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Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors.

Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, Echigo S, Ohkubo Y, Fukumoto M - Cancer Med (2014)

Bottom Line: Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ.To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS-R, from SAS cells.We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, 980-8575, Japan.

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(A) Fractionated radiation (2 Gy/day) with Everolimus suppressed tumor growth in SAS and SAS-R tumors. Everolimus with 2 Gy/day of X-rays effectively reduced tumor volumes of SAS and SAS-R tumors. Mean ± SD of three independent mice. (B) Everolimus sensitivity of SAS and SAS-R cells and HMVECs determined by a cell proliferation assay. Everolimus sensitivity was similar among all cell lines examined. Mean ± SD in triplicate. (C) Radiation sensitivity of SAS and SAS-R cells and HMVECs with or without Everolimus. Everolimus significantly radiosensitized HMVECs, but not SAS or SAS-R cells, even at exposure to 2 Gy of X-rays. Mean ± SD in triplicate *P < 0.05. FR, fractionated radiation; HMVEC, Human dermal microvascular endothelial cells.
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fig04: (A) Fractionated radiation (2 Gy/day) with Everolimus suppressed tumor growth in SAS and SAS-R tumors. Everolimus with 2 Gy/day of X-rays effectively reduced tumor volumes of SAS and SAS-R tumors. Mean ± SD of three independent mice. (B) Everolimus sensitivity of SAS and SAS-R cells and HMVECs determined by a cell proliferation assay. Everolimus sensitivity was similar among all cell lines examined. Mean ± SD in triplicate. (C) Radiation sensitivity of SAS and SAS-R cells and HMVECs with or without Everolimus. Everolimus significantly radiosensitized HMVECs, but not SAS or SAS-R cells, even at exposure to 2 Gy of X-rays. Mean ± SD in triplicate *P < 0.05. FR, fractionated radiation; HMVEC, Human dermal microvascular endothelial cells.

Mentions: Until 10 days after each treatment, the tumor volume of SAS increased; thereafter, it gradually decreased in all the treatment groups with FR, FR with Everolimus, and Everolimus alone during the experimental period. The volume of SAS tumors with vehicle continuously increased (Fig. 4A). On the other hand, until 10 days after Everolimus treatment the tumor volume of SAS-R increased followed by gradual decrease, but the tumor volume remained larger than that at the beginning. SAS-R tumors grew by 5 days of the treatment with Everolimus and FR. Thereafter, the tumor volume shrunk. On day 30, the volume of SAS-R tumors treated with FR and Everolimus was smaller than the initial volume (day 0). The most effective treatment for the control of SAS-R tumors was the combination of FR with Everolimus.


Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors.

Kuwahara Y, Mori M, Kitahara S, Fukumoto M, Ezaki T, Mori S, Echigo S, Ohkubo Y, Fukumoto M - Cancer Med (2014)

(A) Fractionated radiation (2 Gy/day) with Everolimus suppressed tumor growth in SAS and SAS-R tumors. Everolimus with 2 Gy/day of X-rays effectively reduced tumor volumes of SAS and SAS-R tumors. Mean ± SD of three independent mice. (B) Everolimus sensitivity of SAS and SAS-R cells and HMVECs determined by a cell proliferation assay. Everolimus sensitivity was similar among all cell lines examined. Mean ± SD in triplicate. (C) Radiation sensitivity of SAS and SAS-R cells and HMVECs with or without Everolimus. Everolimus significantly radiosensitized HMVECs, but not SAS or SAS-R cells, even at exposure to 2 Gy of X-rays. Mean ± SD in triplicate *P < 0.05. FR, fractionated radiation; HMVEC, Human dermal microvascular endothelial cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3987081&req=5

fig04: (A) Fractionated radiation (2 Gy/day) with Everolimus suppressed tumor growth in SAS and SAS-R tumors. Everolimus with 2 Gy/day of X-rays effectively reduced tumor volumes of SAS and SAS-R tumors. Mean ± SD of three independent mice. (B) Everolimus sensitivity of SAS and SAS-R cells and HMVECs determined by a cell proliferation assay. Everolimus sensitivity was similar among all cell lines examined. Mean ± SD in triplicate. (C) Radiation sensitivity of SAS and SAS-R cells and HMVECs with or without Everolimus. Everolimus significantly radiosensitized HMVECs, but not SAS or SAS-R cells, even at exposure to 2 Gy of X-rays. Mean ± SD in triplicate *P < 0.05. FR, fractionated radiation; HMVEC, Human dermal microvascular endothelial cells.
Mentions: Until 10 days after each treatment, the tumor volume of SAS increased; thereafter, it gradually decreased in all the treatment groups with FR, FR with Everolimus, and Everolimus alone during the experimental period. The volume of SAS tumors with vehicle continuously increased (Fig. 4A). On the other hand, until 10 days after Everolimus treatment the tumor volume of SAS-R increased followed by gradual decrease, but the tumor volume remained larger than that at the beginning. SAS-R tumors grew by 5 days of the treatment with Everolimus and FR. Thereafter, the tumor volume shrunk. On day 30, the volume of SAS-R tumors treated with FR and Everolimus was smaller than the initial volume (day 0). The most effective treatment for the control of SAS-R tumors was the combination of FR with Everolimus.

Bottom Line: Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ.To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS-R, from SAS cells.We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, 980-8575, Japan.

Show MeSH
Related in: MedlinePlus