Protocol for CHAMPION study: a prospective study of maximal-cytoreductive therapies for patients with de novo metastatic hormone-sensitive prostate cancer who achieve oligopersistent metastases during systemic treatment with apalutamide plus androgen deprivation therapy.

BACKGROUND: The proposed trial is to examine the feasibility of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-guided cytoreduction plus apalutamide and androgen deprivation therapy (ADT) for newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) at oligometastatic state. METHODS: CHAMPION (NCT05717582) is an open-label, single-arm, phase II trial, planning to enroll newly diagnosed mHSPC cases with oligometastases (≤ 10 distant metastatic sites in conventional imaging). Patients will receive 6 cycles of apalutamide plus ADT. Patients with oligometastatic disease at PSMA PET/CT after 3 treatment cycles will receive cytoreductive radical prostatectomy. PSMA PET/CT-guided metastasis-directed external radiation therapy will be determined by the investigators. Apalutamide plus ADT will be continued for 2 weeks postoperatively. The primary endpoint is the proportion of patients with undetectable prostate-specific antigen (PSA), no disease progression, and no symptom deterioration after 6 cycles of apalutamide plus ADT. Secondary endpoints include the percentage of patients with PSA ≤ 0.2 ng/mL and oligometastases by the end of 3 treatment cycles, PSA response rate, and safety. Fleming's two-stage group sequential design will be adopted in the study, where the null hypothesis is that the rate of patients with an undetectable PSA is ≤ 40% after 6 cycles of treatment, while the alternate hypothesis is an undetectable PSA of > 60%; with one-sided α = 0.05, power = 0.80, and an assumed dropout rate of 10%, the required number of patients for an effective analysis is 47. Enrolment in the study commenced in May 2023. DISCUSSION: The multi-modal therapy based on treatment response may improve the prognosis of newly diagnosed mHSPC patients with oligometastases. TRIAL REGISTRATION: The study is registered with Clinical Trials.Gov (NCT05717582). Registered on 8th February 2023.

Quantitative analysis from ultrafast dynamic contrast-enhanced breast MRI using population-based versus individual arterial input functions, and comparison with semi-quantitative analysis.

PURPOSE: To evaluate the value of inline quantitative analysis of ultrafast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a population-based arterial input function (P-AIF) compared with offline quantitative analysis with an individual AIF (I-AIF) and semi-quantitative analysis for diagnosing breast cancer. METHODS: This prospective study included 99 consecutive patients with 109 lesions (85 malignant and 24 benign). Model-based parameters (Ktrans, kep, and ve) and model-free parameters (washin and washout) were derived from CAIPIRINHA-Dixon-TWIST-VIBE (CDTV) DCE-MRI. Univariate analysis and multivariate logistic regression analysis with forward stepwise covariate selection were performed to identify significant variables. The AUC and F1 score were assessed for semi-quantitative and two quantitative analyses. RESULTS: kep from inline quantitative analysis with P-AIF for diagnosing breast cancer provided an AUC similar to kep from offline quantitative analysis with I-AIF (0.782 vs 0.779, p = 0.954), higher compared to washin from semi-quantitative analysis (0.782 vs 0.630, p = 0.034). Furthermore, the inline quantitative analysis with P-AIF achieved the larger F1 score (0.920) compared with offline quantitative analysis with I-AIF (0.780) and semi-quantitative analysis (0.480). There were no statistically significant differences for kep values between the two quantitative analysis schemes (p = 0.944). CONCLUSION: The inline quantitative analysis with P-AIF from CDTV in characterizing breast lesions could offer similar diagnostic accuracy to offline quantitative analysis with I-AIF, and higher diagnostic accuracy to semi-quantitative analysis.

Heterogeneity of [68Ga]Ga-PSMA-11 PET/CT in metastatic castration-resistant prostate cancer: genomic characteristics and association with abiraterone response.

PURPOSE: The aim of this study was to evaluate the impact of the spatial heterogeneity of prostate-specific membrane antigen (PSMA) uptake on circulating tumor DNA (ctDNA) characteristics and the response rate to new hormonal agent (NHA) treatment. METHODS: This retrospective study included 153 patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent gallium-68 [68 Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and ctDNA sequencing with a less than 2-week interval. SUVhetero was defined as the variance of SUVmean for each PSMA-positive lesion. SUVmax-mean was obtained by subtracting the SUVmax by the SUVmean. Patients receiving abiraterone treatment after [68 Ga]Ga-PSMA-11 PET/CT and ctDNA sequencing and with complete follow-up record were included into prostate-specific antigen (PSA) response rate analysis. PSA response was defined as a reduction of greater than 50% from baseline. RESULTS: The ctDNA detection rate was 65% (100/153). Higher SUVhetero value contributed to higher ctDNA% (Spearman's rho = 0.278, p < 0.002). A total of 60 patients were included in PSA response rate analysis. The median follow-up was 19.3 (IQR 16.2-23.2) months. Compare to patients with higher SUVhetero value, patients with NA SUVhetero had a higher PSA response rate (52% vs. 90%, p = 0.036). A higher SUVmax-mean value was strongly correlated with higher SUVhetero (Spearman's rho = 0.833, p < 0.0001). Patients with higher SUVmax-mean value also had a higher PSA response rate compared to patients with lower SUVmax-mean value (83.3% vs. 53.3%, p = 0.024). An external cohort confirmed baseline SUVmax-mean value was associated with enzalutamide treatment response rate. Patients with alterations in AR, DNA damage repair pathway, TP53, AR-associated pathway, cell cycle pathway, or WNT pathway had higher SUVmax-mean value compared to those without (p < 0.05). CONCLUSION: Spatial heterogeneity of the PSMA uptake was associated with ctDNA characteristics and response rate to NHA treatment.

The value of imaging combined with clinicopathological features in the diagnosis of high-risk breast lesions.

Background: The upgrade of high-risk breast lesions (HRLs) is closely related to subsequent treatment, but the current predictors for upgrade are limited to intratumoral features of single imaging mode. Methods: We retrospectively reviewed 230 HRLs detected by mammography, ultrasound, and magnetic resonance imaging (MRI) before biopsy at the Fudan University Cancer Hospital from January 2017 to March 2018. The clinical features, imaging data according to the Breast Imaging Reporting and Data System (BI-RADS) lexicon, and tumor upgrade situation were received. Based on the different risks of upgrade reported, the lesions were classified into high-risk I [HR-I, with atypical hyperplasia (AH)] and high-risk II (HR-II, without AH). We analyzed the association between clinicopathological and imaging factors and upgrade. We used the receiver operating characteristic (ROC) curve to compare the efficacy of three imaging modes for predicting upgrade. Results: We included 230 HRLs in 230 women in the study, and the overall upgrade rate was 20.4% (47/230). The upgrade rate was higher in HR-I compared to HR-II (38.5% vs. 4.1%, P<0.01). In patients with AH, estrogen receptor-positive (ER+) patients accounted for 81.0% (64/79). For all HRLs and HR-I, in clinical characteristics, age, maximum size of lesion, and menopausal status were significantly associated with upgrade (P<0.05). In imaging factors, MRI background parenchymal enhancement (BPE), signs of MRI and ultrasound were significantly correlated with upgrade (P<0.05). Patients with negative MRI or ultrasound manifestations had lower upgrade rates (P<0.01). For HR-II, only BPE showed a significant difference between groups (P=0.001). Multifactorial analysis of all HRLs showed that age and BPE were independent predictors of upgrade (P<0.01). The areas under the ROC cure (AUCs) for predicting upgrade in mammography, ultrasound, and MRI were 0.606, 0.590, and 0.913, respectively, indicating that MRI diagnosis was significantly better than mammography and ultrasound (P<0.001). Conclusions: HRLs with AH had a higher rate of upgrade and increased ER expression. Among three imaging modes, MRI was more effective than ultrasound and mammography in diagnosing the upgrade of HRLs. Older age and moderate to marked BPE can indicate malignant upgrade. MRI can provide a certain value for the diagnosis and follow-up of HRLs.

Increased DNA Polymerase Epsilon Catalytic Subunit Expression Predicts Tumor Progression and Modulates Tumor Microenvironment of Hepatocellular Carcinoma.

Backgrounds: Liver hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and POLE, playing an important role in maintaining genetic stability, is closely connected with cancer prognosis. This study aimed to explore the significance role of POLE in HCC prognosis, clinical treatment and tumor immune microenvironment based on large-scale multiply cohorts. Methods: First, we found that the expression of POLE was prominently higher in tumor tissues than in normal tissues, and was closely related to clinical stage, grade and patient outcomes. Second, we found that patients with high POLE expression had significantly aggressive progression, indicating effective predictive role of POLE expression for Asian, male, low-risk HCC patients. Additionally, POLE mutation frequency was detected in several datasets with available genomic-wide data. Results: 130 HCC samples from real-world Renji cohort were included to demonstrate that elevated POLE expression was significantly connected to the invasive progression and poor prognosis. More importantly, the expression of POLE was closely related to the anti-tumoral activity of immune cells and immune checkpoints expression, suggesting a bright prospect of POLE as a predictive biomarker in immunotherapy. Conclusion: In conclusion, this study revealed that high expression of POLE significantly correlated to the malignant progression, poor prognosis and anti-tumoral activity of immune cells in HCC. Thus, POLE could function as a biomarker for the early diagnosis, prognosis, immune-excluded tumor microenvironment and response to immunotherapy of HCC.

Fat Attenuation Index of Renal Cell Carcinoma Reveals Biological Characteristics and Survival Outcome.

Purpose: The computed tomography fat attenuation index (FAI) is an ideal quantifiable imaging factor to identify the inflammation degree of peri-tumor adipose tissue. We aimed to verify whether FAI could reflect peri-tumor adipose inflammation, predict the survival outcome of renal cell carcinoma (RCC), and discover transcriptomic features of tumor tissues and adjacent adipocytes. Materials and Methods: Two clinical cohorts (Fudan University Shanghai Cancer Center [FUSCC] cohort [n=129] and TCGA cohort [n=218]) were used to explore the association between FAI and clinical outcome. A prospective cohort (n = 19) was used to discover the molecular phenotyping of peri-tumor adipose tissue and tumor tissue according to their FAI value. A clinical cohort (n = 32) in which patients received cyto-reductive surgery was used to reveal the dynamic change of FAI. Results: A high peri-tumor FAI was significantly associated with a worse outcome in both the FUSCC (HR = 2.28, p = 0.01) and the TCGA cohort (HR = 2.24, p <0.001). The analysis of the RNA expression of paired RCC tissue and peri-tumor fat tissue showed synchronized alterations in pathways such as cytokine-cytokine receptor interaction and complement and coagulation cascades. RCC tissues showed significant alterations in the neuroactive ligand-receptor interaction pathway. Immune deconvolution analysis showed enhanced infiltration of macrophages in high FAI tumor tissues with a lower angiogenesis level. We also observed synchronous dynamic changes in FAI and tumor size after targeted therapy. Conclusion: In summary, FAI could be used in RCC to reflect the biological characteristics and tumor immune micro-environment of both the tumor and the peri-tumor adipose. High peri-tumor FAI had the potential to predict a worse survival outcome in various cohorts. This study demonstrates that the crosstalk exists between a tumor and its micro-environment and could be reflected easily by imaging procedures, which could facilitate clinical decision making.

Percentage of Tumor Invasion at Pretreatment High-Resolution Magnetic Resonance Imaging: Associating With Aggressive and Tumor Response in Chinese T3 Rectal Cancer-Preliminary Results.

Purpose: The purpose of the study was to assess the ability of percentage of tumor invasion (PTI) of T3 rectal cancer on pretreatment MRI as an imaging biomarker to reflect aggressiveness and to predict tumor response after neoadjuvant chemoradiation (NCRT) in Chinese population. Methods: A total of 107 Chinese rectal cancer patients who underwent pretreatment MRI staging as T3 were included. The extramural depth of tumor invasion (EMD), the distance between outer border of muscularis propria (MP) and mesorectal fascia (MRF) we called "thickness of the mesorectum (TM)") at the same slice and direction were measured at pretreatment MRI, and PTI was equal to EMD/TM, was calculated. The EMD and PTI of subgroups based on pretreatment CEA, CA19-9 levels; N category and pathological complete response (pCR) were compared. The parameters, which described tumor invasion, were compared between pCR and non-pCR group. Student t-tests and logistic analysis were applied. Results: The pretreatment PTI was higher in CEA ≥5.2 ng/ml patients (58.52% ± 27.68%) than in CEA <5.2 ng/ml patients (47.27% ± 24.15%) (p = 0.034). The pretreatment EMD in non-pCR group (7.21 ± 2.85 mm) was higher than in pCR group (6.14 ± 3.56 mm) (p = 0.049). The pretreatment PTI in non-pCR group (57.4% ± 26.4%) was higher than in pCR group (47.3% ± 29.1%) (p = 0.041). Compared with patients with PTI ≥50%, MRF (+), more patients with PTI <50%, MRF (-) showed pCR (OR = 8.44, p = 0.005; OR = 6.32, p = 0.024). Conclusion: The PTI obtained at pretreatment MRI may serve as an imaging biomarker to reflect tumor aggressiveness and predict which T3 rectal cancer patients may benefit from NCRT in Chinese population.

Improved Readout-Segmented Echo-Planner Diffusion-Weighted Magnetic Resonance Imaging of Nasopharyngeal Carcinoma Using Simultaneous Multislice Acquisitions at 3 T.

PURPOSE: This study systematically compared the images from readout-segmented echo-planar diffusion-weighted imaging (RESOLVE-DWI [RS-DWI]) and simultaneous multislice accelerated RESOLVE-DWI (SMS-RS-DWI) in patients with nasopharyngeal carcinoma (NPC) in qualitative and quantitative aspects. METHOD: Forty-four patients with NPC were included. The RS-DWI and prototypic SMS-RS-DWI sequences were performed on all patients. Images were qualitatively evaluated by 4 independent radiologists using a 5-point Likert scale. For quantitative evaluation, the maximum and minimum diameters and the maximum tumor areas were determined for both DWI sequences and compared with the T2-weighted imaging (T2WI) to evaluate image distortions. The apparent diffusion coefficient was measured in the slice with the maximum tumor profile. RESULTS: The SMS-RS-DWI was superior to RS-DWI with respect to overall image quality (3.40 ± 0.53 vs 2.71 ± 0.48, P < 0.0001) and tumor edge sharpness (3.29 ± 0.65 vs 2.64 ± 0.47, P < 0.0001). Susceptibility artifacts were significantly less severe in SMS-RS-DWI than in RS-DWI (0.85 ± 0.57 vs 1.36 ± 0.57, P < 0.0001). There was no significant overestimation or underestimation of the tumor geometry using the SMS-RS-DWI or RS-DWI compared with T2WI. The quantitative analysis showed a slightly higher agreement for SMS-RS-DWI with T2WI than RS-DWI for maximum diameter, minimum diameter, and maximum tumor area. The apparent diffusion coefficient values showed no significant differences between the 2 DWI techniques ( P > 0.05). CONCLUSIONS: At 3 T, SMS-RS-DWI is a useful technique for diagnosing NPC. It substantially improves different aspects of image quality by providing higher spatial resolution and fewer susceptibility artifacts with more extensive anatomic coverage compared with RS-DWI.

Stereotactic Radiotherapy for Lesions Detected via 68Ga-Prostate-specific Membrane Antigen and 18F-Fluorodexyglucose Positron Emission Tomography/Computed Tomography in Patients with Nonmetastatic Prostate Cancer with Early Prostate-specific Antigen Progression on Androgen Deprivation Therapy: A Prospective Single-center Study.

BACKGROUND: Dual-tracer positron emission tomography/computed tomography (PET/CT) with a 68Ga-labelled prostate-specific membrane antigen (PSMA) ligand and 18F-fluorodeoxyglucose (FDG) improves detection of metastatic heterogeneity and burden in patients with nonmetastatic prostate cancer (nmPCa). However, there is limited prospective evidence regarding its impact on the efficacy of stereotactic body radiotherapy (SBRT). OBJECTIVE: To evaluate metastasis-free survival (MFS) and toxicity after SBRT to dual-tracer PET/CT-detected metastases in patients with nmPCa and early prostate-specific antigen (PSA) progression on androgen deprivation therapy (ADT; PSA ≤2 ng/ml). DESIGN, SETTING, AND PARTICIPANTS: Patients were prospectively screened using dual-tracer PET/CT between April 2019 and October 2020. SBRT was recommended for patients with five or fewer nonvisceral metastases (SBRT group). Patients without detectable metastases (N-/M- group) and those who refused SBRT (ADT group) continued to receive ADT. Patients were followed with conventional imaging. INTERVENTION: SBRT to each PET/CT-detected metastasis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier methods were used to determine MFS. Toxicity was evaluated using Common Terminology Criteria for Adverse Event v4.0. RESULTS AND LIMITATIONS: Seventy-four consecutive patients were screened. The median PSA and PSA doubling time were 0.59 ng/ml and 4.56 mo, respectively. Overall, 54 patients had metastases and 17 had PSMA-/FDG+ disease. Seven patients were excluded from the MFS analysis, including two with a history of abiraterone treatment and five with more than five metastases. The median follow-up was 21.4 mo. The ADT group had shorter MFS than the SBRT group (11.0 mo vs not reached; hazard ratio [HR] 4.69, 95% confidence interval [CI] 2.92-25.0; p < 0.001) and the N-/M- group (11.0 mo vs not reached; HR 8.78, 95% CI 4.04-40.30; p < 0.001). There was no significant difference in median MFS between the SBRT group and the N-/M- group (p = 0.261). A PSA response >90% was achieved by 86% of patients in the SBRT group. There were no grade ≥3 adverse events after SBRT. The nonrandomized design is the major study limitation. CONCLUSIONS: Dual-tracer PET/CT-guided SBRT delivered superior local control rates in comparison to ADT alone and had minimal toxicity. PATIENT SUMMARY: We investigated metastasis-targeted radiotherapy for patients with up to five prostate cancer metastases detected with two different radioisotope scans. Our results show that this approach yields promising metastasis-free survival and low toxicity.

[Study on anti-hygroscopic technology based on correlations between particle spatial properties and hygroscopicity of Chinese medicinal extracts].

This study was designed to investigate the correlations of the spatial structure properties of Chinese medicinal extracts with hygroscopicity and the anti-hygroscopic techniques. With Poria extract used as the model drug, pregelatinised starch and microcrystalline cellulose at different ratios were added into Poria fluid extract for preparing powder particles with diverse spatial structures using different drying processes. Then, their hygroscopic behaviours were characterized by equilibrium hygroscopicity(F~∞) and semi-hygroscopic time(t_(1/2)). The correlations of the hygroscopicity of each powder with the spatial structure properties such as particle size(D_(90)), porosity(ε), true density(ρ_t), and surface element distribution were analyzed using partial least-squares method. The F~∞ and t_(1/2) values of Poria extract prepared by three drying methods were sorted in a descending order as follows: F~∞(spray drying>drying at ordinary pressure>drying at reduced pressure); t_(1/2)(drying at reduced pressure>drying at ordinary pressure>spray drying). The powder obtained by spray drying showed a spherical structure with the smallest particle size and intra-particle ε but relatively stronger hygroscopicity. The large-scale surface element enrichment of the powders dried by reduced pressure effectively reduced their hygroscopicity. F~∞ and t_(1/2) were negatively correlated with ε but positively with D_(90), and the interactive influence of each spatial structural properties was not significant. There existed a correlation between the spatial structure of the powder particles of Chinese medicine extracts and their hygroscopicity, and the hygroscopicity could be improved by designing the spatial structure. This study has provided some practical basis for developing the moisture-proof technology of Chinese medicinal preparations.

Fibroglandular Tissue and Background Parenchymal Enhancement on Breast MR Imaging Correlates With Breast Cancer.

OBJECTIVES: To evaluate the association of breast cancer with both the background parenchymal enhancement intensity and volume (BPEI and BPEV, respectively) and the amount of fibroglandular tissue (FGT) using an automatic quantitative assessment method in breast magnetic resonance imaging (MRI). MATERIALS AND METHODS: Among 17,274 women who underwent breast MRI, 132 normal women (control group), 132 women with benign breast lesions (benign group), and 132 women with breast cancer (cancer group) were randomly selected and matched by age and menopausal status. The area under the receiver operating characteristic curve (AUC) was compared in Cancer vs Control and Cancer vs Benign groups to assess the discriminative ability of BPEI, BPEV and FGT. RESULTS: Compared with the control groups, the cancer group showed a significant difference in BPEV with a maximum AUC of 0.715 and 0.684 for patients in premenopausal and postmenopausal subgroup, respectively. And the cancer group showed a significant difference in BPEV with a maximum AUC of 0.622 and 0.633 for patients in premenopausal and postmenopausal subgroup, respectively, when compared with the benign group. FGT showed no significant difference when breast cancer group was compared with normal control and benign lesion group, respectively. Compared with the control groups, BPEI showed a slight difference in the cancer group. Compared with the benign group, no significant difference was seen in cancer group. CONCLUSION: Increased BPEV is correlated with a high risk of breast cancer While FGT is not.

Evaluation of Background Parenchymal Enhancement and Histogram-Based Diffusion-Weighted Image in Determining the Molecular Subtype of Breast Cancer.

RATIONALE AND OBJECTIVES: This study aimed to evaluate the value of background parenchymal enhancement (BPE) and diffusion-weighted image (DWI) histogram features in differentiating among different molecular subtypes of breast cancers and investigate the relationship between BPE and DWI features. MATERIALS AND METHODS: We prospectively enrolled 142 patients with breast cancer between January and November 2018. All patients underwent breast magnetic resonance imaging before core needle biopsy. The quantitative BPE from dynamic enhanced images and the first-order histogram features extracted from DWI were analyzed. Univariate analysis of variance was used to compare differences in DWI histogram features and BPE characteristics among different molecular subtypes. Spearman test was used to compare the correlation between these imaging indexes. RESULTS: A total of 142 patients had 142 lesions, including 17 cases of triple-negative breast cancer, 12 cases of luminal A type breast cancer, 39 cases of luminal B type breast cancer, and 74 cases of human epidermal growth factor receptor 2-positive breast cancer. The apparent diffusion coefficient (ADC) 95th percentile, ADC kurtosis, and BPE were significantly different among 4 subtype groups (P < 0.05), especially between the triple-negative subtype and any other subtype (P < 0.05 in pairwise comparisons). There was a weak but significant correlation between BPE and kurtosis of ADC (r = -0.176, P = 0.036). CONCLUSIONS: Diffusion-weighted image histogram features (95th percentile ADC value and kurtosis value of ADC) and BPE features were different in the 4 molecular subtypes of breast cancer, especially in the triple-negative breast cancer subtype. Background parenchymal enhancement was negatively correlated with the kurtosis value of ADC.

Segmentation of whole breast and fibroglandular tissue using nnU-Net in dynamic contrast enhanced MR images.

PURPOSE: Segmentation of the whole breast and fibroglandular tissue (FGT) is important for quantitatively analyzing the breast cancer risk in the dynamic contrast-enhanced magnetic resonance (DCE-MR) images. The purpose of this study is to improve the accuracy and efficiency of the segmentation of the whole breast and FGT in 3-D fat-suppressed DCE-MR images with a versatile deep learning (DL) framework. METHODS: We randomly collected 100 breast DCE-MR scans from Shanghai Cancer Hospital of Fudan University. The MR scans in the dataset were different in both the spatial resolution and the MR scanners employed. Furthermore, four breast density categories were assessed by radiologists based on Breast Imaging Reporting and Data System (BI-RADS) of American College of Radiology. The dataset was separated into the training and the testing sets, while keeping a balanced distribution of scans with different imaging parameters and density categories. The nnU-Net has been recently proposed to automatically adapt preprocessing strategies and network architectures for a given medical image dataset, thus showing a great potential in the systematic adaptation of DL methods to different datasets. In this study, we applied the nnU-Net to segment the whole breast and FGT in 3-D fat-suppressed DCE-MR images. Five-fold cross validation was employed to train and validate the segmentation method. RESULTS: The segmentation performance was evaluated with the volume and surface agreement metrics between the DL-based automatic and the manually delineated masks, as quantified with the following measures: the average Dice volume overlap (0.968 ± 0.017 and 0.877 ± 0.081), the average surface distances (0.201 ± 0.080 mm and 0.310 ± 0.043 mm), and the Pearson correlation coefficient of masks (0.995 and 0.972) between the automatic and the manually delineated masks, as calculated for the whole breast and the FGT segmentation, respectively. The correlation coefficient between the breast densities obtained with the DL-based segmentation and the manual delineation was 0.981. There was a positive bias of 0.8% (DL-based relative to manual) in breast density measurement with the Bland-Altman plot. The execution time of the DL-based segmentation was approximately 20 s for the whole breast segmentation and 15 s for the FGT segmentation. CONCLUSIONS: Our DL-based segmentation framework using nnU-Net could robustly achieve high accuracy and efficiency across variable MR imaging settings without extra pre- or post-processing procedures. It would be useful for developing DCE-MR-based CAD systems to quantify breast cancer risk and to be integrated into the clinical workflow.

Multi-omics reveals novel prognostic implication of SRC protein expression in bladder cancer and its correlation with immunotherapy response.

PURPOSE: This study aims to identify potential prognostic biomarkers of bladder cancer (BCa) based on large-scale multi-omics data and investigate the role of SRC in improving predictive outcomes for BCa patients and those receiving immune checkpoint therapies (ICTs). METHODS: Large-scale multi-comic data were enrolled from the Cancer Proteome Atlas, the Cancer Genome Atlas and gene expression omnibus based on machining-learning methods. Immune infiltration, survival and other statistical analyses were implemented using R software in cancers (n = 12,452). The predictive value of SRC was performed in 81 BCa patients receiving ICT from aa validation cohort (n = 81). RESULTS: Landscape of novel candidate prognostic protein signatures of BCa patients was identified. Differential BECLIN, EGFR, PKCALPHA, ANNEXIN1, AXL and SRC expression significantly correlated with the outcomes for BCa patients from multiply cohorts (n = 906). Notably, risk score of the integrated prognosis-related proteins (IPRPs) model exhibited high diagnostic accuracy and consistent predictive ability (AUC = 0.714). Besides, we tested the clinical relevance of baseline SRC protein and mRNA expression in two independent confirmatory cohorts (n = 566) and the prognostic value in pan-cancers. Then, we found that elevated SRC expression contributed to immunosuppressive microenvironment mediated by immune checkpoint molecules of BCa and other cancers. Next, we validated SRC expression as a potential biomarker in predicting response to ICT in 81 BCa patient from FUSCC cohort, and found that expression of SRC in the baseline tumour tissues correlated with improved survival benefits, but predicts worse ICT response. CONCLUSION: This study first performed the large-scale multi-omics analysis, distinguished the IPRPs (BECLIN, EGFR, PKCALPHA, SRC, ANNEXIN1 and AXL) and revealed novel prediction model, outperforming the currently traditional prognostic indicators for anticipating BCa progression and better clinical strategies. Additionally, this study provided insight into the importance of biomarker SRC for better prognosis, which may inversely improve predictive outcomes for patients receiving ICT and enable patient selection for future clinical treatment.

Ferrous-activated persulfate oxidation of triclosan in soil and groundwater: The roles of natural mineral and organic matter.

Contamination of antimicrobial agents such as Triclosan (TCS) in soil and groundwater possess high risk to human health and ecological systems. Present study systematically studied the degradation of TCS in soil and groundwater by Fe2+ activated persulfate (Fe2+/PS) oxidation process and special attention was paid on revealing the influence of remediation process on soil physicochemical and microbial characteristics. Experimental results demonstrated that TCS was readily degraded in soil upon Fe2+/PS oxidation system. Higher Fe2+/PS concentration and lower pH value may promote the TCS degradation. Besides added Fe2+, the naturally present Fe (III)-O and dissolved Fe from iron containing minerals may also activate PS for TCS degradation. SO4•-, HO•, R• and 1O2 were identified to be involved in the reaction system while addition of Fe2+-chelating agents, e.g., oxalic acid and ethylene diamine tetraacetic acid (EDTA) may slightly promote the degradation. Low concentration of Cl- facilitated TCS degradation and high concentration of Cl- slowed down the degradation. The presence of HCO3- may inhibit the degradation. Fe2+/PS oxidation process may partly reduce the soil organic matter content and diversely affect the composition of various C functional groups on soil. It also induced the breakdown of large soil aggregates and reduced the soil porosity, especially at macroporosity region. Phospholipid Fatty Acid test indicated that soil microbial community structure has been altered and the actinomycetes, fungi and Gram-negative bacteria decreased largely. The feasibility of remediation of TCS using Fe2+/PS oxidation in various natural groundwater samples was evaluated. Finally, five degradation intermediates of TCS by Fe2+/PS oxidation in soil were enriched by solid phase extraction and were identified by liquid chromatography-triple quadrupole mass spectrometry for proposing detailed transformation pathways.

Comparison of intravoxel incoherent motion imaging, diffusion kurtosis imaging, and conventional DWI in predicting the chemotherapeutic response of colorectal liver metastases.

PURPOSE: To assess the usefulness and performance of intravoxel incoherent motion imaging (IVIM) with diffusion kurtosis imaging (DKI) and conventional DWI for predicting the chemotherapeutic response of colorectal liver metastases (CRLMs). METHOD: A prospective study was conducted. Up to February 2018, forty consecutive patients treated with the standard first-line chemotherapy regimens were enrolled. MRI was performed within 1 week before chemotherapy, as well as 2-3 weeks and 6-8 weeks after chemotherapy. The apparent diffusion coefficient map, IVIM and DKI parameter maps were calculated using a prototype postprocessing software. The response was assessed by the Response Evaluation Criteria in Solid Tumors. The parameters were compared between the responding group (complete and partial response) and the nonresponding group (stable and progressive disease). RESULTS: A total of 15 responding and 25 nonresponding patients were evaluated. Low baseline ADC, Dslow, and D values (P = 0.001, <0.001, and =0.003, respectively) and a high baseline K value (P = 0.002) were independently associated with a good response to chemotherapy. The combination of all the significant parameters yielded an AUC of 0.867. After treatment, the ADC, Dslow, and D values all showed an upward trend, while the K value showed a decreasing trend, but there were no significant differences (P > 0.05). CONCLUSION: The study showed that the pretreatment IVIM (Dslow), DKI (D and K), and conventional DWI (ADC) parameters all demonstrated a good diagnostic performance in predicting the chemotherapeutic response of CRLMs.

Fatty Acid Synthase Correlates With Prognosis-Related Abdominal Adipose Distribution and Metabolic Disorders of Clear Cell Renal Cell Carcinoma.

Purpose: Lipid metabolism reprogramming is a major pathway in tumor evolution. This study investigated fatty acid synthase (FASN) mRNA expression in anthropometric adipose tissue and elucidated the prognostic value and potential mechanism of clear cell renal cell carcinoma (ccRCC). Materials and Methods: Transcription profiles were obtained from 533 ccRCC samples in The Cancer Genome Atlas (TCGA) cohorts. Real-time quantitative PCR (RT-qPCR) and immunohistochemistry were performed to detect FASN expression in 380 paired ccRCC and normal tissues from the Fudan University Shanghai Cancer Center (FUSCC). Visceral adipose tissue (VAT) and subcutaneous adipose tissue were at the level of the umbilicus as measured by magnetic resonance imaging (MRI). Non-targeted metabolomics and in vitro experiments were used to reveal the biological functions of FASN. Results: Increased FASN expression was significantly relevant to advanced T, N, and American Joint Committee on Cancer (AJCC) stages (p < 0.01) and significantly correlated to poor progression-free survival (PFS) and overall survival (OS) of 913 ccRCC patients in FUSCC and TCGA cohorts. Pearson's correlation coefficient indicated that FASN amplification was positively correlated to VAT% (r = 0.772, p < 0.001), which significantly correlated to poor PFS (HR = 2.066, p = 0.028) and OS (HR = 2.773, p = 0.023) in the FUSCC cohort. Transient inhibition or overexpression of FASN significantly regulated A498 and 786O cell proliferation and migration by regulating epithelial-mesenchymal transition. Inhibition of FASN led to a higher apoptotic rate and decreased lipid droplet formation compared with normal control in ccRCC cells. Non-targeted metabolomics showed that decreased de novo lipogenesis might be required to sustain an elevation of glycolytic activity in 786O cells by regulating galactinol, dl-lactate, N-acetylaspartylglutamate, and sucrose, thereby participating in carcinogenesis and progression of ccRCC. Conclusion: This study demonstrated that FASN expression is positively related to aggressive cell proliferation, migration, apoptosis, and lipid droplet formation and regulates metabolic disorders of the ccRCC microenvironment. Additionally, elevated FASN mRNA expression is significantly correlated to the abdominal obesity distribution, especially VAT%, which is a significant predictor of a poor prognosis for ccRCC patients.

Bioreducible crosslinked cationic nanopolyplexes from clickable polyethylenimines enabling robust cancer gene therapy.

Bioreducible crosslinked polyplexes from branched polyethylenimine (BPEI, 10 kDa) were successfully constructed through DNA neutralization by disulfide-linked azidated BPEI (PAZ) and subsequent DNA condensation by azadibenzocyclooctyne-modified BPEI (PDB), following their self-crosslinking via azide-azadibenzocyclooctyne click chemistry. Click-crosslinked cationic polyplexes (c-polyplexes) revealed high extracellular colloidal stability against negative heparin and ions while intracellular bioreducible degradability for efficient gene unpacking. In vitro gene transfection in cancer cells indicated that the c-polyplexes produced markedly higher transfection efficiency than non-crosslinked counterparts in the serum. The c-polyplexes also had prolonged circulation kinetics, elevated gene accumulation level in SKOV-3 tumor xenografted in a mouse model and in turn superior transgene expression in the tumor. By small hairpin RNA for VEGF silencing, the c-polyplexes exerted significant tumor growth inhibition following with low systemic toxicity in the mouse. This study highlights the design of clickable polycations to construct crosslinked cationic nanopolyplexes for intravenous gene delivery against cancer.

Bioreducible poly(urethane amine)s for robust nucleic acid transfection in stem cells.

The search for cationic polymeric carriers enabling robust gene transfection against stem cells remains a challenge. Herein, linear bioreducible poly(urethane amine)s (denoted as SSPUAs) with repeated disulfide and protonable amino groups were prepared and used as non-viral vectors for in vitro gene transfection of different stem cells. The polyurethane copolymers (denoted as SSBT) with varied molar ratios of 1,4-bis(3-aminopropyl)piperazine (BAP) and tris(2-aminoethyl) amine (TAA) moieties could lead to superb transfection activity against human adipose-derived stem cells (hADSCs) and human bone marrow stem cells (hBMSCs). Data indicated that under optimal transfection conditions, SSBT10 with a BAP/TAA molar ratio of 90/10 caused the transfection of ∼60% of green fluorescence protein-positive (GFP+) hADSCs, and SSBT30 with the ratio of 70/30 resulted in the transfection of ∼40% of GFP+ hBMSCs. Also, the SSBT30 and polyurethane with BAP residues (denoted as SSBAP) could mediate efficient gene transfer into bone marrow stem cells of experimental animals such as SD rats, beagle dogs and rhesus monkeys, with ∼40-70% of GFP+ cells. Additionally, the SSBAP elicited robust transfection ability (∼60% of GFP+ cells) against E14 mouse embryonic stem cells without compromising the expression of multipotent stemness-related markers of the cells. Importantly, the transfection efficiencies of these SSPUAs were higher as compared to those yielded by 25 kDa branched polyethylenimine and Lipofectamine 2000 reagents as positive controls. The SSBT30 was further practical to deliver siRNAs into hADSCs for BCL2L2 or TRIB2 gene silencing, causing superior gene silencing efficacy to Lipofectamine 2000. Besides their high gene transfection or silencing efficacy, these SSPUAs revealed low cytotoxicity against stem cells. This study highlights the SSPUA system as a distinct platform for robust nucleic acid delivery into stem cells.

Distribution by influence factors of pyrene removal in chemical enhancers assisted microbial phytoremediation of Scirpus triqueter in co-contaminated soils.

The rehabilitation of soil co-contaminated by heavy metals and polycyclic aromatic hydrocarbons (PAHs) has become a serious global issue. Chemical enhancers and strains are often used to remove PAHs from contaminated soil. In this paper, the effects of chemical enhancers, strain HD-1, and Scirpus triqueter in removing pyrene from co-contaminated soil are studied. In the pot experiment, chemical enhancers and HD-1 were added to the co-contaminated soil. On the 60th day, the plants and soil were taken out for measurement. The result showed that the addition of chemical enhancers and microorganisms (Group PBC) alleviated the inhibition effect of plants on pollution. The accumulation of pyrene in plants of Group PC (chemical enhancers) and Group PBC (chemical enhancers and HD-1) were much higher than those in other groups. Plant enrichment was not the major way to remove pyrene from soil (less than 0.3%). Compared with the contributions of chemical enhancers, HD-1, and Scirpus triqueter, HD-1 had stronger effects on the removal of pyrene (17.23-22.80%). This study indicates that the combination of chemical enhancers, HD-1, and Scirpus triqueter constituted a beneficial composite system, in which the three elements interacted with each other and ultimately achieved the goal of removing pyrene from co-contaminated soil.