Enzyme Regulation*

Ding, Xunshan; Zhang, Q.-Y.

doi:10.1016/b978-0-08-046884-6.00402-4

Cited by 2 publications

(1 citation statement)

References 204 publications

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“…Enzymes involved in xenobiotic biotransformation can be induced in response to their substrates 30 . To test whether this regulatory mechanism is also functional in PDAC cells, we measured CYP3A5 mRNA and protein in PACO lines at steady state and in response to 10 μM dasatinib or erlotinib.…”

Section: Resultsmentioning

confidence: 99%

CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma

Noll

Eisen

Stenzinger

et al. 2016

Nat Med

198

192

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Although subtypes of pancreatic ductal adenocarcinoma (PDAC) were described, this malignancy is clinically still treated as a single disease. Here, we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identify two markers—HNF1A and KRT81—that enable stratification of tumors into different subtypes by immunohistochemistry. Individuals bearing tumors of these subtypes show significant differences in overall survival and their tumors differ in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. Cytochrome P450 3A5 (CYP3A5) metabolizes these compounds in tumors of the exocrine-like subtype, and pharmacological or shRNA-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Whereas hepatocyte nuclear factor 4 alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC, and is highly expressed in several additional malignancies. These findings designate CYP3A5 as predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance.

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Section: Resultsmentioning

confidence: 99%

CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma

Noll

Eisen

Stenzinger

et al. 2016

Nat Med

198

192

View full text Add to dashboard Cite

show abstract

Genetic distance and the difference in new firm entry between countries

2019

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Does genetic distance between countries explain differences in the level of entrepreneurship between them? Genetic distance, or very long-term divergence in intergenerationally transmitted traits across populations, has been recently tied to a variety of outcomes ranging from differences in economic development to differences in risk preferences between countries. Extending this recent work, we ask whether the genetic distance between countries is associated with differences in new firm entry. Based on a sample of 103 countries and 5,253 country-pair observations and controlling for a large variety of factors, we find that genetic distance is positively associated with between country differences in new firm entry. The effects sizes, as expected, are small. In assessing the differences in entrepreneurial activity between countrypairs, policymakers could consider adjusting for genetic distance as an explanation for differences in entrepreneurial activity.

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Enzyme Regulation*

Cited by 2 publications

References 204 publications

CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma

CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma

Genetic distance and the difference in new firm entry between countries

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