Predictive value of radiomic signature based on 2-[18F]FDG PET/CT in HER2 status determination for primary breast cancer with equivocal IHC results.

PURPOSE: To evaluate the predictive power of 2-[18F]FDG PET/CT-derived radiomic signature in human epidermal growth factor receptor 2 (HER2) status determination for primary breast cancer (BC) with equivocal immunohistochemistry (IHC) results for HER2. METHODS: A total of 154 primary BC with equivocal IHC results for HER2 were retrospectively enrolled in the study. First, the following five conventional PET parameters (SUVmax, SUVmean, SUVpeak, MTV, TLG) were measured and compared between HER2-positive and HER2-negative cohorts. After quantitative radiomic features extraction and reduction, the least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a radiomic signature model. Then, the area under the curve (AUCs) after a receiver operator characteristic (ROC) analysis, accuracy, sensitivity and specificity were calculated and used as the main outcomes. Finally, a total of 37 BC patients from an external institution were included to perform an external validation. RESULTS: All the five conventional PET parameters were unable to discriminate between HER2-positive and HER2-negative cohorts for BC (P = 0.104-0.544). Whereas, the developed radiomic signature model was potentially predictive of HER2 status with an of AUC 0.887 (95% confidence interval [CI], 0.824-0.950) in the training cohort and 0.766 (95% CI, 0.616-0.916) in the validation cohort, respectively. For external validation, the AUC for the external test cohort was 0.788 (95% CI, 0.633-0.944). CONCLUSIONS: Radiomic signature based on 2-[18F]FDG PET/CT images was capable of non-invasively predicting the HER2 status with a comparable ability to FISH assay, especially for those with equivocal IHC results for HER2.

Asiatic acid attenuates tubular injury in diabetic kidney disease by regulating mitochondrial dynamics via the Nrf-2 pathway.

BACKGROUND: Mitochondrial dynamics plays a crucial role in tubular injury in diabetic kidney disease (DKD). Asiatic acid (AA) has demonstrated renal protective effects in DKD; however, its therapeutic effect on tubular injury in DKD remains unclear. PURPOSE: This study aimed to verify the effects of AA on tubular injury in DKD and underlying mechanisms. STUDY DESIGN: In the present study, the effects of AA on tubular injury were assessed in rats with streptozotocin-induced diabetes and advanced glycation end products (AGEs)-stimulated HK-2 cells models. METHODS: After oral administration with or without AA for ten weeks, body weight and levels of fast blood glucose, serum creatinine (sCr), blood urea nitrogen (BUN), urinary albumin, and kidney injury molecule-1 (KIM-1) were detected. Histological analysis was performed to evaluate the renal function of rats. Moreover, the expression of proteins associated with the Nrf-2 pathway and mitochondrial dynamics was analyzed. AGEs-stimulated HK-2 cells were examined to evaluate the tubular protection and the mechanism of AA in vitro. RESULTS: AA remarkably decreased albumin levels, KIM-1 levels in urine, and serum Cr, and BUN levels. In addition, AA prevented tubular injury and mitochondrial injury by regulating the Nrf-2 pathway and mitochondrial dynamics. Furthermore, the effects of AA on mitochondrial dynamics and tubular protection were eliminated after treatment with ML385 (Nrf2 inhibitor). CONCLUSION: These findings suggested that AA might be developed as a potential candidate for the treatment of tubular injury in DKD, and its effects are potentially mediated via the regulation of the Nrf-2 pathway and mitochondrial dynamics.

Evaluation and characterization of starch nanoparticles for adsorption of urea from dialysates.

Starch nanoparticles (SNPs) was produced from type-A, B and C native starches (corn, potato and Trichosanthes kirilowii pulp starches respectively), via the nanoprecipitation method. The SNPs showed different amylose contents, water contact angles, surface morphologies and urea clearance performances. In this work, to examine the parameters of SNPs that may change the urea adsorption capacity, urea adsorption performance in adsorption environments with different pH values, urea concentrations, and adsorption times was examined. Thereafter, the characteristics of SNPs were tested by water contact angle measurements (WCA), transmission electron microscopy, specific surface area measurements, gel permeation chromatography, and zeta potential analysis. The results showed that the Trichosanthes kirilowii pulp (C) SNPs show better adsorption than the corn (A) and potato (B) SNPs. The hydrophobicity of SNPs promotes the urea adsorption of the SNPs. Using grey relational analysis, it was found that WCA and Mn are the critical parameter affecting the adsorption performance, with WCA and Mn within the ranges of 31-33° and 1900-2100 kDa, respectively, were found to be the conditions for optimal urea adsorption.

SENP1 promotes triple-negative breast cancer invasion and metastasis via enhancing CSN5 transcription mediated by GATA1 deSUMOylation.

TNBC is characterized by high incidence of visceral metastasis and lacks effective clinical targets. This study aims to delineate the molecular mechanisms of SENP1 in TNBC invasion and metastasis. By using IHC to test the SENP1 expression in TNBC tissues, we analyzed the relationship between SENP1 expression and TNBC prognosis. We showed that SENP1 expression was higher in TNBC tumor tissues and related to TNBC prognosis, supporting SENP1 as an independent risk factor. High expression of SENP1 was significantly associated with histologic grade and tumor lymph node invasion. Intriguingly, the expression levels of SENP1 in TNBC tumors were significantly correlated with that of CSN5, GATA1 and ZEB1. Importantly, SENP1 promoted TNBC cell migration and invasion by regulating ZEB1 deubiquitination and expression through CSN5. Further studies showed that deSUMOylation at lysine residue K137 of GATA1 enhanced the binding of GATA1 to the CSN5 promoter and transactivated CSN5 expression. In addition, we showed that ZEB1 is deubiquitinated at lysine residue K1108. Our in vivo studies also indicated that reduction in SENP1 expression upregulated GATA1 SUMOylation, and thus resulted in decreased expression of CSN5 and ZEB1 in the tumor microenvironment, which decelerated TNBC progression and metastasis. SENP1 promoted CSN5-mediated ZEB1 protein degradation via deSUMOylation of GATA1, and thus influenced TNBC progression. These findings suggest that SENP1 could be utilized as a potential target for blockade of TNBC development and thus provide a totally new approach for TNBC treatment.

Cyclocarya paliurus triterpenoids attenuate glomerular endothelial injury in the diabetic rats via ROCK pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus (Batal.) Iljinskaja. (C. paliurus) is a distinctive traditional Chinese herb, with remarkable hypoglycemic capacity. Emerging evidence suggested that glomerular endothelial injury is a crucial pathological process of diabetic kidney disease (DKD). Our previous research found that C. paliurus triterpenoids fraction (CPT) has ameliorative effects on DKD. However, whether C. paliurus could counteract the glomerular endothelial injury of DKD is still undefined. AIM OF THE STUDY: We aimed to investigate the effects of CPT on glomerular endothelial function and explore its underlying mechanisms with in vivo and in vitro experiments. MATERIALS AND METHODS: The effects and possible mechanisms of CPT on glomerular endothelial injury in streptozotocin (STZ)-induced diabetic rats and H2O2-challenged primary rat glomerular endothelial cells were successively investigated. RESULTS: In vivo, we found that CPT treatment obviously decreased the levels of blood glucose, microalbumin, BUN and mesangial expansion. Additionally, CPT could ameliorate renal endothelium function by reducing the content of VCAM-1 and ICAM-1, and blocking the loss of glycocalyx. In vitro, CPT could also alleviate H2O2-induced endothelial injury. Mechanistically, CPT remarkably increased the phosphorylation levels of Akt and eNOS, decreased the expression of ROCK and Arg2in vivo and in vitro. Noticeably, the favorable effects mediated by CPT were abolished following ROCK overexpression with plasmid transfection. CONCLUSION: These findings suggested that CPT could be sufficient to protect against glomerular endothelial injury in DKD through regulating ROCK pathway.

The Predictive Role of Immune Related Subgroup Classification in Immune Checkpoint Blockade Therapy for Lung Adenocarcinoma.

Background: In lung adenocarcinoma (LUAD), the predictive role of immune-related subgroup classification in immune checkpoint blockade (ICB) therapy remains largely incomplete. Methods: Transcriptomics analysis was performed to evaluate the association between immune landscape and ICB therapy in lung adenocarcinoma and the associated underlying mechanism. First, the least absolute shrinkage and selection operator (LASSO) algorithm and K-means algorithm were used to identify immune related subgroups for LUAD cohort from the Cancer Genome Atlas (TCGA) database (n = 572). Second, the immune associated signatures of the identified subgroups were characterized by evaluating the status of immune checkpoint associated genes and the immune cell infiltration. Then, potential responses to ICB therapy based on the aforementioned immune related subgroup classification were evaluated via tumor immune dysfunction and exclusion (TIDE) algorithm analysis, and survival analysis and further Cox proportional hazards regression analysis were also performed for LUAD. In the end, gene set enrichment analysis (GSEA) was performed to explore the metabolic mechanism potentially responsible for immune related subgroup clustering. Additionally, two LUAD cohorts from the Gene Expression Omnibus (GEO) database were used as validation cohort. Results: A total of three immune related subgroups with different immune-associated signatures were identified for LUAD. Among them, subgroup 1 with higher infiltration scores for effector immune cells and immune checkpoint associated genes exhibited a potential response to IBC therapy and a better survival, whereas subgroup 3 with lower scores for immune checkpoint associated genes but higher infiltration scores for suppressive immune cells tended to be insensitive to ICB therapy and have an unfavorable prognosis. GSEA revealed that the status of glucometabolic reprogramming in LUAD was potentially responsible for the immune-related subgroup classification. Conclusion: In summary, immune related subgroup clustering based on distinct immune associated signatures will enable us to screen potentially responsive LUAD patients for ICB therapy before treatment, and the discovery of metabolism associated mechanism is beneficial to comprehensive therapeutic strategies making involving ICB therapy in combination with metabolism intervention for LUAD.

Molecular subtype classification of breast cancer using established radiomic signature models based on 18F-FDG PET/CT images.

Backgrounds: To evaluate the predictive power of 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) derived radiomics in molecular subtype classification of breast cancer (BC). Methods: A total of 273 primary BC patients who underwent a 18F-FDG PET/CT imaging prior to any treatment were included in this retrospective study, and the values of five conventional PET parameters were calculated, including the maximum standardized uptake value (SUVmax), SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG). The ImageJ 1.50i software and METLAB package were used to delineate the contour of BC lesions and extract PET/CT derived radiomic features reflecting heterogeneity. Then, the least absolute shrinkage and selection operator (LASSO) algorithm was used to select optimal subsets of radiomic features and establish several corresponding radiomic signature models. The predictive powers of individual PET parameters and developed PET/CT derived radiomic signature models in molecular subtype classification of BC were evaluated by using receiver operating curves (ROCs) analyses with areas under the curve (AUCs) as the main outcomes. Results: All of the three SUV parameters but not MTV nor TLG were found to be significantly underrepresented in luminal and non-triple (TN) subgroups in comparison with corresponding non-luminal and TN subgroups. Whereas, no significant differences existed in all the five conventional PET parameters between human epidermal growth factor receptor 2+ (HER2+) and HER2- subgroups. Furthermore, all of the developed radiomic signature models correspondingly exhibited much more better performances than all the individual PET parameters in molecular subtype classification of BC, including luminal vs. non-luminal, HER2+ vs. HER2-, and TN vs. non-TN classification, with a mean value of 0.856, 0.818, and 0.888 for AUC. Conclusions: PET/CT derived radiomic signature models outperformed individual significant PET parameters in molecular subtype classification of BC.

Identification of markers associated with brain metastasis from breast cancer through bioinformatics analysis and verification in clinical samples.

BACKGROUND: Brain metastasis from breast cancer (BC) is an important cause of BC-related death. The present study aimed to identify markers of brain metastasis from BC. METHODS: Datasets were downloaded from the public databases Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Weighted gene co-expression network analysis (WGCNA) was performed to identify metastasis-associated genes (MAGs). Least absolute shrinkage and selection operator (LASSO) Cox proportional hazards regression models were constructed for screening key MAGs. Survival analysis and receiver operating characteristic (ROC) curves were used for evaluating the prognostic value. The factors associated with tumor metastasis were integrated to create a nomogram of TCGA data using R software. Gene Set Enrichment Analyses (GSEA) was performed for detecting the potential mechanisms of identified MAGs. Immunohistochemistry (IHC) was used to verify the expression of the key genes in clinical samples. RESULTS: The genes in 2 modules were identified to be significantly associated with metastasis through WGCNA. LASSO Cox proportional hazards regression models were constructed successfully. Subsequently, a clinical prediction model was constructed, and a nomogram was mapped, which had better sensitivity and specificity for BC metastasis. Two key genes, discs large homolog 3 (DLG3) and growth factor independence 1 (GFI1), were highly expressed in clinical samples, and the expression of these 2 genes was associated with patients' survival time. CONCLUSIONS: We successfully constructed a clinical prediction model for brain metastasis from BC, and identified that the expression of DLG3 and GFI1 were strongly associated with brain metastasis from BC.

Value of pretreatment 18F-FDG PET/CT in prognosis and the reflection of tumor burden: a study in pediatric patients with newly diagnosed neuroblastoma.

Fluorine-18 fluorodeoxyglucose (18F-FDG) PET/CT has been commonly used in pediatric patients with newly diagnosed neuroblastoma (NB) for diagnosis. We retrospectively reviewed 40 pediatric patients with newly diagnosed NB who underwent 18F-FDG PET/CT. Clinicopathological factors and metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) on PET/CT were evaluated as predictive factors for progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analysis. Spearman rank correlation analyses were used to estimate the correlations between clinical factors and PET findings. The mean follow-up after 18F-FDG-PET/CT was 32.9 months. During the follow-up period 15 (37.5%) patients experienced progression, and 9 (22.5%) died. MTV (P=0.001) and TLG (p=0.004) remained significant predictive factors for tumor progression, along with lactate dehydrogenase (LDH), neuron-specific enolase (NSE) and bone metastasis. Univariate analysis showed that bone metastasis, LDH (>1064 IU/L), NSE (>364.4 ug/L), MTV (>191 cm3) and TLG (>341.41 g) correlated with PFS, and LDH (>1064 IU/L), NSE (>364.4 ug/L) and MTV (>191 cm3) correlated with OS (p<0.05). In multivariate analysis, MTV and bone metastasis were independent prognostic factors for PFS (p=0.001 and 0.023, respectively), and MTV remained the only independent prognostic factor for OS (p= 0.004). We also found that there were correlations between semiquantitative PET/CT parameters and clinical features in NB. Our results suggested that 18F-FDG PET/CT was a useful tool to predictive progression and to reflect tumor burden for patients with NB.

18F-FHBG PET-CT Reporter Gene Imaging of Adoptive CIK Cell Transfer Immunotherapy for Breast Cancer in a Mouse Model.

BACKGROUND: To further improve the efficiency of adoptively transferred cytokine-induced killer (CIK) cell immunotherapy in breast cancer (BC), a reliable imaging method is required to visualize and monitor these transferred cells in vivo. METHODS: Herpes simplex virus 1-thymidine kinase (HSV1-TK) and 9-(4-[18F]fluoro-3-(hydroxymethyl)butyl)guanine (18F-FHBG) were used as a pair of reporter gene/reporter probe for positron emission tomography (PET) imaging in this study. Following the establishment of subcutaneous BC xenograft-bearing nude mice models, induced human CIK cells expressing reporter gene HSV1-TK through lentiviral transduction were intravenously injected to nude mice. γ-radioimmunoassay was used to determine the specific uptake of 18F-FHBG by these genetically engineered CIK cells expressing HSV1-TK in vitro, and 18F-FHBG micro positron emission tomography-computed tomography (PET-CT) imaging was performed to visualize these adoptively transferred CIK cells in tumor-bearing nude mice. RESULTS: Specific uptake of 18F-FHBG by CIK cells expressing HSV1-TK was clearly observed in vitro. Consistently, the localization of adoptively transferred CIK cells in tumor target could be effectively visualized by 18F-FHBG micro PET-CT reporter gene imaging. CONCLUSION: PET-CT reporter gene imaging using 18F-FHBG as a reporter probe enables the visualization and monitoring of adoptively transferred CIK cells in vivo.

Value of metabolic parameters in distinguishing primary mediastinal lymphomas from thymic epithelial tumors.

Objective: A high rate of unnecessary thymectomies has been reported. This study aimed to distinguish primary mediastinal lymphomas (PMLs) from thymic epithelial tumors (TETs) by evaluating volumetric and metabolic parameters with 18F-FDG PET/CT. Methods: A total of 136 patients who were pathologically diagnosed with TETs or PMLs were enrolled, and 18F-FDG PET/CT was performed before therapy. Volumetric parameters, including the mean SUV (SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax, were determined and compared between the 2 subtypes. The diagnostic performance of these parameters was evaluated with receiver operating characteristic (ROC) curve analysis. Results: All parameters significantly differed between patients with PMLs and TETs. Patients with lymphomas were younger and had higher SUVmean, SUVmax, TLG, and MTV values than patients with TETs. The MTV and TLG values had similar diagnostic performance. ROC analysis indicated that the areas under the curves of the SUVmean and SUVmax values performed similarly (approximately 0.76) in differentiating patients with PMLs from TETs, and both values were better than the MTV and TLG values. When age was included with the SUVmax in differentiating TETs from PMLs, the AUC was 0.91, and the sensitivity and specificity increased to 80% and 93%, respectively. Conclusions: The SUVmax and volumetric parameters of 18F-FDG PET/CT can be used to distinguish patients with PMLs versus TETs, and thus may aid in preventing unnecessary thymectomies or other invasive operations.

Enhanced glucose metabolism mediated by CD147 is associated with 18 F-FDG PET/CT imaging in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is one of the most deadly thoracic tumors. Reprogrammed glycolytic metabolism is a hallmark of cancer cells and significantly affects several cellular functions. In the current study, we aimed to investigate cluster of differentiation 147 (CD147)-mediated glucose metabolic regulation in LUAD and its association with 18 F-FDG PET/CT imaging. METHODS: The expression profile and prognostic potential of CD147 in LUAD were analyzed using UALCAN and a Kaplan-Meier plotter. Tissue immunohistochemical analyses and PET metabolic parameters were used to identify the relationship between CD147 expression and reprogrammed glycolysis. The role of CD147 in glucose metabolic reprogramming was assessed by radioactive uptake of 18 F-FDG through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo. Western blotting assays were used to determine the expression level of monocarboxylate transporter 1 (MCT1) and MCT4 in established human LUAD cell lines (ie, HCC827 and H1975) with different CD147 expression levels via lentiviral transduction. RESULTS: CD147 was highly expressed in LUAD. A significant positive correlation existed between CD147 expression and PET metabolic parameters(SUVmax,SUVmean, SUVpeak). CD147 could promote radioactive uptake of 18 F-FDG in vitro and in vivo, suggesting the ability of CD147 to enhance glycolytic metabolism. Furthermore, as an obligate chaperone for MCT1 and MCT4, CD147 positively correlated with MCT1 and MCT4 expression in LUAD tissues and established cell lines with different CD147 expression. CONCLUSIONS: Our study revealed that CD147 is a promising novel target for LUAD treatment and CD147-mediated glucose metabolism demonstrated its contribution to the predictive role of 18 F-FDG PET/CT imaging for targeted therapeutic efficacy.

Enhanced glucose metabolism mediated by CD147 contributes to immunosuppression in hepatocellular carcinoma.

From a metabolic perspective, cancer may be considered as a metabolic disease characterized by reprogrammed glycolytic metabolism. The aim of the present study was to investigate CD147-mediated glucose metabolic regulation in hepatocellular carcinoma (HCC) and its contribution to altered immune responses in the tumor microenvironment. Several HCC cell lines and corresponding nude mice xenografts models differing in CD147 expressions were established to directly investigate the role of CD147 in the reprogramming of glucose metabolism, and to determine the underlying molecular mechanisms. Immunohistochemistry (IHC) analyses and flow cytometry were used to identify the relationship between reprogrammed glycolysis and immunosuppression in HCC. Upregulated CD147 expressions were found to be associated with enhanced expressions of GLUT1, MCT1 in HCC tumorous tissues. CD147 promoted the glycolytic metabolism in HCC cell lines in vitro via the PI3K/Akt/mTOR signaling pathway. A positive correlation existed between a profile of immunosuppressive lymphocytes infiltration and CD147 expression in HCC tissues. Accumulation of FOXP3-expressing regulatory T cells was induced under a stimulation with lactate in vitro. In conclusion, CD147 promoted glycolytic metabolism in HCC via the PI3K/Akt/mTOR signaling pathway, and was related to immunosuppression in HCC.

[Exploring molecular mechanisms of fucoidan in improving human proximal renal tubular epithelial cells aging by targeting autophagy signaling pathways].

Fucoidan(FPS) is an effective component of the Chinese patent medicine named Haikun Shenxi, which treats schronic renal failure in clinics, and has the potential anti-aging effects. However, it is still unclear whether FPS can improve renal aging, especially the molecular mechanism of its anti-aging. The human proximal renal tubular epithelial cells(HK-2) in vitro were divided into normal group(N), D-gal model group(D), low dose of FPS group(L-FPS), high dose of FPS group(H-FPS) and vitamin E group(VE), and treated by the different measures, respectively. More specifically, the HK-2 cells in each group were separately treated by 1 mL of 1% fetal bovine serum(FBS) or D-galactose(D-gal, 75 mmol·L~(-1)) or D-gal(75 mmol·L~(-1))+FPS(25 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+FPS(50 µg·mL~(-1)) or D-gal(75 mmol·L~(-1))+VE(50 µg·mL~(-1)). After the treatment for 24 h, firstly, the effects of D-gal on senescence-associated ß-galactosidase(SA-ß-gal) staining characteristics and klotho, P53 and P21 protein expression le-vels, as well as adenosine monophosphate activated protein kinase(AMPK)-uncoordinated 51-like kinase 1(ULK1) signaling pathway activation in the HK-2 cells were detected, respectively. Secondly, the effects of FPS and VE on SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal were investigated, respectively. Finally, the effects of FPS and VE on microtubule-associated protein 1 light chain 3(LC3) protein expression level and AMPK-ULK1 signaling pathway activation in the HK-2 cells exposed to D-gal were examined severally. The results indicated that, for the HK-2 cells, the dose of 75 mmol·L~(-1) D-gal could induce the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels. That is causing cells aging. FPS and VE could both ameliorate the changes of SA-ß-gal staining characteristics and klotho, P53 and P21 protein expression levels in the HK-2 cells exposed to D-gal. That is anti-cells aging, here, the functions of FPS and VE are similar. D-gal could not only induce cell aging but also increase LC3Ⅱ, phosphorylated-AMPK(p-AMPK) and phosphorylated-ULK1(p-ULK1) protein expressions, and activate autophagy-related AMPK-ULK1 signaling pathway. FPS and VE could both improve the changes of LC3Ⅱ, p-AMPK and p-ULK1 protein expression levels in the HK-2 cells exposed to D-gal. That is inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. On the whole, for the human proximal renal tubular epithelial cells aging models induced by D-gal, FPS similar to VE, can ameliorate renal cells aging by possibly inhibiting autophagy-related AMPK-ULK1 signaling pathway activation. This finding provides the preliminary pharmacologic evidences for FPS protecting against renal aging.

Predictive Power of a Radiomic Signature Based on 18F-FDG PET/CT Images for EGFR Mutational Status in NSCLC.

Radiomics has become an area of interest for tumor characterization in 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging. The aim of the present study was to demonstrate how imaging phenotypes was connected to somatic mutations through an integrated analysis of 115 non-small cell lung cancer (NSCLC) patients with somatic mutation testings and engineered computed PET/CT image analytics. A total of 38 radiomic features quantifying tumor morphological, grayscale statistic, and texture features were extracted from the segmented entire-tumor region of interest (ROI) of the primary PET/CT images. The ensembles for boosting machine learning scheme were employed for classification, and the least absolute shrink age and selection operator (LASSO) method was used to select the most predictive radiomic features for the classifiers. A radiomic signature based on both PET and CT radiomic features outperformed individual radiomic features, the PET or CT radiomic signature, and the conventional PET parameters including the maximum standardized uptake value (SUVmax), SUVmean, SUVpeak, metabolic tumor volume (MTV), and total lesion glycolysis (TLG), in discriminating between mutant-type of epidermal growth factor receptor (EGFR) and wild-type of EGFR- cases with an AUC of 0.805, an accuracy of 80.798%, a sensitivity of 0.826 and a specificity of 0.783. Consistently, a combined radiomic signature with clinical factors exhibited a further improved performance in EGFR mutation differentiation in NSCLC. In conclusion, tumor imaging phenotypes that are driven by somatic mutations may be predicted by radiomics based on PET/CT images.

18 Fluorodeoxyglucose-positron emission tomography/computed tomography features of suspected solitary pulmonary lesions in breast cancer patients following previous curative treatment.

BACKGROUND: Differentiating pulmonary metastasis from primary lung cancer can be challenging in patients with breast malignancy. This study aimed to characterize the imaging features of 18 fluorodeoxyglucose-positron emission tomography/computed tomography (18 F-FDG-PET/CT) for distinguishing between these diseases. METHODS: We enrolled 52 patients who received curative treatment for breast cancer but later presented with suspected solitary pulmonary lesions (SPLs) and subsequently underwent 18 F-FDG-PET/CT to investigate. RESULTS: Subsolid lesions, ill-defined borders, lung lesions with negative maximum standardized uptake value, and lesions without 18 F-FDG-PET/CT-diagnosed hilar and/or mediastinal lymph nodes and pleural metastases were more likely to be associated with primary lung cancer. CONCLUSIONS: CT border, FDG uptake, hilar and/or mediastinal lymph node metastasis, and pleural metastasis are potential markers for diagnosis.

CD147-mediated glucose metabolic regulation contributes to the predictive role of 18 F-FDG PET/CT imaging for EGFR-TKI treatment sensitivity in NSCLC.

The aim of this study is to investigate the role of CD147 in glucose metabolic regulation and its association with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) treatment sensitivity prediction using 18 F-fluorodeoxyglucose (18 F-FDG) PET/CT imaging in non-small cell lung cancer (NSCLC). In this study, four human NSCLC cell lines with different EGFR-TKI responses were used to detect p-EGFR/EGFR and CD147 expression via Western blotting and flow cytometric analyses. Radioactive uptake of 18 F-FDG by established stable NSCLC cell lines (HCC827, H1975) with different levels of CD147 expression and the corresponding xenografts was assessed through γ-radioimmunoassays in vitro and micro-PET/CT imaging in vivo to study the role of CD147 in glucose metabolic reprogramming. Correlation analyses were performed to investigate the association between CD147 expression and PD-L1 expression in stable NSCLC cell lines. Higher CD147 expression was found in EGFR-TKI-sensitive NSCLC cell lines than in relatively resistant NSCLC cell lines (HCC827>PC9>A549>H1975). CD147 could promote 18 F-FDG uptake by HCC827 and H1975 cells in vitro and in vivo through an EGFR-initiated Akt/mTOR-dependent signaling pathway. Programmed cell death-ligand 1 (PD-L1) expression was positively correlated with CD147 expression in human NSCLC cell lines. EGFR-TKI treatment sensitivity prediction in NSCLC using 18 F-FDG PET/CT imaging significantly correlated with CD147-mediated glucose metabolic regulation via the Akt/mTOR-dependent pathway. Moreover, PD-L1 expression in NSCLC cell lines could be regulated by CD147, suggesting a potential immunosuppression induced by the upregulation of tumor glucose metabolism.

Preclinical and clinical applications of specific molecular imaging for HER2-positive breast cancer.

Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2 (HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.

A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma.

Natural T cells [cluster of differentiation (CD) 3+CD56+] and natural killer (NK) cells (CD3-CD56+) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis. The abundance of natural T cells and NK cells was decreased in TILs vs. NILs (natural T cells, 6.315±1.002 vs. 17.16±1.804; NK cells, 6.324±1.559 vs. 14.52±2.336, respectively). However such results were not observed in PBMCs from HCC patients vs. that of healthy donors. Notably, a substantial fraction of the natural T cells (21.96±5.283) in TILs acquired forkhead box P3 (FOXP3) expression, and the FOXP3+ natural T cells lost the expression of interferon-γ and perforin. Conversely, being similar to the conventional FOXP3+ regulatory T cells, the FOXP3+ natural T cells assumed a specific phenotype that was characteristic of CD25+, CD45RO+ and cytotoxic T-lymphocyte-associated protein 4+. Consistent with the phenotypic conversion, the present functional results indicate that FOXP3 expression in natural T cells contributes to the acquisition of a potent immunosuppressive capability. In conclusion, the present study describes a different representation of natural T cells and NK cells in local tumor tissues and in the periphery blood of patients with HCC, and identified a new type of FOXP3-expressing natural T cell spontaneously arising in the TILs of HCC.

(18)F-fluorodeoxyglucose positron emission tomography/computed tomography comparison of gastric lymphoma and gastric carcinoma.

AIM: To compare (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) features in gastric lymphoma and gastric carcinoma. METHODS: Patients with newly diagnosed gastric lymphoma or gastric carcinoma who underwent (18)F-FDG PET/CT prior to treatment were included in this study. We reviewed and analyzed the PET/CT features of gastric wall lesions, including FDG avidity, pattern (focal/diffuse), and intensity [maximal standard uptake value: (SUVmax)]. The correlation of SUVmax with gastric clinicopathological variables was investigated by χ(2) test, and receiver-operating characteristic (ROC) curve analysis was performed to determine the differential diagnostic value of SUVmax-associated parameters in gastric lymphoma and gastric carcinoma. RESULTS: Fifty-two patients with gastric lymphoma and 73 with gastric carcinoma were included in this study. Abnormal gastric FDG accumulation was found in 49 patients (94.23%) with gastric lymphoma and 65 patients (89.04%) with gastric carcinoma. Gastric lymphoma patients predominantly presented with type I and type II lesions, whereas gastric carcinoma patients mainly had type III lesions. The SUVmax (13.39 ± 9.24 vs 8.35 ± 5.80, P < 0.001) and SUVmax/THKmax (maximal thickness) (7.96 ± 4.02 vs 4.88 ± 3.32, P < 0.001) were both higher in patients with gastric lymphoma compared with gastric carcinoma. ROC curve analysis suggested a better performance of SUVmax/THKmax in the evaluation of gastric lesions between gastric lymphoma and gastric carcinoma in comparison with that of SUVmax alone. CONCLUSION: PET/CT features differ between gastric lymphoma and carcinoma, which can improve PET/CT evaluation of gastric wall lesions and help differentiate gastric lymphoma from gastric carcinoma.