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1.
Cells ; 8(9)2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31540078

RESUMO

Loss of the Adenomatous Polyposis Coli (APC) tumor suppressor in colorectal cancer elicits rapid signaling through the Wnt/ß-catenin signaling pathway. In contrast to this well-established role of APC, recent studies from our laboratory demonstrated that APC functions through Wnt-independent pathways to mediate in vitro and in vivo models of breast tumorigenesis. Pancreatic ductal adenocarcinoma (PDAC) has an overall median survival of less than one year with a 5-year survival rate of 7.2%. APC is lost in a subset of pancreatic cancers, but the impact on Wnt signaling or tumor development is unclear. Given the lack of effective treatment strategies for pancreatic cancer, it is important to understand the functional implications of APC loss in pancreatic cancer cell lines. Therefore, the goal of this project is to study how APC loss affects Wnt pathway activation and in vitro tumor phenotypes. Using lentiviral shRNA, we successfully knocked down APC expression in six pancreatic cancer cell lines (AsPC-1, BxPC3, L3.6pl, HPAF-II, Hs 766T, MIA PaCa-2). No changes were observed in localization of ß-catenin or reporter assays to assess ß-catenin/TCF interaction. Despite this lack of Wnt/ß-catenin pathway activation, the majority of APC knockdown cell lines exhibit an increase in cell proliferation. Cell migration assays showed that the BxPC-3 and L3.6pl cells were impacted by APC knockdown, showing faster wound healing in scratch wound assays. Interestingly, APC knockdown had no effect on gemcitabine treatment, which is the standard care for pancreatic cancer. It is important to understand the functional implications of APC loss in pancreatic cancer cells lines, which could be used as a target for therapeutics.


Assuntos
Proteína da Polipose Adenomatosa do Colo/deficiência , Proteína da Polipose Adenomatosa do Colo/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Via de Sinalização Wnt/genética
2.
Animals (Basel) ; 6(2)2016 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-26848694

RESUMO

Long-distance dog transfer programs are a topic of burgeoning interest in the animal welfare community, but little research has focused on such programs. This exploratory study, which surveyed 193 individuals associated with animal shelter and rescue organizations in the United States, evaluated factors that impacted organizations' decisions to transfer in dogs over long distances (>100 miles) and assessed what criteria were commonly valued by destination organizations. Specifically, we examined the following aspects of long-distance transfer programs: (1) logistics of long-distance dog transfers; (2) factors impacting dog selection; (3) medical requirements; (4) partnerships formed between source and destination organizations; and (5) perceptions of long-distance dog transfer programs by individuals affiliated with the destination organizations. This study revealed that many logistical considerations factor into transfer decisions and the formation of healthy partnerships between source and destination organizations. Participants indicated their organization's willingness to receive dogs of various sizes, coat colors and ages, but organizations often had restrictions regarding the breeds they would accept. Study findings indicate some organizations have strict quarantine policies and pre-transfer medical requirements, while others have no such requirements.

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