Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor-bearing mice is involved in the immune response

Xu, Qingyu; Gu, Junfei; Lv, You; Yuan, Jiarui; Yang, Nan; Chen, Juan; Wang, Chunfei; Hou, Xuefeng; Jia, Xiao‐Bin; Feng, Liang; Yin, Guowen

doi:10.3892/ol.2018.7734

Cited by 18 publications

(19 citation statements)

References 58 publications

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“…It was shown to promote the efficiency of chemotherapy during the treatment of advanced non-small cell lung cancer phase II/III clinical trials [ 97 ]. Preclinical studies of Endostar also showed anti-angiogenic effects in HCC in vitro [ 98 ] and in vivo [ 99 ], suggesting that combination therapy with Endostar could be considered for the treatment of HCC.…”

Section: Pericellular Proteoglycan: Collagen Xviii/endostatinmentioning

confidence: 99%

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Tanaka

Tateishi

Koike

2018

IJMS

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Proteoglycans, which consist of a protein core and glycosaminoglycan chains, are major components of the extracellular matrix and play physiological roles in maintaining tissue homeostasis. In the carcinogenic tissue microenvironment, proteoglycan expression changes dramatically. Altered proteoglycan expression on tumor and stromal cells affects cancer cell signaling pathways, which alters growth, migration, and angiogenesis and could facilitate tumorigenesis. This dysregulation of proteoglycans has been implicated in the pathogenesis of diseases such as hepatocellular carcinoma (HCC) and the underlying mechanism has been studied extensively. This review summarizes the current knowledge of the roles of proteoglycans in the genesis and progression of HCC. It focuses on well-investigated proteoglycans such as serglycin, syndecan-1, glypican 3, agrin, collagen XVIII/endostatin, versican, and decorin, with particular emphasis on the potential of these factors as biomarkers and therapeutic targets in HCC regarding the future perspective of precision medicine toward the “cure of HCC”.

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Section: Pericellular Proteoglycan: Collagen Xviii/endostatinmentioning

confidence: 99%

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Tanaka

Tateishi

Koike

2018

IJMS

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“…Such normalized tumor blood vessels can transport more chemotherapeutic agents to tumor tissues, make cytotoxic agents more effectively. 3 In order to improve the efficacy of chemotherapy, endostar can be used to improve NACT reactivity, DEC-MRI can be used to monitor NACT reactivity in real time. DCE-MRI was based on T1-weighted images and then injected with contrast agent to obtain a series of images of contrast agent transport, distribution and outflow of tumor tissue.…”

Section: Introductionmentioning

confidence: 99%

<p>Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment</p>

Guan¹

2020

OTT

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Background The incidence rate of cervical cancer is the highest in the reproductive tract and is not sensitive to chemotherapy. An appropriate amount of anti-angiogenic agents can reconstruct tumor blood vessels in a short period of time and form vascular homeostasis, increase the function of blood vessel perfusion and reverse the multidrug resistance of chemotherapy, which is also called “vascular normalization.” Endostar (a recombinant human endostatin) was developed by China and as a multi-target anti-angiogenesis agent. Many reports about endostar involved the treatment of non-small cell lung cancer, fewer reports are on cervical cancer. Purpose To determine whether endostar can rebuild tumor vascular homeostasis and enhance chemotherapy effects for patients with cervical cancer. Methods In this study, the patients with cervical cancer within stage IIB2 were selected, endostar combined with cisplatin+paclitaxel neoadjuvant chemotherapy (NACT) before radical surgical operation was adopted, patients outcome and adverse reaction were followed up. The changes of tumor vascular structure and perfusion function before and after endostar given were evaluated by histopathology and dynamic contrast-enhanced magnetic resonance imaging (DEC-MRI). VEGF-Notch signal pathway was detected for the regulating mechanism of vascular proliferation in different groups. GraphPad Prism 6 software was used for statistical analysis of the study results. Results Endostar enhanced the short-term (2 year) overall survival (OS), progression-free survival (PFS) rates for cervical cancer patients. All the same, endostar increased long-term (5 year) OS for cervical cancer patients. Endostar therapy exhibited with mild adverse reaction. MRI showed endostar+NACT further reduce tumor volume than NACT alone. The parameters of Ktrans, Ve for DEC-MRI in endostar group exhibited obviously increase than NACT group. Tumor vascular maturation index α-SMA/CD31 in endostar group increased obviously than NACT group, correspondingly Ki67 staining for tumor proliferative rates, lymphovascular space invasion in endostar group further declined than NACT group. The genes and proteins expression of VEGFR2, Notch1, Notch 4 , Dll4 , Jag1 were obviously downregulated in endostar group comparing to NACT group. Conclusion Endostar restored vascular homeostasis in cervical cancer temporarily, enhanced chemotherapeutic agents effects in cervical cancer, increased patient OS ratio. Endostar+NACT treatment may provide a new target therapy for cervical cancer.

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“…The elevated interstitial fluid pressure (IFP) in B16F10 tumor keep drugs out of vascular wall probably accounted for that 41–43. We further administrated Endostar to promote tumor vessel normalization following procedure addressed before,44,45 expected to normalize the tumor microenvironment (improving vascular integrity, reducing IFP, and so on). The alternation of vasculatures of tumor was presented in Figure 12A and B.…”

Section: Resultsmentioning

confidence: 99%

<p>Remarkable Boron Delivery Of iRGD-Modified Polymeric Nanoparticles For Boron Neutron Capture Therapy</p>

Chen¹,

Yang²,

Liu³

et al. 2019

IJN

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PurposeBoron neutron capture therapy (BNCT) is an emerging binary radiotherapy, which is limited for application due to the challenge of targeted delivery into tumor nowadays. Here, we propose the use of iRGD-modified polymeric nanoparticles for active targeted delivery of boron and doxorubicin (DOX) in BNCT.Methods10B-enriched BSH was covalently grafted to PEG-PCCL to prepare 10B-polymer, then surface-modified with iRGD. And, DOX was physically incorporated into polymers afterwards. Characterization of prepared polymers and in vitro release profile of DOX from polymers were determined by several methods. Cellular uptake of DOX was observed by confocal microscope. Accumulation of boron in cells and tissues was analyzed by ICP-MS. Biodistribution of DOX was studied by ex vivo fluorescence imaging and quantitative measurement. Tumor vascular normalization of Endostar for promoting delivery efficiency of boron on refractory B16F10 tumor was also studied.ResultsThe polymers were monodisperse and spheroidal in water with an average diameter of 24.97 nm, which were relatively stable at physiological pH and showed a sustained release of DOX, especially at endolysosomal pH. Enhanced cellular delivery of DOX was found in iRGD-modified polymer group. Cellular boron uptake of iRGD-modified polymers in A549 cells was remarkably raised fivefold (209.83 ng 10B/106 cells) compared with BSH. The polymers represented prolonged blood circulation, enhanced tumor accumulation of 10B against BSH, and favorable tumor:normal tissue boron concentration ratios (tumor:blood = 14.11, tumor:muscle = 19.49) in A549 tumor-bearing mice 24 hrs after injection. Both fluorescence imaging and quantitative measurement showed the highest tumor accumulation of DOX at 24 hrs after injecting of iRGD-modified polymers. Improvement of vascular integrity and reduction of vascular mimicries were found after Endostar injection, and raised tumor accumulation of boron as well.ConclusionThe developed nanoparticle is an inspiring candidate for the safe clinical application for BNCT.

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Angiogenesis for tumor vascular normalization of Endostar on hepatoma 22 tumor-bearing mice is involved in the immune response

Cited by 18 publications

References 58 publications

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

Proteoglycans Are Attractive Biomarkers and Therapeutic Targets in Hepatocellular Carcinoma

<p>Endostar Rebuilding Vascular Homeostasis and Enhancing Chemotherapy Efficacy in Cervical Cancer Treatment</p>

<p>Remarkable Boron Delivery Of iRGD-Modified Polymeric Nanoparticles For Boron Neutron Capture Therapy</p>

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