DKI can distinguish high-grade gliomas from IDH1-mutant low-grade gliomas and correlate with their different nuclear-to-cytoplasm ratio: a localized biopsy-based study.

OBJECTIVES: To explore whether differences in diffusional kurtosis imaging (DKI) between therapy-naïve high-grade gliomas (HGGs) and low-grade gliomas (LGGs) are related to the cellularity and/or the nuclear-to-cytoplasmic (N/C) ratio. METHODS: We analyzed 44 and 40 diffuse glioma samples that were pathologically confirmed as HGGs and IDH1-mutant LGGs, respectively. The DKI parameters included kurtosis metrics (mean kurtosis [MK], axial kurtosis [K//], and radial kurtosis [K⊥]), and the diffusional metrics (fractional anisotropy [FA], mean diffusion [MD], axial diffusion [λ//], and radial diffusion [λ⊥]). The cellularity and the N/C ratio were compared within LGGs and HGGs using the Mann-Whitney U test (significant level, p < 0.007 [0.05/7]); Bonferroni correction). Spearman's correlation analysis was used to calculate the correlation coefficients among DKI metrics, cellularity, and the N/C ratio at a significant level of p = 0.05. RESULTS: Excluding FA, all DKI metrics showed significant differences between HGGs and LGGs (all p ≤ 0.001). The N/C ratio of HGGs was significantly higher than that of LGGs; however, differences in cellularity were not significant between the two glioma groups (p = 0.525). Similarly, excluding FA, all DKI metrics were significantly correlated with the N/C ratio in LGGs, with correlation coefficients of - 0.365 (MD), - 0.313 (λ//), - 0.376 (λ⊥), 0.859 (MK), 0.772 (K//), and 0.842 (K//). There was a non-significant correlation between any DKI parameters and the cellularity in LGGs. Additionally, the cellularity and N/C ratios in HGGs did not correlate with any DKI metrics. CONCLUSIONS: DKI differentiate LGGs from HGGs associated with their different N/C ratios. CLINICAL RELEVANCE STATEMENT: This study shows that DKI differentiates LGGs from HGGs may correlated with their different N/C ratios, this could provide a possible histopathological mechanism about why DKI can DKI differentiate LGGs from HGGs. KEY POINTS: • Excluding FA, all DKI metrics showed a significant difference between high-grade gliomas and IDH1-mutant low-grade gliomas. • The nuclear-to-cytoplasm ratios in high-grade gliomas were significantly more extensive than that in IDH1-mutant low-grade gliomas, but not the cellularity. • Significant associations were seen between DKI measures and the N/C ratio; a non-significant correlation was noted between any DKI metric and cellularity in glioma specimens.

Multi-b-value diffusion stretched-exponential model parameters correlate with MIB-1 and CD34 expression in Glioma patients, an intraoperative MR-navigated, biopsy-based histopathologic study.

Background: To understand the pathological correlations of multi-b-value diffusion-weighted imaging (MDWI) stretched-exponential model (SEM) parameters of α and diffusion distribution index (DDC) in patients with glioma. SEM parameters, as promising biomarkers, played an important role in histologically grading gliomas. Methods: Biopsy specimens were grouped as high-grade glioma (HGG) or low-grade glioma (LGG). MDWI-SEM parametric mapping of DDC1500, α1500 fitted by 15 b-values (0-1,500 sec/mm2)and DDC5000 and α5000 fitted by 22 b-values (0-5,000 sec/mm2) were matched with pathological samples (stained by MIB-1 and CD34) by coregistered localized biopsies, and all SEM parameters were correlated with these pathological indices pMIB-1(percentage of MIB-1 expression positive rate) and CD34-MVD (CD34 expression positive microvascular density for each specimen). The two-tailed Spearman's correlation was calculated for pathological indexes and SEM parameters, as well as WHO grades and SEM parameters. Results: MDWI-derived α1500 negatively correlated with CD34-MVD in both LGG (6 specimens) and HGG (26 specimens) (r=-0.437, P =0.012). MDWI-derived DDC1500 and DDC5000 negatively correlated with MIB-1 expression in all glioma patients (P<0.05). WHO grades negatively correlated with α1500(r=-0.485; P=0.005) and α5000(r=-0.395; P=0.025). Conclusions: SEM-derived DDC and α are significant in histologically grading gliomas, DDC may indicate the proliferative ability, and CD34 stained microvascular perfusion may be an important determinant of water diffusion inhomogeneity α in glioma.

Correlations between intravoxel incoherent motion-derived fast diffusion and perfusion fraction parameters and VEGF- and MIB-1-positive rates in brain gliomas: an intraoperative MR-navigated, biopsy-based histopathologic study.

OBJECTIVES: To explore the correlations between histopathologic findings and intravoxel incoherent motion (IVIM)-derived perfusion and diffusion parameters in brain gliomas. METHODS: Thirty-two biopsy samples from twenty-one patients with newly diagnosed gliomas from a previous prospective cohort study were retrospectively analyzed. All patients underwent diffusion-weighted MRI with 22 b values (0-5000 s/mm2), followed by intraoperative MR-guided biopsy surgery and surgical resection. All 32 biopsy samples underwent immunohistochemical staining followed by quantitative analysis of cell density (cellularity), percent of MIB-1 (Ki67)-positive expression (pMIB-1), number of CD34-stained vessels (CD34-MVD), and percent of VEGF-positive expressing cells (pVEGF) using a multispectral phenotyping microscope. Based on the co-registered localized biopsy, correlation analysis was performed between the IVIM-derived biexponential model-based parameters (Dfast1500 and Dfast5000, Dslow1500 and Dslow5000, PF1500 and PF5000) and the above four pathological biomarkers and glioma grades. RESULTS: Significant positive correlations were revealed between Dfast5000 and pVEGF (rho (r) = 0.466, p = 0.007), and Dfast1500 and pVEGF (r = 0.371, p = 0.037). A significant negative correlation was revealed between PF5000 with pMIB-1 (r = - 0.456, p = 0.01). Moderate to good positive correlations were shown between Dfast5000 and glioma grades (r = 0.509, p = 0.003) and Dfast1500 and glioma grades (r = 0.476, p = 0.006). CONCLUSIONS: IVIM-DWI-derived Dfast and PF correlate, respectively, with intratumor pVEGF and pMIB-1. When using the wide-high b value scheme, IVIM-derived Dfast and PF tend to demonstrate better efficacy in evaluating malignancy-related characteristics such as angiogenesis and cellular proliferation in gliomas. KEY POINTS: • Intravoxel incoherent motion-diffusion-weighted imaging (IVIM-DWI)-derived fast diffusion (Dfast) and perfusion fraction (PF) can quantitatively reflect intratumor pVEGF and pMIB-1. • IVIM-DWI-derived Dfast and PF tend to demonstrate better efficacy in evaluating glioma malignancy when an optimized scheme is used. • IVIM-DWI-derived Dfast5000 and PF5000 are promising non-invasive parameters correlating with pVEGF and pMIB-1 in gliomas.

Expression of Tspan29 in breast cancer tissues and its effect on malignant biological behaviors of MCF-7 and MDA-MB-231 cells / 中国肿瘤生物治疗杂志

@#Objective: To investigate the expression of tetraspanins-29 (Tspan29) in breast cancer tissues and cell lines and to explore the effect of Tspan29 knockdown on proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of breast cancer MCF-7 and MDA-MB-231 cells. Methods:Atotal of20pairsofbreast cancer tissues and corresponding para-cancerous tissues resected in Minhang Branch of Cancer HospitalAffiliated to Fudan University from June 2017 to February 2018 were collected for this study; in addition, breast cancer celllinesMCF-7,MDA-MB-231andhumanbreastepithelialMDA-kb2cellswerealsocollected.ThemRNAand protein expressions of Tspan29 in above mentioned tissues and cell lines were detected by Real-time quantitative (qPCR) and Western blotting. The expression of Tspan29 in MCF-7 and MDA-MB-231 cells was interfered by siRNA. qPCR was used to detect the mRNA and protein expressions of Tspan29. PCR microarray was used to examine the expressions of EMT-related genes in MCF-7 cells. CCK-8 assayandTranswellwereusedtodetectcellproliferation, migration and invasion of MCF-7 and MDA-MB-231 cells. Results: The mRNA and protein expressions of Tspan29 in breast cancer tissues were significantly higher than that in para-cancerous tissues (all P<0.01); and the mRNA and protein expressions of Tspan29 in MCF-7 and MDA-MB-231 cells were significantly higher than that in MDA-kb2 cells (P<0.01). After being interfered with siTspan29, the mRNA and protein expressions of Tspan29 were significantly down-regulated in MCF-7 cells (all P<0.05); the proliferation, invasion and migration of MCF-7 and MDA-MB-231 cells were significantly inhibited (all P<0.05); and among the EMT-related genes, two were significantly up-regulated while 7 were down-regulated. Conclusion: Tspan29 is significantly up-regulated in breast cancer tissues and cell lines, and knockdown of Tspan29 significantly inhibits the proliferation, invasion and migration of breast cancer cells. ··

3D-ASL perfusion correlates with VEGF expression and overall survival in glioma patients: Comparison of quantitative perfusion and pathology on accurate spatial location-matched basis.

BACKGROUND: There is a need for an imaging-based tool for measuring vascular endothelial growth factor (VEGF) expression and overall survival (OS) in patients with glioma. PURPOSE: To assess the correlation between cerebral blood flow (CBF), measured by 3D pseudo-continuous arterial spin-labeling (3D-ASL), and VEGF expression in gliomas on the basis of coregistered localized biopsy, and investigate whether CBF correlated with survival month (SM) in glioma patients. STUDY TYPE: Prospective cohort. SUBJECTS: Thirty-seven patients with gliomas from whom 63 biopsy specimens were obtained. SEQUENCE: 3D-ASL acquired with a 3.0T MR unit. ASSESSMENT: Biopsy specimens were grouped as high-grade (HGG) or low-grade glioma (LGG). CBF measurements were spatially matched with VEGF expression by coregistered localized biopsies, and the CBF value was correlated with quantitative VEGF expression for each specimen. Patients' survival information was derived and connected with CBF. STATISTICAL TESTS: Patients' OS was analyzed by Kaplan-Meier and Cox-regression methods. VEGF expression and CBF were compared in both LGG and HGG. The Spearman rank correlation was calculated for CBF and VEGF expression, SM. Significance level, P < 0.05. RESULTS: CBF-derived 3D-ASL positively correlated significantly with VEGF expression in both LGG (31 specimens) and HGG (32 specimens), r = 0.604 (P < 0.001) and r = 0.665 (P < 0.001), respectively. LGG and HGG together gave a correlation coefficient r = 0.728 (P < 0.001). Median survival for LGG and HGG patients was 34.19 and 17.17 months, respectively (P = 0.037); CBF value negatively correlated significantly with SM with r = -0.714 (P < 0.001) regardless of glioma grade. CBF was an independent risk factor for OS with HR = 1.027 (P = 0.044), 1.028 (P = 0.010) for univariate/multivariate regression analysis. DATA CONCLUSION: CBF determined by 3D-ASL correlates with VEGF expression in glioma and is an independent risk factor for OS in these patients. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;50:209-220.

I-7ab inhibited the growth of TNBC cells via targeting HDAC3 and promoting the acetylation of p53.

Triple negative breast cancer (TNBC) is a heterogenous disease with high aggressive and poor outcome. The lack of biomarkers and targeted therapies makes it a challenge for the treatment of TNBC. Histone deacetylase inhibitors (HDACis) are emerging as novel anti-tumor agents in many types of human cancers. In this study, we found that I-7ab, a novel HDACi, inhibited the cell viability of TNBC cells and induced the cell apoptosis. Mechanistically, I-7ab specifically decreased the expression of HDAC3 and promoted the acetylation of p53 at both Lys373 and Lys382 amino acids. The up-regulated acetylation of p53 promoted the transcriptional activity of p53 and induced the expression of p21, which consequently caused cell cycle arrest at G1 phase. Administration of I-7ab inhibited the colony formation of TNBC cells. Collectively, these results indicated I-7ab as a promising anti-cancer agent in the treatment of TNBC.

Diffusional kurtosis imaging for differentiating between high-grade glioma and primary central nervous system lymphoma.

BACKGROUND: The aim of this study was to assess the diagnostic accuracy of diffusion kurtosis magnetic resonance imaging parameters for differentiating high-grade gliomas (HGGs) from primary central nervous system lymphomas (PCNSLs). METHODS: Diffusion parameters, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ// ), radial diffusivity (λ⊥ ); and kurtosis parameters, including mean kurtosis (MK), axial kurtosis (K// ), and radial kurtosis (K⊥ ), were normalized to contralateral normal-appearing white matter (NAWMc) to decrease inter-individual and inter-regional changes across the entire brain, and then compared with the solid parts of 20 HGGs and 11 PCNSLs [median 95% confidence interval (CI), P < 0.004; 0.05/14], significance level, Kolmogorov-Smirnov test, Bonferroni correction]. RESULTS: FA, MD, λ// , and λ⊥ values were higher in HGGs than in PCNSLs, but not significantly [HGGs: 0.209 (95% CI, 0.134-0.338), 1.385 (95% CI, 1.05-1.710), 1.655 (95% CI, 1.30-2.060), 1.228 (95% CI, 0.932-1.480), respectively; PCNSLs: 0.143 (95% CI, 0.110-0.317), 1.070 (95% CI, 0.842-1.470), 1.260 (95% CI, 0.960-1.930), 1.010 (95% CI, 0.782-1.240)], respectively; P = 0.120, 0.010, 0.004, and 0.004, respectively). However, MK and K// were significantly higher in PCNSLs compared with HGGs [PCNSLs: 0.765 (95% CI, 0.697-0.890), 0.787 (95% CI, 0.615-1.030), respectively; HGGs: 0.531 (95% CI, 0.402-0.766), 0.532 (95% CI, 0.432-0.680], respectively; P = 0.001, 0.000, respectively); but not K⊥ [0.774 (95% CI, 0.681-0.899) for PCNSLs; 0.554 (95% CI, 0.389-0.954) for HGGs; P = 0.024]. CONCLUSION: There were significant differences in kurtosis parameters (MK and K// ) between HGGs and PCNSLs, while differences in diffusion parameters between them did not reach significance; hence, better separation was achieved with these parameters than with conventional diffusion imaging parameters. J. Magn. Reson. Imaging 2016;44:30-40.

Bilateral spontaneous urinary extravasation shown by computed tomography urography in a patient with benign prostatic hyperplasia.

Spontaneous extravasation of urine (SUE) is a rare urologic manifestation. Predisposing conditions of SUE include ureteric calculus, retrograde pyelography, pregnancy, abdominal aorta aneurysm, tumors, or enlargement of the prostate gland. Usually, SUE is a self-limiting condition that mandates differentiaton from other catastrophic conditions of pelviureteric ruptures. Most reported cases of SUE based on urograms are unilateral in presentation. Herein, we report a case of bilateral SUE evident on computed tomography urography in a patient with benign prostatic hyperplasia. We also review the literature briefly.