Microbubble and ultrasound radioenhancement of bladder cancer

Tran, William T.; Iradji, Sara; Sofroni, Ervis; Giles, Anoja; Eddy, David; Czarnota, Gregory J.

doi:10.1038/bjc.2012.279

Cited by 62 publications

(104 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparable results were found in bladder tumors by Tran et al [69]. An additional study by Kwok et al [70] demonstrated the potency of USMB treatments combined with radiation in a breast cancer xenograft model.…”

Section: • Mechanisms Behind Mechanical Perturbation Of Cell Membranesmentioning

confidence: 63%

Biomechanical Effects of Microbubbles: From Radiosensitization to Cell Death

Kaffas

Czarnota

2015

Future Oncol.

View full text Add to dashboard Cite

Ultrasound-stimulated microbubbles have been demonstrated to mechanically perturb cell membranes, resulting in the activation of biological signaling pathways that significantly enhance the effects of radiation. The underlying mechanism involves augmented ceramide production following both microbubble stimulation and irradiation, leading to rapid and extensive endothelial apoptosis and tumor cell death as a result of vascular collapse. Endothelial cells are particularly sensitive to ceramide-induced cell death due to an enriched presence of sphingomyelinase in their membranes. In tumors, this consequent rapid vascular shutdown translates to an overall increase in tumor responses to radiation treatments. This review summarizes the groundwork behind endothelial-based radiation enhancement with ultrasound-stimulated microbubbles, and presents ongoing research on the use of microbubbles as therapeutic agents in cancer therapy.

show abstract

Section: • Mechanisms Behind Mechanical Perturbation Of Cell Membranesmentioning

confidence: 63%

Biomechanical Effects of Microbubbles: From Radiosensitization to Cell Death

Kaffas

Czarnota

2015

Future Oncol.

View full text Add to dashboard Cite

show abstract

“…It has been shown that the growth of colon cancer in mice was effectively inhibited by USMBs, which was achieved by blood vessel disruption and tumor tissue damage [23]. Based on the susceptibility of endothelial cells to microbubbles, it was confirmed that USMBs can significantly enhance the radiosensitivity of a variety of tumors, such prostate, bladder, and breast cancers [5,24,25].…”

Section: Introductionmentioning

confidence: 75%

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

Deng

Cai

Feng

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded as a promising radiosensitizer. In this study, we investigated the effect of USMBs on the sensitivity of nasopharyngeal carcinoma (NPC) to radiation. Methods: Human NPC (CNE-2) cells and human umbilical vein endothelial cells (HUVECs) were exposed to radiation (0, 2, and 8 Gy) alone or in combination with USMBs. Cell viability and apoptosis were measured with the MTT assay and flow cytometry, respectively. The angiogenic activity of HUVECs was detected using matrigel tubule formation. The in vitro effects induced by these treatments were confirmed in vivo with xenograft models of CNE-2 cells in nude mice by examining vascular integrity using color Doppler flow imaging and cell survival using immunohistochemistry. Additionally, the in vivo and in vitro expressions of angiotensin II (ANG II) and its receptor (AT1R) were detected by immunohistochemistry and western blotting, respectively. With CNE-2 cells and HUVECs transfected with control, ANG II, or AT1R, perindopril (an inhibitor of angiotensin-converting enzyme) and candesartan (an inhibitor of AT1R) were used to verify the role of ANG II and AT1R in the radiosensitivity of tumor and endothelial cells by USMBs, by determining cell viability and apoptosis and angiogenic activity. Results: In the NPC xenografts, USMBs slightly reduced blood flow and CD34 expression, increased tumor cell death and ANG II and AT1R expression, and significantly enhanced the effects of radiation. With CNE-2 cells and HUVECs, the USMBs further enhanced the inhibition of tumor cell viability and endothelial tubule formation and further enhanced the increase in ANG II and AT1R due to radiation. Furthermore, perindopril and candesartan significantly enhanced the inhibitory effect of radiation and USMBs on tumor cell growth and angiogenesis in vitro. Conclusions: We have demonstrated for the first time that USMB exposure can significantly enhance the destructive effect on NPC of radiation, and this effect might be further increased by ANG II and AT1R inhibition. Our findings suggest that USMBs can be used as a promising sensitizer of radiotherapy to treat NPC, and the clinical effect might be increased by ANG II and AT1R inhibition.

show abstract

“…Exposure parameters are similar to that used with diagnostic ultrasound scans, with the exception that greater quantities of microbubbles are used to elicit an effect. On their own, the ultrasound effects described here result in minimal damage from which tissues recover but, when combined with radiation, result in striking amounts of cell death in tumours (AlMahrouki et al, 2012;Czarnota et al, 2012a,b;Tran et al, 2012;Nofiele et al, 2013).…”

Section: Microbubbles and Ultrasoundmentioning

confidence: 91%

Ultrasound-stimulated microbubble enhancement of radiation response

Czarnota¹

2015

Biological Chemistry

View full text Add to dashboard Cite

Cancer therapies result in the killing of cancer cells but remain largely ineffective, with most patients dying of their disease. The methodology described here is a new image-guided cancer treatment under development that relies on physical methods to alter tumour biology. It enhances tumour responses to radiation significantly by synergistically destroying tumour blood vessels using microbubbles. It achieves tumour specificity by confining the ultrasonic fields that stimulate microbubbles to tumour location only. By perturbing tumour vasculature and activating specific genetic pathways in endothelial cells, the technique has been demonstrated to sensitise the targeted tissues to subsequent therapeutic application of radiation, resulting in significantly enhanced cell killing through a ceramide-dependent pathway initiated at the cell membrane. The treatment reviewed here destroys blood vessels, significantly enhancing the anti-vascular effect of radiation and improving tumour cure. The significant enhancement of localised tumour cell kill observed with this method means that radiation-based treatments can be potentially made more potent and lower doses of radiation utilised. The technique has the potential to have a profound impact on the practice of radiation oncology by offering a novel and safe means of reducing normal tissue toxicity while at the same time significantly increasing treatment effectiveness.

show abstract

Microbubble and ultrasound radioenhancement of bladder cancer

Cited by 62 publications

References 27 publications

Biomechanical Effects of Microbubbles: From Radiosensitization to Cell Death

Biomechanical Effects of Microbubbles: From Radiosensitization to Cell Death

Ultrasound-Stimulated Microbubbles Enhance Radiosensitization of Nasopharyngeal Carcinoma

Ultrasound-stimulated microbubble enhancement of radiation response

Contact Info

Product

Resources

About