東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back to Search results for [ null ]

Switch To: Labeled | MARC Mode | ISBD

Linked to FindBook

Google Book

Amazon

博客來

p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance.

Record Type:	Electronic resources : Monograph/item
Title/Author:	p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance./
Author:	Cheteh, Emarndeena H.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2020,
Description:	58 p.
Notes:	Source: Dissertations Abstracts International, Volume: 82-08, Section: B.
Contained By:	Dissertations Abstracts International82-08B.
Subject:	Cellular biology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28420728
ISBN:	9798582530701

p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance.
Cheteh, Emarndeena H.

p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance. - Ann Arbor : ProQuest Dissertations & Theses, 2020 - 58 p.

Source: Dissertations Abstracts International, Volume: 82-08, Section: B.

Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2020.

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

Drug resistance remains as a major problem and a daunting challenge to successful anti cancer treatment. Cancer cells are masters of adaptation. Novel drugs that attack cancer in new ways and target key drivers of cancer cell growth are, therefore, urgently needed. At the same time, the more genetically stable cells of the tumor microenvironment are being recognized as important players in tumor development that can confer resistance to anticancer drugs. Increasing attention is being paid to the tumor microenvironment, including cancer-associated fibroblasts (CAFs). Furthermore, the tumor suppressor gene TP53, which codes for the p53 protein, plays an important role in tumor suppression and cellular stress responses to DNA damage and anti-cancer agents. For this reason, the TP53 gene is frequently mutated in cancer. In the absence of mutations, the p53 protein is often downregulated or inactivated through other mechanisms.This thesis aims to elucidate pathways or mechanisms that contribute to CAF-mediated drug resistance in prostate cancer. The thesis is also focused on investigating a combinatorial therapeutic strategy to improve the effectiveness of the mutant p53-reactivating compoundAPR-246.The studies in paper I and II revealed that CAFs can enhance cell survival, and affect the sensitivity of prostate cancer cells carrying wild type p53 to chemotherapeutic drugs through different mechanisms. In the paper I, we showed that glutathione, produced by CAFs, protects cancer cells from drug-induced oxidative stress and DNA damage, as it also decreases drug accumulation. In the paper II, we demonstrated that IL-6, one of the soluble factors secreted by CAFs, attenuates the drug-induced p53 response through STAT3 andMDM2. The increased resistance to chemotherapeutic drugs is likely to be a result of the combined effect of glutathione and cytokines like IL-6. In the paper III, we found that inhibition of the efflux pump MRP1 enhances APR-246-induced mutant p53 cancer cell death both in vitro and in vivo. This study also highlighted the impact of the cellular redox status and glutathione content on cancer cell survival and anti-tumor activity of APR-246.In conclusion, pathways or factors that potentially contribute to drug resistance have been the focus of this thesis. Manipulation of these targets in combination with traditional therapies may lead to a more efficient cancer therapy. This thesis also highlights CAFs as a potential target for anti-stromal therapies in prostate cancer.

ISBN: 9798582530701Subjects--Topical Terms:

3172791
Cellular biology.
Subjects--Index Terms:

Drug resistance

p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance.
LDR:03845nmm a2200409 4500 001 2346140
005 20220613065112.5
008 241004s2020 ||||||||||||||||| ||eng d
020 $a 9798582530701
035 $a (MiAaPQ)AAI28420728
035 $a (MiAaPQ)Karolinska_1061647340
035 $a AAI28420728
040 $a MiAaPQ $c MiAaPQ
100 1 $a Cheteh, Emarndeena H. $3 3685187
245 1 0 $a p53 and Cancer-Associated Fibroblasts: Implications for Cancer Therapy and Drug Resistance.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2020
300 $a 58 p.
500 $a Source: Dissertations Abstracts International, Volume: 82-08, Section: B.
500 $a Advisor: Wiman, Klas G.;Ostman, Arne.
502 $a Thesis (Ph.D.)--Karolinska Institutet (Sweden), 2020.
506 $a This item must not be sold to any third party vendors.
520 $a Drug resistance remains as a major problem and a daunting challenge to successful anti cancer treatment. Cancer cells are masters of adaptation. Novel drugs that attack cancer in new ways and target key drivers of cancer cell growth are, therefore, urgently needed. At the same time, the more genetically stable cells of the tumor microenvironment are being recognized as important players in tumor development that can confer resistance to anticancer drugs. Increasing attention is being paid to the tumor microenvironment, including cancer-associated fibroblasts (CAFs). Furthermore, the tumor suppressor gene TP53, which codes for the p53 protein, plays an important role in tumor suppression and cellular stress responses to DNA damage and anti-cancer agents. For this reason, the TP53 gene is frequently mutated in cancer. In the absence of mutations, the p53 protein is often downregulated or inactivated through other mechanisms.This thesis aims to elucidate pathways or mechanisms that contribute to CAF-mediated drug resistance in prostate cancer. The thesis is also focused on investigating a combinatorial therapeutic strategy to improve the effectiveness of the mutant p53-reactivating compoundAPR-246.The studies in paper I and II revealed that CAFs can enhance cell survival, and affect the sensitivity of prostate cancer cells carrying wild type p53 to chemotherapeutic drugs through different mechanisms. In the paper I, we showed that glutathione, produced by CAFs, protects cancer cells from drug-induced oxidative stress and DNA damage, as it also decreases drug accumulation. In the paper II, we demonstrated that IL-6, one of the soluble factors secreted by CAFs, attenuates the drug-induced p53 response through STAT3 andMDM2. The increased resistance to chemotherapeutic drugs is likely to be a result of the combined effect of glutathione and cytokines like IL-6. In the paper III, we found that inhibition of the efflux pump MRP1 enhances APR-246-induced mutant p53 cancer cell death both in vitro and in vivo. This study also highlighted the impact of the cellular redox status and glutathione content on cancer cell survival and anti-tumor activity of APR-246.In conclusion, pathways or factors that potentially contribute to drug resistance have been the focus of this thesis. Manipulation of these targets in combination with traditional therapies may lead to a more efficient cancer therapy. This thesis also highlights CAFs as a potential target for anti-stromal therapies in prostate cancer.
590 $a School code: 0658.
650 4 $a Cellular biology. $3 3172791
650 4 $a Oncology. $3 751006
650 4 $a Pathology. $3 643180
650 4 $a Biochemistry. $3 518028
653 $a Drug resistance
653 $a Anti cancer treatment
653 $a Cancer-associated fibroblasts
653 $a CAF-mediated drug resistance
653 $a Prostate cancer
653 $a Wild type p53
690 $a 0379
690 $a 0992
690 $a 0487
690 $a 0571
710 2 $a Karolinska Institutet (Sweden). $3 3557748
773 0 $t Dissertations Abstracts International $g 82-08B.
790 $a 0658
791 $a Ph.D.
792 $a 2020
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=28420728