Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization

Lei, Xueping; Chen, Minfeng; Huang, Maohua; Li, Xiaobo; Shi, Changzheng; Zhang, Dong; Luo, Liangping; Zhang, Youwei; Ma, Nan; Chen, Heru; Liang, Hua-Feng; Ye, Wen‐Cai; Zhang, Dongmei

doi:10.7150/thno.22222

Cited by 19 publications

(13 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mice for the MRI examinations were randomly divided into four groups and then intraperitoneally injected with normal saline (Group A or control group), bevacizumab (5 mg/kg; Group B), oxaliplatin (4 mg/kg; Group C), and oxaliplatin combined with bevacizumab (Group D) on days 1, 4, 7, 10, and 13. The tumor volume was calculated using the following formula: (a 2 × b × 0.5) mm 3 , where a refers to the smaller diameter and b is the diameter perpendicular to a, measured with a slide caliper (19). The tumor inhibition rate refers to (tumor size of untreated mice-tumor size of treated mice)/tumor size of untreated mice × 100%.…”

Section: Tumor Model and Groupingmentioning

confidence: 99%

Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment

Liang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

Objectives: This study aimed to detect the time window of vascular normalization during anti-vascular treatment using intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). Simultaneously, we evaluated the tumor invasiveness and vasculogenic mimicry and performed synthetic assessment of treatment efficacy of angiogenesis inhibitor combined with conventional chemotherapy using IVIM-DWI. Materials and Methods: HCT116 cells were subcutaneously administered into the right flank of BALB/C nude mice to build a colon cancer xenograft model. Thirty-two tumor-bearing mice were randomly divided into four groups and intraperitoneally administered with normal saline (Group A or control group), bevacizumab (Group B), oxaliplatin monotherapy (Group C), and oxaliplatin combined with bevacizumab (Group D). The IVIM-DWI was performed on days 0, 3, 6, 9, 12, and 15 after the treatments. Another 51 tumor-bearing mice were included in the pathological examinations. α-Smooth muscle actin (SMA) and CD31 double-staining, periodic acid-Schiff (PAS) and CD31 double-staining, hematoxylin and eosin (HE), Ki-67, and E-cadherin staining were performed. The tumor growth and dynamic change of each parameter were noted. Results: The mice in Group D manifested the smallest tumor volume and highest tumor inhibition rate. Microvessel density was significantly decreased but accompanied by increased vasculogenic mimicry after antiangiogenic treatment. The trend was reversed by oxaliplatin treatment. Treated with bevacizumab, the vessel maturity index shared a similar trend with D * and f-values during days 3-12, which slowly increased from days 0 to 9 and then decreased briefly. D-value significantly correlated with vasculogenic mimicry and Ki-67, while D * and f-values showed positive correlations with microvessel density and E-cadherin, an indicator of epithelial-mesenchymal transition. Liang et al. IVIM-DWI Used in Vasculogenic Mimicry Conclusion: Oxaliplatin performed an inhibited effect on vasculogenic mimicry. Bevacizumab can enhance the tumor chemotherapy through vascular normalization within a transient time period, which can be detected by IVIM-DWI. D * and f-values are able to predict the tumor invasiveness while D is superior in reflecting vasculogenic mimicry and Ki-67 expression during antitumor treatment.

show abstract

Section: Tumor Model and Groupingmentioning

confidence: 99%

Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment

Liang

et al. 2020

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…Previous studies suggested that thrombin increased the microvascular permeability by activating PAR1 pathway, which increased the activity of downstream protein kinases, such as p21‐activated kinase‐1 (PAK1) . Several lines of evidence also indicated that the phosphorylation of Src or PAK1 was involved in the degradation and loss of VE‐cadherin …”

Section: Introductionmentioning

confidence: 99%

“…19 Several lines of evidence also indicated that the phosphorylation of Src or PAK1 was involved in the degradation and loss of VE-cadherin. [22][23][24][25] In this study, we hypothesized that thrombin-induced hydrocephalus was related to the PAR1 signaling pathway which resulted in the decline of VE-cadherin in choroid plexuses. And this process may shed light on the formation of hydrocephalus after IVH.…”

mentioning

confidence: 98%

Thrombin disrupts vascular endothelial‐cadherin and leads to hydrocephalus via protease‐activated receptors‐1 pathway

Hao

Zhang

et al. 2019

CNS Neurosci Ther

View full text Add to dashboard Cite

Summary Aims Previous studies indicated that intraventricular injection of thrombin would induce hydrocephalus. But how thrombin works in this process remains unclear. Since cadherin plays a critical role in hydrocephalus, we aimed to explore the mechanisms of how thrombin acted on choroid plexus vascular endothelium and how thrombin interacted with vascular endothelial‐cadherin (VE‐cadherin) during hydrocephalus. Methods There were two parts in this study. Firstly, rats received an injection of saline or thrombin into the right lateral ventricle. Magnetic resonance imaging was applied to measure the lateral ventricle volumes. Albumin leakage and Evans blue content were assessed to test the blood‐brain barrier function. Immunofluorescence and Western blot were applied to detect the location and the expression of VE‐cadherin. Secondly, we observed the roles of protease‐activated receptors‐1 (PAR1) inhibitor (SCH79797), Src inhibitor (PP2), p21‐activated kinase‐1 (PAK1) inhibitor (IPA3) in the thrombin‐induced hydrocephalus, and their effects on the regulation of VE‐cadherin. Results Our study demonstrated that intraventricular injection of thrombin caused significant downregulation of VE‐cadherin in choroid plexus and dilation of ventricles. In addition, the inhibition of PAR1/p‐Src/p‐PAK1 pathway reversed the decrease of VE‐cadherin and attenuated thrombin‐induced hydrocephalus. Conclusions Our results suggested that the thrombin‐induced hydrocephalus was associated with the inhibition of VE‐cadherin via the PAR1/p‐Src/p‐PAK1 pathway.

show abstract

“…They were treated with normal saline (Group A), 4 mg/kg of doxorubicin (Group B), 2 mg/kg (Group C), and 4 mg/kg of cRGD-PLGA@DOX (Group D) via the tail vein once every 2 days. The tumor volume was calculated using the following formula: (a 2 × b × 0.5) mm 3 , where a refers to the smaller diameter and b is the diameter perpendicular to a, measured with a slide caliper ( 17 ). The tumor inhibition rate refers to (tumor size of untreated mice−tumor size of treated mice)/tumor size of untreated mice × 100%.…”

Section: Methodsmentioning

confidence: 99%

Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging

Huang

Liang

et al. 2020

Front. Oncol.

Self Cite

View full text Add to dashboard Cite

Objectives Nano-drug delivery system is an interesting field in precise cancer treatment, but few study has reported the microenvironmental changes after such treatment. This study aimed to detect the hemodynamic and microenvironmental changes in a lung cancer xenograft model after treated with doxorubicin (DOX) encapsulated by a cyclic arginine-glycine-aspartic acid polypeptide modified poly-(lactic-co-glycolic acid) nanosystem (cRGD-PLGA@DOX) using functional magnetic resonance imaging. Materials and Methods Thirty-two tumor-bearing mice were randomly divided into four groups. Group A was treated with 0.9% saline, Group B with 4 mg/kg of doxorubicin, Group C with 2 mg/kg of cRGD-PLGA@DOX, and Group D with 4 mg/kg of cRGD-PLGA@DOX. Intravoxel incoherent motion diffusion-weighed imaging (IVIM-DWI) and R2 ∗ mapping were performed, and D ∗ , f, D, and R2 ∗ values were obtained before and1, 2, and 3 weeks after treatment. They were sacrificed for pathological examination after examinations. Results The reconstructed cRGD-PLGA@DOX was homogeneous, well-dispersed, and spherical in shape, with an average size of 180 nm. Group D demonstrated the smallest tumor volume and highest tumor inhibition rate in 3 weeks. D value of Group B, C, and D manifested an upward trend in 3 weeks with the highest increase in Group D. D ∗ values shared a similar increased trends with f values in Group A, B, and C in 3 weeks, except Group D. R2 ∗ value of Group A gradually increased in 3 weeks, but the trends were reversed in the treatment groups. D value was significantly negative with Ki-67 expression ( r = −0.757, P < 0.001) but positive with TUNEL ( r = 0.621, P < 0.001), and phosphate and tension homology deleted on chromosome ten (PTEN) staining ( r = 0.57, P = 0.004). R2 ∗ value was closely correlated with HIF-1a ( r = 0.721, P < 0.001). Conclusion The nano-drug demonstrated an enhanced anti-tumor effect without the need of increased chemotherapeutic dosage. The tumor microenvironment such as cellular and perfusion changes during treatment can be non-invasively detected by two functional MRI including IVIM-DWI and R2 ∗ mapping.

show abstract

Desacetylvinblastine Monohydrazide Disrupts Tumor Vessels by Promoting VE-cadherin Internalization

Cited by 19 publications

References 62 publications

Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment

Application of IVIM-DWI in Detecting the Tumor Vasculogenic Mimicry Under Antiangiogenesis Combined With Oxaliplatin Treatment

Thrombin disrupts vascular endothelial‐cadherin and leads to hydrocephalus via protease‐activated receptors‐1 pathway

Evaluating the Treatment Efficacy of Nano-Drug in a Lung Cancer Model Using Advanced Functional Magnetic Resonance Imaging

Contact Info

Product

Resources

About