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Related Concept Videos

Hypoxia01:23

Hypoxia

1.5K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
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Cancer Therapies02:49

Cancer Therapies

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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...
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Related Experiment Video

Updated: Nov 15, 2025

Analysis of Global RNA Synthesis at the Single Cell Level following Hypoxia
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Floxuridine Oligomers Activated under Hypoxic Environment.

Kunihiko Morihiro1, Takuro Ishinabe1, Masako Takatsu2

  • 1Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Journal of the American Chemical Society
|March 2, 2021
PubMed
Summary
This summary is machine-generated.

New anticancer drugs, floxuridine oligomer prodrugs, are activated by tumor hypoxia. These prodrugs show reduced toxicity in normal conditions and effectively suppress tumor growth in mice.

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Area of Science:

  • Oligonucleotide therapeutics
  • Cancer microenvironment
  • Prodrug strategies

Background:

  • Floxuridine oligomers are anticancer drugs with enhanced cytotoxicity due to intracellular release of floxuridine monophosphate.
  • Clinical application is hindered by poor selectivity, leading to off-target effects in healthy cells.
  • Solid tumors are characterized by hypoxic microenvironments, offering a potential target for selective drug activation.

Purpose of the Study:

  • To develop hypoxia-activated floxuridine oligomer prodrugs for improved cancer cell selectivity.
  • To investigate the conditional control of medicinal efficacy based on oxygen levels.
  • To evaluate the in vivo efficacy of these novel prodrugs in a tumor model.

Main Methods:

  • Design and synthesis of two floxuridine oligomer prodrugs incorporating hypoxia-responsive moieties.
  • In vitro cytotoxicity assays under normoxia (20% O2) and hypoxia (1% O2) conditions.
  • In vivo studies in mice to assess tumor growth suppression.

Main Results:

  • Floxuridine oligomer prodrugs exhibited significantly lower cytotoxicity under normoxia compared to the parent compound.
  • Anticancer effects were maintained under hypoxic conditions, similar to the parent floxuridine oligomer.
  • The developed prodrugs demonstrated effective tumor growth suppression in live mice.

Conclusions:

  • Hypoxia-responsive floxuridine oligomer prodrugs offer a strategy for conditional activation in the tumor microenvironment.
  • This approach enhances selectivity and reduces toxicity in non-hypoxic tissues.
  • Represents a novel method for controlling the therapeutic efficacy of oligonucleotide anticancer drugs.