Experimental concepts for toxicity prevention and tissue restoration after central nervous system irradiation

Several experimental strategies of radiation-induced central nervous system toxicity prevention have recently resulted in encouraging data. The present review summarizes the background for this research and the treatment results. It extends to the perspectives of tissue regeneration strategies, based for example on stem and progenitor cells. Preliminary data suggest a scenario with individually tailored strategies where patients with certain types of comorbidity, resulting in impaired regeneration reserve capacity, might be considered for toxicity prevention, while others might be "salvaged" by delayed interventions that circumvent the problem of normal tissue specificity. Given the complexity of radiation-induced changes, single target interventions might not suffice. Future interventions might vary with patient age, elapsed time from radiotherapy and toxicity type. Potential components include several drugs that interact with neurodegeneration, cell transplantation (into the CNS itself, the blood stream, or both) and creation of reparative signals and a permissive microenvironment, e.g., for cell homing. Without manipulation of the stem cell niche either by cell transfection or addition of appropriate chemokines and growth factors and by providing normal perfusion of the affected region, durable success of such cell-based approaches is hard to imagine

L'effet de la superoxyde dismutase sur le système nerveux central irradié à propos d'études pilotes expérimentales chez le rat

Il a été constaté que la superoxyde dismutase bovine (SOD) pouvait faire régresser certaines complications chroniques de la radiothérapie. Pour cette raison cette enzyme a été utilisée chez le rat pour traiter des encéphalites radiques étudiées par le test de l'évitement actif bilatéral. La SOD a permis une régression significative des troubles dans deux études d'encéphalite chronique et deux études d'encéphalite aiguë. Par ailleurs une autre étude a montré que la SOD prévenait les troubles cognitifs engendrés par un stimulus douloureux important. Ainsi la SOD s'est révélée capable d'améliorer les performances cérébrales après une agression spécifique (radiothérapie) ou non spécifique (stimulus douloureux important). Cette constatation ouvre des perspectives intéressantes pour la thérapeutique

Dysfonctionnement cognitif induit par irradiation corporelle totale à prépondérance neutronique chez le rat : effet de la superoxyde dismutase liposomale Cu/Zn bovine

Afin de définir l'action de la superoxyde dismutase Cu/Zn liposomale (LIPSOD) sur le dysfonctionnement d'apprentissage induit chez le rat Sprague-Dawley après irradiation corporelle totale à prépondérance neutronique, une étude comportementale (évitement actif uni et bilatéral) a été réalisée. Sur le test déévitement unilatéral débuté 23 jours après irradiation, chez les rats non traités, le groupe irradié obtient des scores de pourcentage d'évitement inférieurs (p = 0,077) à ceux du groupe non irradié. Cet effet est empêché par la LIPSOD (p = 0,000) qui néanmoins agit de manière inhibitrice chez le groupe non irradié (p = 0,024). Quant à l'évitement bilatéral, le groupe “irradiés-traités”, obtient des valeurs significativement supérieures aux trois autres groupes

Thymidine phosphorylase to dihydropyrimidine dehydrogenase ratio as a predictive factor of response to preoperative chemoradiation with capecitabine in patients with advanced rectal cancer

Purpose: To identify if thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and ratio TP/DPD levels in tumor tissues are potential predictive factors for response to combined preoperative chemoradiation with capecitabine, in patients with locally advanced rectal cancer (LARC). Methods And Patients: Between 2004 and 2006, 28 patients with LARC (cT2-T4, N0-N2) were treated with neoadjuvant chemoradiation. Total radiation dose was 50.4 Gy and daily dose was 1.8 Gy in 5.5 weeks. Capecitabine was administrated 1,650 mg/m2/day, 7 days/week. Preoperative staging was based on combined computer tomography and endorectal ultrasound. Tissue samples, both neoplastic and normal ones, were endoscopically taken before treatment for TP and DPD measurement with ELISA. Levels of total proteins were calculated by the Bradford method. Results: Median TP, DPD, ratio TP/DPD levels in the primary tumors were 32.85 U/mg, 18.73 U/mg, and 1.64 respectively. Median ratio TP/DPD of patients with proven pathological "response" (downstaging of the disease) was higher than the "no response" group, 4.40 and 1.42, respectively (P = 0.0001). Levels of TP and DPD in tumor tissue did not reveal any statistically important difference between the two groups. Conclusions: TP/DPD ratio is a possible predictive factor for tumor response after concomitant preoperative chemoradiation with capecitabine in LARC. © 2009 Wiley-Liss, Inc

Thymidine phosphorylase to dihydropyrimidine dehydrogenase ratio as a predictive factor of response to preoperative chemoradiation with capecitabine in patients with advanced rectal cancer

Purpose: To identify if thymidine phosphorylase (TP), dihydropyrimidine dehydrogenase (DPD), and ratio TP/DPD levels in tumor tissues are potential predictive factors for response to combined preoperative chemoradiation with capecitabine, in patients with locally advanced rectal cancer (LARC). Methods And Patients: Between 2004 and 2006, 28 patients with LARC (cT2-T4, N0-N2) were treated with neoadjuvant chemoradiation. Total radiation dose was 50.4 Gy and daily dose was 1.8 Gy in 5.5 weeks. Capecitabine was administrated 1,650 mg/m2/day, 7 days/week. Preoperative staging was based on combined computer tomography and endorectal ultrasound. Tissue samples, both neoplastic and normal ones, were endoscopically taken before treatment for TP and DPD measurement with ELISA. Levels of total proteins were calculated by the Bradford method. Results: Median TP, DPD, ratio TP/DPD levels in the primary tumors were 32.85 U/mg, 18.73 U/mg, and 1.64 respectively. Median ratio TP/DPD of patients with proven pathological "response" (downstaging of the disease) was higher than the "no response" group, 4.40 and 1.42, respectively (P = 0.0001). Levels of TP and DPD in tumor tissue did not reveal any statistically important difference between the two groups. Conclusions: TP/DPD ratio is a possible predictive factor for tumor response after concomitant preoperative chemoradiation with capecitabine in LARC. © 2009 Wiley-Liss, Inc