BATF promotes tumor progression and association with FDG PET-derived parameters in colorectal cancer.

PURPOSE: The purpose of the study was to evaluate the expression and function of basic leucine zipper ATF-like transcription factor (BATF) in colorectal cancer (CRC), and its correlation with 2-deoxy-2[18F]fluoro-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) parameters. METHODS: The TIMER database, GEPIA database, TCGA, and GEO database were used to analyze the expression profile of BATF in human cancers. The reverse transcription­quantitative PCR and western blot analyses were used to evaluate the mRNA level and protein expression in different CRC cell lines. The expression of BATF in SW620 and HCT116 cells was silenced and cell counting kit-8 assays and clonogenic assay were utilized to evaluate the role of BATF in CRC proliferation. The expression of tumor BATF and glucose transporter 1 (GLUT-1) were examined using immunohistochemical tools in 37 CRC patients undergoing preoperative 18F-FDG PET/CT imaging. The correlation between the PET/CT parameters and immunohistochemical result was evaluated. RESULTS: In database, BATF was highly expressed in pan-cancer analyses, including CRC, and was associated with poor prognosis in CRC. In vitro, the results showed that knocking down of BATF expression could inhibit the proliferation of SW620 and HCT116 cells. In CRC patients, BATF expression was upregulated in tumor tissues compared with matched para-tumoral tissues, and was related with gender and Ki-67 levels. BATF expression was positively related to GLUT-1 expression and PET/CT parameters, including tumor size, maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis. The multiple logistic analyses showed that SUVmax was an independent predictor of BATF expression. With 15.96 g/cm3 as the cutoff, sensitivity was 85.71%, specificity 82.61%, and area-under-the-curve 0.854. CONCLUSION: BATF may be an oncogene associated with 18F-FDG PET/CT parameters in CRC. SUVmax may be an independent predictor of BATF expression.

Predicting event-free survival after induction of remission in high-risk pediatric neuroblastoma: combining 123I-MIBG SPECT-CT radiomics and clinical factors.

BACKGROUND: Accurately quantifying event-free survival after induction of remission in high-risk neuroblastoma can lead to better subsequent treatment decisions, including whether more aggressive therapy or milder treatment is needed to reduce unnecessary treatment side effects, thereby improving patient survival. OBJECTIVE: To develop and validate a 123I-metaiodobenzylguanidine (MIBG) single-photon emission computed tomography-computed tomography (SPECT-CT)-based radiomics nomogram and evaluate its value in predicting event-free survival after induction of remission in high-risk neuroblastoma. MATERIALS AND METHODS: One hundred and seventy-two patients with high-risk neuroblastoma who underwent an 123I-MIBG SPECT-CT examination were retrospectively reviewed. Eighty-seven patients with high-risk neuroblastoma met the final inclusion and exclusion criteria and were randomized into training and validation cohorts in a 7:3 ratio. The SPECT-CT images of patients were visually analyzed to assess the Curie score. The 3D Slicer software tool was used to outline the region of interest of the lumbar 3-5 vertebral bodies on the SPECT-CT images. Radiomics features were extracted and screened, and a radiomics model was constructed with the selected radiomics features. Univariate and multivariate Cox regression analyses were used to determine clinical risk factors and construct the clinical model. The radiomics nomogram was constructed using multivariate Cox regression analysis by incorporating radiomics features and clinical risk factors. C-index and time-dependent receiver operating characteristic curves were used to evaluate the performance of the different models. RESULTS: The Curie score had the lowest efficacy for the assessment of event-free survival, with a C-index of 0.576 and 0.553 in the training and validation cohorts, respectively. The radiomics model, constructed from 11 radiomics features, outperformed the clinical model in predicting event-free survival in both the training cohort (C-index, 0.780 vs. 0.653) and validation cohort (C-index, 0.687 vs. 0.667). The nomogram predicted the best prognosis for event-free survival in both the training and validation cohorts, with C-indices of 0.819 and 0.712, and 1-year areas under the curve of 0.899 and 0.748, respectively. CONCLUSION: 123I-MIBG SPECT-CT-based radiomics can accurately predict the event-free survival of high-risk neuroblastoma after induction of remission The constructed nomogram may enable an individualized assessment of high-risk neuroblastoma prognosis and assist clinicians in optimizing patient treatment and follow-up plans, thereby potentially improving patient survival.

Diagnostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in pediatric opsoclonus myoclonus ataxia syndrome presenting with neuroblastoma.

BACKGROUND: Early precision diagnosis and effective treatment of opsoclonus myoclonus ataxia syndrome (OMAS) patients presenting with neuroblastoma can prevent serious neurological outcomes. OBJECTIVE: To assess the diagnostic value of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in pediatric OMAS with neuroblastoma. MATERIALS AND METHODS: A retrospective evaluation of 45 patients diagnosed with OMAS who underwent 18F-FDG PET/CT was performed. A univariate analysis was performed to compare clinical characteristics between OMAS with and without neuroblastoma. Univariate and multivariate logistic regression analyses were applied to identify independent risk factors for OMAS with neuroblastoma and to develop the clinical model. Finally, independent risk factors and PET/CT were fitted to build the combined model for the diagnosis of OMAS with neuroblastoma and presented as a nomogram. Receiver operating characteristic curve, decision curve, and calibration curve analyses were conducted to evaluate the performance of the models. RESULTS: Among 45 patients, 27 were PET/CT-positive, 23/27 lesions were neuroblastoma, and four were false positives. One of the false positive patients was confirmed to be adrenal reactive hyperplasia by postoperative pathology, and the symptoms of OMAS disappeared in the remaining three cases during clinical follow-up. The average maximal standardized uptake value of PET/CT-positive lesions was 2.6. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of PET/CT were 100%, 81.8%, 85.2%, 100%, and 91.1%, respectively. Age at diagnosis, lactate dehydrogenase, and neuron-specific enolase showed statistically significant differences between OMAS with and without neuroblastoma. Lactate dehydrogenase was identified as the independent risk factor to develop the clinical model, and the clinical model demonstrated an area under the curve (AUC) of 0.82 for the diagnosis of OMAS with neuroblastoma, with an AUC as high as 0.91 when combined with PET/CT. The decision curve analysis and calibration curve demonstrated that the nomogram had good consistency and clinical usefulness. CONCLUSION: In patients with OMAS, 18F-FDG PET/CT has a high diagnostic accuracy in detecting tumors of the neuroblastoma, especially when combined with the independent risk factor serum lactate dehydrogenase.

Identification of six genes associated with COVID-19-related circadian rhythm dysfunction by integrated bioinformatic analysis.

Patients with coronavirus disease 2019 (COVID-19) might cause long-term burden of insomnia, while the common pathogenic mechanisms are not elucidated. The gene expression profiles of COVID-19 patients and healthy controls were retrieved from the GEO database, while gene set related with circadian rhythm was obtained from GeneCards database. Seventy-six shared genes were screened and mainly enriched in cell cycle, cell division, and cell proliferation, and 6 hub genes were found out including CCNA2, CCNB1, CDK1, CHEK1, MKI67, and TOP2A, with positive correlation to plasma cells. In the TF-gene regulatory network, NFYA, NFIC, MEF2A, and FOXC1 showed high connectivity with hub genes. This study identified six hub genes and might provide new insights into pathogenic mechanisms and novel clinical management strategies.

Prognostic value of 18F-FDG PET/CT in malignant pleural mesothelioma: a meta-analysis.

BACKGROUND: Several FDG PET/CT parameters have been utilized to evaluate the prognosis in malignant pleural mesothelioma (MPM). However, there are still controversial results due to the low incidence of MPM. PURPOSE: To assess the prognostic value of 18F-FDG PET/CT in MPM. MATERIAL AND METHODS: A systematic literature search was performed in PubMed, Embase, Medline, and The Cochrane Library to identify eligible studies from inception to 12 February 2020. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of several variables, such as maximum standardized uptake value (SUVmax), the reduction of SUVmax after treatment (ΔSUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and the reduction of TLG after treatment (ΔTLG), were calculated. Meta-regression with subsequent subgroup analyses were conducted to determine the heterogeneity of cutoff values, treatment regimen, study design, uptake time, and scanners across various studies. RESULTS: In total, 19 eligible studies including 1819 patients were enrolled in the meta-analysis. The univariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, TLG, and ΔTLG were 1.29 (1.16-1.42), 1.12 (1.05-1.19), 1.15 (1.00-1.33), 1.47 (1.23-1.76), and 1.27 (1.12-1.45), respectively. The multivariate analysis showed that the pooled HRs (95% CI) of SUVmax, ΔSUVmax, MTV, and TLG for overall survival (OS) were 1.20 (1.08-1.33), 1.10 (1.02-1.19), 0.95 (0.81-1.11), and 1.13 (1.08-1.18), respectively. CONCLUSION: SUVmax, ΔSUVmax, TLG, and ΔTLG are significant prognostic indicators for OS, while more clinical studies are needed to confirm the prognostic value of MTV in MPM.

Theranostic application of 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody in pancreatic cancer tumor models.

PURPOSE: Pancreatic cancer is a malignant tumor with a high degree of malignancy, strong heterogeneity, and high lethality. Trop2 is a transmembrane glycoprotein associated with the occurrence, development, and poor prognosis of pancreatic cancer. This study aims to develop 64Cu/177Lu-labeled anti-Trop2 monoclonal antibody (hIMB1636) for positron emission tomography (PET) imaging and radioimmunotherapy (RIT) application in pancreatic cancer tumor models. METHODS: The binding kinetics of hIMB1636 to Trop2 antigen was measured by Biolayer interferometry (BLI). Western blotting was used to screen the Trop2 expression of pancreatic cancer cell lines. Flow cytometry and cell immunofluorescence were used to evaluate the binding ability of hIMB1636 and Trop2 on the cell surface. hIMB1636 were conjugated with p-SCN-Bn-NOTA (NOTA) and DOTA-NHS-ester (DOTA) for 64Cu and 177Lu radiolabeling respectively. ImmunoPET imaging and RIT studies were performed using 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 in subcutaneous pancreatic cancer tumor models. RESULTS: hIMB1636 had a strong binding affinity to Trop2 according to the results of BLI. The T3M-4 cell line showed the strongest expression of Trop2 and specific binding ability of hIMB1636 according to the results of Western blotting, flow cytometry, and cell immunofluorescence. The radiochemical purity of 64Cu-NOTA-hIMB1636 and 177Lu-DOTA-hIMB1636 exceeded 95%. PET imaging showed gradually an accumulation of 64Cu-NOTA-hIMB1636 in T3M-4 tumor models. The maximum tumor uptake was 8.95 ± 1.07%ID/g (n = 4) at 48 h post injection (p.i.), which had significant differences with T3M-4-blocked and PaTu8988-negative groups (P < 0.001). The high-177Lu-hIMB1636 group demonstrated the strongest tumor suppression with standardized tumor volume about 94.24 ± 14.62% (n = 5) at 14 days p.i., significantly smaller than other groups (P < 0.05). Ex vivo biodistribution and histological staining verified the in vivo PET imaging and RIT results. CONCLUSIONS: This study demonstrated that 64Cu/177Lu-labeled hIMB1636 could noninvasively evaluate the expression level of Trop2 and inhibit the Trop2-overexpressed tumor growth in pancreatic cancer tumor models. Further clinical evaluation and translation of Trop2-targeted drug may be of great help in the stratification and management of pancreatic cancer patients.

Multiparameter diagnostic model based on 18F-FDG PET and clinical characteristics can differentiate thymic epithelial tumors from thymic lymphomas.

OBJECTIVE: To evaluate the diagnostic performance of combined multiparametric 18F-fluorodeoxyglucose positron emission tomography (18FDG PET) with clinical characteristics in differentiating thymic epithelial tumors (TETs) from thymic lymphomas. PATIENTS AND METHODS: A total of 173 patients with 80 TETs and 93 thymic lymphomas who underwent 18F-FDG PET/CT before treatment were enrolled in this retrospective study. All patients were confirmed by pathology, and baseline characteristics and clinical data were also collected. The semi-parameters of 18F-FDG PET/CT, including lesion size, SUVmax (maximum standard uptake value), SUVmean (mean standard uptake value), TLG (total lesion glycolysis), MTV (metabolic tumor volume) and SUVR (tumor-to-normal liver standard uptake value ratio) were evaluated. The differential diagnostic efficacy was evaluated using the receiver operating characteristic (ROC) curve. Integrated discriminatory improvement (IDI) and net reclassification improvement (NRI), and Delong test were used to evaluate the improvement in diagnostic efficacy. The clinical efficacy was evaluated by decision curve analysis (DCA). RESULTS: Age, clinical symptoms, and metabolic parameters differed significantly between patients with TETs and thymic lymphomas. The ROC curve analysis of SUVR showed the highest differentiating diagnostic value (sensitivity = 0.763; specificity = 0.888; area under the curve [AUC] = 0.881). The combined diagnostics model of age, clinical symptoms and SUVR resulted in the highest AUC of 0.964 (sensitivity = 0.882, specificity = 0.963). Compared with SUVR, the diagnostic efficiency of the model was improved significantly. The DCA also confirmed the clinical efficacy of the model. CONCLUSIONS: The multiparameter diagnosis model based on 18F-FDG PET and clinical characteristics had excellent value in the differential diagnosis of TETs and thymic lymphomas.

Pathogenesis and Therapeutic Targets of Focal Cortical Dysplasia Based on Bioinformatics Analysis.

Focal cortical dysplasia (FCD), a malformation of cortical development, is the most common cause of intractable epilepsy in children. However, the causes and underlying molecular events of FCD need further investigation. The microarray dataset GSE62019 and GSE97365 were obtained from Gene Expression Omnibus. To examine critical genes and signaling pathways, bioinformatics analysis tools such as protein-protein interaction (PPI) networks, miRNA-mRNA interaction networks, and immune infiltration in FCD samples were used to fully elucidate the pathogenesis of FCD. A total of 534 differentially expressed genes (DEGs) and 71 differentially expressed miRNAs (DEMs) were obtained. The DEGs obtained were enriched in ribosomal, protein targeting, and pathways of neurodegeneration multiple diseases, whereas the target genes of DEMs were enriched in signaling pathways such as transforming growth factor beta, Wnt, PI3K-Akt, etc. Finally, four hub genes (RPL11, FAU, RPS20, RPL27) and five key miRNAs (hsa-let-7b, hsa-miR-185, hsa-miR-23b, hsa-miR-222 and hsa-miR-92b) were obtained by PPI network, miRNA-mRNA network, and ROC analysis. The immune infiltration results showed that the infiltration levels of five immune cells (MDSC, regulatory T cells, activated CD8+ T cells, macrophage and effector memory CD8+ T cells) were slightly higher in FCD samples than in control samples. Moreover, the gene expressions of RPS19, RPL19, and RPS24 were highly correlated with the infiltration levels and immune characteristics of 28 immune cells. It broadens the understanding of the molecular mechanisms underlying the development of FCD and enlightens the identification of molecular targets and diagnostic biomarkers for FCD.

Noninvasive Evaluation of Multidrug Resistance via Imaging of ABCG2/BCRP Multidrug Transporter in Lung Cancer Xenograft Models.

Chemotherapy is an important method for the treatment of lung cancer, but multidrug resistance (MDR) greatly reduces the efficacy. The superfamily of ATP-binding cassette (ABC) transport proteins is related to MDR. As a subfamily of ABC proteins, ABCG2/BCRP (breast cancer resistance protein, BCRP) is considered a major player in the development of cancer MDR. For the stratification of chemotherapeutic choices, we constructed Cy5.5- or 89Zr-labeled ABCG2-targeted monoclonal antibody (mAb) ABCG2-PKU1 for noninvasive evaluation of ABCG2 expression in lung cancer xenograft models. ABCG2 expression was screened in H460/MX (mitoxantrone resistant), H460, and H1299 human lung cancer cell lines using Western blotting. ELISA, flow cytometry, and cell immunofluorescent staining were used to evaluate the binding ability of ABCG2-PKU1 to ABCG2 antigen. Lung cancer murine xenograft models were built for in vivo experiments. ABCG2-PKU1 was labeled with Cy5.5 (Cy5.5-ABCG2) for fluorescent imaging and radiolabeled with 89Zr (89Zr-DFO-ABCG2) for immunoPET imaging following the conjugation with p-SCN-deferoxamine (DFO). In vivo imaging was performed in lung cancer models at 2, 24, 48, 72, 96, 120, 144, and 168 h postinjection. Ex vivo biodistribution was conducted after the terminal time point of imaging. Finally, tissue immunohistochemical staining was used to evaluate the tumor expression of ABCG2. Western blotting showed that the H460/MX cells had a high ABCG2 expression level whereas H460 and H1299 had moderate and low levels. ELISA, flow cytometry, and cell immunofluorescent staining results validated the good binding affinity between ABCG2-PKU1 and ABCG2. The H460/MX and H460 cells were used to build positive lung cancer models, and H1299 cells were used to build negative models. The fluorescent imaging showed that the tumor average radiant efficiency of Cy5.5-ABCG2 reached the maximum at 72 and 120 h in H460/MX and H460 respectively (n = 3, P < 0.01). The tumor uptake of Cy5.5-ABCG2 in H1299 (n = 3) was significantly lower than H460/MX and H460 (P < 0.01). ImmunoPET imaging showed that the tumor uptake of 89Zr-DFO-ABCG2 in H460/MX was significantly higher than H460, with a maximum of 4.15 ± 0.41 %ID/g and 2.81 ± 0.24 %ID/g at 168 and 144 h, respectively (n = 5, P < 0.01). The H1299 tumors showed significantly lower uptake than H460/MX and H460 (n = 5, P < 0.01). The radioactive uptake of 89Zr-DFO-ABCG2 among three groups in the heart, liver, and kidney gradually decreased over time. Ex vivo biodistribution verified the differential tumor uptake among the three groups (P < 0.01). Immunohistochemical staining revealed that the H460/MX tumor had the highest expression of ABCG2, whereas H460 and H1299 had the moderate and lowest expression, respectively. Therefore, in this study, fluorescent and immunoPET imaging of lung cancer MDR models using Cy5.5-ABCG2 and 89Zr-DFO-ABCG2 noninvasively evaluated the differential expression of ABCG2, which are expected to be used for the diagnosis and the selection for clinical treatment options for lung cancer MDR patients in future applications.

Clinical parameters combined with radiomics features of PET/CT can predict recurrence in patients with high-risk pediatric neuroblastoma.

BACKGROUND: This retrospective study aimed to develop and validate a combined model based [18F]FDG PET/CT radiomics and clinical parameters for predicting recurrence in high-risk pediatric neuroblastoma patients. METHODS: Eighty-four high-risk neuroblastoma patients were retrospectively enrolled and divided into training and test sets according to the ratio of 3:2. [18F]FDG PET/CT images of the tumor were segmented by 3D Slicer software and the radiomics features were extracted. The effective features were selected by the least absolute shrinkage and selection operator to construct the radiomics score (Rad_score). And the radiomics model (R_model) was constructed based on Rad_score for prediction of recurrence. Then, univariate and multivariate analyses were used to screen out the independent clinical risk parameters and construct the clinical model (C_model). A combined model (RC_model) was developed based on the Rad_score and independent clinical risk parameters and presented as radiomics nomogram. The performance of the above three models was assessed by the area under the receiver operating characteristic curve (AUC) and decision curve analysis (DCA). RESULTS: Seven radiomics features were selected for building the R_model. The AUCs of the C_model in training and test sets were 0.744 (95% confidence interval [CI], 0.595-0.874) and 0.750 (95% CI, 0.577-0.904), respectively. The R_model yielded AUCs of 0.813 (95% CI, 0.685-0.916) and 0.869 (95% CI, 0.715-0.985) in the training and test sets, respectively. The RC_model demonstrated the largest AUCs of 0.889 (95% CI, 0.794-0.963) and 0.892 (95% CI, 0.758-0.992) in the training and test sets, respectively. DCA demonstrated that RC_model added more net benefits than either the C_model or the R_model for predicting recurrence in high-risk pediatric neuroblastoma. CONCLUSIONS: The combined model performed well for predicting recurrence in high-risk pediatric neuroblastoma, which can facilitate disease follow-up and management in clinical practice.

Migration behavior and leaching ability of radioactive uranium during incineration of uranium-containing strippable coating wastes.

It is currently thought that the incineration approach is an effective method to minimize the volume of radioactive wastes. In this paper, we used an incinerator to burn uranium-containing strippable coating waste. The migration behavior of radioactive uranium during the incineration process were investigated based on hierarchical sampling and mass spectrometry. Results shows that the radioactive uranium is more easily to adhere to the particles with smaller size. The leaching abilities of radioactive uranium in the bottom ash and the fly ash were analyzed. The leaching rate of the uranium from the fly ash and bottom ash were 1% and 6%, respectively, indicating that most of the radioactive uranium was fixed in the ash and the same storage/disposal methods can be used for both the fly ash and bottom ash. According to x-ray spectrometry and SEM-EDS, mineral compositions of the original uranium ore and the bottom ash were mostly the same. Calcium plays an important role in uranium fixation during incineration. The potential mechanism of the uranium special transformation during uranium-containing strippable coating waste combustion was revealed. Our research results can provide technical support for nuclear emergency waste treatment and disposal.

Correlation between glucose metabolism parameters derived from FDG and tumor TNM stages and metastasis-associated proteins in colorectal carcinoma patients.

BACKGROUND: The aim of this study was to investigate the relationship between multiple metabolism parameters derived from FDG and tumor TNM stages as well as tumor metastasis-associated protein of GLUT-1 and MACC1 in colorectal carcinoma (CRC). METHODS: Thirty-eight patients (24 males and 14 females) with primary CRC confirmed by elective surgery pathological, who also accepted 18F-FDG PET/CT scans during 2017 to 2019 were included in this study. The tumor classification of T, N and M is explained by the 7th American Joint Committee on Cancer (AJCC). 18F-FDG parameters of SUVmax, SUVmean, TLG and MTV were measured by drawing a region of interest on the primary lesions. The expression of GLUT-1 and MACC1 was quantified by immunohistochemical, and the correlation between metabolism parameters and tumor biomarkers were analyzed. RESULTS: According to our analysis, the 18F-FDG parameters of SUVmean was significantly correlated with tumor M status (P = 0.000) of primary CRC. The primary tumor lesion with higher SUVmax, TLG and MTV values prone to a high-T status (P = 0.002, 0.002 and 0.001, respectively). The high expression of GLUT-1/MACC1 weas more frequently involved with T3-4 stage and was poorly differentiated in CRC patients. Multivariate analysis found that the expression of GLUT-1 protein was correlated with SUVmax and MTV (R2 = 0.42, P = 0.013 and 0.004, respectively), moreover, the expression of MACC1 protein was correlated with TLG (R2 = 0.372, P = 0.000). CONCLUSION: Glucose metabolism parameters derived from FDG provides a noninvasive assessment of M status and T status in CRC patients. The expression of GLUT-1 and MACC1 was associated with 18F-FDG uptake in CRC patients.

Clinical value of 68Ga-DOTA-SSTR PET/CT in the diagnosis and detection of neuroendocrine tumors of unknown primary origin: a systematic review and meta-analysis.

BACKGROUND: The ability of 68Ga-DOTA-SSTR to detect the primary sites of neuroendocrine tumors (NETs) remains undetermined, and the clinical benefit of this imaging agent is not clear. PURPOSE: To evaluate the diagnostic accuracy of 68Ga-DOTA-SSTR for carcinoma unknown primary (CUP) neuroendocrine tumors and to further analyze the detection rate of 68Ga-DOTA-SSTR for primary and metastatic sites. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE and ScienceDirect was performed in October 2019 in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: A total of 10 studies (484 patients, mean age = 56.6 ± 4.3 years) were included in the study. The pooled sensitivity and specificity of 68Ga-DOTA-SSTR in identifying CUP-NETs were 82% and 55%, respectively. The area under the receiver operating characteristic curve was 69%. Regarding metastasis sites, 68Ga-DOTA-SSTR found the most metastases in the liver (57.9%), followed by the lymph nodes (22.8%), bones (12.8%), lung (2.8%), and others (1.7%). The pooled detection rate of 68Ga-DOTA-SSTR for CUP-NETs was 61%. CONCLUSION: The present study demonstrated the high diagnostic sensitivity of 68Ga-DOTA-SSTR for CUP-NETs. 68Ga-DOTA-SSTR PET/CT was highly effective in locating the primary and metastatic sites of CUP-NETs.

Elevated expression of the V-ATPase D2 subunit triggers increased energy metabolite levels in KrasG12D -driven cancer cells.

Mutations of the Ras oncogene are frequently detected in human cancers. Among Ras-mediated tumorigenesis, Kras-driven cancers are the most dominant mutation types. Here, we investigated molecular markers related to the Kras mutation, which is involved in energy metabolism in Kras mutant-driven cancer. We first generated a knock-in KrasG12D cell line as a model. The genotype and phenotype of the Kras G12D -driven cells were first confirmed. Dramatically elevated metabolite characterization was observed in Kras G12D -driven cells compared with wild-type cells. Analysis of mitochondrial metabolite-related genes showed that two of the 84 genes in Kras G12D -driven cells differed from control cells by at least twofold. The messenger RNA and protein levels of ATP6V0D2 were significantly upregulated in Kras G12D -driven cells. Knockdown of ATP6V0D2 expression inhibited motility and invasion but did not affect the proliferation of Kras G12D -driven cells. We further investigated ATP6V0D2 expression in tumor tissue microarrays. ATP6V0D2 overexpression was observed in most carcinoma tissues, such as melanoma, pancreas, and kidney. Thus, we suggest that ATP6V0D2, as one of the V-ATPase (vacuolar-type H + -ATPase) subunit isoforms, may be a potential therapeutic target for Kras mutation cancer.

Contribution of 18F-FDG PET/CT in a case-mix of fever of unknown origin and inflammation of unknown origin: a meta-analysis.

BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are challenging medical problems. Previous studies have shown that 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) plays an important role in the diagnosis of FUO, but few studies have explored this diagnostic technique in relation to IUO. PURPOSE: To systematically review and perform a meta-analysis of published data on the diagnostic performance of PET/CT in the diagnosis of FUO and IUO. MATERIAL AND METHODS: A comprehensive literature search was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines published in March 2018. Meta-analysis of diagnostic performance was performed using STATA 12.0 software. Subgroup analysis was performed by stratification based on study design, number of patients, geographic area, and final diagnosis based on 18F-FDG PET/CT. Meta-regression analyses were performed to recognize heterogeneity. RESULTS: Our meta-analysis included 23 studies, comprising a total sample size of 1927 patients. The pooled diagnosis performance was calculated with a per-patient-based analysis: sensitivity = 0.84 (95% confidence interval [CI] = 0.79-0.89), specificity = 0.63 (95% CI = 0.49-0.75), positive likelihood ratio = 2.3 (95% CI = 1.5-3.4), negative likelihood ratio = 0.25 (95% CI = 0.16-0.38), diagnostic odds ratio = 9 (95% CI = 4.0-20), and AUC = 0.84 (95% CI = 0.81-0.87). CONCLUSION: In patients with non-specific symptoms and signs, 18F-FDG PET/CT is very helpful for recognizing and excluding diseases, directing further diagnostic decisions, and avoiding unnecessary invasive examinations. We recommend that 18F-FDG PET/CT should be considered among the first-line diagnostic tools for patients with FUO and IUO.

68Ga-somatostatin receptor analogs and 18F-FDG PET/CT in the localization of metastatic pheochromocytomas and paragangliomas with germline mutations: a meta-analysis.

BACKGROUND: Metastatic pheochromocytoma and paraganglioma (PCs/PGLs) show high germline mutation, and 18F-FDG and 68Ga-DOTA peptide positron emission tomography/computed tomography (PET/CT) imaging are recommended for the diagnosis of metastatic of PCs. However, there has been lack of direct comparison of the two modalities in the diagnosis of metastatic of PCs up to now. PURPOSE: To evaluate and compare the value of localization of 68Ga-somatostatin receptor analogs and 18F-FDG in the diagnosis of metastatic PCs/PGLs. MATERIAL AND METHODS: A comprehensive literature search of PubMed/MEDLINE, ScienceDirect, and Web of Science was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines published in August 2016. We critically reviewed all studies based on the PICOS criteria. QUADAS-2 was used to evaluate the quality of the methodology of the included studies. RESULTS: This meta-analysis included 17 studies (629 patients, average age [mean ± SD] = 42.7 ± 6.3 years). The pooled sensitivity and specificity of 18F-FDG and 68Ga peptides were 0.85 (95% confidence interval [CI] = 0.78-0.91) and 0.55 (95% CI = 0.37-0.73), and 0.95 (95% CI = 0.92-0.97) and 0.87 (95% CI = 0.63-0.96), respectively. The area under the sROC curves of the 18F-FDG and 68Ga peptides were 0.88 (95% CI = 0.85-0.91) and 0.78 (95% CI = 0.74-0.81), respectively. A subgroup analysis demonstrated that the difference at the per-lesion level and gene mutation level was significant. CONCLUSION: Compared to 18F-FDG PET/CT, the 68Ga-somatostatin receptor demonstrated good performance in the localization of metastatic PCs/PGLs, especially those with germline mutations. The use of the 68Ga-somatostatin receptor can be a new tool in the diagnosis of metastatic PCs/PGLs.

Tim3/galectin-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-kB signaling pathway.

Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease. Studies showed that T helper 1 (Th1), Th2, and Th17 cells play important roles in the pathology of TAO. Tim-3 and its only known ligand Galectin-9 (Gal-9) is related to the suppression of Th1 and Th17 cytokine secretion. This study aims to investigate the role of Tim3/Gal-9 in the inflammatory response of TAO. In this study, the levels of Tim3, Gal-9, and cytokines of Th1 (TNF-α and IFN-γ), Th2 (IL-4), and Th17 (IL-17) cells were analyzed in the blood samples of TAO patients and healthy controls as well as in orbital fibroblasts. Tim3 overexpression and Gal-9 neutralizing antibody were used in TAO and LPS-stimulated control orbital fibroblasts to further investigate the role and mechanism of Tim3/Gal-9 on the inflammation of TAO. We found Tim3 and Gal-9 expression was significantly downregulated in TAO patients and further lower in active TAO than inactive TAO or controls. Th1, Th2, and Th17 cytokines were all increased in TAO patients. Th1 and Th17 cytokines were higher in active TAO patients than in inactive TAO patients, while Th2 cytokines were enhanced in inactive TAO. Tim3 overexpression decreased the levels of Th1 and Th17 cytokines, but not Th2 cytokine in TAO or LPS-stimulated control orbital fibroblasts. These effects were abrogated by Gal-9 neutralizing antibody. Moreover, Tim3 reduced the levels of p-Akt and p-p65 in TAO or LPS-induced control orbital fibroblasts that were reversed by Gal-9 blocking. In conclusion, Tim3/Gal-9 alleviates the inflammation of TAO patients via suppressing Akt/NF-κB signaling pathway.

Magnetic resonance imaging characteristics and treatment aspects of ventricular tuberculosis in adult patients.

BACKGROUND: Ventricular involvement in neurotuberculosis is rare. The literature regarding the characteristics of magnetic resonance imaging (MRI) in ventricular tuberculosis is very limited. PURPOSE: To describe MRI characteristics of ventricular tuberculosis and discuss the medical treatment along with the clinical outcome. MATERIAL AND METHODS: Ten patients (6 men, 4 women; average age, 39 years) were diagnosed with ventricular tuberculosis during a period of 3 years. Four patients had the history of pulmonary/pleural tuberculosis. The clinical and MRI features of these patients were reviewed retrospectively. RESULTS: On a brain MRI, three patients showed ependymitis associated with contrast enhancement of the ependymal lining of the ventricular walls. One patient had choroid plexitis associated with prominent swollen and marked enhancement of the choroid plexus. One patient had intraventricular tuberculoma associated with an intraventricular nodule. Two patients had both ependymitis and choroid plexitis. Three patients had both intraventricular tuberculoma and choroid plexitis. Four patients had hydrocephalus. All patients underwent intrathecal injection of isoniazid and dexamethasone combined with multidrug anti-tuberculosis treatment. All patients had a good clinical recovery, except for one who developed hemi-paralysis due to cerebral infarction. On the repeated MRI of eight patients after therapy, all lesions disappeared or decreased in size, apart from in one patient who showed ventricular separation. CONCLUSION: MRI characteristics of ventricular tuberculosis included ependymal enhancement, swelling, and enhancement of the choroid plexus and intraventricular tuberculomas. Intrathecal injection of isoniazid and dexamethasone along with multidrug chemotherapy showed good efficacy in ventricular tuberculosis.

The diagnostic value of 11C-methionine PET in hyperparathyroidism with negative 99mTc-MIBI SPECT: a meta-analysis.

Background 99mTc-sestamibi (MIBI) parathyroid SPECT is generally regarded as the best preoperative localizing method in patients with hyperparathyroidism (HPT). However, 99mTc-MIBI SPECT is false negative in approximately 25% of adenomas. 11C-methionine positron emission tomography (PET) has been used in HPT with negative 99mTc-MIBI SPECT scan results. Purpose To systematically review and conduct a meta-analysis of published data on the performance of 11C-methionine PET in patients with HPT with negative 99mTc-MIBI SPECT. Material and Methods A comprehensive review of the literature was performed. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT and a negative 99mTc-MIBI SPECT was calculated on a per-patient basis using receiver-operating characteristic (ROC) methodology. Results Nine studies that met all inclusion and exclusion criteria were included into our meta-analysis, comprising a total sample size of 137 patients. Pooled sensitivity and specificity of 11C-methionine PET in patients with HPT with negative or inconclusive 99mTc-MIBI SPECT scans was 86% and 86%, respectively. The area under the ROC curve was 0.87. Conclusion By merit of the high overall sensitivity, specificity, and accuracy, 11C-methionine PET can potentially complement the diagnostic workup of patients with HPT and negative or inconclusive 99mTc-MIBI SPECT. 11C-methionine PET appears to be a promising diagnostic modality in complicated cases with HPT.

The value of anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT in the diagnosis of recurrent prostate carcinoma: a meta-analysis.

BACKGROUND: Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-18F-FACBC) positron emission tomography/computed tomography (PET/CT), 11 C-choline PET/CT, 111In-capromab pendetide, and T2-weighted magnetic resonance imaging (MRI) have been used for detecting prostate carcinoma relapse. PURPOSE: To systematically review and perform a meta-analysis of published data regarding the performance of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma. MATERIAL AND METHODS: A comprehensive review of the literature regarding the role of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma was performed. Pooled sensitivity, specificity, and the area under the receiver-operating characteristic of 18F-FACBC PET/CT in the diagnosis of recurrent prostate carcinoma were calculated based on the included studies. RESULTS: Six studies comprising 251 patients, suspicious of prostate carcinoma recurrence, were included in this meta-analysis. 18F-FACBC PET/CT had an 87% pooled sensitivity, 66% pooled specificity, 0.93 the area under the receiver-operating characteristic curve on a per patient-based analysis in detecting prostate carcinoma recurrence. CONCLUSION: 18F-FACBC PET/CT was a non-invasive, metabolic imaging technique in the diagnosis of prostate carcinoma relapse.