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Acetazolamide Potentiates the Anti-T...

Bayat Mokhtari, Reza .

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Acetazolamide Potentiates the Anti-Tumor Efficacy of Sulforaphane and HDAC Inhibitor, MS-275, on Bronchial Carcinoids and Neuroblastoma.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Acetazolamide Potentiates the Anti-Tumor Efficacy of Sulforaphane and HDAC Inhibitor, MS-275, on Bronchial Carcinoids and Neuroblastoma./
作者:	Bayat Mokhtari, Reza .
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	357 p.
附註:	Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Contained By:	Dissertations Abstracts International81-05B.
標題:	Medicine. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=27540563
ISBN:	9781392585191

Acetazolamide Potentiates the Anti-Tumor Efficacy of Sulforaphane and HDAC Inhibitor, MS-275, on Bronchial Carcinoids and Neuroblastoma.
Bayat Mokhtari, Reza .

Acetazolamide Potentiates the Anti-Tumor Efficacy of Sulforaphane and HDAC Inhibitor, MS-275, on Bronchial Carcinoids and Neuroblastoma. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 357 p.

Source: Dissertations Abstracts International, Volume: 81-05, Section: B.

Thesis (Ph.D.)--University of Toronto (Canada), 2019.

This item must not be sold to any third party vendors.

Bronchial carcinoids (BC) and neuroblastoma (NB) are subgroups of neuroendocrine tumors of the lung and peripheral nervous system, respectively. BC present mainly in adults, and NB in children. BC accounts for 1-5% of all invasive lung malignancies and the atypical variant has a poor prognosis. NB accounts for 7-8% of all childhood cancers portending <50% survival in advanced stages. Current therapies have only moderately improved progression-free survival in the advanced stages. Therefore, a different therapeutic approach is needed. Previous studies in our lab identified dietary polyphenolic potent anti-tumor agents (nutraceuticals) against NB. Epidemiological evidence pointed to anti-cancer nutraceuticals , with chemopreventive activity, present in the Mediterranean diet, e.g., the isothiocyanate, sulforaphane (SFN). Previously, we found that carbonic anhydrases (CA) play an important role in tumour cell survival through maintenance of critical pH homeostasis, and showed that the pan-CA inhibitor, acetazolamide (AZ), suppressed carcinoid growth and survival. We thus reasoned that AZ could potentiate the anti-tumor ability of SFN by disrupting the tumor microenvironment along with targeting critical tumor survival pathways and inhibiting important transcriptional factors mediating progression such as VEGF and HIFs. Since SFN was shown to act as a histone deacetylase inhibitor (HDACi), we posited that other HDACi, like the semisynthetic clinically trialed HDACi, MS-275, could also be potentiated. Therefore, we evaluated SFN and MS-275 alone and in combination with AZ on BC and NB, respectively, in-vitro, and in-vivo models. We now show efficacy for SFN and MS-275 alone, and a potentiating effect in combination with AZ. BC and NB growth, and tumorigenicity were significantly compromised. Our studies support a new concept in cancer therapy utilizing nutraceutical compounds with intrinsically low cytotoxicity and HDACi activity that can be potentiated by targeting pH homeostasis. Thus, such combinations might present a promising therapeutic regimen for translation into clinical trials.

ISBN: 9781392585191Subjects--Topical Terms:

641104
Medicine.
Subjects--Index Terms:

Acetazolamide

Acetazolamide Potentiates the Anti-Tumor Efficacy of Sulforaphane and HDAC Inhibitor, MS-275, on Bronchial Carcinoids and Neuroblastoma.
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