transforming-growth-factor-beta and Thoracic-Neoplasms

Radiation-induced lung injury (RILI) is the most common, dose-limiting complication of thoracic radio- and radiochemotherapy. Unfortunately, predicting which patients will suffer from this complication is extremely difficult. Ideally, individual phenotype- and genotype-based risk profiles should be able to identify patients who are resistant to RILI and who could benefit from dose escalation in chemoradiotherapy. This could result in better local control and overall survival. We review the risk predictors that are currently in clinical use--dosimetric parameters of radiotherapy such as normal tissue complication probability, mean lung dose, V20 and V30--as well as biomarkers that might individualize risk profiles. These biomarkers comprise a variety of proinflammatory and profibrotic cytokines and molecules including transforming growth factor beta1 that are implicated in development and persistence of RILI. Dosimetric parameters of radiotherapy show a low negative predictive value of 60% to 80%. Depending on the studied molecule, negative predictive value of biomarkers is approximately 50%. The predictive power of biomarkers might be increased if they are coupled with radiogenomics, e.g., genotyping analysis of single nucleotide polymorphisms in transforming growth factor beta1, transforming growth factor beta1 pathway genes, and other cytokines. Genetic variability and the complexity of RILI and its underlying molecular mechanisms make identification of biological risk predictors challenging. Further investigations are needed to develop more effective risk predictors of RILI.

Topics: Animals; Dose-Response Relationship, Radiation; Humans; Interleukins; Prognosis; Radiation Pneumonitis; Risk Factors; Thoracic Neoplasms; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Transforming Growth Factor beta

Radiation therapy (RT) is an important therapeutic modality in the treatment of thoracic tumors. The maximum doses to these tumors are often limited by the radiation tolerance of lung tissues. Lung injury from ionizing radiation is believed to be a consequence of oxidative stress and a cascade of cytokine activity. Superoxide dismutase (SOD) is a key enzyme in cellular defenses against oxidative damage. The objective of this study was to determine whether the SOD mimetic AEOL 10113 [manganese (III) mesotetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP(5+))] increases the tolerance of lung to ionizing radiation. AEOL 10113 was able to significantly reduce the severity of RT-induced lung injury. This was strongly supported with histopathology results and measurements of collagen deposition (hydroxyproline content). There was a significant reduction in the plasma level of the profibrogenic cytokine transforming growth factor-beta (TGF-beta) in the group of rats receiving RT + AEOL 10113. In conclusion, the novel SOD mimetic, AEOL 10113, demonstrates a significant protective effect from radiation-induced lung injury.

Topics: Animals; Antioxidants; Collagen; Female; Fibrosis; Free Radicals; Hydroxyproline; Immunohistochemistry; Lung; Lung Injury; Metalloporphyrins; Radiation Injuries; Rats; Rats, Inbred F344; Respiration; Superoxide Dismutase; Thoracic Neoplasms; Time Factors; Transforming Growth Factor beta