Establishment of in-vitro models of chemotherapy resistance

2007 ◽  
Vol 18 (7) ◽  
pp. 749-754 ◽  
Author(s):  
Mark B. Watson ◽  
Michael J. Lind ◽  
Lynn Cawkwell
Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2689
Author(s):  
Igor Fischer ◽  
Ann-Christin Nickel ◽  
Nan Qin ◽  
Kübra Taban ◽  
David Pauck ◽  
...  

In cancer pharmacology, a drug candidate’s therapeutic potential is typically expressed as its ability to suppress cell growth. Different methods in assessing the cell phenotype and calculating the drug effect have been established. However, inconsistencies in drug response outcomes have been reported, and it is still unclear whether and to what extent the choice of data post-processing methods is responsible for that. Studies that systematically examine these questions are rare. Here, we compare three established calculation methods on a collection of nine in vitro models of glioblastoma, exposed to a library of 231 clinical drugs. The therapeutic potential of the drugs is determined on the growth curves, using growth inhibition 50% (GI50) and point-of-departure (PoD) as the criteria. An effect is detected on 36% of the drugs when relying on GI50 and on 27% when using PoD. For the area under the curve (AUC), a threshold of 9.5 or 10 could be set to discriminate between the drugs with and without an effect. GI50, PoD, and AUC are highly correlated. The ranking of substances by different criteria varies somewhat, but the group of the top 20 substances according to one criterion typically includes 17–19 top candidates according to another. In addition to generating preclinical values with high clinical potential, we present off-target appreciation of top substance predictions by interrogating the drug response data of non-cancer cells in our calculation technology.


2014 ◽  
Vol 226 (06) ◽  
Author(s):  
D William ◽  
M Linnebacher ◽  
CF Classen

Author(s):  
Kavitha K ◽  
Asha S ◽  
Hima Bindu T.V.L ◽  
Vidyavathi M

The safety and efficacy of a drug is based on its metabolism or metabolite formed. The metabolism of drugs can be studied by different in vitro models, among which microbial model became popular. In the present study, eight microbes were screened for their ability to metabolize phenobarbital in a manner comparable to humans with a model to develop alternative systems to study human drug metabolism. Among the different microbes screened, a filamentous fungi Rhizopus stolonifer metabolized phenobarbital to its metabolite which is used for further pharmacological and toxicological studies. The transformation of phenobarbital was identified by high- performance liquid chromatography (HPLC). Interestingly, Rhizopus stolonifer sample showed an extra metabolite peak at 3.11min. compared to its controls. The influence of different carbon sources in media used for growth of fungus, on metabolite production was studied, to find its effect in production of metabolite as the carbon source may influence the growth of the cell.


2020 ◽  
Vol 27 (29) ◽  
pp. 4778-4788 ◽  
Author(s):  
Victoria Heredia-Soto ◽  
Andrés Redondo ◽  
José Juan Pozo Kreilinger ◽  
Virginia Martínez-Marín ◽  
Alberto Berjón ◽  
...  

Sarcomas are tumours of mesenchymal origin, which can arise in bone or soft tissues. They are rare but frequently quite aggressive and with a poor outcome. New approaches are needed to characterise these tumours and their resistance mechanisms to current therapies, responsible for tumour recurrence and treatment failure. This review is focused on the potential of three-dimensional (3D) in vitro models, including multicellular tumour spheroids (MCTS) and organoids, and the latest data about their utility for the study on important properties for tumour development. The use of spheroids as a particularly valuable alternative for compound high throughput screening (HTS) in different areas of cancer biology is also discussed, which enables the identification of new therapeutic opportunities in commonly resistant tumours.


2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.


2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.


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