Publications related to Combination therapy

Resistance mechanism to Notch inhibition and combination therapy in human T cell acute lymphoblastic leukemia

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy caused by acquisition of genetic alterations during T-cell development. The 5-year overall survival of pediatric T-ALL patients has improved considerably over the past 30 ...

EPFL2023

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, i ...

EPFL2022

Structure-Based Drug Design and Characterization of Sulfonyl-Piperazine Benzothiazinone Inhibitors of DprE1 from Mycobacterium tuberculosis

Stewart Cole, Anthony Vocat, Jérémie Piton, Shi-Yan Caroline Foo, Andréanne Lupien

Macozinone (MCZ) is a tuberculosis (TB) drug candidate that specifically targets the essential flavoenzyme DprE1, thereby blocking synthesis of the cell wall precursor decaprenyl phosphoarabinose (DPA) and provoking lysis of Mycobacterium tuberculosis. As ...

AMER SOC MICROBIOLOGY2018

Optimized Background Regimen for Treatment of Active Tuberculosis with the Next-Generation Benzothiazinone Macozinone (PBTZ169)

Stewart Cole, Anthony Vocat, Shi-Yan Caroline Foo, Andréanne Lupien, Jean-Yves Gillon

The efficacy of the standardized four-drug regimen (comprising isoniazid, rifampin, pyrazinamide, and ethambutol) for the treatment of tuberculosis (TB) is menaced by the emergence of multidrug-resistant (MDR) and extensively drugresistant (XDR) strains of ...

AMER SOC MICROBIOLOGY2018

Drug Combination for Treatment of Proliferative Diseases

Paul Joseph Dyson, Patrycja Nowak-Sliwinska, Hubert van den Bergh

Angiogenesis inhibitory drug combination obtained according to a specific algorithm, preferably a FSC, in which an initial combination of drugs is iteratively adjusted. The drug combination according to the invention may advantageously comprise a RAPTA-C c ...

2017

TUCUXI: TUCUXI: An Intelligent System for Personalized Medicine from Individualization of Treatments to Research Databases and Back

Karl Aberer, Alevtina Dubovitskaya, Yann Thoma, Michael Ignaz Schumacher, Thierry Buclin

Therapeutic Drug Monitoring (TDM) is a key concept in precision medicine. The goal of TDM is to avoid therapeutic failure or toxic effects of a drug due to insufficient or excessive circulating concentration exposure related to between-patient variability ...

2017

Optimization of drug combinations using Feedback System Control

Paul Joseph Dyson, Hubert van den Bergh, Patrycja Nowak-Sliwinska

We describe a protocol for the discovery of synergistic drug combinations for the treatment of disease. Synergistic drug combinations lead to the use of drugs at lower doses, which reduces side effects and can potentially lead to reduced drug resistance, w ...

Nature Publishing Group2016

Rapid optimization of drug combinations for the optimal angiostatic treatment of cancer

Paul Joseph Dyson, Hubert van den Bergh, Patrycja Nowak-Sliwinska

Drug combinations can improve angiostatic cancer treatment efficacy and enable the reduction of side effects and drug resistance. Combining drugs is non-trivial due to the high number of possibilities. We applied a feedback system control (FSC) technique w ...

2015

Preclinical combination therapy of the investigational drug NAMI-A(+) with doxorubicin for mammary cancer

Paul Joseph Dyson, Tina Riedel, Gianni Sava

Aim of the study The tumor metastases targeting ruthenium complex NAMI-A synergistically improves the activity of gemcitabine in combination therapies. High-throughput screening was used to identify other potential drug combinations from a library of FDA a ...

Springer2015

A streamlined search technology for identification of synergistic drug combinations

Hubert van den Bergh, Paul Joseph Dyson, Patrycja Nowak-Sliwinska

A major key to improvement of cancer therapy is the combination of drugs. Mixing drugs that already exist on the market may offer an attractive alternative. Here we report on a new model-based streamlined feedback system control (s-FSC) method, based on a ...

Nature Publishing Group2015

Combinations of beta-Lactam Antibiotics Currently in Clinical Trials Are Efficacious in a DHP-I-Deficient Mouse Model of Tuberculosis Infection

John McKinney, Neeraj Dhar

We report here a dehydropeptidase-deficient murine model of tuberculosis (TB) infection that is able to partially uncover the efficacy of marketed broad-spectrum beta-lactam antibiotics alone and in combination. Reductions of up to 2 log CFU in the lungs o ...

American Society for Microbiology2015

Towards a new combination therapy for tuberculosis with next generation benzothiazinones

Paul Joseph Dyson, Stewart Cole, Florence Pojer, Ruben Hartkoorn, Ming Zhang, Joao Pedro De Almeida Neres, Anthony Vocat, Benoit Lechartier, Thierry Buclin

The benzothiazinone lead compound, BTZ043, kills Mycobacterium tuberculosis by inhibiting the essential flavo-enzyme DprE1, decaprenylphosphoryl-beta-D-ribose 2-epimerase. Here, we synthesized a new series of piperazine-containing benzothiazinones (PBTZ) a ...

2014

In Vitro and In Vivo Activities of Three Oxazolidinones against Nonreplicating Mycobacterium tuberculosis

Stewart Cole, Neeraj Dhar, Claudia Sala, Ming Zhang, Anthony Vocat

Oxazolidinones represent a new class of antituberculosis drugs that exert their function by inhibiting protein synthesis. Here, we compared the activities of three oxazolidinones, linezolid, PNU-100480, and AZD5847, against latent tuberculosis using a simp ...

Amer Soc Microbiology2014

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy

Paul Joseph Dyson, Gianni Sava

The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination ...

2006