Proctitis

Description

The direct effect of ionizing radiation during radiation therapy damages the DNA, lipids, and proteins of cells (both cancerous and non-cancerous) in the GI tract. In the rodent models, proctitis is induced with either a single bolus of acute radiation, or 8 fractionated, smaller doses, directed at approximately the most distal 2 cm of the colon (a lead shield protects the remainder of the animal’s body). Animals are monitored daily and evaluated for overall health and survival in addition to diarrhea and bloody stool incidence. A major readout in the model is proctitis severity determined via longitudinal video endoscopic assessments over the course of the study. Peak disease differs based on the method of induction, with disease persisting through the final evaluation which typically includes histopathology.

  • Advantages: short model duration, consistent disease incidence, direct model of clinical disease induction.
  • Disadvantages: smaller market than IBD.
Model Systems
  • Sprague Dawley Rat, Lewis Rat
  • C57Bl/6 Mice
Standard Readouts
  • Percent weight change
  • Survival
  • Diarrhea and bloody stool Incidence
  • Endoscopy: proctitis scoring
  • Terminal colon weight and length measurement
  • Terminal histopathology and/or IHC analyses
Additional Readouts
  • Tissue localized protein analyses
  • Peripheral lymphoid organ immunophenotyping
  • Intestinal lamina propria immunophenotyping
  • Custom assays
Representative DataClick Image to Enlarge
Acute Radiation Induced Proctitis Scoring

Proctitis severity is assessed longitudinally using video endoscopy at multiple timepoints during an acute radiation-induced proctitis study.

Acute Radiation Induced Proctitis Endoscopy

Proctitis severity is assessed longitudinally using video endoscopy at multiple timepoints during an acute radiation-induced proctitis study.

Fractionated Radiation Induced Proctitis Scoring

Proctitis severity is assessed longitudinally using video endoscopy at multiple timepoints during a fractionated radiation-induced proctitis study.

Fractionated Radiation Induced Proctitis Endoscopy

Proctitis severity is assessed longitudinally using video endoscopy at multiple timepoints during a fractionated radiation-induced proctitis study.

Fractionated Radiation Induced Proctitis- Histopathology

Following fractionated radiation treatment, rectal tissue is collected. (A) Photomicrograph showing histological appearance of normal rectal mucosa. (B) Photomicrograph showing histological appearance of inflamed rectal mucosa.

Daniel Lichtman

Managing Partner