Related Experiment Video

Updated: Jul 6, 2026

A Patient-Derived Xenograft Model for Venous Malformation
06:51

A Patient-Derived Xenograft Model for Venous Malformation

Published on: June 15, 2020

Mammalian target of rapamycin (mTOR) is activated in cutaneous vascular malformations in vivo

Farheen Shirazi1, Cynthia Cohen, Levi Fried

  • 1Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA.

Lymphatic Research and Biology
|March 29, 2008
PubMed
Abstract

Insights

Vascular malformations, often linked to Akt signaling, show elevated phosphorylated S6. This suggests potential treatment with rapamycin for conditions like Sturge-Weber syndrome.

Area of Science:

  • Dermatology
  • Molecular Biology
  • Oncology

Background:

  • Vascular malformation signaling pathways remain poorly understood.
  • Akt overexpression in endothelial cells is implicated in vascular malformations.
  • No Akt inhibitors are currently approved for clinical use.

Purpose of the Study:

  • To investigate phosphorylated S6 ribosomal protein as a downstream marker of Akt activity in vascular malformations.
  • To assess the potential of rapamycin as a therapeutic agent for vascular malformations.

Main Methods:

  • Immunohistochemistry was performed on vascular malformation specimens from Sturge-Weber patients.
  • Expression of phosphorylated S6 ribosomal protein (phospho-S6k) was analyzed.

Main Results:

  • 70.8% of vascular malformation specimens showed immunopositivity for phospho-S6k.
  • Elevated phospho-S6 expression indicates potential sensitivity to rapamycin.

Conclusions:

  • Endothelial Akt signaling influences tumor response to rapamycin.
  • Elevated phosphorylated S6 expression in vascular malformations supports rapamycin therapy.
  • Findings provide a rationale for rapamycin clinical trials in Sturge-Weber and Klippel-Trenaunay-Weber patients.

More Related Videos

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells06:09

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells

Published on: June 7, 2019

Related Concept Videos

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...
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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...