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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) Immunohistochemical analysis of CD34-positive blood vessels (arrow heads) in xenografted tumors without any treatments. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors. (B) Blood vessel density determined by tomato lectin labeling in SAS and SAS-R tumors. Tomato lectin labeling of the luminal endothelial cell surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors. (C) Immunohistochemical staining of VEGF-A. SAS-R tumor cells had stronger immunostaining for VEGF-A than SAS tumor cells. (D) VEGF-A production from SAS and SAS-R cells in vitro determined by ELISA. Twofold secretion of VEGF-A from SAS-R cells compared to SAS was detected. *P < 0.01. MVD, microvessel density; VEGF, vascular endothelial growth factor.
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fig02: (A) Immunohistochemical analysis of CD34-positive blood vessels (arrow heads) in xenografted tumors without any treatments. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors. (B) Blood vessel density determined by tomato lectin labeling in SAS and SAS-R tumors. Tomato lectin labeling of the luminal endothelial cell surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors. (C) Immunohistochemical staining of VEGF-A. SAS-R tumor cells had stronger immunostaining for VEGF-A than SAS tumor cells. (D) VEGF-A production from SAS and SAS-R cells in vitro determined by ELISA. Twofold secretion of VEGF-A from SAS-R cells compared to SAS was detected. *P < 0.01. MVD, microvessel density; VEGF, vascular endothelial growth factor.

Mentions: Connective tissues were more abundant in SAS-R tumors than in SAS tumors (Fig. 1B). This observation prompted us to examine MVD in SAS and SAS-R tumors. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors (Fig. 2A). Tomato lectin labeling of the luminal EC surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors (Fig. 2B). This suggested that angiogenesis was activated in SAS-R tumors. MVD was also higher in HeLa-R tumors than in HeLa tumors (data not shown).


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) Immunohistochemical analysis of CD34-positive blood vessels (arrow heads) in xenografted tumors without any treatments. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors. (B) Blood vessel density determined by tomato lectin labeling in SAS and SAS-R tumors. Tomato lectin labeling of the luminal endothelial cell surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors. (C) Immunohistochemical staining of VEGF-A. SAS-R tumor cells had stronger immunostaining for VEGF-A than SAS tumor cells. (D) VEGF-A production from SAS and SAS-R cells in vitro determined by ELISA. Twofold secretion of VEGF-A from SAS-R cells compared to SAS was detected. *P < 0.01. MVD, microvessel density; VEGF, vascular endothelial growth factor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig02: (A) Immunohistochemical analysis of CD34-positive blood vessels (arrow heads) in xenografted tumors without any treatments. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors. (B) Blood vessel density determined by tomato lectin labeling in SAS and SAS-R tumors. Tomato lectin labeling of the luminal endothelial cell surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors. (C) Immunohistochemical staining of VEGF-A. SAS-R tumor cells had stronger immunostaining for VEGF-A than SAS tumor cells. (D) VEGF-A production from SAS and SAS-R cells in vitro determined by ELISA. Twofold secretion of VEGF-A from SAS-R cells compared to SAS was detected. *P < 0.01. MVD, microvessel density; VEGF, vascular endothelial growth factor.
Mentions: Connective tissues were more abundant in SAS-R tumors than in SAS tumors (Fig. 1B). This observation prompted us to examine MVD in SAS and SAS-R tumors. CD34 immunostaining confirmed that MVD in SAS-R tumors was higher than in SAS tumors (Fig. 2A). Tomato lectin labeling of the luminal EC surface showed that MVD with blood flow was higher in SAS-R tumors compared to in SAS tumors (Fig. 2B). This suggested that angiogenesis was activated in SAS-R tumors. MVD was also higher in HeLa-R tumors than in HeLa tumors (data not shown).

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