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Characterization of the tumor microe...

Kane, Jonathan Lawrence.

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Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery./
Author:	Kane, Jonathan Lawrence.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
Description:	117 p.
Notes:	Source: Dissertation Abstracts International, Volume: 78-02(E), Section: B.
Contained By:	Dissertation Abstracts International78-02B(E).
Subject:	Biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10169335
ISBN:	9781369235319

Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery.
Kane, Jonathan Lawrence.

Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 117 p.

Source: Dissertation Abstracts International, Volume: 78-02(E), Section: B.

Thesis (Ph.D.)--Oakland University, 2016.

Radiation therapy is a key component in the clinical management of most solid tumors. The goal of RT is to produce DNA double strand breaks in malignant cells and induce direct cell death via mitotic and apoptotic mechanisms [1,2]. In response to cell death caused by RT, intratumoral hypoxia develops causing a cascade of cellular signaling recruiting regulatory cells to aid in tumor re-growth. The purpose of this study is to characterize the recruitment and localization of bone marrow-derived HSPCs within the TME after changes in RT.

ISBN: 9781369235319Subjects--Topical Terms:

522710
Biology.

Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery.
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100 1 $a Kane, Jonathan Lawrence. $3 3282961
245 1 0 $a Characterization of the tumor microenvironment and bone marrow derived-cell migration in response to changes in radiation delivery.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 117 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-02(E), Section: B.
500 $a Adviser: Gerard James Madlambayan.
502 $a Thesis (Ph.D.)--Oakland University, 2016.
520 $a Radiation therapy is a key component in the clinical management of most solid tumors. The goal of RT is to produce DNA double strand breaks in malignant cells and induce direct cell death via mitotic and apoptotic mechanisms [1,2]. In response to cell death caused by RT, intratumoral hypoxia develops causing a cascade of cellular signaling recruiting regulatory cells to aid in tumor re-growth. The purpose of this study is to characterize the recruitment and localization of bone marrow-derived HSPCs within the TME after changes in RT.
520 $a Here, we demonstrate that a hypofractionated radiation delivery regimen (2x15 Gy) significantly reduced tumor volumes and slowed tumor re-growth rates compared with non-irradiated controls. In addition, we found that the number of CD133+ HSPCs present in irradiated tumors was higher than in non-irradiated tumors during early, late, and terminal stages of regrowth post RT. This finding was further verified through PET/CT imaging and growth rate analysis based on SUV indicating that the recruitment of HSPCs directly correlated to the extent of re-growth and intra-tumor cell activity post RT. In addition, BM-derived tumor-associated CD 133+ HSPCs successfully formed hematopoietic colonies and engrafted into recipient BM post-irradiation. Based on these findings we explored clinically relevant and novel radiation delivery regimens to observe if the TME can be manipulated to offer therapeutic benefit. Here we showed that PRT was more effective than SRT at reducing tumor volume and growth rate. Histopathology analysis showed a significant comparative reduction in the levels of Ki-67, hypoxia, VEGF, SDF-la as well as a concomitant decrease in CD45+ BMDC migration after PRT. Based on the finding that HSPCs maintain their functionality within the tumor we hypothesized that a supportive niche exists within the TME similar to that of the BM. Here we will investigate the effects of PRT and SRT on known factors expressed in the TME that are involved in BMDC activity in the bone marrow.
520 $a Overall our studies implicate that radiation can be used as a tool to manipulate the TME ultimately offering superior therapeutic benefit; therefore personalizing treatment to specific tumor types, like PRT, should be considered in advancing cancer therapies.
590 $a School code: 0446.
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650 4 $a Immunology. $3 611031
650 4 $a Cellular biology. $3 3172791
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710 2 $a Oakland University. $3 1019306
773 0 $t Dissertation Abstracts International $g 78-02B(E).
790 $a 0446
791 $a Ph.D.
792 $a 2016
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10169335