The identification of individuals at high risk for large bowel cancer.An overview

Lipkin, Martin

doi:10.1002/1097-0142(197711)40:5+<2523::aid-cncr2820400919>3.0.co;2-x

Cited by 12 publications

(1 citation statement)

References 35 publications

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“…Familial Adenomatous Polyposis (FAP) is characterized by hundreds to thousands of adenomatous polyps throughout the colorectum [5, 6]. The majority of FAP patients carry a germline mutation in the adenomatous polyposis coli ( APC ) tumor suppressor, a negative regulator of WNT signaling and regulator of cell proliferation [7].…”

Section: Introductionmentioning

confidence: 99%

ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer

Witherspoon

Sandu

et al. 2019

Oncotarget

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Ethylmalonic Encephalopathy Protein 1 ( ETHE1 ) is a sulfur dioxygenase that regulates cellular H 2 S levels. We previously demonstrated a significant increase of ETHE1 expression in "single-hit" colon epithelial cells from crypts of patients with Familial Adenomatous Polyposis (FAP). Here, we report elevated levels of ETHE1 expression and increased mitochondrial density occurring in-situ in phenotypically normal FAP colorectal mucosa. We also found that constitutive expression of ETHE1 increased aerobic glycolysis ("Warburg effect"), oxidative phosphorylation, and mitochondrial biogenesis in colorectal cancer (CRC) cell lines, thereby depleting H 2 S which relieved the inhibition of phosphodiesterase (PDE), and increased adenosine monophosphate (AMP) levels. This led to activation of the energy sensing AMP-activated protein kinase (AMPKp), Sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), a master regulator of mitochondrial biogenesis. By contrast, shRNA silencing of ETHE1 reduced PDE activity, AMPKp/SIRT1/PGC1α levels and mitochondrial biogenesis. Constitutive expression of ETHE1 accelerated both CRC cell xenograft and orthotopic patient derived xenograft CRC cell growth in vivo . Overall, our data nominate elevated ETHE1 expression levels as a novel biomarker and potential therapeutic target for the prevention of CRC tumorigenesis.

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Section: Introductionmentioning

confidence: 99%

ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer

Witherspoon

Sandu

et al. 2019

Oncotarget

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Results of a Mass Screening Program for Colorectal Cancer

Miller

Stanley²

1988

Arch Surg

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Chemoprevention of development of colonic adenomatosis and carcinomatosis with intrarectal dose of 5-FU on animal model

Narisawa¹,

Kohno²,

Yamaguchi³

et al. 1980

Cancer

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This study concerns the treatment by chemotherapy of carcinogenically-induced cancers in the colons of rats. These cancers mimic adenomatosis and carcinomatosis in humans. We believed that they could be prevented or regulated from growing into grossly visible tumors by the intrarectal administration of 5-fluorouracil if the treatment was started on nascent cancers. The incidence of colon carcinoma and the number of tumors per rat were significantly lower in rats treated by this method than in the control rats. Furthermore, some of the small tumors visible by endoscopy disappeared with treatment. This beneficial effect appeared to be due to the direct delivery of an active form of anticancer drug administered in high concentration to the target lesions in the colon mucosa, and carried fewer side effects when compared to other parenteral administrations.

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The identification of individuals at high risk for large bowel cancer.An overview

Cited by 12 publications

References 35 publications

ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer

ETHE1 overexpression promotes SIRT1 and PGC1α mediated aerobic glycolysis, oxidative phosphorylation, mitochondrial biogenesis and colorectal cancer

Results of a Mass Screening Program for Colorectal Cancer

Chemoprevention of development of colonic adenomatosis and carcinomatosis with intrarectal dose of 5-FU on animal model

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