Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

ANXA1 Promotes Tumor Immune Evasion by Binding PARP1 and Upregulating Stat3-Induced Expression of PD-L1 in Multiple Cancers.

The deregulation of Annexin A1 (ANXA1), a regulator of inflammation and immunity, leads to cancer growth and metastasis. However, whether ANXA1 is involved in cancer immunosuppression is still unclear. Here, we report that ANXA1 knockdown (i) dramatically downregulates programmed cell death-ligand 1 (PD-L1) expression in breast cancer, lung cancer, and melanoma cells; (ii) promotes T cell-mediated killing of cancer cells in vitro; and (iii) inhibits cancer immune escape in immune-competent mice via downregulating PD-L1 expression and increasing the number and killing activity of CD8+ T cells. Mechanistically, ANXA1 functioned as a sponge molecule for interaction of PARP1 and Stat3. Specifically, binding of ANXA1 to PARP1 decreased PARP1's binding to Stat3, which reduced poly(ADP-ribosyl)ation and dephosphorylation of Stat3 and thus, increased Stat3's transcriptional activity, leading to transcriptionally upregulated expression of PD-L1 in multiple cancer cells. In clinical samples, expression of ANXA1 and PD-L1 was significantly higher in breast cancer, non-small cell lung cancer, and skin cutaneous melanoma compared with corresponding normal tissues and positively correlated in cancer tissues. Moreover, using both ANXA1 and PD-L1 proteins for predicting efficacy of anti-PD-1 immunotherapy and patient prognosis was superior to using individual proteins. Our data suggest that ANXA1 promotes cancer immune escape via binding PARP1 and upregulating Stat3-induced expression of PD-L1, that ANXA1 is a potential new target for cancer immunotherapy, and combination of ANXA1 and PD-L1 expression is a potential marker for predicting efficacy of anti-PD-1 immunotherapy in multiple cancers.

Combined texture analysis of dynamic contrast-enhanced MRI with histogram analysis of diffusion kurtosis imaging for predicting IDH mutational status in gliomas.

BACKGROUND: Non-invasive detection of isocitrate dehydrogenase (IDH) mutational status in gliomas is clinically meaningful for molecular stratification of glioma; however, it remains challenging. PURPOSE: To investigate the usefulness of texture analysis (TA) of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and histogram analysis of diffusion kurtosis imaging (DKI) maps for evaluating IDH mutational status in gliomas. MATERIAL AND METHODS: This retrospective study enrolled 84 patients with histologically confirmed gliomas, comprising IDH-mutant (n = 34) and IDH-wildtype (n = 50). TA was performed for the quantitative parameters derived by DCE-MRI. Histogram analysis was performed for the quantitative parameters derived by DKI. Unpaired Student's t-test was used to identify IDH-mutant and IDH-wildtype gliomas. Logistic regression and receiver operating characteristic (ROC) curve analyses were used to compare the diagnostic performance of each parameter and their combination for predicting the IDH mutational status in gliomas. RESULTS: Significant statistical differences in the TA of DCE-MRI and histogram analysis of DKI were observed between IDH-mutant and IDH-wildtype gliomas (all P < 0.05). Using multivariable logistic regression, the entropy of Ktrans, skewness of Ve, and Kapp-90th had higher prediction potential for IDH mutations with areas under the ROC curve (AUC) of 0.915, 0.735, and 0.830, respectively. A combination of these analyses for the identification of IDH mutation improved the AUC to 0.978, with a sensitivity and specificity of 94.1% and 96.0%, respectively, which was higher than the single analysis (P < 0.05). CONCLUSION: Integrating the TA of DCE-MRI and histogram analysis of DKI may help to predict the IDH mutational status.

Diffusion-relaxation correlation spectrum imaging for predicting tumor consistency and gross total resection in patients with pituitary adenomas: a preliminary study.

OBJECTIVE: To evaluate the ability of diffusion-relaxation correlation spectrum imaging (DR-CSI) to predict the consistency and extent of resection (EOR) of pituitary adenomas (PAs). METHODS: Forty-four patients with PAs were prospectively enrolled. Tumor consistency was evaluated at surgery as either soft or hard, followed by histological assessment. In vivo DR-CSI was performed and spectra were segmented following to a peak-based strategy into four compartments, designated A (low ADC), B (mediate ADC, short T2), C (mediate ADC, long T2), and D (high ADC). The corresponding volume fractions ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]) along with the ADC and T2 values were calculated and assessed using univariable analysis for discrimination between hard and soft PAs. Predictors of EOR > 95% were analyzed using logistic regression model and receiver-operating-characteristic analysis. RESULTS: Tumor consistency was classified as soft (n = 28) or hard (n = 16). Hard PAs presented higher [Formula: see text] (p = 0.001) and lower [Formula: see text] (p = 0.013) than soft PAs, while no significant difference was found in other parameters. [Formula: see text] significantly correlated with the level of collagen content (r = 0.448, p = 0.002). Knosp grade (odds ratio [OR], 0.299; 95% confidence interval [CI], 0.124-0.716; p = 0.007) and [Formula: see text] (OR, 0.834, per 1% increase; 95% CI, 0.731-0.951; p = 0.007) were independently associated with EOR > 95%. A prediction model based on these variables yielded an AUC of 0.934 (sensitivity, 90.9%; specificity, 90.9%), outperforming the Knosp grade alone (AUC, 0.785; p < 0.05). CONCLUSION: DR-CSI may serve as a promising tool to predict the consistency and EOR of PAs. CLINICAL RELEVANCE STATEMENT: DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs and may serve as a promising tool to predict the tumor consistency and extent of resection in patients with PAs. KEY POINTS: • DR-CSI provides an imaging dimension for characterizing tissue microstructure of PAs by visualizing the volume fraction and corresponding spatial distribution of four compartments ([Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text]). • [Formula: see text] correlated with the level of collagen content and may be the best DR-CSI parameter for discrimination between hard and soft PAs. • The combination of Knosp grade and [Formula: see text] achieved an AUC of 0.934 for predicting the total or near-total resection, outperforming the Knosp grade alone (AUC, 0.785).

ANXA1-derived peptide for targeting PD-L1 degradation inhibits tumor immune evasion in multiple cancers.

BACKGROUND: Immune checkpoint inhibitors (ICIs) therapy targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) shows promising clinical benefits. However, the relatively low response rate highlights the need to develop an alternative strategy to target PD-1/PD-L1 immune checkpoint. Our study focuses on the role and mechanism of annexin A1 (ANXA1)-derived peptide A11 degrading PD-L1 and the effect of A11 on tumor immune evasion in multiple cancers. METHODS: Binding of A11 to PD-L1 was identified by biotin pull-down coupled with mass spectrometry analysis. USP7 as PD-L1's deubiquitinase was found by screening a human deubiquitinase cDNA library. The role and mechanism of A11 competing with USP7 to degrade PD-L1 were analyzed. The capability to enhance the T cell-mediated tumor cell killing activity and antitumor effect of A11 via suppressing tumor immune evasion were investigated. The synergistic antitumor effect of A11 and PD-L1 mAb (monoclonal antibody) via suppressing tumor immune evasion were also studied in mice. The expression and clinical significance of USP7 and PD-L1 in cancer tissues were evaluated by immunohistochemistry. RESULTS: A11 decreases PD-L1 protein stability and levels by ubiquitin proteasome pathway in breast cancer, lung cancer and melanoma cells. Mechanistically, A11 competes with PD-L1's deubiquitinase USP7 for binding PD-L1, and then degrades PD-L1 by inhibiting USP7-mediated PD-L1 deubiquitination. Functionally, A11 promotes T cell ability of killing cancer cells in vitro, inhibits tumor immune evasion in mice via increasing the population and activation of CD8+ T cells in tumor microenvironment, and A11 and PD-1 mAb possess synergistic antitumor effect in mice. Moreover, expression levels of both USP7 and PD-L1 are significantly higher in breast cancer, non-small cell lung cancer and skin melanoma tissues than those in their corresponding normal tissues and are positively correlated in cancer tissues, and both proteins for predicting efficacy of PD-1 mAb immunotherapy and patient prognosis are superior to individual protein. CONCLUSION: Our results reveal that A11 competes with USP7 to bind and degrade PD-L1 in cancer cells, A11 exhibits obvious antitumor effects and synergistic antitumor activity with PD-1 mAb via inhibiting tumor immune evasion and A11 can serve as an alternative strategy for ICIs therapy in multiple cancers.

CT perfusion with increased temporal sampling interval to predict target mismatch status in patients with acute ischemic stroke.

PURPOSE: To evaluate the feasibility of using CT perfusion (CTP) with increased temporal sampling interval to predict the target mismatch status in acute ischemic stroke (AIS) patients with anterior circular large-vessel occlusion (LVO). METHODS: CTP with a sampling interval of 1.7 s (CTP1.7 s) was scanned in 77 AIS patients for pre-treatment evaluation. Simulated CTP data with sampling interval of 3.4 s (CTP3.4 s) or 5.1 s (CTP5.1 s) were reconstructed, respectively. Target mismatch was defined according to the EXTEND-IA (Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial) and DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trial criteria, respectively. Pearson correlation analysis, Mann-Whitney U test, Bland-Altman analysis, and chi-square test were used for statistical analysis as appropriate. RESULTS: Significant correlations were found on the volume of ischemic core, hypo-perfused area, mismatch area, and ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p < 0.001). There was no significant difference on the volume of ischemic core, hypo-perfused area, mismatch area, and mismatch ratio between CTP1.7 s and CTP3.4 s or CTP5.1 s (all p > 0.05). Compared with CTP1.7 s, CTP3.4 s or CTP5.1 s showed comparable performance in predicting the target mismatch status in the AIS patients with LVO (both p > 0.05). CONCLUSIONS: CTPs with increased temporal sampling intervals that lead to reduced radiation doses are feasible and may provide comparable performance in predicting target mismatch status in AIS patients with LVO.

Temporal changes in plaque characteristics after treatment and their relationship with stroke recurrence: a quantitative study using magnetic resonance imaging.

Background: Intracranial atherosclerotic disease (ICAD) is the major cause of ischemic stroke. Despite aggressive medical therapy, around 15% of patients with ICAD experience recurrence. The aim of the present study was to evaluate the temporal changes in intracranial arteriosclerotic plaques after medical treatment based on vessel wall magnetic resonance imaging (VWMRI) and to explore their relationship with stroke recurrence. Methods: A total of 67 symptomatic patients with ICAD who underwent initial and follow-up VWMRI were recruited into this retrospective cohort study. Stroke recurrence was defined as an ipsilateral stroke symptom after the initial attack. The clinical characteristics and plaque features, including stenosis ratio (measured based on luminal diameter or area), plaque thickness, plaque burden (PB), enhancement ratio (ER), and enhancement grade, were evaluated and compared between the initial and follow-up examinations. Changes in plaque characteristics were compared between patients with or without recurrence by univariable analyses. Multivariable regression was performed to investigate imaging markers for recurrent stroke. Results: The median interval between baseline and follow-up VWMRI was 334 days. A total of 13 cases (19.4%) experienced a stroke recurrence. After treatment, significant decreases in the stenosis ratio (area), PB, and ER were observed in cases without recurrence (all P<0.05), while no significant difference in plaque features was found for cases with recurrence. Univariable analyses showed that changes in stenosis ratio (area), plaque thickness, PB, and ER were significantly different between patients with and without recurrence (all P<0.05). Multivariable regression indicated that PB change was the only significant marker associated with stroke recurrence [odds ratio (OR) =1.112 per 1% increase, 95% confidence interval (CI): 1.010 to 1.224, P=0.031]. Conclusions: Patients with arteriosclerotic plaques who benefit from medical treatment show obvious decreases in stenosis (area), PB, and ER. The progression of PB may serve as an independent marker for predicting stroke recurrence.

A New Prognostic Model Covering All Stages of Intrahepatic Cholangiocarcinoma.

Background and Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy that causes a poor survival. We aimed to identify its prognostic factors and to develop a nomogram that will predict survival of ICC patients among all stages. Methods: A total of 442 patients with pathology-proven ICC registered at the Fifth Medical Center of PLA General Hospital between July 2007 and December 2019 were enrolled. Subjects were followed for survival status until June 30, 2020. A prognostic model visualized as a nomogram was constructed in the training cohort using multivariate cox model, and was then validated in the validation cohort. Results: The median age was 55 years. With a median follow-up of 50.4 months, 337 patients died. The median survival was 11.6 months, with 1-, 3- and 5-year survival rates of 48.3%, 22.7% and 16.2%, respectively. Factors associated with overall survival were multiple tumors, lymph node involvement, vascular invasion, distant metastasis, decreased albumin, elevated lactate dehydrogenase (LDH), decreased iron, elevated fibrinogen, elevated CA125 and elevated CA19-9. A nomogram predicting survival of ICC patients at the time of diagnosis achieved a Harrel's c-statistic of 0.758, significantly higher than the 0.582 of the TNM stage alone. Predicted median survivals of those within the low, mid and high-risk subgroups were 35.6, 12.1 and 6.2 months, respectively. Conclusions: A nomogram based on imaging data and serum biomarkers at diagnosis showed good ability to predict survival in patients with all stages of ICC. Further studies are needed to validate the prognostic capability of our new model.

Incremental value of Alberta Stroke Program Early CT Score to collateral score for predicting target mismatch in stroke patients with extended time window or unknown onset time.

PURPOSE: To evaluate whether Alberta Stroke Program Early CT Score (ASPECTS) could provide incremental value to collateral score, and their integration could be an effective surrogate of CTP in predicting target mismatch. MATERIAL AND METHODS: One hundred and fifty-nine stroke patients (onset time 6-16 h or with unknown onset time) with MCA and/or ICA occlusion underwent non-contrast computed tomography (NCCT) and CT perfusion (CTP) scan for initial assessment. Simulated single-phase CT angiography (sCTA, peak arterial phase) and multiphase CTA (mCTA) were reconstructed from CTP. ASPECTS was assessed on NCCT and sCTA. Collateral score was evaluated on mCTA. Target mismatch was defined as infarct core volume < 70 mL, the mismatch ratio ≥ 1.8, and the absolute mismatch volume ≥ 15 mL. Pearson correlation analysis, Mann-Whitney U test, chi-square test, and receiver operating characteristic curve analyses were performed. RESULTS: Median CTA source image (CTA-SI) ASPECTS was significantly lower than NCCT ASPECTS (p = 0.001). NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score correlated significantly with infarct core volume and mismatch ratio (all p < 0.05). Mismatch group showed significantly higher NCCT ASPECTS, CTA-SI ASPECTS, and mCTA collateral score than non-mismatch group (all p < 0.001). NCCT ASPECTS and CTA-SI ASPECTS showed comparable predicting performance with mCTA collateral score (p > 0.05). Adding CTA-SI ASPECTS to mCTA collateral score improved the performance of mCTA in predicting target mismatch (area under curve, 0.905 vs. 0.804, p = 0.003). CONCLUSION: ASPECTS can provide incremental information to collateral score in predicting target mismatch. If CTP scan fails, clinical decision based on ASPECTS and collateral score might be reasonable.

ANXA1­derived peptides suppress gastric and colon cancer cell growth by targeting EphA2 degradation.

EphA2 (EPH receptor A2) (erythropoietin­producing hepatocellular receptor tyrosine kinase subtype A2) plays a crucial role in human cancers, and is a promising target for the development of new anticancer drugs. In this study, we showed that the interaction of Annexin A1 (ANXA1) and EphA2 increased EphA2 stability by inhibiting its proteasome degradation in gastric cancer (GC) and colon cancer (CC) cells, and the amino acid residues 20­30 and 28­30 of ANXA1 N terminal were responsible for binding and stabilizing EphA2. Based on the amino acid residues of ANXA1 responsible for binding EphA2, we developed ANXA1­derived 3 amino acid­long (SKG) and 11 amino acid­long peptides (EYVQTVKSSKG) in fusion to cell­penetrating peptide, named as A1(28­30) and A1(20­30) respectively, and found that A1(28­30) and A1(20­30) blocked the binding of ANXA1 with EphA2, targeted EphA2 degradation, and suppressed the growth of GC and CC cells in vitro and in mice. Our data demonstrated that ANXA1 was able to bind and stabilize EphA2 in GC and CC cells, and disruption of ANXA1­EphA2 interaction by the two ANXA1­derived peptides inhibited the growth of GC and CC cells by targeting EphA2 degradation, presenting a potential strategy for treating GC and CC with these peptides.

Y772 phosphorylation of EphA2 is responsible for EphA2-dependent NPC nasopharyngeal carcinoma growth by Shp2/Erk-1/2 signaling pathway.

EphA2 is an important oncogenic protein and emerging drug target, but the oncogenic role and mechanism of ligand-independent phosphorylation of EphA2 at tyrosine 772 (pY772-EphA2) is unclear. In this study, we established nasopharyngeal carcinoma (NPC) cell lines with stable expression of exogenous EphA2 and EphA2-Y772A (phosphorylation inactivation) using endogenous EphA2-knockdown cells, and observed that pY772A EphA2 was responsible for EphA2-promoting NPC cell proliferation and anchorage-independent and in vivo growth in mice. Mechanistically, EphA2-Y772A mediated EphA2-activating Shp2/Erk-1/2 signaling pathway in the NPC cells, and Gab1 (Grb2-associated binder 1) and Grb2 (growth factor receptor-bound protein 2) were involved in pY772-EphA2 activating this signaling pathway. Our results further showed that Shp2/Erk-1/2 signaling mediated pY772-EphA2-promoting NPC cell proliferation and anchorage-independent growth. Moreover, we observed that EphA2 tyrosine kinase inhibitor ALW-II-41-27 inhibited pY772-EphA2 and EphA2-Y772A decreased the inhibitory effect of ALW-II-41-27 on NPC cell proliferation. Collectively, our results demonstrate that pY772-EphA2 is responsible for EphA2-dependent NPC cell growth in vitro and in vivo by activating Shp2/Erk-1/2 signaling pathway, and is a pharmacologic target of ALW-II-41-27, suggesting that pY772-EphA2 can serve as a therapeutic target in NPC and perhaps in other cancers.

ANXA1 Binds and Stabilizes EphA2 to Promote Nasopharyngeal Carcinoma Growth and Metastasis.

Overexpression of ANXA1 and EphA2 has been linked to various cancers and both proteins have attracted considerable attention for the development of new anticancer drugs. Here we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination and degradation in nasopharyngeal carcinoma (NPC). Binding of ANXA1 to EphA2 promoted NPC cell growth and metastasis in vitro and in vivo by elevating EphA2 levels and increasing activity of EphA2 oncogenic signaling (pS897-EphA2). Expression of ANXA1 and EphA2 was positively correlated and both were significantly higher in NPC tissues than in the normal nasopharyngeal epithelial tissues. Patients with high expression of both proteins presented poorer disease-free survival and overall survival relative to patients with high expression of one protein alone. Furthermore, amino acid residues 20-30aa and 28-30aa of the ANXA1 N-terminus bound EphA2. An 11 amino acid-long ANXA1-derived peptide (EYVQTVKSSKG) was developed on the basis of this N-terminal region, which disrupted the connection of ANXA1 with EphA2, successfully downregulating EphA2 expression and dramatically suppressing NPC cell oncogenicity in vitro and in mice. These findings suggest that ANXA1 promotes NPC growth and metastasis via binding and stabilization of EphA2 and present a strategy for targeting EphA2 degradation and treating NPC with a peptide. This therapeutic strategy may also be extended to other cancers with high expression of both proteins. SIGNIFICANCE: These findings show that EphA2 is a potential target for NPC therapeutics and an ANXA1-derived peptide suppresses NPC growth and metastasis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/20/4386/F1.large.jpg.

HDAC7 promotes the oncogenicity of nasopharyngeal carcinoma cells by miR-4465-EphA2 signaling axis.

HDAC7 plays a crucial role in cancers, and is the main drug target of several HDAC inhibitors. However, the role and mechanism of HDAC7 in nasopharyngeal carcinoma (NPC) are still unclear. In this study, we observed that HDAC7 was significantly upregulated in the NPC tissues relative to normal nasopharyngeal mucosa (NNM) tissues, HDAC7 expression levels were positively correlated with NPC progression and negatively correlated with patient prognosis, and HDAC7 knockdown dramatically inhibited the in vitro proliferation, migration, and invasion of NPC cells, and the growth of NPC xenografts in mice, indicating the HDAC7 promotes the oncogenicity of NPC. Mechanistically, HDAC7 promoted the in vitro proliferation, migration, and invasion of NPC cells by upregulating EphA2, in which miR-4465 mediated HDAC7-regulating EphA2, a direct target gene of miR-4465. We further showed that miR-4465 was significantly downregulated in the NPC tissues relative to NNM tissues, and inhibited the in vitro proliferation, migration, and invasion of NPC cells by targeting EphA2 expression. Moreover, we observed that the expressions of HDAC7, miR-4465, and EphA2 in NPC tissues were correlated. The results suggest that HDAC7 promotes the oncogenicity of NPC by downregulating miR-4465 and subsequently upregulating EphA2, highlighting HDAC7 as a potential therapeutic target for NPC.

Heterozygous p53-R280T Mutation Enhances the Oncogenicity of NPC Cells Through Activating PI3K-Akt Signaling Pathway.

A heterozygous point mutation of p53 gene at codon 280 from AGA to ACA (R280T) frequently occurs in nasopharyngeal carcinoma (NPC) cell lines, and about 10% NPC tissues. However, the role of this mutation in the pathogenesis of NPC remains unclear. In this study, we generated p53 knockout (KO) NPC cell lines from CNE2 cells carrying heterozygous p53 R280T (p53-R280T) mutation and C666-1 cells carrying wild-type p53 by CRISPR-Cas9 gene editing system, and found that KO of heterozygous p53-R280T significantly decreased NPC cell proliferation and increased NPC cell apoptosis, whereas KO of wild-type p53 had opposite effects on NPC cell proliferation and apoptosis. Moreover, KO of heterozygous p53-R280T inhibited the anchorage-independent growth and in vivo tumorigenicity of NPC cells. mRNA sequencing of heterozygous p53-R280T KO and control CNE2 cells revealed that heterozygous p53-R280T mutation activated PI3K-Akt signaling pathway. Moreover, blocking of PI3K-Akt signaling pathway abolished heterozygous p53-R280T mutation-promoting NPC cell proliferation and survival. Our data indicate that p53 with heterozygous R280T mutation functions as an oncogene, and promotes the oncogenicity of NPC cells by activating PI3K-Akt signaling pathway.

Quantitative assessment of diffusion kurtosis imaging depicting deep myometrial invasion: a comparative analysis with diffusion-weighted imaging.

PURPOSE: We aimed to investigate histogram analysis of diffusion kurtosis imaging (DKI) and conventional diffusion-weighted imaging (DWI) to distinguish between deep myometrial invasion and superficial myometrial invasion in endometrial carcinoma (EC). METHODS: A total of 118 pathologically confirmed EC patients with preoperative DWI were included. The data were postprocessed with a DKI (b value of 0, 700, 1400, and 2000 s/mm2) model for quantitation of apparent diffusion values (D) and apparent kurtosis coefficient values (K) for non-Gaussian distribution. The apparent diffusion coefficient (ADC) was postprocessed with a conventional DWI model (b values of 0 and 800 s/mm2). A whole-tumor analysis approach was used. Comparisons of the histogram parameters of D, K, and ADC were carried out for the deep myometrial invasion and superficial myometrial invasion subgroups. Diagnostic performance of the imaging parameters was assessed. RESULTS: The Dmean, D10th, and D90th in deep myometrial invasion group were significantly lower than those in superficial invasion group (P < 0.001, P < 0.001, and P = 0.023, respectively), as well as the ADCmean, ADC10th, and ADC90th (P = 0.001, P = 0.001, and P = 0.042, respectively). The Kmean and K90th were significantly higher in deep invasion group than those in superficial myometrial invasion group (P = 0.002 and P = 0.026, respectively). The D10th, Kmean, and ADC10th had a relatively higher area under the curve (AUC) (0.72, 0.66, and 0.71, respectively) than other parameters for distinguishing deep myometrial invasion of EC. D10th showed a relatively higher AUC than ADC10th for the differentiation of lesions with deep myometrial invasion from those with superficial myometrial invasion (0.72 vs. 0.71), but the variation was not statistically significant (P = 0.35). CONCLUSION: Distribution of DKI and conventional DWI parameters characterized by histogram analysis may represent an indicator for deep myometrial invasion in EC. Both DKI and DWI models showed relatively equivalent effectiveness.

Texture Analysis of High b-Value Diffusion-Weighted Imaging for Evaluating Consistency of Pituitary Macroadenomas.

BACKGROUND: Preoperative evaluation of the consistency of pituitary macroadenomas is important for neurosurgeons to prepare the surgical plan. PURPOSE: To evaluate the diagnostic performance of texture analysis (TA) of diffusion-weighted imaging (DWI) at a standard b-value (b = 1000 s/mm2 ) and a high b-value (b = 2000 s/mm2 ) for their ability to assess the tumor consistency of pituitary macroadenomas. STUDY TYPE: Retrospective. POPULATION/SUBJECTS: Fifty patients with histologically confirmed pituitary macroadenomas were classified as soft (n = 37) or hard (n = 13) types. FIELD STRENGTH/SEQUENCE: Coronal T2 -weighted imaging (T2 WI), Readout Segmentation of Long Variable Echo-trains (RESOLVE) DWI at b = 1000 s/mm2 and b = 2000 s/mm2 were acquired with 3.0T MRI. ASSESSMENT: The corresponding apparent diffusion coefficient (ADC) maps (ADC1000 and ADC2000 ) were registered to T2 WI. Regions of interest (ROIs) were manually drawn along the solid part of the tumor from the coregistered T2 WI-ADC images. The texture parameters from T2 WI, ADC1000 , and ADC2000 were acquired. STATISTICAL TESTS: The texture parameters were compared between the two types by using unpaired Student's t-test. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to assess their diagnostic performance. RESULTS: Significant differences in TA parameters of ADC1000 and ADC2000 were observed between soft and hard types (P < 0.05 for all), whereas the TA of T2 WI resulted in no significant difference (P > 0.05 for all). TA of ADC2000 provided a superior diagnostic performance compared with that of ADC1000 (P = 0.038). A combination of mean value and entropy of ADC2000 yielded an AUC, a sensitivity, and a specificity of 0.911, 78.4% and 92.3%, respectively. DATA CONCLUSION: TA of ADC values were useful for assessing the tumor consistency of pituitary macroadenomas. ADC2000 may facilitate better type discrimination. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1507-1513.

Comparison of CT angiography collaterals for predicting target perfusion profile and clinical outcome in patients with acute ischemic stroke.

OBJECTIVES: To compare collateral status on single-phase CT angiography (sCTA) and multiphase CT angiography (mCTA) and their ability to predict a target mismatch on CT perfusion (CTP) and clinical outcome in patients with acute ischemic stroke (AIS). METHODS: Seventy-three AIS patients with stroke onset between 5 and 15 h or with unclear onset time and occlusions in the M1/M2 segment of the middle cerebral artery and/or intracranial internal carotid artery underwent head non-contrast CT and CTP. Simulated sCTA and mCTA were reconstructed from CTP data and were compared for collaterals assessment. The ability to predict target mismatch on CTP (an ischemic core < 70 ml, a mismatch ratio ≥ 1.8, and an absolute difference ≥ 15 ml) and 90-day modified Rankin Scale (mRS) score of 0-2 was compared between sCTA and mCTA by using receiver operating curve analysis. RESULTS: sCTA underestimated the collateral status when compared with mCTA (p < 0.01). The ability of mCTA to predict target mismatch (AUC = 0.902, 95% confidence interval [CI] 0.809, 0.959) and clinical outcome (AUC = 0.771; 95% CI, 0.655, 0.864) was better than that of sCTA (p < 0.05 overall). A mCTA collateral score of > 3 best identified the target mismatch (sensitivity, 78.4%; specificity, 90.9%) and predicted 90-day mRS score of 0-2 (sensitivity, 84.8%; specificity, 69.4%). CONCLUSIONS: The collaterals were better estimated by mCTA compared with sCTA. A mCTA collateral score of > 3 optimized the prediction of a target mismatch on CTP and a good clinical outcome in patients with AIS. KEY POINTS: • Collateral circulation is a key determinant of ischemic core and penumbra. Better collaterals are associated with smaller ischemic core volumes and larger mismatch ratios on CT perfusion. • The collaterals can be better estimated by multiphase CTA compared with single-phase CTA. • A collateral score of > 3 on multiphase CTA best identifies patients with target mismatch on CT perfusion and predicts 90-day mRS score of 0-2.

[Corrigendum] ANXA1­derived peptides suppress gastric and colon cancer cell growth by targeting EphA2 degradation.

Following the publication of the above article, the authors have realized that one of the data panels featured in Fig. 5D was selected incorrectly. Specifically, the wrong image was selected for the A1 (28­30), HCT116 experiment. The authors have revisited their original sources to identify the correct data panel, and can confirm that the error arose unintentionally during the process of compiling the figure. The correct version of Fig. 5, featuring corrected data panel for Fig. 5D, is shown on the next page. The authors confirm that this error did not affect the conclusions reported in this study, and are grateful to the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. Furthermore, the authors apologize to the readership of the Journal for any inconvenience caused. [the original article was published in International Journal of Oncology 57: 1203­1213, 2020; DOI: 10.3892/ijo.2020.5119].

Hypoxic conditioned medium derived from bone marrow mesenchymal stromal cells protects against ischemic stroke in rats.

In recent years, studies have shown that the secretome of bone marrow mesenchymal stromal cells (BMSCs) contains many growth factors, cytokines, and antioxidants, which may provide novel approaches to treat ischemic diseases. Furthermore, the secretome may be modulated by hypoxic preconditioning. We hypothesized that conditioned medium (CM) derived from BMSCs plays a crucial role in reducing tissue damage and improving neurological recovery after ischemic stroke and that hypoxic preconditioning of BMSCs robustly improves these activities. Rats were subjected to ischemic stroke by middle cerebral artery occlusion and then intravenously administered hypoxic CM, normoxic CM, or Dulbecco modified Eagle medium (DMEM, control). Cytokine antibody arrays and label-free quantitative proteomics analysis were used to compare the differences between hypoxic CM and normoxic CM. Injection of normoxic CM significantly reduced the infarct area and improved neurological recovery after stroke compared with administering DMEM. These outcomes may be associated with the attenuation of apoptosis and promotion of angiogenesis. Hypoxic preconditioning significantly enhanced these therapeutic effects. Fourteen proteins were significantly increased in hypoxic CM compared with normoxic CM as measured by cytokine arrays. The label-free quantitative proteomics analysis revealed 163 proteins that were differentially expressed between the two groups, including 107 upregulated proteins and 56 downregulated proteins. Collectively, our results demonstrate that hypoxic CM protected brain tissue from ischemic injury and promoted functional recovery after stroke in rats and that hypoxic CM may be the basis of a potential therapy for stroke patients.

Intergrating conventional MRI, texture analysis of dynamic contrast-enhanced MRI, and susceptibility weighted imaging for glioma grading.

BACKGROUND: The application of conventional magnetic resonance imaging (MRI) in glioma grading is limited and non-specific. PURPOSE: To investigate the application values of MRI, texture analysis (TA) of dynamic contrast-enhanced MRI (DCE-MRI) and intratumoral susceptibility signal (ITSS) on susceptibility weighted imaging (SWI), alone and in combination, for glioma grading. MATERIAL AND METHODS: Fifty-two patients with pathologically confirmed gliomas who underwent DCE-MRI and SWI were enrolled in this retrospective study. Conventional MRIs were evaluated by the VASARI scoring system. TA of DCE-MRI-derived parameters and the degree of ITSS were compared between low-grade gliomas (LGGs) and high-grade gliomas (HGGs). The diagnostic ability of each parameter and their combination for glioma grading were analyzed. RESULTS: Significant statistical differences in VASARI features were observed between LGGs and HGGs ( P < 0.05), of which the enhancement quality had the highest area under the curve (AUC) (0.873) with 93.3% sensitivity and 80% specificity. The TA of DCE-MRI derived parameters were significantly different between LGGs and HGGs ( P < 0.05), of which the uniformity of Ktrans had the highest AUC (0.917) with 93.3% sensitivity and 90% specificity. The degree of ITSS was significantly different between LGGs and HGGs ( P < 0.001). The AUC of the ITSS was 0.925 with 93.3% sensitivity and 90% specificity. The best discriminative power was obtained from a combination of enhancement quality, Ktrans- uniformity, and ITSS, resulting in 96.7% sensitivity, 100.0% specificity, and AUC of 0.993. CONCLUSION: Combining conventional MRI, TA of DCE-MRI, and ITSS on SWI may help to improve the differentiation between LGGs and HGGs.