Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-ß1/Smad 3 signaling pathway.

To investigate the effect of adipose-derived stem cells (ASCs) transplantation on radiation-induced lung injury (RILI), Sprague-Dawley rats were divided into phosphate-buffered saline (PBS) group, ASCs group, Radiation + PBS group, and Radiation + ASCs group. Radiation + PBS and Radiation + ASCs groups received single dose of 30 Gy X-ray radiation to the right chest. The Radiation + PBS group received 1 mL PBS suspension and Radiation + ASCs group received 1 mL PBS suspension containing 1 × 107 CM-Dil-labeled ASCs. The right lung tissue was collected on Days 30, 90, and 180 after radiation. Hematoxylin-eosin and Masson staining were performed to observe the pathological changes and collagen fiber content in the lung tissue. Immunohistochemistry (IHC) and western blot (WB) were used to detect levels of fibrotic markers collagen I (Collal), fibronectin (FN), as well as transforming growth factor-ß1 (TGF-ß1), p-Smad 3, and Smad 3. Compared with the non-radiation groups, the radiation groups showed lymphocyte infiltration on Day 30 after irradiation and thickened incomplete alveolar walls, collagen deposition, and fibroplasia on Days 90 and 180. ASCs relieved these changes on Day 180 (Masson staining, P = 0.0022). Compared with Radiation + PBS group, on Day 180 after irradiation, the Radiation + ASCs group showed that ASCs could significantly decrease the expressions of fibrosis markers Collal (IHC: P = 0.0022; WB: P = 0.0087) and FN (IHC: P = 0.0152; WB: P = 0.026) and inhibit the expressions of TGF-ß1 (IHC: P = 0.026; WB: P = 0.0152) and p-Smad 3 (IHC: P = 0.0043; WB: P = 0.0087) in radiation-induced injured lung tissue. These indicated that ASCs could relieve RILI by inhibiting TGF-ß1/Smad 3 signaling pathway.

Pathological response and serum VEGF changes during chemoradiotherapy for esophageal carcinoma.

The aim of this study was to observe pathological response and change in serum vascular endothelial growth factor (VEGF) in esophageal carcinoma (EC) during chemoradiotherapy (CRT).Eighty-nine patients diagnosed with EC were treated with radiotherapy at the Department of Radiotherapy of the Second People's Hospital of Changzhou between May 2008 and December 2014, including 65 patients with CRT. Gastroscopy and pathological examination were conducted 4 weeks afterwards. The pathological responses were classified as complete response (CR) and non-CR. Serum samples were collected from the patients before radiotherapy, during week 4 of radiotherapy, and 1 week after radiotherapy. The VEGF changes were classified as increase, stable, and decrease.The median overall survival (OS) and median progression-free survival (PFS) in the pathological CR group was significantly longer than that of the non-CR group (P < .001). The 1-, 3-, and 5-year OS rates in the non-CR group were lower than that in the CR group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the non-CR group were lower than that in the CR group (P < .05). VEGF serum level was decreased during and after radiotherapy compared with pre-radiotherapy, and the differences were statistically significant (P < .05). The 1-, 3-, and 5-year OS rates in the increased group were lower than that in the decreasing group (P < .05). Moreover, the 1-, 3-, and 5-year PFS rates in the increasing group were lower than that in the decreasing group (P < .05). Pathological response (P < .05), serum VEGF trend (P < .05), and tumor-node-metastasis stage (P < .05) in response to CRT were factors that influenced patient prognosis.Pathological response and serum VEGF change during CRT can predict prognosis of nonsurgical patients with EC. Monitoring these changes is of significance in individualized treatment.

Pathologic response during chemo-radiotherapy and variation of serum VEGF levels could predict effects of chemo-radiotherapy in patients with esophageal cancer.

BACKGROUND: To investigate the relationship between pathologic tumor response to concurrent chemo- radiotherapy and variation of serum VEGF in patients with esophageal cancer. MATERIALS AND METHODS: Forty six patients with esophageal cancer who were treated with concurrent chemo-radiotherapy were enrolled. Endoscopic and pathologic examination was conducted before and four weeks afterwards. Serum level of VEGF was documented before, four weeks later and after chemo-radiotherapy. The relationship between pathologic response and the variation of serum level of VEGF and its influence on the prognosis were investigated. RESULTS: Serum level of VEGF decreased remarkably during and after chemo-radiotherapy in patients whose pathologic response was severe (F=5.393, 4.587, P(0.05). There were no statistical differences of serum VEGF level before, during and after chemo-radiotherapy for patients whose pathologic response was moderate or mild. There were 18 (85.7%), 7 (53.8%) and 6 patients (50.0%) whose serum VEGF level dropped in the severe, moderate and mild group, respectively, with significant differences among these groups (p=0.046). Two year survival rates of patients with severe, moderate and mild pathologic response were 61.9%, 53.8% and 33.3% respectively, and no statistically difference between severe and mild group regarding OS (p=0.245) was tested. CONCLUSIONS: Tumor pathologic response during chemo-radiotherapy and the changes of serum VEGF lever could predict curative effects of chemo-radiotherapy in patients with esophageal cancer.

Clinical trial of thalidomide combined with radiotherapy in patients with esophageal cancer.

AIM: To investigate the short-term efficacy and tolerability of radiotherapy plus thalidomide in patients with esophageal cancer (EC). METHODS: Serum samples from 86 EC patients were collected before, during, and after radiotherapy, and the vascular endothelial growth factor (VEGF) level was examined by ELISA. According to the change in serum VEGF level during radiotherapy, the patients were divided into two groups: in the drug group, VEGF level was increased or remained unchanged, and thalidomide was administered up to the end of radiotherapy; in the non-drug group, VEGF level was decreased and radiotherapy was given alone. Thirty healthy volunteers served as controls. The efficacy and safety of radiotherapy plus thalidomide therapy were investigated. RESULTS: The 86 EC patients had a significantly higher level of VEGF compared with the 30 healthy controls before radiotherapy (P < 0.01), and the VEGF level was significantly correlated with primary tumor size, lymph node metastasis, histopathologic type, and clinical stage (P < 0.01). Of 83 evaluable cases, VEGF level was significantly decreased after radiotherapy in 32 patients in the drug group (P < 0.05), with an effective rate of 71.88%. The incidence of dizziness and/or burnout in the drug group and non-drug group was 62.50% and 15.69%, respectively (P = 0.000), and the incidence of somnolence was 12.50% and 0%, respectively (P = 0.019). No significant differences were observed. CONCLUSION: Thalidomide can down-regulate serum VEGF level in EC patients, and combined with radiotherapy may improve treatment outcome. Thalidomide was well tolerated by EC patients.