Targeting the vasculature of visceral tumors: novel insights and treatment perspectives

Klotz, L.; Eichhorn, Martin; Schwarz, Bettina; Seeliger, Hendrik; Angele, Martin K.; Jauch, Karl Walter; Bruns, Christiane

doi:10.1007/s00423-012-0946-4

Cited by 4 publications

(2 citation statements)

References 78 publications

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“…Molecular targeting of tumour vasculature is a relatively new therapeutic approach intended to curtail tumour angiogenesis, growth and metastatic potential. Several antiangiogenic agents are now available for the treatment of certain solid cancers, most of which inhibit the Vascular Endothelial Growth Factor (VEGF) signalling pathway [5]. However, lack of significant therapeutic gain indicates that tumour angiogenesis may be mediated not only through VEGF, but also through several alternative routes [6,7].…”

Section: Introductionmentioning

confidence: 99%

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

et al. 2020

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Purpose The current treatment outcomes in cholangiocarcinoma are poor with cure afforded only by surgical extirpation. The efficacy of targeting the tumoural endothelial marker CD105 in cholangiocarcinoma, as a basis for potential microbubble-based treatment, is unknown and was explored here. Methods Tissue expression of CD105 was quantified using immunohistochemistry in 54 perihilar cholangiocarcinoma samples from patients who underwent resection in a single centre over a ten-year period, and analysed against clinicopathological data. In vitro flow assays using microbubbles functionalised with CD105 antibody were conducted to ascertain specificity of binding to murine SVR endothelial cells. Finally, CD105-microbubbles were intravenously administered to 10 Balb/c nude mice bearing heterotopic subcutaneous human extrahepatic cholangiocarcinoma (TFK-1 and EGI-1) xenografts after which in vivo binding was assessed following contrast-enhanced destruction replenishment ultrasound application. Results Though not significantly associated with any examined clinicopathological variable, we found that higher CD105 expression was independently associated with poorer patient survival (median 12 vs 31 months; p = 0.002). In vitro studies revealed significant binding of CD105-microbubbles to SVR endothelial cells in comparison to isotype control (p = 0.01), as well as in vivo to TFK-1 (p = 0.02) and EGI-1 (p = 0.04) mouse xenograft vasculature. Conclusion Our results indicate that CD105 is a biomarker eminently suitable for cholangiocarcinoma targeting using functionalised microbubbles.

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Section: Introductionmentioning

confidence: 99%

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

et al. 2020

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“…Recently, another treatment approach has achieved great attention. Rather than directly targeting the neoplastic cells, this strategy tried to block the tumor's blood support system by targeting the tumor vasculature [1, 2]. …”

Section: Introductionmentioning

confidence: 99%

Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD) ₃‐tTF

Huang

Zhao

Luo

et al. 2013

The Scientific World Journal

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Purpose. Truncated tissue factor (tTF) fusion protein targeting tumor vasculature can induce tumor vascular thrombosis and necrosis. Here, we generated (RGD)3-tTF in which three arginine-glycine-aspartic (RGD) targeting integrin α v β 3 and tTF induce blood coagulation in tumor vessels. Methods. The bioactivities of (RGD)3-tTF including coagulation activity, FX activation, and binding with integrin α v β 3 were performed. The fluorescent labeled (RGD)3-tTF was intravenously injected into tumor-bearing mice and traced in vivo. The tumor growth, volume, blood vessel thrombosis, tumor necrosis, and survival time of mice treated with (RGD)3-tTF were evaluated. Results. The clotting time and FX activation of (RGD)3-tTF were similar to that of TF (P > 0.05) but different with that of RGD (P < 0.05). (RGD)3-tTF presented a higher binding with α v β 3 than that of RGD and TF at the concentration of 0.2 μmol/L (P < 0.05). (RGD)3-tTF could specifically assemble in tumor and be effective in reducing tumor growth by selectively inducing tumor blood vessels thrombosis and tumor necrosis which were absent in mice treated with RGD or TF. The survival time of mice treated with (RGD)3-tTF was higher than that of mice treated with TF or RGD (P < 0.05). Conclusion. (RGD)3-tTF may be a promising strategy for the treatment of colorectal cancer.

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Estrogen receptor β promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network

et al. 2018

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Recent studies indicated that the estrogen receptor beta (ERβ) could affect the progression of prostate and bladder tumors, however, its roles in the renal cell carcinoma (RCC), remain to be elucidated. Here, we provide clinical evidence that ERβ expression is correlated in a negative manner with the overall survival/disease-free survival in RCC patients. Mechanism dissection revealed that targeting ERβ with ERβ-shRNA and stimulating the transactivation of ERβ with 17β-estradiol or environmental endocrine disrupting chemicals, all resulted in altering the lncRNA HOTAIR expression. The ERβ-modulated HOTAIR is able to function via antagonizing several microRNAs, including miR-138, miR-200c, miR-204, or miR-217 to impact various oncogenes, including ADAM9, CCND2, EZH2, VEGFA, VIM, ZEB1, and ZEB2, to promote RCC proliferation and invasion. Together, the identification of the ERβ-HOTAIR axis may provide us new biomarkers and/or therapeutic targets to better suppress RCC progression in the future.

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Targeting the vasculature of visceral tumors: novel insights and treatment perspectives

Cited by 4 publications

References 78 publications

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD) ₃‐tTF

Estrogen receptor β promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network

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Targeting the vasculature of visceral tumors: novel insights and treatment perspectives

Cited by 4 publications

References 78 publications

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

CD105 is a prognostic marker and valid endothelial target for microbubble platforms in cholangiocarcinoma

Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD) 3‐tTF

Estrogen receptor β promotes renal cell carcinoma progression via regulating LncRNA HOTAIR-miR-138/200c/204/217 associated CeRNA network

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Targeting the Vasculature of Colorectal Carcinoma with a Fused Protein of (RGD) ₃‐tTF