Cell‐specific Cytotoxicity of Human Pancreatic Adenocarcinoma Cells Using Rat Insulin Promoter Thymidine Kinase‐directed Gene Therapy

Tirone, Thomas A.; Wang, Xaio-Ping; Templeton, Nancy Smyth; Lee, Tim; Nguyen, Liz; Fisher, William E.; Brunicardi, F. Charles

doi:10.1007/s00268-004-7291-x

Cited by 21 publications

(40 citation statements)

References 47 publications

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“…So far, PDX1 has been proved to promote Kras G12D oncogenic proteininduced development of PanIN, metaplasia and PDAC. Overexpression of PDX1 in benign human cells (HEK293 and Human pancreatic ductal cells), as well as PDAC cell lines (PANC1 and MiaPaca2) and insulinoma cell lines (Min6 and βTC6 cells) lead to significant increases in cell proliferation, invasion and colony formation in vitro, as well as promotion of tumor growth in xenograft severe combined immunodeficiency (SCID) mouse models (8)(9)(10)(11)(12). These studies suggest that PDX1 is involved in tumorigenesis of both PDAC and insulinoma.…”

Section: Pdx1 and Pdx1 Involved Diseasesmentioning

confidence: 82%

PDX1 associated therapy in translational medicine

Yu¹,

Liu²,

Sanchez³

et al. 2016

Ann. Transl. Med.

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely poor prognosis and a low median survival due to lack of the early and reliable detection and effective therapeutic options, despite improvements observed for many other cancers in last decade. Pancreatic and duodenal homeobox 1 (PDX1), which is a homeodomain-containing transcription factor and a key regulator for insulin gene expression, β cell maturation and proper β cell function maintenance in the pancreas. Our previous studies revealed that PDX1 promotes tumorigenesis and it is a promising therapeutic target for PDAC. For translational purposes, we developed three therapeutic platforms utilizing RNA interference (RNAi), gene therapy and small inhibitory drug targeting PDX1, and further validated them in PDAC preclinical models both in vitro and in vivo. These PDX1 targeted therapies significantly inhibited PDX1 expression in PDAC cells, ablated PDX1-expressing human PDAC xenograft tumor growth, and prolonged survival in the PDAC mouse models. The data from these preclinical studies proved the translational potentials of PDX1 targeted therapies in PDAC and suggest that the strategy of developing PDX1 targeted therapies would permit a rapid bench-to-bedside translation of other relevant gene therapies, which would eventually benefit the patients suffering from this deadly disease.

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Section: Pdx1 and Pdx1 Involved Diseasesmentioning

confidence: 82%

PDX1 associated therapy in translational medicine

Yu¹,

Liu²,

Sanchez³

et al. 2016

Ann. Transl. Med.

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“…25,26 In this study, we used the PTCH1 gene promoter to construct a transgenic vector. It has been recently reported that there are seven alternative first exons of PTCH1 (exon 1a, exon 1a 0 , exon 1b, exon 1c, exon 1c 0 , exon 1d and exon 1e), which are differentially regulated by independent promoters in various normal and tumor tissues.…”

Section: Discussionmentioning

confidence: 99%

Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer

Gao

Chen

et al. 2006

Gene Ther

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“…Over the past decade, there has been a large body of evidence supporting the aberrant expression of PDX-1 in malignant tumors, including pancreatic (6), prostate (7), stomach (8,9), colon (10) and breast cancers (11,12). In pancreatic cancer, PDX-1 induces increased cell proliferation, invasion and colony formation in vitro.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: A mechanism of proliferation and apoptosis in cancer

et al. 2012

Molecular Medicine Reports

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Abstract. Pancreatic-duodenal homeobox 1 (PDX-1) is a transcription factor that regulates embryological pancreas development and insulin expression in adult islets. The current study investigated the expression profile and potential role of PDX-1 in breast cancer. Immunohistochemistry was performed to determine the expression pattern of PDX-1 in breast cancer and adjacent benign breast tissues. In addition, cell proliferation and the cell cycle were evaluated following the transient inhibition of PDX-1 with antisense oligonucleotides in MCF-7 human breast cancer cells. Real-time PCR and western blotting were conducted to investigate the correlation between PDX-1, P53, Ki-67, Caspase 3 and Caspase 8. These experiments demonstrated that PDX-1 was downregulated in human breast cancer tissue compared with adjacent normal breast tissue. Knockdown of PDX-1 expression in vitro in MCF-7 breast cancer cells promoted cell proliferation and disrupted the cell cycle, as demonstrated by the overexpression of P53 and Ki-67 at the mRNA and protein levels. In conclusion, the current study shows that PDX-1 regulates cell proliferation and the cell cycle in human breast cancer cells by altering the expression of the cell cycle-related genes, P53 and Ki-67. These data suggest that PDX-1 is a putative tumor suppressor in breast cancer.

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Cell‐specific Cytotoxicity of Human Pancreatic Adenocarcinoma Cells Using Rat Insulin Promoter Thymidine Kinase‐directed Gene Therapy

Cited by 21 publications

References 47 publications

PDX1 associated therapy in translational medicine

PDX1 associated therapy in translational medicine

Antisense Smo under the control of the PTCH1 promoter delivered by an adenoviral vector inhibits the growth of human pancreatic cancer

Downregulation of pancreatic-duodenal homeobox 1 expression in breast cancer patients: A mechanism of proliferation and apoptosis in cancer

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