東華大學圖書館 |

Language: English

Help

回圖書館首頁

手機版館藏查詢

Back

Switch To: Labeled | MARC Mode | ISBD

Genome-wide CRISPR Screen Reveals Re...

Han, Han.

Linked to FindBook

Google Book

Amazon

博客來

Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma./
Author:	Han, Han.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2023,
Description:	130 p.
Notes:	Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
Contained By:	Dissertations Abstracts International85-03B.
Subject:	Biology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30310979
ISBN:	9798380367875

Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma.
Han, Han.

Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma. - Ann Arbor : ProQuest Dissertations & Theses, 2023 - 130 p.

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

Thesis (Ph.D.)--State University of New York at Stony Brook, 2023.

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

Pancreatic ductal adenocarcinomas (PDACs) are resistant to systemic treatments including immunotherapy. Over 90% of PDACs have oncogenic KRAS mutations, and phosphoinositide 3- kinases (PI3Ks) are direct effectors of KRAS. Previously, we demonstrated that genetic ablation of PI3K isoform, Pik3ca in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line induced complete tumor elimination by infiltrating T cells in a mouse model. However, clinical trials using PI3K inhibitors for PDAC patients exhibited limited efficacy due to drug resistance. To identify potential contributors to PI3K inhibitor resistance, we conducted an in vivo genome-wide gene-deletion screen using the Pik3ca-/- KPC (αKO) cells implanted in the mouse pancreas and identified propionyl-CoA carboxylase subunit B (PCCB) modulates PIK3CA-mediated immune evasion. Deletion of Pccb gene in αKO cells (named p-αKO) allowed tumor progression causing death of host mice even though p-αKO tumors are infiltrated with T cells. Single-cell RNA sequencing revealed that infiltrating clonally expanded T cells in p-αKO tumors were more exhausted as compared to T cells founds in αKO tumors. Blockade of PD-L1/PD1 interaction reversed T cell exhaustion, slowed tumor growth and improved the survival of mice implanted with p-αKO cells. These results indicate that propionyl-CoA carboxylase activity can modulate PIK3CA-regulated immune surveillance of PDAC.

ISBN: 9798380367875Subjects--Topical Terms:

522710
Biology.
Subjects--Index Terms:

CRISPR screen

Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma.
LDR:02755nmm a2200421 4500 001 2393904
005 20240414211918.5
006 m o d
007 cr#unu||||||||
008 251215s2023 ||||||||||||||||| ||eng d
020 $a 9798380367875
035 $a (MiAaPQ)AAI30310979
035 $a AAI30310979
040 $a MiAaPQ $c MiAaPQ
100 1 $a Han, Han. $3 1033727
245 1 0 $a Genome-wide CRISPR Screen Reveals Regulators of PI3K Inhibitor Resistance in Pancreatic Ductal Adenocarcinoma.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2023
300 $a 130 p.
500 $a Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
500 $a Advisor: Lin, Richard Z.
502 $a Thesis (Ph.D.)--State University of New York at Stony Brook, 2023.
506 $a This item must not be sold to any third party vendors.
520 $a Pancreatic ductal adenocarcinomas (PDACs) are resistant to systemic treatments including immunotherapy. Over 90% of PDACs have oncogenic KRAS mutations, and phosphoinositide 3- kinases (PI3Ks) are direct effectors of KRAS. Previously, we demonstrated that genetic ablation of PI3K isoform, Pik3ca in the KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cell line induced complete tumor elimination by infiltrating T cells in a mouse model. However, clinical trials using PI3K inhibitors for PDAC patients exhibited limited efficacy due to drug resistance. To identify potential contributors to PI3K inhibitor resistance, we conducted an in vivo genome-wide gene-deletion screen using the Pik3ca-/- KPC (αKO) cells implanted in the mouse pancreas and identified propionyl-CoA carboxylase subunit B (PCCB) modulates PIK3CA-mediated immune evasion. Deletion of Pccb gene in αKO cells (named p-αKO) allowed tumor progression causing death of host mice even though p-αKO tumors are infiltrated with T cells. Single-cell RNA sequencing revealed that infiltrating clonally expanded T cells in p-αKO tumors were more exhausted as compared to T cells founds in αKO tumors. Blockade of PD-L1/PD1 interaction reversed T cell exhaustion, slowed tumor growth and improved the survival of mice implanted with p-αKO cells. These results indicate that propionyl-CoA carboxylase activity can modulate PIK3CA-regulated immune surveillance of PDAC.
590 $a School code: 0771.
650 4 $a Biology. $3 522710
650 4 $a Bioengineering. $3 657580
650 4 $a Biomedical engineering. $3 535387
650 4 $a Oncology. $3 751006
650 4 $a Molecular biology. $3 517296
653 $a CRISPR screen
653 $a T cells
653 $a Pancreatic cancer
653 $a Immunotherapy
653 $a PI3K inhibitor resistance
690 $a 0306
690 $a 0202
690 $a 0992
690 $a 0541
690 $a 0307
710 2 $a State University of New York at Stony Brook. $b Biomedical Engineering. $3 3287237
773 0 $t Dissertations Abstracts International $g 85-03B.
790 $a 0771
791 $a Ph.D.
792 $a 2023
793 $a English
856 4 0 $u https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=30310979