Related Experiment Video

Updated: Jul 21, 2026

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics
08:29

Ex Vivo Treatment Response of Primary Tumors and/or Associated Metastases for Preclinical and Clinical Development of Therapeutics

Published on: October 2, 2014

Activation of iCaspase-9 in neovessels inhibits oral tumor progression

M S Pinsky1, W Song, Z Dong

  • 1Angiogenesis Research Laboratory, Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, 48109, USA.

Journal of Dental Research
|April 25, 2006
PubMed

Insights

Activating an artificial death switch in oral tumor neovascular endothelial cells inhibited tumor growth. This targeted approach reduced microvessel density, demonstrating a novel strategy for oral cancer treatment.

Area of Science:

  • Oncology
  • Vascular Biology
  • Gene Therapy

Background:

  • Oral cavity tumors are highly vascularized malignancies.
  • Disrupting tumor neovascular networks can limit nutrient and oxygen supply, inhibiting tumor progression.
  • Targeting tumor vasculature offers a potential therapeutic strategy.

Purpose of the Study:

  • To evaluate the effect of activating an artificial death switch (iCaspase-9) in neovascular endothelial cells on oral tumor progression.
  • To investigate the therapeutic potential of targeting tumor-associated microvessels.

Main Methods:

  • Co-implantation of human dermal microvascular endothelial cells expressing iCaspase-9 (HDMEC-iCasp9) with oral cancer cells in immunodeficient mice.
  • Local injection of a targeted adenovirus (Ad-VEGFR2-iCasp-9) to deliver iCaspase-9 to neovascular endothelial cells.
  • Assessment of tumor progression using in vivo bioluminescence and microvessel density via immunohistochemistry.

Main Results:

  • Activation of iCaspase-9 in tumor-associated microvessels significantly inhibited oral tumor progression.
  • A decrease in microvessel density was observed following iCaspase-9 activation.
  • The study demonstrated successful targeted gene therapy in a xenograft model.

Conclusions:

  • Activation of iCaspase-9 in neovascular endothelial cells is sufficient to inhibit the progression of xenografted oral tumors.
  • Targeting tumor neovasculature through artificial death switches presents a promising therapeutic avenue for oral cancer.

More Related Videos

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo08:19

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

Quantification of Immunostained Caspase-9 in Retinal Tissue05:18

Quantification of Immunostained Caspase-9 in Retinal Tissue

Published on: July 25, 2022

Related Concept Videos

Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...