LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

The use of nanomedicine for antitumor therapy has been extensively investigated for a long time. Enhanced permeability and retention (EPR) effect-mediated drug delivery is currently regarded as an effective way to bring drugs to tumors, especially macromolecular drugs and drug-loaded pharmaceutical nanocarriers. However, a disordered vessel network, and occluded or embolized tumor blood vessels seriously limit the EPR effect. To augment the EPR effect and improve curative effects, in this review, we focused on the perspective of tumor blood vessels, and analyzed the relationship among abnormal angiogenesis, abnormal vascular structure, irregular blood flow, extensive permeability of tumor vessels, and the EPR effect. In this commentary, nanoparticles including liposomes, micelles, and polymers extravasate through the tumor vasculature, which are based on modulating tumor vessels, to increase the EPR effect, thereby increasing their therapeutic effect.

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Baseline and contrast-enhanced ultrasound features of hepatic epithelioid angiomyolipoma

Clinical Hemorheology and Microcirculation ◽

10.3233/ch-211305 ◽

2021 ◽

pp. 1-15

Author(s):

Pei-Li Fan ◽

Zheng-Biao Ji ◽

Jia-Ying Cao ◽

Chen Xu ◽

Yi Dong ◽

...

Keyword(s):

Resistive Index ◽

Malignant Potential ◽

Arterial Phase ◽

Hepatic Tumors ◽

Contrast Enhanced Ultrasound ◽

Uncertain Malignant Potential ◽

Epithelioid Angiomyolipoma ◽

Tumor Vessels ◽

Contrast Enhanced ◽

Ultrasound Features

BACKGROUND: Recurrence or metastasis after surgery had been reported in hepatic epithelioid angiomylipoma (epi-AML). Most hepatic epi-AMLs were misdiagnosed with hepatocellular carcinoma or other hepatic tumors before surgery. OBJECTIVE: To describe the baseline and contrast-enhanced ultrasound (CEUS) features of hepatic epi-AMLs and to explore the potential ultrasonic features for prognosis. METHODS: The retrospective study enrolled 67 patients (56 females, 11 males) with 67 pathologically confirmed hepatic epi-AML lesions. All the lesions were examined by baseline ultrasound and 42 lesions were examined using CEUS with SonoVue (Bracco, Milan, Italy) before surgery. RESULTS: Baseline ultrasound features of hepatic epi-AMLs included heterogeneous echo (86.6%), well-defined border (68.7%), hypoecho (64.2%), regular morphology (62.7%), peripheral-tumor arc-shaped or ring-like vessels (53.7%), and low value of resistive index (0.51±0.08). CEUS features of hepatic epi-AMLs included arterial phase hyper-enhancement with smooth and well-defined margin (100%), peripheral-tumor ring-like vessels (57.1%), and intra-tumor vessels (52.4%). Some CEUS features, including arterial phase heterogeneously tortuous filling, intra-tumor vessels and peripheral-tumor ring-like vessels were more commonly found in hepatic epi-AMLs of uncertain malignant potential/malignant than in benign hepatic epi-AMLs (p < 0.05). CONCLUSIONS: Baseline ultrasound and CEUS features may be useful in diagnosis of hepatic epi-AML, and some CEUS features may be indicative of its malignant potential.

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Immunomodulation of Tumor Vessels: It Takes Two to Tango

Trends in Immunology ◽

10.1016/j.it.2018.08.001 ◽

2018 ◽

Vol 39 (10) ◽

pp. 801-814 ◽

Cited By ~ 16

Author(s):

Anna Johansson-Percival ◽

Bo He ◽

Ruth Ganss

Keyword(s):

Tumor Vessels

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Thymidine kinase-1/CD31 double immunostaining for identifying activated tumor vessels

Biotechnic & Histochemistry ◽

10.1080/10520295.2018.1499962 ◽

2018 ◽

Vol 94 (1) ◽

pp. 60-64 ◽

Cited By ~ 4

Author(s):

S. Okamura ◽

T. Osaki ◽

K. Nishimura ◽

H. Ohsaki ◽

M. Shintani ◽

...

Keyword(s):

Thymidine Kinase ◽

Double Immunostaining ◽

Thymidine Kinase 1 ◽

Tumor Vessels

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Modulating Sphingosine-1-Phosphate receptors to improve chemotherapy delivery to Ewing sarcoma

10.1101/805655 ◽

2019 ◽

Author(s):

Enrica Marmonti ◽

Hannah Savage ◽

Aiqian Zhang ◽

Claudia Alvarez ◽

Miriam Morrell ◽

...

Keyword(s):

G Protein ◽

Ewing Sarcoma ◽

Tyrosine Kinases ◽

Tumor Vasculature ◽

Cell Junction ◽

Tumor Vessels ◽

S1p Receptors ◽

Vessel Permeability ◽

Sphingosine 1 Phosphate ◽

G Protein Coupled

ABSTRACTTumor vasculature is innately dysfunctional. Poorly functional tumor vessels inefficiently deliver chemotherapy to tumor cells; vessel hyper-permeability promotes chemotherapy delivery primarily to a tumor’s periphery. Here we identify a method for enhancing chemotherapy delivery and efficacy in Ewing sarcoma (ES) in mice by modulating tumor vessel permeability. Vessel permeability is partially controlled by the G protein-coupled Sphinosine-1-phosphate receptors 1 and 2 (S1PR1 and S1PR2) on endothelial cells. S1PR1 promotes endothelial cell junction integrity while S1PR2 destabilizes it. We hypothesize that an imbalance of S1PR1:S1PR2 is partially responsible for the dysfunctional vascular phenotype characteristic of ES and that by altering the balance in favor of S1PR1, ES vessel hyper-permeability can be reversed. In this study, we demonstrate that pharmacologic activation of S1PR1 by SEW2871 or inhibition of S1PR2 by JTE-013 caused more organized, mature, and functional tumor vessels. Importantly, S1PR1 activation or S1PR2 inhibition improved chemotherapy delivery to the tumor and anti-tumor efficacy. Our data suggests that pharmacologic targeting of S1PR1 and S1PR2 may be a useful adjuvant to standard chemotherapy for ES patients.NOVELTY AND IMPACTThis study demonstrates that Sphingosine-1-Phosphate (S1P) receptors are potential novel targets for tumor vasculature remodeling and adjuvant therapy for the treatment of Ewing Sarcoma. Unlike receptor tyrosine kinases that have already been extensively evaluated for use as vascular normalizing agents in oncology, S1P receptors are G protein-coupled receptors, which have not been well studied in tumor endothelium. Pharmacologic activators and inhibitors of S1P receptors are currently in clinical trials for treatment of auto-immune and cardiovascular diseases, indicating potential for clinical translation of this work.

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