Visualization and treatment of the HIF-1-active microenvironments in tumors: Drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments

Masashi Ueda, Hideo Saji

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

A tumor-specific microenvironment is characterized by hypoxia, a condition inwhich the oxygen tension is considerably lower than that existing in normal tissues. Insuch hypoxic regions, the transcription factor, hypoxia-inducible factor-1 (HIF-1), isexpressed. HIF-1 is a master transcriptional activator of various genes related to glucosemetabolism, angiogenesis, invasion, and metastasis; therefore, HIF-1-active regionscontribute to tumor malignancy and treatment failures. Thus, we believe that noninvasivevisualization and effective treatment of HIF-1-active microenvironments will provideuseful information for the development of novel strategies for cancer treatment; thedevelopment of such techniques will prove beneficial. HIF-1 is a heterodimer consistingof an oxygen-sensitive a-subunit (HIF-1α) and a constitutively expressed ß-subunit(HIF-1β).HIF-1α is degraded in an oxygen-dependent manner under normoxic conditions;however, under hypoxic conditions, it is stable and controls HIF-1 transcriptionalactivity. Because the oxygen-dependent degradation of HIF-1α is regulated by a unique domain, called the oxygen-dependent degradation domain (ODD), present in HIF-1α,probes containing the ODD and that are degraded in a similar manner as HIF-1α can beused to evaluate HIF-1 activity In Vivo. Furthermore, by conjugating a cytotoxic proteinto the ODD, a targeted therapy for HIF-1-active microenvironments can be developed. In this chapter, we review probes that contain the ODD and selectively function in HIF-1-active microenvironments for the purpose of imaging and treating HIF-1-active tumors.

Original languageEnglish
Title of host publicationHypoxia: Causes, Types and Management
PublisherNova Science Publishers, Inc.
Pages221-236
Number of pages16
ISBN (Print)9781620817698
Publication statusPublished - Jan 2013
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Molecular Imaging
Tumor Microenvironment
Drug Design
Oxygen
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Visualization and treatment of the HIF-1-active microenvironments in tumors : Drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments. / Ueda, Masashi; Saji, Hideo.

Hypoxia: Causes, Types and Management. Nova Science Publishers, Inc., 2013. p. 221-236.

Research output: Chapter in Book/Report/Conference proceedingChapter

@inbook{af7c630e87c043e48f6ee7890ecba126,
title = "Visualization and treatment of the HIF-1-active microenvironments in tumors: Drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments",
abstract = "A tumor-specific microenvironment is characterized by hypoxia, a condition inwhich the oxygen tension is considerably lower than that existing in normal tissues. Insuch hypoxic regions, the transcription factor, hypoxia-inducible factor-1 (HIF-1), isexpressed. HIF-1 is a master transcriptional activator of various genes related to glucosemetabolism, angiogenesis, invasion, and metastasis; therefore, HIF-1-active regionscontribute to tumor malignancy and treatment failures. Thus, we believe that noninvasivevisualization and effective treatment of HIF-1-active microenvironments will provideuseful information for the development of novel strategies for cancer treatment; thedevelopment of such techniques will prove beneficial. HIF-1 is a heterodimer consistingof an oxygen-sensitive a-subunit (HIF-1α) and a constitutively expressed {\ss}-subunit(HIF-1β).HIF-1α is degraded in an oxygen-dependent manner under normoxic conditions;however, under hypoxic conditions, it is stable and controls HIF-1 transcriptionalactivity. Because the oxygen-dependent degradation of HIF-1α is regulated by a unique domain, called the oxygen-dependent degradation domain (ODD), present in HIF-1α,probes containing the ODD and that are degraded in a similar manner as HIF-1α can beused to evaluate HIF-1 activity In Vivo. Furthermore, by conjugating a cytotoxic proteinto the ODD, a targeted therapy for HIF-1-active microenvironments can be developed. In this chapter, we review probes that contain the ODD and selectively function in HIF-1-active microenvironments for the purpose of imaging and treating HIF-1-active tumors.",
author = "Masashi Ueda and Hideo Saji",
year = "2013",
month = "1",
language = "English",
isbn = "9781620817698",
pages = "221--236",
booktitle = "Hypoxia: Causes, Types and Management",
publisher = "Nova Science Publishers, Inc.",

}

TY - CHAP

T1 - Visualization and treatment of the HIF-1-active microenvironments in tumors

T2 - Drug design and application of oxygen-dependent degradable probes for molecular imaging of HIF-1-active microenvironments

AU - Ueda, Masashi

AU - Saji, Hideo

PY - 2013/1

Y1 - 2013/1

N2 - A tumor-specific microenvironment is characterized by hypoxia, a condition inwhich the oxygen tension is considerably lower than that existing in normal tissues. Insuch hypoxic regions, the transcription factor, hypoxia-inducible factor-1 (HIF-1), isexpressed. HIF-1 is a master transcriptional activator of various genes related to glucosemetabolism, angiogenesis, invasion, and metastasis; therefore, HIF-1-active regionscontribute to tumor malignancy and treatment failures. Thus, we believe that noninvasivevisualization and effective treatment of HIF-1-active microenvironments will provideuseful information for the development of novel strategies for cancer treatment; thedevelopment of such techniques will prove beneficial. HIF-1 is a heterodimer consistingof an oxygen-sensitive a-subunit (HIF-1α) and a constitutively expressed ß-subunit(HIF-1β).HIF-1α is degraded in an oxygen-dependent manner under normoxic conditions;however, under hypoxic conditions, it is stable and controls HIF-1 transcriptionalactivity. Because the oxygen-dependent degradation of HIF-1α is regulated by a unique domain, called the oxygen-dependent degradation domain (ODD), present in HIF-1α,probes containing the ODD and that are degraded in a similar manner as HIF-1α can beused to evaluate HIF-1 activity In Vivo. Furthermore, by conjugating a cytotoxic proteinto the ODD, a targeted therapy for HIF-1-active microenvironments can be developed. In this chapter, we review probes that contain the ODD and selectively function in HIF-1-active microenvironments for the purpose of imaging and treating HIF-1-active tumors.

AB - A tumor-specific microenvironment is characterized by hypoxia, a condition inwhich the oxygen tension is considerably lower than that existing in normal tissues. Insuch hypoxic regions, the transcription factor, hypoxia-inducible factor-1 (HIF-1), isexpressed. HIF-1 is a master transcriptional activator of various genes related to glucosemetabolism, angiogenesis, invasion, and metastasis; therefore, HIF-1-active regionscontribute to tumor malignancy and treatment failures. Thus, we believe that noninvasivevisualization and effective treatment of HIF-1-active microenvironments will provideuseful information for the development of novel strategies for cancer treatment; thedevelopment of such techniques will prove beneficial. HIF-1 is a heterodimer consistingof an oxygen-sensitive a-subunit (HIF-1α) and a constitutively expressed ß-subunit(HIF-1β).HIF-1α is degraded in an oxygen-dependent manner under normoxic conditions;however, under hypoxic conditions, it is stable and controls HIF-1 transcriptionalactivity. Because the oxygen-dependent degradation of HIF-1α is regulated by a unique domain, called the oxygen-dependent degradation domain (ODD), present in HIF-1α,probes containing the ODD and that are degraded in a similar manner as HIF-1α can beused to evaluate HIF-1 activity In Vivo. Furthermore, by conjugating a cytotoxic proteinto the ODD, a targeted therapy for HIF-1-active microenvironments can be developed. In this chapter, we review probes that contain the ODD and selectively function in HIF-1-active microenvironments for the purpose of imaging and treating HIF-1-active tumors.

UR - http://www.scopus.com/inward/record.url?scp=84892251873&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84892251873&partnerID=8YFLogxK

M3 - Chapter

AN - SCOPUS:84892251873

SN - 9781620817698

SP - 221

EP - 236

BT - Hypoxia: Causes, Types and Management

PB - Nova Science Publishers, Inc.

ER -