Molecular and Cellular Pharmacology of the Hypoxia-Activated Prodrug TH-302
- F. Meng, James W. Evans, C. Hart
- BiologyMolecular Cancer Therapeutics
- 6 December 2011
Th-302 showed much enhanced potency in H460 spheroids compared with H460 monolayer cells under normoxia and much improved dose potency relative to tirapazamine, and was characterized in the three-dimensional tumor spheroid and multicellular layer models.
Chromosomal radiosensitivity at intrachromosomal telomeric sites
- Luis C Alvarez, James W. Evans, Rebecah Wilks, J. Lucas, J. Brown, A. Giaccia
- BiologyGenes, Chromosomes and Cancer
- 1 September 1993
It is shown that intrachromosomal or interstitial telomeric sites in this cell line and in another CHO cell line, HA‐1, are radiosensitive in that they are more prone to breakage than would be expected based on the percentage of the genome composed of telomersic sequences.
Potent and highly selective hypoxia-activated achiral phosphoramidate mustards as anticancer drugs.
- Jianxin Duan, H. Jiao, M. Matteucci
- Biology, ChemistryJournal of Medicinal Chemistry
- 8 February 2008
A series of achiral hypoxia-activated prodrugs synthesized on the basis of the DNA cross-linking toxin of the prodrug, ifosfamide, have emerged as a promising antitumor agent that shows excellent in vivo efficacy and is currently being evaluated in the clinic.
WNT antagonists exhibit unique combinatorial antitumor activity with taxanes by potentiating mitotic cell death
- M. Fischer, B. Cancilla, T. Hoey
- BiologyScience Advances
- 1 June 2017
By blocking WNT/β-catenin signaling before mitotic blockade by paclitaxel, this treatment effectively sensitizes cancer stem cells to taxanes, and this combination strategy and treatment regimen has been incorporated into ongoing clinical testing for vantictumab and ipafricept.
Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells.
- James W. Evans, S. Chernikova, J. Brown
- BiologyCancer Research
- 2008
An overall model of tirapazamine damage is presented, in which DNA single-strand breaks, base damage, and DNA-protein cross-links produce stalling and collapse of replication forks, the resolution of which results in DSB intermediates, requiring homologous recombination and XPF/ERCC1 for their repair.
Selective radiosensitization of hypoxic cells using BCCA621C: a novel hypoxia activated prodrug targeting DNA-dependent protein kinase
- Kirstin E. Lindquist, Jordan Cran, A. Minchinton
- Biology, Medicine
- 3 June 2013
It is found that DNA-PK deficient hypoxic cells are radiosensitive compared to hypoxicDNA-PK proficient cells and that this effect can be observed using both a small molecule inhibitor of DNA- PK, IC86621, as well as with a genetically deficient model cell line.
Selective inhibitors of mTORC1 activate 4EBP1 and suppress tumor growth
- Bianca J. Lee, Jacob A. Boyer, N. Rosen
- Chemistry, BiologyNature Chemical Biology
- 24 June 2021
In preclinical models, selective inhibitors of mTORC1 potently inhibit tumor growth while causing less toxicity and receptor reactivation as compared to pan-mTOR inhibitors.
Analysis of restriction enzyme‐induced chromosomal aberrations by fluorescence in situ hybridization
- E. A. Columna, A. Giaccia, James W. Evans, B. L. Yates, W. Morgan
- BiologyEnvironmental and Molecular Mutagenesis
- 1993
Fluorescence in situ hybridization and Giemsa staining of metaphase chromosomes were used to determine the relative frequencies of symmetric exchange aberrations (translocations) and asymmetric exchange Aberrations after exposure of human lymphoblastoid cells to restriction enzymes or X‐rays.
RSPO3 antagonism inhibits growth and tumorigenicity in colorectal tumors harboring common Wnt pathway mutations
- M. Fischer, V. Yeung, T. Hoey
- BiologyScientific Reports
- 10 November 2017
The combination of RSPO3 inhibition and taxane treatment provides an approach to effectively target oncogenic WNT signaling in a significant number of patients with colorectal and other intestinal cancers.
Abstract 1907: Wnt pathway antagonist OMP-54F28 (FZD8-Fc) inhibits tumor growth and reduces tumor-initiating cell frequency in patient-derived hepatocellular carcinoma and ovarian cancer xenograft…
- P. Yeung, L. Beviglia, A. Kapoun
- Biology
- 1 October 2014
Wnt pathway antagonist OMP-54F28 (FZD8-Fc) inhibits tumor growth and reduces tumor-initiating cell frequency in patient-derived hepatocellular carcinoma and ovarian cancer xenograft models.
...
...