Search

Your search keyword '"Mangala, L. S"' showing total 6 results
Start Over Author "Mangala, L. S" Publication Year Range Last 10 years
6 results on '"Mangala, L. S"'

4. Role of CTGF in Sensitivity to Hyperthermia in Ovarian and Uterine Cancers

Author

Hatakeyama, H., Wu, S. Y., Lyons, Y. A., Pradeep, S., Wang, W., Huang, Q., Court, K. A., Liu, T., Nie, S., Rodriguez-Aguayo, C., Shen, F., Huang, Y., Hisamatsu, T., Mitamura, T., Jennings, N., Shim, J., Dorniak, P. L., Mangala, L. S., Petrillo, Marco, Petyuk, V. A., Schepmoes, A. A., Shukla, A. K., Torres-Lugo, M., Lee, J. -S., Rodland, K. D., Fagotti, Anna, Lopez-Berestein, G., Li, C., Sood, A. K., Petrillo M., Fagotti A. (ORCID:0000-0001-5579-335X), Hatakeyama, H., Wu, S. Y., Lyons, Y. A., Pradeep, S., Wang, W., Huang, Q., Court, K. A., Liu, T., Nie, S., Rodriguez-Aguayo, C., Shen, F., Huang, Y., Hisamatsu, T., Mitamura, T., Jennings, N., Shim, J., Dorniak, P. L., Mangala, L. S., Petrillo, Marco, Petyuk, V. A., Schepmoes, A. A., Shukla, A. K., Torres-Lugo, M., Lee, J. -S., Rodland, K. D., Fagotti, Anna, Lopez-Berestein, G., Li, C., Sood, A. K., Petrillo M., and Fagotti A. (ORCID:0000-0001-5579-335X)

Abstract

Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. CTGF silencing aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.

Published
2016

6. Antiangiogenic and tumour inhibitory effects of downregulating tumour endothelial FABP4

Author

Harjes, U, Bridges, E, Gharpure, K M, Roxanis, I, Sheldon, H, Miranda, F, Mangala, L S, Pradeep, S, Lopez-Berestein, G, Ahmed, A, Fielding, B, Sood, A K, and Harris, A L

Abstract

Fatty acid binding protein 4 (FABP4) is a fatty acid chaperone, which is induced during adipocyte differentiation. Previously we have shown that FABP4 in endothelial cells is induced by the NOTCH1 signalling pathway, the latter of which is involved in mechanisms of resistance to antiangiogenic tumour therapy. Here, we investigated the role of FABP4 in endothelial fatty acid metabolism and tumour angiogenesis. We analysed the effect of transient FABP4 knockdown in human umbilical vein endothelial cells on fatty acid metabolism, viability and angiogenesis. Through therapeutic delivery of siRNA targeting mouse FABP4, we investigated the effect of endothelial FABP4 knockdown on tumour growth and blood vessel formation. In vitro, siRNA-mediated FABP4 knockdown in endothelial cells led to a marked increase of endothelial fatty acid oxidation, an increase of reactive oxygen species and decreased angiogenesis. In vivo, we found that increased NOTCH1 signalling in tumour xenografts led to increased expression of endothelial FABP4 that decreased when NOTCH1 and VEGFA inhibitors were used in combination. Angiogenesis, growth and metastasis in ovarian tumour xenografts were markedly inhibited by therapeutic siRNA delivery targeting mouse endothelial FABP4. Therapeutic targeting of endothelial FABP4 by siRNA in vivo has antiangiogenic and antitumour effects with minimal toxicity and should be investigated further.

Published
2017
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results