Acquisitions: May 16 - August 15, 1956

Bliss, Carey S.

doi:10.2307/3816176

Cited by 2 publications

(2 citation statements)

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“…6B). In contrast, when these data were used to predict combined responses under the assumption of Bliss independence 39 , the expected activation in response to TNFα+TSA was 13% (i.e., 12% in response to TNFα only and 1% in response to TSA only) (Fig. 6C).…”

Section: Resultsmentioning

confidence: 98%

Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

et al. 2012

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Section: Resultsmentioning

confidence: 98%

Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

et al. 2012

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“…To use RNAi signatures to determine the relative effective contribution of multiple drugs with additive toxicities within a single NP, we first conducted a Bliss Independence 21 analysis (Figure S9) to confirm that the three drugs used in this investigation display additive toxicity rather than synergistic or antagonistic toxicity. Given an additive drug combination, it should be possible to extract the contribution of each drug to the cell killing mechanism using constrained linear regression methods (if a synergistic drug combination were used, the RNAi signature assay would be dominated by the signature of a single drug in the combination).…”

Section: Resultsmentioning

confidence: 99%

Using an RNAi Signature Assay To Guide the Design of Three-Drug-Conjugated Nanoparticles with Validated Mechanisms, In Vivo Efficacy, and Low Toxicity

et al. 2016

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Single-nanoparticle (NP) combination chemotherapeutics are quickly emerging as attractive alternatives to traditional chemotherapy due to their ability to increase drug solubility, reduce off-target toxicity, enhance blood circulation lifetime, and increase the amount of drug delivered to tumors. In the case of NP-bound drugs, that is, NP-prodrugs, the current standard of practice is to assume that the subcellular mechanism of action for each drug released from the NP mirrors that of the unbound, free-drug. Here, we use an RNAi signature assay for the first time to examine the mechanism of action of multidrug-conjugated NP prodrugs relative to their small molecule prodrugs and native drug mechanisms of action. Additionally, the effective additive contribution of three different drugs in a single-NP platform is characterized. The results indicate that some platinum(IV) cisplatin prodrugs, although cytotoxic, may not have the expected mechanism of action for cisplatin. This insight was utilized to develop a novel platinum(IV) oxaliplatin prodrug and incorporate it into a three-drug-conjugated NP, where each drug’s mechanism of action is preserved, to treat tumor-bearing mice with otherwise lethal levels of chemotherapy.

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Acquisitions: May 16 - August 15, 1956

Cited by 2 publications

References 0 publications

Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

Chromatin accessibility at the HIV LTR promoter sets a threshold for NF-κB mediated viral gene expression

Using an RNAi Signature Assay To Guide the Design of Three-Drug-Conjugated Nanoparticles with Validated Mechanisms, In Vivo Efficacy, and Low Toxicity

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