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2.
Eur Radiol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750169

RESUMO

OBJECTIVES: To evaluate signal enhancement ratio (SER) for tissue characterization and prognosis stratification in pancreatic adenocarcinoma (PDAC), with quantitative histopathological analysis (QHA) as the reference standard. METHODS: This retrospective study included 277 PDAC patients who underwent multi-phase contrast-enhanced (CE) MRI and whole-slide imaging (WSI) from three centers (2015-2021). SER is defined as (SIlt - SIpre)/(SIea - SIpre), where SIpre, SIea, and SIlt represent the signal intensity of the tumor in pre-contrast, early-, and late post-contrast images, respectively. Deep-learning algorithms were implemented to quantify the stroma, epithelium, and lumen of PDAC on WSIs. Correlation, regression, and Bland-Altman analyses were utilized to investigate the associations between SER and QHA. The prognostic significance of SER on overall survival (OS) was evaluated using Cox regression analysis and Kaplan-Meier curves. RESULTS: The internal dataset comprised 159 patients, which was further divided into training, validation, and internal test datasets (n = 60, 41, and 58, respectively). Sixty-five and 53 patients were included in two external test datasets. Excluding lumen, SER demonstrated significant correlations with stroma (r = 0.29-0.74, all p < 0.001) and epithelium (r = -0.23 to -0.71, all p < 0.001) across a wide post-injection time window (range, 25-300 s). Bland-Altman analysis revealed a small bias between SER and QHA for quantifying stroma/epithelium in individual training, validation (all within ± 2%), and three test datasets (all within ± 4%). Moreover, SER-predicted low stromal proportion was independently associated with worse OS (HR = 1.84 (1.17-2.91), p = 0.009) in training and validation datasets, which remained significant across three combined test datasets (HR = 1.73 (1.25-2.41), p = 0.001). CONCLUSION: SER of multi-phase CE-MRI allows for tissue characterization and prognosis stratification in PDAC. CLINICAL RELEVANCE STATEMENT: The signal enhancement ratio of multi-phase CE-MRI can serve as a novel imaging biomarker for characterizing tissue composition and holds the potential for improving patient stratification and therapy in PDAC. KEY POINTS: Imaging biomarkers are needed to better characterize tumor tissue in pancreatic adenocarcinoma. Signal enhancement ratio (SER)-predicted stromal/epithelial proportion showed good agreement with histopathology measurements across three distinct centers. Signal enhancement ratio (SER)-predicted stromal proportion was demonstrated to be an independent prognostic factor for OS in PDAC.

3.
Insights Imaging ; 15(1): 10, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38228821

RESUMO

OBJECTIVES: Creeping fat is a kind of unique abnormal mesenteric tissue at the sites of diseased bowel of Crohn's disease. By using dual-energy CT enterography, this study aimed to evaluate the feasibility of spectral parameters in the quantitative analysis of mesenteric adipose tissue or creeping fat. METHODS: In this study, patients with known or suspected Crohn's disease who underwent dual-energy CT enterography from March 1, 2019, to March 31, 2021, were enrolled. Among them, 40 patients with surgery and pathology-proven creeping fat were selected as the creeping fat Crohn's disease group, and 40 normal patients were selected as the control group. The quantitative spectral parameters including the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction at the enteric phases were obtained. Mann-Whitney U test, Kruskal-Wallis H test, and receiver operating characteristic curve analysis were applied to compare quantitative parameters among various groups. RESULTS: A significant difference was observed in the slope of the Hounsfield unit curve, normalised fat-water concentration, normalised fat-iodine concentration, and normalised fat volume fraction between mesenteric adipose tissue and creeping fat with Crohn's disease at the enteric phase (all p < 0.001). The slope of the Hounsfield unit curve of creeping fat at the enteric phase had a better capability to distinguish inactive and active Crohn's disease (AUC = 0.93, p < 0.001). CONCLUSION: Dual-energy CT enterography with quantitative spectral parameters is a potentially novel noninvasive tool for evaluating creeping fat in Crohn's disease. CRITICAL RELEVANCE STATEMENT: Energy spectral parameters of creeping fat in Crohn's disease are significantly different from normal mesenteric adipose tissues and are correlated with inflammatory activity. KEY POINTS: • Dual-energy CT enterography allows quantitatively assessing creeping fat with spectral parameters. • The creeping fat has distinct spectral parameters to normal mesenteric adipose. • The spectral parameters accurately differentiate active and inactive Crohn's disease.

4.
Int J Surg ; 110(2): 740-749, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38085810

RESUMO

BACKGROUND: Undetectable occult liver metastases block the long-term survival of pancreatic ductal adenocarcinoma (PDAC). This study aimed to develop a radiomics-based model to predict occult liver metastases and assess its prognostic capacity for survival. MATERIALS AND METHODS: Patients who underwent surgical resection and were pathologically proven with PDAC were recruited retrospectively from five tertiary hospitals between January 2015 and December 2020. Radiomics features were extracted from tumors, and the radiomics-based model was developed in the training cohort using LASSO-logistic regression. The model's performance was assessed in the internal and external validation cohorts using the area under the receiver operating curve (AUC). Subsequently, the association of the model's risk stratification with progression-free survival (PFS) and overall survival (OS) was then statistically examined using Cox regression analysis and the log-rank test. RESULTS: A total of 438 patients [mean (SD) age, 62.0 (10.0) years; 255 (58.2%) male] were divided into the training cohort ( n =235), internal validation cohort ( n =100), and external validation cohort ( n =103). The radiomics-based model yielded an AUC of 0.73 (95% CI: 0.66-0.80), 0.72 (95% CI: 0.62-0.80), and 0.71 (95% CI: 0.61-0.80) in the training, internal validation, and external validation cohorts, respectively, which were higher than the preoperative clinical model. The model's risk stratification was an independent predictor of PFS (all P <0.05) and OS (all P <0.05). Furthermore, patients in the high-risk group stratified by the model consistently had a significantly shorter PFS and OS at each TNM stage (all P <0.05). CONCLUSION: The proposed radiomics-based model provided a promising tool to predict occult liver metastases and had a great significance in prognosis.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Radiômica , Estudos Retrospectivos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia
5.
JHEP Rep ; 5(9): 100806, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37575884

RESUMO

Background & Aims: Distinct vascular patterns, including microvascular invasion (MVI) and vessels encapsulating tumour clusters (VETC), are associated with poor outcomes of hepatocellular carcinoma (HCC). Imaging surrogates of these vascular patterns potentially help to predict post-resection recurrence. Herein, a prognostic model integrating imaging-based surrogates of these distinct vascular patterns was developed to predict postoperative recurrence-free survival (RFS) in patients with HCC. Methods: Clinico-radiological data of 1,285 patients with HCC from China undergoing surgical resection were retrospectively enrolled from seven medical centres between 2014 and 2020. A prognostic model using clinical data and imaging-based surrogates of MVI and VETC patterns was developed (n = 297) and externally validated (n = 373) to predict RFS. The surrogates (i.e. MVI and VETC scores) were individually built from preoperative computed tomography using two independent cohorts (n = 360 and 255). Whether the model's stratification was associated with postoperative recurrence following anatomic resection was also evaluated. Results: The MVI and VETC scores demonstrated effective performance in their respective training and validation cohorts (AUC: 0.851-0.883 for MVI and 0.834-0.844 for VETC). The prognostic model incorporating serum alpha-foetoprotein, tumour multiplicity, MVI score, and VETC score achieved a C-index of 0.748-0.764 for the developing and external validation cohorts and generated three prognostically distinct strata. For patients at model-predicted medium risk, anatomic resection was associated with improved RFS (p <0.05). By contrast, anatomic resection had no impact on RFS in patients at model-predicted low or high risk (both p >0.05). Conclusions: The proposed model integrating imaging-based surrogates of distinct vascular patterns enabled accurate prediction for RFS. It can potentially be used to identify HCC surgical candidates who may benefit from anatomic resection. Impact and implications: MVI and VETC are distinct vascular patterns of HCC associated with aggressive biological behaviour and poor outcomes. Our multicentre study provided a model incorporating imaging-based surrogates of these patterns for preoperatively predicting RFS. The proposed model, which uses imaging detection to estimate the risk of MVI and VETC, offers an opportunity to help shed light on the association between tumour aggressiveness and prognosis and to support the selection of the appropriate type of surgical resection.

6.
Clin Cancer Res ; 29(15): 2816-2825, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37223896

RESUMO

PURPOSE: To assess the safety and efficacy of local ablation plus PD-1 inhibitor toripalimab in previously treated unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: In the multicenter, two-stage, and randomized phase 1/2 trial, patients were randomly assigned to receive toripalimab alone (240 mg, every 3 weeks), subtotal local ablation followed by toripalimab starting on post-ablation day 3 (Schedule D3), or on post-ablation day 14 (Schedule D14). The first endpoint of stage 1 was to determine which combination schedule could continue and progression-free survival (PFS) as the primary endpoint for stage 1/2. RESULTS: A total of 146 patients were recruited. During stage 1, Schedule D3 achieved numerically higher objective response rate (ORR) than Schedule D14 for non-ablation lesions (37.5% vs. 31.3%), and was chosen for stage 2 evaluation. For the entire cohort of both stages, patients with Schedule D3 had a significantly higher ORR than with toripalimab alone (33.8% vs. 16.9%; P = 0.027). Moreover, patients with Schedule D3 had improved median PFS (7.1 vs. 3.8 months; P < 0.001) and median overall survival (18.4 vs. 13.2 months; P = 0.005), as compared with toripalimab alone. In addition, six (9%) patients with toripalimab, eight (12%) with Schedule D3, and 4 (25%) with Schedule D14 developed grade 3 or 4 adverse events, and one patient (2%) with Schedule D3 manifested grade 5 treatment-related pneumonitis. CONCLUSIONS: In patients with previously treated unresectable HCC, subtotal ablation plus toripalimab improved the clinical efficacy as compared with toripalimab alone, with an acceptable safety profile.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos
7.
Radiology ; 307(4): e222729, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37097141

RESUMO

Background Prediction of microvascular invasion (MVI) may help determine treatment strategies for hepatocellular carcinoma (HCC). Purpose To develop a radiomics approach for predicting MVI status based on preoperative multiphase CT images and to identify MVI-associated differentially expressed genes. Materials and Methods Patients with pathologically proven HCC from May 2012 to September 2020 were retrospectively included from four medical centers. Radiomics features were extracted from tumors and peritumor regions on preoperative registration or subtraction CT images. In the training set, these features were used to build five radiomics models via logistic regression after feature reduction. The models were tested using internal and external test sets against a pathologic reference standard to calculate area under the receiver operating characteristic curve (AUC). The optimal AUC radiomics model and clinical-radiologic characteristics were combined to build the hybrid model. The log-rank test was used in the outcome cohort (Kunming center) to analyze early recurrence-free survival and overall survival based on high versus low model-derived score. RNA sequencing data from The Cancer Image Archive were used for gene expression analysis. Results A total of 773 patients (median age, 59 years; IQR, 49-64 years; 633 men) were divided into the training set (n = 334), internal test set (n = 142), external test set (n = 141), outcome cohort (n = 121), and RNA sequencing analysis set (n = 35). The AUCs from the radiomics and hybrid models, respectively, were 0.76 and 0.86 for the internal test set and 0.72 and 0.84 for the external test set. Early recurrence-free survival (P < .01) and overall survival (P < .007) can be categorized using the hybrid model. Differentially expressed genes in patients with findings positive for MVI were involved in glucose metabolism. Conclusion The hybrid model showed the best performance in prediction of MVI. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Summers in this issue.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/genética , Estudos Retrospectivos , Invasividade Neoplásica/patologia , Tomografia Computadorizada por Raios X/métodos
8.
Curr Med Imaging ; 19(4): 407-413, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35708091

RESUMO

INTRODUCTION: Extrauterine endometrial stromal sarcoma (EESS) arising from Deep pelvic endometriosis (DPE) has a poor life quality and is difficult to diagnose pre-operatively. However, the patient's quality of life can be improved when it is diagnosed precisely and managed successfully. CASE REPORT: A 35-year-old woman presented to our hospital with a 3-month history of hematochezia and anal pain. Initially, she was misdiagnosed as a rectal stromal tumor and then precisely diagnosed as having EESS from DPE following several multidisciplinary team (MDT) meetings. The lesion was shrunk by gonadotrophin-releasing hormone agonist (GnRH-α) treatment and then resected with minimal trauma. CONCLUSION: MDT is crucial in the treatment of the patient. It can promote individualized treatment and improve patient's quality of life.


Assuntos
Neoplasias do Endométrio , Endometriose , Sarcoma do Estroma Endometrial , Feminino , Humanos , Adulto , Sarcoma do Estroma Endometrial/diagnóstico por imagem , Sarcoma do Estroma Endometrial/cirurgia , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/cirurgia , Endometriose/complicações , Endometriose/diagnóstico por imagem , Endometriose/patologia , Qualidade de Vida , Equipe de Assistência ao Paciente
9.
Int J Biol Sci ; 18(5): 1878-1895, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35342334

RESUMO

The biological functions of exosomes and microRNAs (miRs) in nasopharyngeal carcinoma (NPC) remain largely unexplored. Here, miR-197-3p was screened and identified, and whose level was reduced in serum and exosomes of patients with NPC. MiR-197-3p might be a good diagnostic and prognostic indicator. Our data showed that miR-197-3p expression was closely related to radioresistance, apoptosis, proliferation, migration, and survival of NPC. Inhibition of miR-197-3p expression in vitro could promote the proliferation and migration of NPC cells, while promotion of miR-197-3p expression in vivo could significantly inhibit the growth and enhance the radiosensitivity of NPC cells. From the perspective of mechanism, miR-197-3p could inhibit AKT/mTOR phosphorylation activation, inhibit an activated pathway of AKT/mTOR, target Heat Shock 70-kDa Protein 5(HSPA5) related to endoplasmic reticulum homeostasis, inhibit HSPA5-mediated autophagy, and reverse the radioresistance of NPC. Interestingly, exosomal miR-197-3p (EXO-miR-197-3p) reduced the proliferation and migration potential of NPC cells in vitro, and tumor growth and radioresistance of NPC cells in vivo. EXO-miR-197-3p inhibited NPC progression and radioresistance by regulating AKT/mTOR phosphorylation activation and HSPA5-mediated autophagy. In conclusion, our results highlight the potential of EXO-miR-197-3p as an effective radiosensitizer and therapeutic agent for refractory NPC.


Assuntos
MicroRNAs , Neoplasias Nasofaríngeas , Radiossensibilizantes , Autofagia/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/radioterapia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
10.
Ann Surg Oncol ; 29(5): 2960-2970, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35102453

RESUMO

BACKGROUND: Prediction models with or without radiomic analysis for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) have been reported, but the potential for model-predicted MVI in surgical planning is unclear. Therefore, we aimed to explore the effect of predicted MVI on early recurrence after anatomic resection (AR) and non-anatomic resection (NAR) to assist surgical strategies. METHODS: Patients with a single HCC of 2-5 cm receiving curative resection were enrolled from 2 centers. Their data were used to develop (n = 230) and test (n = 219) two prediction models for MVI using clinical factors and preoperative computed tomography images. The two prediction models, clinico-radiologic model and clinico-radiologic-radiomic (CRR) model (clinico-radiologic variables + radiomic signature), were compared using the Delong test. Early recurrence based on model-predicted high-risk MVI was evaluated between AR (n = 118) and NAR (n = 85) via propensity score matching using patient data from another 2 centers for external validation. RESULTS: The CRR model showed higher area under the curve values (0.835-0.864 across development, test, and external validation) but no statistically significant improvement over the clinico-radiologic model (0.796-0.828). After propensity score matching, difference in 2-year recurrence between AR and NAR was found in the CRR model predicted high-risk MVI group (P = 0.005) but not in the clinico-radiologic model predicted high-risk MVI group (P = 0.31). CONCLUSIONS: The prediction model incorporating radiomics provided an accurate preoperative estimation of MVI, showing the potential for choosing the more appropriate surgical procedure between AR and NAR.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Hepatectomia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Invasividade Neoplásica , Estudos Retrospectivos
11.
Ann Transl Med ; 9(6): 485, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33850882

RESUMO

BACKGROUND: Tumor resistance to radiotherapy is one of the main obstacles to the clinical treatment of nasopharyngeal carcinoma (NPC). Improving the radiosensitivity of tumor cells has an important clinical significance in treatment of clinical NPC. This study aimed to identify that miR-138-1-3p as a novel therapeutic target in radioresistant NPC cells and found its targets, CRIPTO and the JAK2/STAT3 pathway. METHODS: Radioresistant C666-IR and HK-1R cells were derived from the NPC cell lines C666-1 and HK-1. The different microRNAs (miRNAs) and their targeting genes were analyzed between C666-1 and C666-IR cells using microarray bioinformatics. Western blot, qRT-PCR, gene transfection, Luciferase reporter assay, and confocal laser scanning microscopy were applied for the analysis of the different genes. RESULTS: MiR-138-1-3p was found to target CRIPTO, which involved in the epithelial-mesenchymal transition (EMT) and JAK2/STAT3 signaling pathways. The luciferase reporter assay confirmed that miR-138-1-3p targeted CRIPTO and downregulated the expression of CRIPTO. Furthermore, miR-138-1-3p affected the stability of the CRIPTO-GRP78 complex on the cell membrane and also reversed the radioresistant characteristics of NPC stem cells, which affected EMT and the JAK2/STAT3 signaling pathway. CONCLUSIONS: The miR-138-1-3p is a small molecule that can modulate radiosensitivity in the radioresistant C666-IR and HK-1R NPC cell lines by inhibiting EMT and targeting CRIPTO to reduce the activation of the JAK2/STAT3 pathway.

12.
Cancer Manag Res ; 12: 1469-1482, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32161499

RESUMO

PURPOSE: In order to clarify which variants of the MMR gene could provide current "healthy" members in affected families a more accurate risk assessment or predictive testing. PATIENTS AND METHODS: One family, which meets the criteria according to both Amsterdam I/II and Bethesda guidelines, is reported in this study. The proband and some relatives of the patient have been investigated for whole genome sequencing, microsatellite instability, immunohistochemical MMR protein staining and verified by Sanger sequencing. RESULTS: A heterozygous insertion of uncertain significance (c.420dup, p.Met141Tyrfs) in MSH2 gene was found in proband (III-16) and part of His relatives. The variant was associated with a lack of expression of MSH2 protein (MMR deficient) and high microsatellite instability analysis (MSI) status in tumor tissues of LS patients. In addition, we found that the variant could affect the expression of MSH2 and the response to chemotherapy drugs in vitro. CONCLUSION: We identified an insertion mutation (rs1114167810, c.420dup, p.Met141Tyrfs) in MSH2 in LS using whole genome-wide sequencing (WGS). We further confirmed that this mutation plays an important role in LS patients of this pedigree based on in vivo and vitro study.

13.
Front Oncol ; 9: 552, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31293979

RESUMO

Background: Conventional methods for predicting treatment response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) are limited. Methods: This study retrospectively recruited 134 LARC patients who underwent standard nCRT followed by total mesorectal excision surgery in our institution. Based on pre-operative axial T2-weighted images, machine learning radiomics was performed. A receiver operating characteristic (ROC) curve was performed to test the efficiencies of the predictive model. Results: Among the 134 patients, 32 (23.9%) achieved pathological complete response (pCR), 69 (51.5%) achieved a good response, and 91 (67.9%) achieved down-staging. For prediction of pCR, good-response, and down-staging, the predictive model demonstrated high classification efficiencies, with an AUC value of 0.91 (95% CI: 0.83-0.98), 0.90 (95% CI: 0.83-0.97), and 0.93 (95% CI: 0.87-0.98), respectively. Conclusion: Our machine learning radiomics model showed promise for predicting response to nCRT in patients with LARC. Our predictive model based on the commonly used T2-weighted images on pelvic Magnetic Resonance Imaging (MRI) scans has the potential to be adapted in clinical practice. Novelty and Impact Statements: Methods for predicting the response of the locally advanced rectal cancer (LARC, T3-4, or N+) to neoadjuvant chemoradiotherapy (nCRT) is lacking. In the present study, we developed a new machine learning radiomics method based on T2-weighted images. As a non-invasive tool, this method facilitates prediction performance effectively. It achieves a satisfactory overall diagnostic accuracy for predicting of pCR, good response, and down-staging show an AUC of 0.908, 0.902, and 0.930 in LARC patients, respectively.

14.
J Cell Mol Med ; 23(10): 6700-6707, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31332944

RESUMO

Breast cancer is the most common malignancy among women worldwide. Kynureninase (KYNU) located in 2q22.2, which was associated with tryptophan utilization and metabolic diseases including cardiac, renal and limb defects syndrome 2. However, the role of KYNU in breast cancer (BC) development remains unclear. The expression of KYNU was examined by immunohistochemistry (IHC) in 137 primary BC tissues, and the correlation of KYNU expression with clinical pathological characteristics and the biomarkers (ER, PR, HER2, E-cad and Ki-67) was analysed. The role of KYNU in cancer cell proliferation, tumour growth and development was evaluated by MTT assay, soft agar colony formation assay and xenograft mouse models. Among 137 primary BC tissues, 46.7% (64/137) had high KYNU expression (IHC scores >4) while 53.3% (73/137) had low KYNU expression (IHC scores ≤4). The expression of KYNU was positively correlated with the expressions of ER (P = .002), PR (P = .007) and E-cad (P = .03), while negatively associated with tumour grade (P = .008), tumour stage (P < .001) and the expressions of HER2 (P = .04) and Ki-67 (P = .019). Overexpression of KYNU significantly inhibited cell proliferation in cell culture, colony formation in soft agar and xenograft BC development in NOD/SCID mice. Kynureninase suppresses BC cell proliferation, tumour growth and development. Kynureninase may function as a tumour suppressor in BC.


Assuntos
Neoplasias da Mama/metabolismo , Carcinoma Ductal/metabolismo , Hidrolases/metabolismo , Adulto , Idoso , Animais , Biomarcadores Tumorais/genética , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Caderinas/metabolismo , Carcinoma Ductal/enzimologia , Carcinoma Ductal/patologia , Proliferação de Células/genética , Feminino , Humanos , Antígeno Ki-67/metabolismo , Células MCF-7 , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Gradação de Tumores , Receptor ErbB-2/metabolismo , Transplante Heterólogo , Regulação para Cima
15.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(3): 264-270, 2019 Mar 28.
Artigo em Chinês | MEDLINE | ID: mdl-30971518

RESUMO

OBJECTIVE: To analyze the correlation of the CT imaging features and CT texture analysis (CTTA) parameters with risk stratifications of the gastric stromal tumors (GSTs).
 Methods: CT (plain scans with portal phase contrast enhanced scans) images from 98 GSTs patients before surgery were collected. CT features of the tumors were retrospectively analyzed and pathological risk stratifications were determined. Feature parameters of CTTA at plain and portal phase were obtained by using a MaZda software. The correlations of CT imaging features and CTTA parameters with the risk stratifications were analyzed.
 Results: CT imaging features including tumor size, growth pattern, shape, margin, the relationship between mass and adjacent organs, enhancement pattern, necrosis or cystic change, and the abnormal tumor vessels were associated with the risk stratifications (P<0.05). For CTTA, entropy was associated with the risk stratifications (P<0.05).
 Conclusion: Certain CT imaging features and CTTA parameters are associated with risk classifications in GSTs.


Assuntos
Tumores do Estroma Gastrointestinal , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Humanos , Estudos Retrospectivos , Neoplasias Gástricas/diagnóstico por imagem
16.
Transl Cancer Res ; 8(3): 1006-1011, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35116842

RESUMO

We report a case of rectal cancer with an initial symptom of rectal bleeding. The clinical, morphological, immunohistochemical, and imaging findings supported a diagnosis of synchronous primary carcinoma of the prostate, rectal adenocarcinoma, and papillary thyroid tumor. The patient, whose poor cardiac function contraindicated surgery, underwent long-course chemoradiotherapy and hormonal therapy. The patient is currently asymptomatic, with stable disease and an improved quality of life. To our knowledge, synchronous primary carcinomas of the prostate, thyroid, and rectum are extremely rare in the literature. There are few published reports addressing parallel treatment and outcomes when such a synchronous diagnosis is made; we share here our experience in formulating a treatment plan.

17.
EPMA J ; 9(4): 421-429, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30538793

RESUMO

OBJECTIVES: This study aims to define a radiomic signature for pre-operative differentiation between subclinical pheochromocytoma (sPHEO) and lipid-poor adrenal adenoma (LPA) in adrenal incidentaloma. The goal was to apply a predictive, preventive, and personalized medical approach to the management of adrenal tumors. PATIENTS AND METHODS: This retrospective study consisted of 265 consecutive patients (training cohort, 212 (LPA, 145; sPHEO, 67); validation cohort, 53 (LPA, 36; sPHEO, 17)). Computed tomography (CT) imaging features were evaluated, including long diameter (LD), short diameter (SD), pre-enhanced CT value (CTpre), enhanced CT value (CTpost), shape, homogeneity, necrosis or cystic degeneration (N/C). Radiomic features were extracted and then were used to construct a radiomic signature (Rad-score) and radiomic nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate their performance. RESULTS: Sixteen of three hundred forty candidate features were used to build a radiomic signature. The signature was significantly different between the sPHEO and LPA groups (AUC: training, 0.907; validation, 0.902). The radiomic nomogram based on enhanced CT features (M1) consisted of Rad-score, LD, SD, CTpre, shape, homogeneity and N/C (AUC: training, 0.957; validation, 0.967). The pre-enhanced CT features based radiomic nomogram (M2) included Rad-score, LD, SD, CTpre, shape, and homogeneity (AUC: training, 0.955; validation, 0.958). CONCLUSIONS: Our radiomic nomograms based on pre-enhanced and enhanced CT images distinguished sPHEO from LPA. In addition, the promising result using pre-enhanced CT images for predictive diagnostics is important because patients could avoid the additional radiation and risk associated with enhanced CT.

18.
J Cancer ; 9(19): 3577-3582, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30310515

RESUMO

Objective: To evaluate the feasibility and accuracy of machine learning based texture analysis of unenhanced CT images in differentiating subclinical pheochromocytoma (sPHEO) from lipid-poor adenoma (LPA) in adrenal incidentaloma (AI). Methods: Seventy-nine patients with 80 LPA and 29 patients with 30 sPHEO were included in the study. Texture parameters were derived using imaging software (MaZda). Thirty texture features were selected and LPA was performed for the features selected. The number of positive features was used to predict results. Logistic multiple regression analysis was performed on the 30 texture features, and a predictive equation was created based on the coefficients obtained. Results: LPA yielded a misclassification rate of 19.39% in differentiating sPHEO from LPA. Our predictive model had an accuracy rate of 94.4% (102/108), with a sensitivity of 86.2% (25/29) and a specificity of 97.5% (77/79) for differentiation. When the number of positive features was greater than 8, the accuracy of prediction was 85.2% (92/108), with a sensitivity of 96.6% (28/29) and a specificity of 81% (64/79). Conclusions: Machine learning-based quantitative texture analysis of unenhanced CT may be a reliable quantitative method in differentiating sPHEO from LPA when AI is present.

19.
Oncol Lett ; 14(4): 4883-4889, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28943967

RESUMO

Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associated with tumor metastasis. Furthermore, a positive correlation between the expression levels of KLF8 and FHL2 was observed. Subsequently, the present study identified KLF8 as a critical inducer of epithelial-to-mesenchymal transition (EMT) and invasion. Of note, the present study demonstrated that KLF8 overexpression induced a strong increase in FHL2 expression, and subsequent promoter reporter assays determined that KLF8 directly bound and activated the FHL2 gene promoter. Furthermore, FHL2 knockdown in KLF8-overexpressing cells partially reversed the EMT and invasive phenotypes. The present study identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human PC invasion.

20.
World Neurosurg ; 104: 318-329, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28512044

RESUMO

OBJECTIVE: To retrospectively review the clinicopathologic features and computed tomography (CT) and magnetic resonance imaging (MRI) findings of spinal solitary fibrous tumor (SFT)/hemangiopericytoma (HPC) tumors. METHODS: Eleven patients with surgically and pathologically confirmed spinal SFT/HPC were enrolled. Their clinicopathologic data and imaging findings were retrospectively reviewed. RESULTS: There were 8 male and 3 female patients with a median age of 42 years (range, 26-65 years). Of the 11 patients, 5 were classified as grade I, 4 were grade II, and the remaining 2 were grade III. CT or MRI showed a well-defined (n = 8) or ill-defined (n = 3), oval (n = 4), irregular (n = 3), dumbbell-shaped (n = 3), and striped (n = 1) mass with heterogeneous (n = 10) or homogeneous (n = 1) density. The lesions appeared isointense (n = 4) or hypointense (n = 5) on T1-weighted MRI and mildly hyperintense (n = 3) or hyperintense (n = 6) on T2-weighted MRI. Bone destruction was observed in 7 cases, including osteolytic (n = 6) and osteoblastic (n = 1) patterns. Calcification was observed in only 1 case. On enhanced CT/MRI, marked (n = 9), mild (n = 1) heterogeneous, and marked homogeneous (n = 1) enhancement were observed in this study. CONCLUSIONS: Spinal SFT/HPC commonly appears as a well-defined solitary mass characterized by a black and white appearance that is marked with heterogeneous enhancement with or without bone destruction.


Assuntos
Hemangiopericitoma/diagnóstico por imagem , Hemangiopericitoma/patologia , Imageamento por Ressonância Magnética , Tumores Fibrosos Solitários/diagnóstico por imagem , Tumores Fibrosos Solitários/patologia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/patologia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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