to further investigate the mechanisms responsible for the difference in prognosis between the two therapies. Methods: In this study, peripheral blood samples were collected from four patients treated with MTT and two patients treated with RFA for liver malignancies at different time points before and after the treatment. Single cell sequencing was performed on the blood samples to compare and analyze the activation pathways of peripheral immune cells following the MTT and RFA treatment. Results: There was no significant effect of either therapy on the composition of immune cells in peripheral blood. However, the differential gene expression and pathway enrichment analysis demonstrated enhanced activation of T cells in the MTT group compared to the RFA group. In particular, there was a remarkable increase in TNF-α signaling via NF-κB, as well as the expression of IFN-α and IFN-γ in the CD8+ effector T (CD8+ Teff) cells subpopulation, when compared to the RFA group. This may be related to the upregulation of PI3KR1 expression after MTT, which promotes the activation of PI3K-AKT-mTOR pathway. Conclusion: This study confirmed that MTT could more effectively activate peripheral CD8+ Teff cells in patients compared with RFA and promote the effector function, thus resulting in a better prognosis. These results provide a theoretical basis for the clinical application of MTT therapy.
Assuntos
Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Fosfatidilinositol 3-Quinases , Transcriptoma , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Ablação por Radiofrequência/métodos , Linfócitos T CD8-PositivosRESUMO
Objectives: To objectively and accurately assess the immediate efficacy of radiofrequency ablation (RFA) on colorectal cancer (CRC) lung metastases, the novel multimodal data fusion model based on radiomics features and clinical variables was developed. Methods: This case-control single-center retrospective study included 479 lung metastases treated with RFA in 198 CRC patients. Clinical and radiological data before and intraoperative computed tomography (CT) scans were retrieved. The relative radiomics features were extracted from pre- and immediate post-RFA CT scans by maximum relevance and minimum redundancy algorithm (MRMRA). The Gaussian mixture model (GMM) was used to divide the data of the training dataset and testing dataset. In the process of modeling in the training set, radiomics model, clinical model and fusion model were built based on a random forest classifier. Finally, verification was carried out on an independent test dataset. The receiver operating characteristic curves (ROC) were drawn based on the obtained predicted scores, and the corresponding area under ROC curve (AUC), accuracy, sensitivity, and specificity were calculated and compared. Results: Among the 479 pulmonary metastases, 379 had complete response (CR) ablation and 100 had incomplete response ablation. Three hundred eighty-six lesions were selected to construct a training dataset and 93 lesions to construct a testing dataset. The multivariate logistic regression analysis revealed cancer antigen 19-9 (CA19-9, p<0.001) and the location of the metastases (p< 0.05) as independent risk factors. Significant correlations were observed between complete ablation and 9 radiomics features. The best prediction performance was achieved with the proposed multimodal data fusion model integrating radiomic features and clinical variables with the highest accuracy (82.6%), AUC value (0.921), sensitivity (80.3%), and specificity (81.4%). Conclusion: This novel multimodal data fusion model was demonstrated efficient for immediate efficacy evaluation after RFA for CRC lung metastases, which could benefit necessary complementary treatment.
RESUMO
PURPOSE: To develop a novel multimodal data fusion model by incorporating computed tomography (CT) images and clinical variables based on deep learning for predicting the invasiveness risk of stage I lung adenocarcinoma that manifests as ground-glass nodules (GGNs) and compare the diagnostic performance of it with that of radiologists. METHODS: A total of 1946 patients with solitary and histopathologically confirmed GGNs with maximum diameter less than 3 cm were retrospectively enrolled. The training dataset containing 1704 GGNs was augmented by resampling, scaling, random cropping, and so forth, to generate new training data. A multimodal data fusion model based on residual learning architecture and two multilayer perceptron with attention mechanism combining CT images with patient general data and serum tumor markers was built. The distance-based confidence scores (DCS) were calculated and compared among multimodal data models with different combinations. An observer study was conducted and the prediction performance of the fusion algorithms was compared with that of the two radiologists by an independent testing dataset with 242 GGNs. RESULTS: Among the whole GGNs, 606 GGNs are confirmed as invasive adenocarcinoma (IA) and 1340 are non-IA. The proposed novel multimodal data fusion model combining CT images, patient general data, and serum tumor markers achieved the highest accuracy (88.5%), area under a ROC curve (0.957), F1 (81.5%), F1weighted (81.9%), and Matthews correlation coefficient (73.2%) for classifying between IA and non-IA GGNs, which was even better than the senior radiologist's performance (accuracy, 86.1%). In addition, the DCSs for multimodal data suggested that CT image had a stronger influence (0.9540) quantitatively than general data (0.6726) or tumor marker (0.6971). CONCLUSION: This study demonstrated that the feasibility of integrating different types of data including CT images and clinical variables, and the multimodal data fusion model yielded higher performance for distinguishing IA from non-IA GGNs.
Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Aprendizado Profundo , Neoplasias Pulmonares , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão/diagnóstico por imagem , Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Invasividade Neoplásica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
Endogenic heat shock proteins and uneven local heat distribution are two main problems in traditional tumor hyperthermia therapy strategies. Aiming at solving these problems, we designed Au-SnSe-PVP nanomaterials (ASNPs) by modifying Au nanoparticles (Au-NPs) and biocompatible PVP on SnSe nanorods via a new reactive oxygen species production strategy. The ASNPs with excellent photothermal conversion performance can produce thermoelectric effects in response to temperature differences during photothermal conversion. The modification of Au-NPs can attract free electron (e-) to accumulate and promote the separation of e- and holes (h+) in the thermoelectric process, thereby further promoting e--rich Au-NPs-induced H2O2 homolysis and h+-H2O half-reaction to generate hydroxyl radicals, realizing the synergistic application of photothermal therapy and pyroelectric dynamic therapy in tumor treatment.
RESUMO
INTRODUCTION: Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Copines-1 (CPNE1) has been shown to be overexpressed in various cancers; however, the role of CPNE1 in CRC remains unknown. Therefore, it is of great importance to elucidate the role of CPNE1 in CRC and its underlying mechanism of action. METHODS: CPNE1 expression in CRC tissues was measured by quantitative real-time PCR and immunohistochemical (IHC) staining. CPNE1 was knocked down (KD) or overexpressed using small inferring RNAs or lentiviral transduction in CRC cells. The proliferation, apoptosis, glycolysis, and mitochondrial respiration of CRC cells were assessed by cell counting kit-8, flow cytometry, and Xfe24 extracellular flux analyzer assays, respectively. The role of CPNE1 in tumor growth and chemoresistance was further confirmed in xenograft and patient-derived tumor xenograft models, respectively. RESULTS: CPNE1 mRNA and protein were upregulated in CRC tissues. CPNE1 promoted proliferation, inhibited apoptosis, increased mitochondrial respiration, enhanced aerobic glycolysis by activating AKT signaling, upregulated glucose transporter 1 (GLUT1) and hexokinase 2 (HK2), and downregulated the production of cleaved Caspase-3 (c-Caspase 3). CPNE1 also contributed to chemoresistance in CRC cells. CPNE1 KD inhibited tumor growth and increased the sensitivity of tumors to oxaliplatin in vivo. CONCLUSION: CPNE1 promotes CRC progression by activating the AKT-GLUT1/HK2 cascade and enhances chemoresistance.
RESUMO
PURPOSE: The purpose of this study was to investigate the clinical efficacy of salvage percutaneous radiofrequency ablation in patients with unresectable colorectal cancer liver metastases. METHODS: The cohort consisted of 81 patients with 126 colorectal cancer liver metastases who underwent radiofrequency ablation between January 2012 and September 2016. The clinical data and ablation data were retrospectively analyzed. The local tumor progression-free survival, overall survival, and prognostic factors were analyzed using the log-rank test and Cox regression model. RESULTS: The technique success rate was 99.21%. The primary efficacy rate was 100% at the 1-month follow-up. Minor complications were observed in 2 patients, which recovered within 1 week. The median local tumor progression-free survival time of all patients was 29.8 months. The absence of subsequent chemotherapy was an independent predictor of a shorter local tumor progression-free survival time (P < 0.001, hazard ratio: 2.823, 95% confidence interval: 1.603, 4.972). The median overall survival time was 26.8 months. A lesion size greater than 3 cm (P = 0.011, hazard ratio: 2.112, 95% confidence interval: 1.188, 3.754) and the presence of early local tumor progression (P = 0.011, hazard ratio: 2.352, 95% confidence interval: 1.217, 4.545) were related to a shorter survival time. CONCLUSIONS: Percutaneous radiofrequency ablation is safe in patients with colorectal cancer liver metastases refractory from chemotherapy. Subsequent chemotherapy is important to enhance local control. Small lesions and favorable early responses are related to prolonged overall survival.
Assuntos
Neoplasias Colorretais/radioterapia , Neoplasias Hepáticas/radioterapia , Recidiva Local de Neoplasia/radioterapia , Ablação por Radiofrequência/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Ablação por Cateter/métodos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Terapia de Salvação , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Purposes: To measure expression levels of CD47 during endometrial carcinoma development, and to determine specific modulatory effects. Methods: CD47 expression levels in endometrial carcinoma tissues and adjacent tissues were analyzed using qRT-PCR. CD47-overexpressed or downregulated cell models were established using CD47 plasmid or CD47 shRNA. The effects of CD47 on HEC-1A and Ishikawa cell growth were evaluated using CCK-8 assays. Migration ability of transfected HEC-1A and Ishikawa cells were examined using wound healing assays. Flow cytometry was used to measure the effects of CD47 on apoptosis and the cell cycle in HEC-1A and Ishikawa cells. Western blot was used to analyze the correlation between CD47 expression level and PI3K/Akt/mTOR signaling pathway. Results: Highly expressed CD47 was observed in endometrial carcinoma tissues, with higher levels in more advanced tissues than in early tissues. Upregulation of CD47 enhanced cell viability and migration ability in HEC-1A and Ishikawa cells, while silencing CD47 caused the opposite results. CD47 overexpression suppressed apoptosis and inhibited cell cycle arrest in HEC-1A and Ishikawa cells. CD47 upregulation contributes to the activation of PI3K/Akt/mTOR signaling pathway in endometrial carcinoma cells. Conclusion: CD47 exerts oncogenic functions in endometrial carcinoma by activating PI3K/Akt/mTOR signaling, suggesting it may be a novel immunotherapeutic target for therapeutic interventions.
RESUMO
Extrapulmonary tuberculosis (TB) is difficult to diagnose. Here, we report a case of extrapulmonary TB in a 68-year-old woman presented with mental fatigue, poor appetite, and weight loss. F-FDG PET/CT revealed elevated F-FDG uptake in the left inferior cervical, left supraclavicular, mediastinal, and splenic hilum lymph nodes and spleen, which were suspected of malignant tumor. To further differentiate benign and malignant diseases, Ga-FAPI PET/CT was performed. Ga-FAPI PET/CT also showed intense Ga-FAPI uptake in the previously mentioned FDG-avid lesions. However, biopsy of the left supraclavicular lymph node demonstrated the presence of TB.
Assuntos
Fluordesoxiglucose F18 , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Quinolinas , Tuberculose/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , HumanosRESUMO
PURPOSE: To assess the effect of contralateral dependent position on procedures and complications of percutaneous computed tomography (CT)-guided core needle biopsy (PCT-CNB) for small (≤ 20 mm) lung lesions adjacent to the pericardium. MATERIALS AND METHODS: Retrospective view was performed to identify patients with small (≤ 20 mm) lung lesions located within 10 mm of the pericardium and who underwent PCT-CNB in the standard supine or prone position (n = 66) or in contralateral dependent position ( n = 35) between March 2010 and January 2020. In 35 patients, CT images in the contralateral dependent position were compared with images in the supine position to assess the mean distance of the lesion from the pericardium and the mean length of interface between these two positions. Complications including rates of pneumothorax, chest tube insertion, and pulmonary hemorrhage were assessed. RESULTS: In comparison with axial images in supine position, the pericardium were located farther from the lesion in the contralateral dependent position; the mean distance of lesions from the pericardium became farther (P < 0.001), and the mean length of interface with the pericardium became shorter (P = 0.008). There was no difference in the complication rates between supine or prone position and contralateral dependent position (pneumothorax, P = 0.098; pulmonary hemorrhage, P = 0.791). CONCLUSION: Placing patients in contralateral dependent position may confer some advantages, including maximizing distance and minimizing length of interface of the lesion to the pericardium during PCT-CNB for small (≤ 20 mm) lung lesions adjacent to the pericardium.
Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Biópsia Guiada por Imagem/métodos , Pneumopatias/diagnóstico , Posicionamento do Paciente/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Pericárdio , Estudos Retrospectivos , Adulto JovemRESUMO
To explore different posttreatment changes between multimode tumor ablation therapy (MTAT) and radiofrequency ablation (RFA) using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and diffusion kurtosis imaging (DKI) in patients with hepatic malignancies.Eighty - seven patients with one hundred and twenty eight hepatic lesions receiving MTAT or RFA underwent IVIM-DWI and DKI before and after treatment. The mean value of apparent diffusion coefficient (ADC), IVIM-DWI parameters, including true diffusion coefficient (D), pseudo-diffusion coefficient (DP), perfusion fraction (f), and DKI parameters including diffusion coefficient (DK), apparent diffusional kurtosis (K) were retrospectively compared prior to and following treatment as well as between treatment groups. The degree of parameters change after ablation was compared between 2 treatment modalities.The mean value of ADC, D, and DK increased while f, and K decreased significantly in MTAT group. In RFA group, just ADC and K showed significantly change following treatment. The ADC and D value were higher in MTAT group than in RFA group 1 month after treatment. While f was lower in MTAT group after treatment compared with RFA group. The ADC, D and DK increased (21.89â±â24.95% versus 8.76â±â19.72%, Pâ=â.04 for ADC, 33.78â±â54.01% versus 7.91â±â25.16%, Pâ=â.03 for D, 25.91â±â36.28% versus 1.75â±â46.42%, Pâ=â.01 for DK) while f declined (-32.62â±â41.48% versus 6.51â±â44.16%, Pâ<â.001) more in MTAT group.The MTAT induced different posttreatment changes on water molecule diffusion and microvasculature related functional MR parameters compared to RFA in patients with liver tumors.
Assuntos
Ablação por Cateter , Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas , Imageamento por Ressonância Magnética/métodos , Microvasos/diagnóstico por imagem , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Feminino , Humanos , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Ablação por Radiofrequência/métodosRESUMO
PURPOSE: To assess the impact of cardiac motion during percutaneous computed tomography (CT)-guided core needle biopsy (PCT-CNB) of small lung lesions near pericardium, focusing on safety and diagnostic accuracy. MATERIALS AND METHODS: Seventy-eight PCT-CNBs were performed between March 2010 and June 2018 in 78 patients with small (≤ 20 mm) lung nodules, each within 10 mm of pericardium. Shifts in distance and length of interface separating lesions from pericardium were calculated and compared by cardiac chambers (left atrium, left ventricle, right atrium, or right ventricle). Risk factors for complications were subjected to univariate analysis, and diagnostic accuracy was assessed. RESULTS: The respective mean values were 0.8 ± 1.1 mm (range 0-5.1 mm) for shifts in distance and 1.5 ± 2.1 mm (range 0-10.8 mm) for length of interface. Neither parameter shifted significantly with respect to cardiac chambers (p > 0.05, both). Pneumothorax ensued in 28 patients (35.9%), and pulmonary hemorrhage occurred in 41 (52.6%). The overall sensitivity, specificity, and accuracy of PCT-CNB were 91.2%, 100%, and 93.2%, respectively. CONCLUSION: Our data indicate that cardiac motion has no impact on either the incidence of complications or the diagnostic accuracy of PCT-CNB in patients with small (≤ 20 mm) lung lesions near pericardium.
Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Radiografia Intervencionista/métodos , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Feminino , Coração/fisiologia , Humanos , Biópsia Guiada por Imagem/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pericárdio/fisiologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Nanotechnology in medicine has greatly expanded the therapeutic strategy that may be explored for cancer treatment by exploiting the specific tumor microenvironment such as mild acidity, high glutathione (GSH) concentration and overproduced hydrogen peroxide (H2O2). Among them, tumor microenvironment responsive chemodynamic therapy (CDT) utilized the Fenton or Fenton-like reaction to produce excess hydroxyl radical (·OH) for the destruction of tumor cells. However, the produced ·OH is easily depleted by the excess GSH in tumors, which would undoubtedly impair the CDT's efficiency. To overcome this obstacle and enhance the treatment efficiency, we design the nanoplatforms for magnetic resonance imaging (MRI)-guided CDT. RESULTS: In this study, we applied the bovine serum albumin (BSA)-templated CuS:Gd nanoparticles (CuS:Gd NPs) for MRI-guided CDT. The Cu2+ in the CuS:Gd NPs could be reduced to Cu+ by GSH in tumors, which further reacted with H2O2 and triggered Fenton-like reaction to simultaneously generate abundant ·OH and deplete GSH for tumor enhanced CDT. Besides, the Gd3+ in CuS:Gd NPs endowed them with excellent MRI capability, which could be used to locate the tumor site and monitor the therapy process preliminarily. CONCLUSIONS: The designed nanoplatforms offer a major step forward in CDT for effective treatment of tumors guided by MRI.
Assuntos
Antineoplásicos/química , Meios de Contraste/química , Nanopartículas Metálicas/química , Soroalbumina Bovina/química , Animais , Antineoplásicos/farmacologia , Cádmio/química , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Feminino , Glutationa/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Imageamento por Ressonância Magnética/métodos , Camundongos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Microambiente Tumoral/efeitos dos fármacosRESUMO
OBJECTIVE: The study aimed to investigate the efficacy of computed tomography (CT)-guided cryoablation debulking of unresectable pelvic recurrent colorectal cancer (CRC). PATIENTS AND METHODS: From January 2013 to April 2016, 30 patients (18 males and 12 females; aged 57.8±10.5 years) with unresectable pelvic recurrent CRC who had previously received radiotherapy or chemotherapy were included. A total of 35 tumors ranging from 1.2 to 6.3 cm underwent cryoablation. Tumor response was evaluated 1 month after cryoablation according to the Modified Response Evaluation Criteria in Solid Tumors. Logistic regression was used to analyze the risk factors for tumor response. Degree of pain palliation was also determined using the Numerical Rating Scale. Cox proportional hazard models were used to identify predictors of outcomes. RESULTS: Cryoablation was successfully performed in all patients. Complete response (CR) was achieved for 27 tumors in 23 patients and partial response was achieved for eight tumors in seven patients 1 month after cryoablation. The rate of CR was 77.14%, and tumor size was an independent risk factor for CR. Pain relief was satisfactory in 21 symptomatic patients (P<0.001), and the median duration of pain relief was 6.0 months (95% CI: 2.67-9.33). Serum carcinoembryonic antigen (CEA) was significantly decreased after cryoablation in 15 patients with elevated CEA (P=0.005). The median progression-free survival (PFS) was 10.0 months (95% CI: 4.43-15.67). Multivariate analysis revealed that tumor size (HR =3.089, P<0.001), sex (HR =0.089, P=0.002), and elevated CEA (HR =7.015, P=0.002) were independent predictors of PFS. CONCLUSION: CT-guided cryoablation is a safe and effective therapeutic option for pelvic recurrent CRC. Tumor size is an important predictor of poor outcomes.