Causes and Pathology of Mucositis
Mucositis
(in vitro studies)
Defention: One of the most debilitating side effects of radiotherapy and chemotherapy treatment. It is characterized by both inflammation and cell loss in the epithelial barrier. Mucositis is a very complex condition: it develops as a series of dynamic interactions that begin in the epithelium but in a later stage involves other tissue mucosal components like the endothelium, extracellular matrix and connective tissue. It is a frequent reason to postpone chemotherapy treatment ultimately leading towards a higher mortality in cancer patients.
The pathobiology can be described in five stages: initiation, message generation, signal amplification, ulceration and healing.
5 stages:
Initiation phase: The initiation phase follows immediately after exposure to radiation or chemotherapy. The treatments cause the production of reactive oxygen species (ROS). These are free radicals that cause DNA strands in epithelium cells to break. Thus arising reversible and irreversible DNA damage.
Message generation phase: In the message generation phase different transcription factors are activated. The most important is nuclear factor-kappa B (NF-κB), this is a regulatory molecule that controls nearly 200 genes of which that encode pro-inflammatory cytokines and cell adhesion molecules. The increase in synthesis of cytokines and other enzymes causes an increase in apoptosis of epithelial cells and fibroblasts.
Signaling and amplification phase: One of the pro -inflammatory cytokines produced is tumor necrosis factor alpha (TNF-α), this molecule damages the cells but also increases the activity of NF-κB. With as result a positive feedback loop that causes amplification of injury that also continues after the cancer therapy. Until now there is little manifestation of symptoms.
Ulceration phase: The real problems begin when there is penetration through the epithelium into the submucosa. There is the beginning of an ulcer and on the
(in vitro studies)
Defention: One of the most debilitating side effects of radiotherapy and chemotherapy treatment. It is characterized by both inflammation and cell loss in the epithelial barrier. Mucositis is a very complex condition: it develops as a series of dynamic interactions that begin in the epithelium but in a later stage involves other tissue mucosal components like the endothelium, extracellular matrix and connective tissue. It is a frequent reason to postpone chemotherapy treatment ultimately leading towards a higher mortality in cancer patients.
The pathobiology can be described in five stages: initiation, message generation, signal amplification, ulceration and healing.
5 stages:
Initiation phase: The initiation phase follows immediately after exposure to radiation or chemotherapy. The treatments cause the production of reactive oxygen species (ROS). These are free radicals that cause DNA strands in epithelium cells to break. Thus arising reversible and irreversible DNA damage.
Message generation phase: In the message generation phase different transcription factors are activated. The most important is nuclear factor-kappa B (NF-κB), this is a regulatory molecule that controls nearly 200 genes of which that encode pro-inflammatory cytokines and cell adhesion molecules. The increase in synthesis of cytokines and other enzymes causes an increase in apoptosis of epithelial cells and fibroblasts.
Signaling and amplification phase: One of the pro -inflammatory cytokines produced is tumor necrosis factor alpha (TNF-α), this molecule damages the cells but also increases the activity of NF-κB. With as result a positive feedback loop that causes amplification of injury that also continues after the cancer therapy. Until now there is little manifestation of symptoms.
Ulceration phase: The real problems begin when there is penetration through the epithelium into the submucosa. There is the beginning of an ulcer and on the