Related Experiment Video

Updated: Jul 28, 2026

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment
04:48

Chemotherapy-induced Vascular Toxicity - Real-time In vivo Imaging of Vessel Impairment

Published on: January 7, 2015

Exploiting oxidative stress and signaling in chemotherapy of resistant neoplasms

N F Schor1, V E Kagan, Ye Liang

  • 1Department of Pediatrics, University of Pittsburgh, Pittsburgh, USA. nfschor@pitt.edu

Biochemistry. Biokhimiia
|February 20, 2004
PubMed

Insights

Childhood neural crest tumors resist chemotherapy due to altered glutathione handling. Novel strategies combine targeted oxygen radicals with antioxidants and reduction-dependent prodrugs to overcome this resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Childhood neural crest tumors exhibit significant resistance to apoptosis induction by conventional chemotherapeutic agents.
  • This resistance is often linked to altered glutathione metabolism and the overexpression of Bcl-2 family proteins.

Purpose of the Study:

  • To design and evaluate novel therapeutic strategies to overcome chemoresistance in neural crest tumors.
  • To investigate the efficacy of combining oxygen radical generators with selective scavenging agents and reduction-dependent prodrugs.

Main Methods:

  • Utilized preclinical model systems to test novel therapeutic approaches.
  • Investigated the adjunctive use of 6-hydroxydopamine (oxygen radical generator) with Tempol (antioxidant selective for normal neural crest cells).
  • Examined the application of reduction-dependent chemotherapeutic prodrugs, such as neocarzinostatin.

Main Results:

  • Demonstrated promising preclinical efficacy for the designed therapeutic strategies.
  • Showcased the potential of targeting altered glutathione handling and apoptosis pathways.

Conclusions:

  • The developed strategies, including the combination of targeted oxygen radical generation and selective antioxidant rescue, offer a promising avenue for treating chemoresistant neural crest tumors.
  • Reduction-dependent prodrugs represent a viable approach to enhance therapeutic outcomes in these challenging pediatric malignancies.

More Related Videos

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity07:58

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity

Published on: May 12, 2020

Related Concept Videos

Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Cancer Therapies02:49

Cancer Therapies

Cancer therapies are various modes of treatment, such as surgery, radiation therapy, and chemotherapy that are administered to cancer patients.
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
Treatment Resistent Cancers02:56

Treatment Resistent Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...