DataSheet_1_Dynamic radiomics for predicting the efficacy of antiangiogenic therapy in colorectal liver metastases.pdf

Background and objectiveFor patients with advanced colorectal liver metastases (CRLMs) receiving first-line anti-angiogenic therapy, an accurate, rapid and noninvasive indicator is urgently needed to predict its efficacy. In previous studies, dynamic radiomics predicted more accurately than conventional radiomics. Therefore, it is necessary to establish a dynamic radiomics efficacy prediction model for antiangiogenic therapy to provide more accurate guidance for clinical diagnosis and treatment decisions.MethodsIn this study, we use dynamic radiomics feature extraction method that extracts static features using tomographic images of different sequences of the same patient and then quantifies them into new dynamic features for the prediction of treatmentefficacy. In this retrospective study, we collected 76 patients who were diagnosed with unresectable CRLM between June 2016 and June 2021 in the First Hospital of China Medical University. All patients received standard treatment regimen of bevacizumab combined with chemotherapy in the first-line treatment, and contrast-enhanced abdominal CT (CECT) scans were performed before treatment. Patients with multiple primary lesions as well as missing clinical or imaging information were excluded. Area Under Curve (AUC) and accuracy were used to evaluate model performance. Regions of interest (ROIs) were independently delineated by two radiologists to extract radiomics features. Three machine learning algorithms were used to construct two scores based on the best response and progression-free survival (PFS).ResultsFor the task that predict the best response patients will achieve after treatment, by using ROC curve analysis, it can be seen that the relative change rate (RCR) feature performed best among all features and best in linear discriminantanalysis (AUC: 0.945 and accuracy: 0.855). In terms of predicting PFS, the Kaplan–Meier plots suggested that the score constructed using the RCR features could significantly distinguish patients with good response from those with poor response (Two-sided PConclusionsThis study demonstrates that the application of dynamic radiomics features can better predict the efficacy of CRLM patients receiving antiangiogenic therapy compared with conventional radiomics features. It allows patients to have a more accurate assessment of the effect of medical treatment before receiving treatment, and this assessment method is noninvasive, rapid, and less expensive. Dynamic radiomics model provides stronger guidance for the selection of treatment options and precision medicine.</p

Descriptive results of ANOVA.

Descriptive results of ANOVA.</p

Phosphorylation of Akt, ERK and eNOS in ischemic muscle following injections of 2HP-β-CD or PBS.

<p>Muscle tissue homogenates from 2HP-β-CD-treated (filled) and PBS-treated (open) mice at post-operative day 28 were subjected to western blot using antibodies against phospho-Akt and total Akt (A), phospho-ERK and total ERK (B), and phospho-eNOS and total eNOS (C) as described in “Materials and Methods”. The quantitative analyses of band densities are also shown. Data represent the mean ± S.E.M. (<i>n</i> = 5 mice per group). * <i>p</i> < 0.05, versus the PBS-treated control mice.</p

The estimated marginal mean profile plots.

The estimated marginal mean profile plots.</p

VFR protocols.

VFR protocols.</p

(2-Hydroxypropyl)-β-Cyclodextrin Is a New Angiogenic Molecule for Therapeutic Angiogenesis

<div><p>Background</p><p>Peripheral artery disease (PAD), which is caused by atherosclerosis, results in progressive narrowing and occlusion of the peripheral arteries and inhibits blood flow to the lower extremities. Therapeutic angiogenesis is a promising strategy for treating ischemia caused by PAD. Nitric oxide (NO) has been shown to be a key mediator of angiogenesis. It has been demonstrated that β-cyclodextrincan stimulate vessel growth in rabbit corneas. In this study, we assessed the mechanism of action and therapeutic potential of a new angiogenic molecule, (2-hydroxypropyl)-β-cyclodextrin (2HP-β-CD).</p><p>Methods and Results</p><p>2HP-β-CD significantly increased vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor BB (PDGF-BB) peptides in human umbilical vein endothelial cells (HUVECs) and also increased basic fibroblast growth factor (bFGF) peptide in human aortic smooth muscle cells (HASMCs). 2HP-β-CD stimulated both proliferation and migration of HUVECs in an endothelial nitric oxide synthase (eNOS)/NO-dependent manner, whereas NO was found to be involved in proliferation, but not migration, of HASMCs. In a unilateral hindlimb ischemia model in mice, 2HP-β-CD injections not only promoted blood flow recovery and increased microvessel densities in ischemic muscle, but also promoted coverage of the vessels with smooth muscle cells, thus stabilizing the vessels. Administration of 2HP-β-CD increased the expression of several angiogenic factors, including VEGF-A, PDGF-BB and transforming growth factor beta-1 (TGF-β1) in ischemic muscle. Injections of 2HP-β-CD also stimulated protein kinase B and extracellular regulated protein kinases (ERK), leading to an increase in phosphorylation of eNOS in ischemic muscle. Treatment with the NOS inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), showed that stimulation of blood flow induced by 2HP-β-CD was partially dependent on NO.</p><p>Conclusions</p><p>Therapeutic angiogenesis by 2HP-β-CD may be beneficial to patients with PAD.</p></div

PVPD protocols.

PVPD protocols.</p

Angiogenesis-related mRNA and peptide expression in HUVECs and HASMCs.

<p>Expression levels of mRNA for angiogenic factors in HUVECs (A) and HASMCs (B) when treated with 2HP-β-CD (filled) and PBS (open) were determined by real-time PCR. GAPDH was used as an endogenous control. Data represent the mean ± S.E.M. (<i>n</i> = 4 per group). * <i>p</i> < 0.05. Angiogenesis-related peptide expression in the supernatants of HUVECs (C) and HASMCs (D) when treated with 2HP-β-CD (filled) and PBS (open) were determined by ELISA. Data are reported in nanograms per mg of proteins and represent the mean ± S.E.M. (<i>n</i> = 3 experiments). * <i>p</i> < 0.05.</p

Effect of L-NAME on 2HP-β-CD induced stimulation of blood flow recovery in C57BL/6 mice.

<p>A, Ischemic/non-ischemic limb blood flow ratio assessed by LDBF imager in mice in 4 experimental groups; PBS-treated mice with or without L-NAME, 2HP-β-CD-treated mice with or without L-NAME. Data represent the mean ± S.E.M. (n = 10 mice per group). * <i>p <</i> 0.05, 2HP-β-CD-treated mice versus PBS-treated mice. <i>§ p <</i> 0.05, 2HP-β-CD-treated mice versus 2HP-β-CD with L-NAME-treated mice; <i>＃ p <</i> 0.05, PBS with L-NAME-treated mice versus 2HP-β-CD with L-NAME-treated mice. B, Immunohistochemical analysis of CD31 in ischemic hindlimbs of PBS-treated and 2HP-β-CD-treated mice with or without L-NAME. Representative images (upper panel) from calf muscle on postoperative day 28 are shown. Quantitative analysis of CD31-positive microvessel density is also shown (lower panel). Data represent the mean ± S.E.M. (n = 5 mice per group). * <i>p <</i> 0.05. Scale bar = 100 μm.</p

The 2.5 m LAT chart.

The 2.5 m LAT chart.</p