Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.
Galectin-1 Inhibitor OTX008 Induces Tumor Vessel Normalization and Tumor Growth Inhibition in Human Head and Neck Squamous Cell Carcinoma Models.
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DOI：
10.3390/ijms18122671
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发表时间：
2017-12-09
影响因子：
5.6
通讯作者：
Dings RPM
中科院分区：
文献类型：
--
作者：
Koonce NA;Griffin RJ;Dings RPM
Galectin-1 is a hypoxia-regulated protein and a prognostic marker in head and neck squamous cell carcinomas (HNSCC). Here we assessed the ability of non-peptidic galectin-1 inhibitor OTX008 to improve tumor oxygenation levels via tumor vessel normalization as well as tumor growth inhibition in two human HNSCC tumor models, the human laryngeal squamous carcinoma SQ20B and the human epithelial type 2 HEp-2. Tumor-bearing mice were treated with OTX008, Anginex, or Avastin and oxygen levels were determined by fiber-optics and molecular marker pimonidazole binding. Immuno-fluorescence was used to determine vessel normalization status. Continued OTX008 treatment caused a transient reoxygenation in SQ20B tumors peaking on day 14, while a steady increase in tumor oxygenation was observed over 21 days in the HEp-2 model. A >50% decrease in immunohistochemical staining for tumor hypoxia verified the oxygenation data measured using a partial pressure of oxygen (pO2) probe. Additionally, OTX008 induced tumor vessel normalization as tumor pericyte coverage increased by approximately 40% without inducing any toxicity. Moreover, OTX008 inhibited tumor growth as effectively as Anginex and Avastin, except in the HEp-2 model where Avastin was found to suspend tumor growth. Galectin-1 inhibitor OTX008 transiently increased overall tumor oxygenation via vessel normalization to various degrees in both HNSCC models. These findings suggest that targeting galectin-1—e.g., by OTX008—may be an effective approach to treat cancer patients as stand-alone therapy or in combination with other standards of care.
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影响因子：
7.3
作者：
Dings, Ruud P. M.;Miller, Michelle C.;Nesmelova, Irina;Astorgues-Xerri, Lucile;Kumar, Nigam;Serova, Maria;Chen, Xuimei;Raymond, Eric;Hoye, Thomas R.;Mayo, Kevin H.
通讯作者：
Mayo, Kevin H.
影响因子：
16.6
作者：
Cumpstey, I;Sundin, A;Nilsson, UJ
通讯作者：
Nilsson, UJ
影响因子：
9.7
作者：
Dings, RPM;van der Schaft, DWJ;Mayo, KH
通讯作者：
Mayo, KH
DOI：
10.4331/wjbc.v2.i9.193
发表时间：
2011-09-26
期刊：
World journal of biological chemistry
影响因子：
--
作者：
Lefranc, Florence;Mathieu, Veronique;Kiss, Robert
通讯作者：
Kiss, Robert
影响因子：
8.4
作者：
Astorgues-Xerri, Lucile;Riveiro, Maria E.;Raymond, Eric
通讯作者：
Raymond, Eric