Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors

Kamei, Ryosuke; Tanaka, Hiroyoshi; Kawano, Takeshi; Morii, Chiharu; Tanaka, Sayaka; Nishihara, Hiroshi; Iwata, Caname; Kano, Mitsunobu R.

doi:10.1111/cas.13216

Cited by 8 publications

(7 citation statements)

References 34 publications

(70 reference statements)

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“…reported that low-doses of TGF-β inhibitor successfully altered the TME including tumor vasculature, which increased the EPR effect with minimal side effects 105. Additionally, TGF-β inhibition in pericyte-abundant BxPC-3 pancreatic cancer vessels increased the uptake of NPs, logically implying the augmented EPR effect 106, 107. The role of other TME-related factors, such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) is under evaluation in terms of TME-remodeling for anti-cancer therapy.…”

Section: Physiological Remodeling Of Tmementioning

confidence: 98%

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

et al. 2019

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The use of nanomedicine for cancer treatment takes advantage of its preferential accumulation in tumors owing to the enhanced permeability and retention (EPR) effect. The development of cancer nanomedicine has promised highly effective treatment options unprecedented by standard therapeutics. However, the therapeutic efficacy of passively targeted nanomedicine is not always satisfactory because it is largely influenced by the heterogeneity of the intensity of the EPR effect exhibited within a tumor, at different stages of a tumor, and among individual tumors. In addition, limited data on EPR effectiveness in human hinders further clinical translation of nanomedicine. This unsatisfactory therapeutic outcome in mice and humans necessitates novel approaches to improve the EPR effect. This review focuses on current attempts at overcoming the limitations of traditional EPR-dependent nanomedicine by incorporating supplementary strategies, such as additional molecular targeting, physical alteration, or physiological remodeling of the tumor microenvironment. This review will provide valuable insight to researchers who seek to overcome the limitations of relying on the EPR effect alone in cancer nanomedicine and go “beyond the EPR effect”.

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Section: Physiological Remodeling Of Tmementioning

confidence: 98%

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

et al. 2019

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“…The latter cancer lacks pericyte coverage and is generally more responsive to chemotherapy. 14,15 We also found that while the CT26 colon carcinoma model with little pericyte coverage shows optimal intratumoral nanoparticle accumulation when treated with the angiogenesis inhibitor Sorafenib, the BxPC-3 model responds only to TGF-b inhibition. 16 This suggests that vessel architecture, notably in relation to pericyte coverage, is an important determinant of nanotherapeutic efficacy.…”

Section: Stromal Barriers To Drug Delivery Within the Tme In Pancreat...mentioning

confidence: 65%

Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

Tanaka

Kano

2018

Cancer Science

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Pancreatic cancer is known for its dismal prognosis despite efforts to improve therapeutic outcome. Recently, cancer nanomedicine, application of nanotechnology to cancer diagnosis and treatment, has gained interest for treatment of pancreatic cancer. The enhanced permeability and retention (EPR) effect that promotes selective accumulation of nanometer‐sized molecules within tumors is the theoretical rationale of treatment. However, it is clear that EPR may be insufficient in pancreatic cancer as a result of stromal barriers within the tumor microenvironment (TME). These limit intratumoral accumulation of macromolecules. The TME and stromal barriers inside it consist of various stromal cell types which interact both with each other and with tumor cells. We are only beginning to understand the complexities of the stromal barriers within the TME and its functional consequences for nanomedicine. Understanding the complex crosstalk between barrier stromal cells is challenging because of the difficulty of modeling pancreatic cancer TME. Here we provide an overview of stromal barriers within the TME. We also describe the preclinical models, both in vivo and in vitro, developed to study them. We furthermore discuss the critical gaps in our understanding, and how we might formulate a better strategy for using nanomedicine against pancreatic cancer.

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“…It is well known that both HNPCs and VECs express Fas/FasL, and IDD angiogenesis is associated with Fas/FasL (Table 1 ). Studies have shown that the regulation of endothelial Fas signaling promotes vascular integrity by mural cells in tumors 69 . Fas-mediated apoptosis plays an essential role in preventing angiogenesis in other tissues 70 , 71 .…”

Section: The Death Receptor Pathway and Iddmentioning

confidence: 99%

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy

Zhang¹,

Hu²,

Peng³

et al. 2021

Int. J. Med. Sci.

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Intervertebral disc (IVD) degeneration (IDD) is a multifactorial pathological process associated with low back pain (LBP). The pathogenesis is complicated, and the main pathological changes are IVD cell apoptosis and extracellular matrix (ECM) degradation. Apoptotic cell loss leads to ECM degradation, which plays an essential role in IDD pathogenesis. Apoptosis regulation may be a potential attractive therapeutic strategy for IDD. Previous studies have shown that IVD cell apoptosis is mainly induced by the death receptor pathway, mitochondrial pathway, and endoplasmic reticulum stress (ERS) pathway. This article mainly summarizes the factors that induce IDD and apoptosis, the relationship between the three apoptotic pathways and IDD, and potential therapeutic strategies. Preliminary animal and cell experiments show that targeting apoptotic pathway genes or drug inhibition can effectively inhibit IVD cell apoptosis and slow IDD progression. Targeted apoptotic pathway inhibition may be an effective strategy to alleviate IDD at the gene level. This manuscript provides new insights and ideas for IDD therapy.

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Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors

Cited by 8 publications

References 34 publications

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

Alliance with EPR Effect: Combined Strategies to Improve the EPR Effect in the Tumor Microenvironment

Stromal barriers to nanomedicine penetration in the pancreatic tumor microenvironment

Targeted therapy for intervertebral disc degeneration: inhibiting apoptosis is a promising treatment strategy

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