Search results for "Genesis"
showing 10 items of 12136 documents
Cancer combination therapies with artemisinin-type drugs
2017
Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy. In the present review, I give a comprehensive overview on synergistic and additive effects of artemisinin-type drugs in combination with different types of cytotoxic agents an…
Drug metabolism by cultured human hepatocytes: how far are we from the in vivo reality?
2004
The investigation of metabolism is an important milestone in the course of drug development. Drug metabolism is a determinant of drug pharmacokinetics variability in human beings. Fundamental to this are phenotypic differences, as well as genotypic differences, in the expression of the enzymes involved in drug metabolism. Genotypic variability is easy to identify by means of polymerase chain reaction-based or DNA chip-based methods, whereas phenotypic variability requires direct measurement of enzyme activities in liver, or, indirectly, measurement of the rate of metabolism of a given compound in vivo. There is a great deal of phenotypic variability in human beings, only a minor part being…
Functional characterization of circulating tumor cells (CTCs) from metastatic ER+/HER2− breast cancer reveals dependence on HER2 and FOXM1 for endocr…
2021
Simple Summary Acquired endocrine resistance and late recurrence in patients with ER+/HER2− breast cancer are complex and not fully understood. Here, we evaluated mechanisms of acquired resistance in circulating tumor cells (CTCs) from an ER+/HER2− breast cancer patient who initially responded but later progressed under endocrine treatment. We found a switch from ERα-dependent to HER2-dependent and ERα-independent expression of FOXM1, which may enable disseminated ER+/HER2− cells to re-initiate tumor cell growth and metastasis formation in the presence of endocrine treatment. We found that NFkB signaling sustains HER2 and FOXM1 expression in CTCs in the presence of ERα inhibitors suggesting…
Shikonin derivatives for cancer prevention and therapy.
2019
Abstract Phytochemicals gained considerable interest during the past years as source to develop new treatment options for chemoprevention and cancer therapy. Motivated by the fact that a majority of established anticancer drugs are derived in one way or another from natural resources, we focused on shikonin, a naphthoquinone with high potentials to be further developed as preventive or therapeutic drug to fight cancer. Shikonin is the major chemical component of Lithospermum erythrorhizon (Purple Cromwell) roots. Traditionally, the root extract has been applied to cure dermatitis, burns, and wounds. Over the past three decades, the anti-inflammatory and anticancer effects of root extracts, …
I10 The anticancer activity of the antimalarial artesunate
2017
More than a decade ago, we initiated a research program on the molecular pharmacology of phytochemicals derived from Chinese medicinal herbs. A promising compound was artemisinin from Artemisia annua L. and its semisynthetic compound artesunate [1] . Artemisinin and artesunate are anti-malarial drugs. Our data indicated profound activity against cancer cells, but also against various viruses, Schistosoma, Trypanosoma, and even plant crown gall tumors. To elucidate the molecular mode of actions against cancer, we applied molecular biological and pharmacogenomic approaches in vitro and in vivo. Different signalling pathways were identified not only in cancer cells but also in cells infected w…
A lipidomic cell-based assay for studying drug-induced phospholipidosis and steatosis
2017
Phospholipidosis and steatosis are two toxic effects, which course with overaccumulation of different classes of lipids in the liver. MS-based lipidomics has become a powerful tool for the comprehensive determination of lipids. LC-MS lipid profiling of HepG2 cells is proposed as an in vitro assay to study and anticipate phospholipidosis and steatosis. Cells with and without pre-incubation with a mixture of free fatty acids (FFA) (i.e., oleic and palmitic) were exposed to a set of well-known steatogenic and phospholipidogenic compounds. The use of FFA pre-loading accelerated the accumulation of phospholipids thus leading to a better discrimination of phospholipidosis, and magnified the lipid…
Myotonic dystrophy type 1 drug development: A pipeline toward the market
2021
Highlights • Myotonic dystrophy, a neuromuscular disease, affects at least around half a million people worldwide. • Close to two dozen preclinical and clinical drug development programs active. • Drugs encompass new chemical entities, repurposing, oligonucleotide, and gene therapy. • Tideglusib, mexiletine, and metformin are close to reaching marketing authorization.
Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis.
2019
Introduction: The advent of biologic agents has revolutionized therapeutic approaches in systemic juvenile idiopatic arthritis (sJIA) as their introduction has been shown to modify disease course and improve overall outcomes, particularly when initiated early. Few studies have reported the drug retention rate (DRR) of biologic drugs in JIA, and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on sJIA. Objectives: The primary aim of the study was to examine the overall DRR of IL-1 blockers in sJIA patients. Secondary aims of our study were to: (i) explore the influence of biologic line of treatment, adverse events (AEs), type of anti-IL-1 agent and the conc…
Dual inhibitors of histone deacetylases and other cancer-related targets: A pharmacological perspective.
2020
International audience; Epigenetic enzymes histone deacetylases (HDACs) are clinically validated anticancer drug targets which have been studied intensively in the past few decades. Although several drugs have been approved in this field, they are still limited to a subset of hematological malignancies (in particular T-cell lymphomas), with therapeutic potential not fully realized and the drug-resistance occurred after a certain period of use. To maximize the therapeutic potential of these classes of anticancer drugs, and to extend their application to solid tumors, numerous combination therapies containing an HDACi and an anticancer agent from other mechanisms are currently ongoing in clin…
Effect of colorectal cancer-derived extracellular vesicles on the immunophenotype and cytokine secretion profile of monocytes and macrophages.
2018
Abstract. Background Macrophages are one of the most important players in the tumor microenvironment. The polarization status of tumor associated macrophages into a pro-inflammatory type M1 or anti-inflammatory type M2 may influence cancer progression and patient survival. Extracellular vesicles (EVs) are membrane-bound vesicles containing different biomolecules that are involved in cell to cell signal transfer. Accumulating evidence suggests that cancer-derived EVs are taken up by macrophages and modulate their phenotype and cytokine profile. However, the interactions of cancer-derived EVs with monocytes and macrophages at various differentiation and polarization states are poorly understo…