Related Experiment Video
Updated: Jan 25, 2026
06:19
Author Spotlight: High-Throughput Screening to Obtain Crystal Hits for Protein Crystallography
Published on: March 10, 2023
5.6K
A cell-based high-throughput screen to identify synergistic TRAIL sensitizers.
Nancy Lynn Booth1, Thomas J Sayers, Alan D Brooks
1Molecular Targets Development Program, Center for Cancer Research, NCI-Frederick, Frederick, MD 21702, USA. nancylynnbooth@gmail.com
Cancer Immunology, Immunotherapy : CII
|December 18, 2008
Summary
Researchers identified new molecules that enhance TRAIL therapy for renal tumors. These compounds sensitize cancer cells to TRAIL-induced apoptosis, offering a promising combination strategy for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Tumor cells often develop resistance to apoptosis-inducing agents like TRAIL.
- Novel therapeutic strategies are needed to overcome this resistance and enhance treatment efficacy.
Purpose of the Study:
- To develop a high-throughput screen (HTS) to identify molecules that synergize with TRAIL for renal tumor cell apoptosis.
- To find compounds that pre-sensitize cancer cells to TRAIL-mediated apoptosis with limited intrinsic toxicity.
Main Methods:
- Utilized a high-throughput screen (HTS) to identify synergistic compounds.
- Assessed individual agent toxicity versus combination effects.
- Conducted preliminary mechanistic studies on synergistic TRAIL sensitizers.
Main Results:
- Identified synergistic, synergistic-toxic, and additive compounds when combined with TRAIL.
- Discovered that some sensitizers rapidly activate caspase-8 following TRAIL binding.
- Observed increased p53 levels in cells treated with representative sensitizers, without proteasome inhibition.
Conclusions:
- Novel TRAIL sensitizers were identified, potentially overcoming resistance to TRAIL-mediated apoptosis.
- Mechanistic insights suggest caspase-8 activation and possibly DNA damage-sensing pathways are involved.
- These findings offer a promising combinatorial approach for treating renal tumors.
Related Concept Videos
01:26Urine Studies II: Urine Culture and Sensitivity Test
971
A urine culture and sensitivity test is a diagnostic procedure used to identify urinary tract bacterial infections and determine the most effective antibiotics for treatment. This test is generally preferred when a patient shows manifestations of a urinary tract infection, such as frequent or painful urination, cloudy or foul-smelling urine, or lower abdominal pain.Purpose of the TestThe primary goals of a urine culture and sensitivity test are to:Determine the specific bacteria causing the...
971
01:14Identifying Statistically Significant Differences: The F-Test
3.3K
The F-test is used to compare two sample variances to each other or compare the sample variance to the population variance. It is used to decide whether an indeterminate error can explain the difference in their values. The underlying assumptions that allow the use of the F-test include the data set or sets are normally distributed, and the data sets are independent of each other. The test statistic F is calculated by dividing one variance by another. In other words, the square of one standard...
3.3K
01:13Sensitivity, Specificity, and Predicted Value
1.2K
In healthcare diagnostics, laboratory tests play a crucial role in identifying and diagnosing a wide range of medical conditions. However, interpreting test results is not always straightforward. An abnormal test result does not always confirm the presence of a disease, just as a normal result does not guarantee its absence. To assess the reliability of these diagnostic tools, healthcare practitioners rely on two key statistical indicators: sensitivity and specificity.
Sensitivity is the...
Sensitivity is the...
1.2K
02:46Genetic Screens
5.6K
Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.6K
01:20Sputum Studies II: Culture and Sensitivity
1.2K
Description
Sputum culture and sensitivity is a medical procedure used to diagnose bacterial infections in the respiratory tract and select the most appropriate antibiotics for treatment. This process involves analyzing sputum samples of thick and opaque secretions produced in the lungs and airways. These samples are collected from patients and then sent to the laboratory for analysis.
The test can identify various pathogens responsible for respiratory infections, including Streptococcus,...
Sputum culture and sensitivity is a medical procedure used to diagnose bacterial infections in the respiratory tract and select the most appropriate antibiotics for treatment. This process involves analyzing sputum samples of thick and opaque secretions produced in the lungs and airways. These samples are collected from patients and then sent to the laboratory for analysis.
The test can identify various pathogens responsible for respiratory infections, including Streptococcus,...
1.2K
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
1.4K
Local anesthetics (LAs) block the sodium channels of nerve trunks, sensory nerve endings, and neuromuscular junctions. Although LAs can block all kinds of nerves, the sensitivity of nerve fibers differs according to nerve types and structures. LAs are known to block myelinated fibers faster than unmyelinated ones. Also, they block pain or sensory neurons at low concentrations without affecting the motor neurons involved in muscle contractions. This helps relieve labor pain without affecting the...
1.4K