Oral Mucositis

Oral ulcerative mucositis is a common, painful, dose-limiting toxicity of drug and radiation therapy for cancer. It is characterized by breakdown of the oral mucosa resulting in the formation of ulcerative lesions. In granulocytopenic patients, these lesions are frequent portals of entry for indigenous oral bacteria, often leading to sepsis or bacteremia.

Mucositis occurs to some degree in more than one third of patients receiving anti-neoplastic drug therapy. It occurs in almost all patients undergoing radiation therapy for cancer of the head and neck as well as a high percentage of patients undergoing bone marrow transplantation.

Currently, supportive care is the primary treatment option for mucositis. Patients can be prescribed analgesics for pain relief and are instructed to maintain good oral hygiene to mitigate risk of infection. Experimental compounds which modify cytokines or otherwise protect tissue from radiation or chemotherapy exposure may be efficacious for mucositis.

Acute Radiation Model in Hamsters

Hamsters provide an excellent model for oral mucositis because of several biological similarities to humans. Furthermore, the cheek pouch is pliable and can be extracted, allowing for radiation to be targeted to the cheek pouch while the rest of the animal is shielded. The result is formation of ulcers on the cheek pouch approximately 16 days following radiation. Primary end points in this model include mucositis scores based on a standardized scale and analysis of the frequency and duration of ulcers.

Study Design Table

Model Description Duration Endpoints
Acute Radiation in Hamsters The cheek pouch is treated with an acute dose of 40 Gy radiation resulting in the formation of ulcers 28 days Mucositis score, Histology

 

Typical Course of Acute Mucositis in Hamsters
Healthy cheek pouch
Cheek pouch with ulcerative mucositis
Fractionated Radiation Model in Hamsters

Patients often undergo several treatments with radiation. Therefore, to model the human treatment cycle, Biomodels has developed a fractionated radiation protocol for hamster mucositis. In this protocol, the radiation treatments are divided into eight fractions over two, four-day cycles. Like in the acute model, this results in the formation of ulcers on the cheek pouch, however, the length of fractionated radiation studies is typically longer. Primary end points include mucositis scores based on a standardized scale and analysis of the frequency and duration of ulcers.

Study Design Table

Model Description Duration Endpoints
Fractionated Radiation in Hamsters The cheek pouch is treated with 8 fractions of radiation resulting in the formation of ulcers Up to 36 days Mucositis score, Histology

 

Chemo-Radiation Model in Hamsters

In many cases, patients receive both chemotherapy and radiation therapy. Therefore, Biomodels has optimized the radiation protocol for use with combined chemotherapy. The endpoints and study duration are similar to the fractionated radiation protocol, but the expected development of mucositis is more severe.

Study Design Table

Model Description Duration Endpoints
Chemo-radiation in Hamsters In addition to the fractionated protocol, hamsters also receive cisplatin chemotherapy treatment Up to 36 days Mucositis score, Histology

 

Acute Radiation Model in Rats or Mice

In some cases, it is advantageous to study more common laboratory animals such as rats or mice. Therefore, Biomodels has developed an acute radiation model of mucositis in these species. In this design, radiation is focused at the tongue (mice) or snout (rats). The tongue is then evaluated, photographed, and scored based on a standardized scale at established time points.

Study Design Table

Model Description Duration Endpoints
Acute Radiation in Rats or Mice Radiation is targeted to the rodents tongue or snout and the tongue is then examined for mucositis 28 days Mucositis score, Histology

 

Chemotherapy Induced Mucositis in Rats

Mucositis is known to occur in approximately one third of patients receiving chemotherapy treatment. Biomodels has modeled chemotherapy induced mucositis in rats by combining chemotherapy administration with a small injury to the tongue. The result is an inflammation of the tongue that peaks at 5-7 days post-induction. The primary endpoints in this model include scoring the injury of the tongue according to a standardized scale.

Study Design Table

Model Description Duration Endpoints
Chemotherapy-Induced Mucositis in Rats Chemotherapy is paired with an acute tongue injury resulting in an inflamed tongue 28 days Mucositis score, Histology

 

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