Radiation fibrosis of human normal tissues is very common in radiotherapy. One of the main fundamental problems yet unsolved in fibrotic tissues is the origin of the chronic activation of myofibroblasts within these tissues. It has been postulated by some researchers that this chronic activation results from a continuous production of activating factors. So fibrosis could be defined as a wound where continuous signals for repair are emitted. Cytokines and growth factors probably play a vital role in this process. Among them transforming growth factor ?1(TGF ?1) is considered as a master switch for the fibrotic program. This review discusses recent evidence on the critical role played by TGF ?1 in the initiation, development, and persistence of radiation fibrosis. It summarized the results concerning this factor after irradiation of various tissues and cells. All these researches show that the TGF ?1 pathway may be a specific target for anti fibrotic agents. [

Background and purpose: The position of thymidine kinase 1 (TK1) expression during cell division is in the cytoplasm. It is a catalytic enzyme to convert deoxythymidine into thymidylate. It is the key enzyme of pyrimidine salvage pathway. The aim of this study was to analyze the serum expression level of TK1 in patients with breast cancer, and explore the application of serum TK1 test in clinical assessments of diagnosis, treatment and prognosis for breast cancer. Methods: Patient data were collected from the patients admitted in Comprehensive Breast Health Center at Rui Jin Hospital. Chemiluminesence dot blot assay was used to detect serum TK1 levels in 145 breast cancer patients and 55 patients with breast ifbroadenoma. The correlations of serum TK1 levels with breast tumor biological behavior was further studied. Results:Serum TK1 expression levels was signiifcantly increased in breast cancer patients [(2.749±0.122)pmol/L] when compared to breast fibroadenoma patients[(1.319±0.126)pmol/L, P<0.000 1]. Serum TK1 levels were statistically increased in patients with lymph node metastasis (P=0.049), distal metastasis (P=0.003 1), and late TNM stages (P=0.01). No serum TK1 level differences were found in patients with different ages (P>0.05), different tumor grades (P=0.453) and different tumor size (P=0.908). Preoperative imaging results including breast ultrasound, breast mammography and breast magnetic resonance were analyzed by assessments of BI-RADS category, and serum TK1 levels in patients with different BI-RADS categories were studied. Serum TK1 levels in patients with breast ultrasound BI-RADS categories 4C-6 were signiifcantly higher than those with category 0-4B (P<0.001). Consistently, the serum TK1 levels in patients with MR BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.005). The serum TK1 levels in patients with mammography BI-RADS categories 4C-6 were higher than categories 0-4B (P=0.032). The serum TK1 levels were signiifcantly increased in patients with ER high expression in breast tumor tissues than those with low expression (P=0.034). Serum TK1 levels had no differences in patients with different expression levels of PR, HER-2 and MIB-1 (P>0.05). Most patients were followed up in our outpatient department for about 2 years. No progression-free survival differences were found in 2years. Conclusion:Serum TK1 test might be a potential tool for screening, prognosis determination and effect evaluations of targeted therapy in breast carcinoma.

Background and purpose:Radiotherapy and endocrine therapy are both important parts of adjuvant therapy for breast cancer, yet few studies have been conducted focusing on the interaction between radiation and endocrine therapy. Up to now, no conclusion has been drawn on the timing sequence of adjuvant radiation and endocrine therapy, which is indeed crucial in clinical practice. This study intended primarily to investigate the effect of concurrent or sequential exemestane combined with radiation on radiosensitivity of MCF-7 cells and its possible mechanism,and further to provide rationale for optimal clinical treatment modality.Methods:MCF-7 cells were arranged into three trial groups: the radiation group, exemestane sequenced with radiation group and exemestane followed radiation group. Radiosensitivity was evaluated by clonogenic assay, cell proliferation was measured by MTT assay, the ability to induce cell apoptosis was evaluated by DAPI staining assay, the changes of Bcl-2 and Bax were detected by Western blot.Results:Sensitive enhancement ratios (SER) were 1.51 and 1.37 in the exemestane sequenced with radiation group and exemestane followed radiation group, respectively. Compared with the radiation group, the percentage of cellular proliferation inhibition and apoptosis increased obviously in the exemestane sequenced with radiation group and exemestane followed radiation group. Exemestane combined with radiation made the Bax protein increase obviously and the Bcl-2 protein lowered significantly.Conclusion:Exemestane can enhance the radiosensitivity of MCF-7 cells, whose mechanism might be relevant to the promotion of cellular apoptosis. However,the treatment sequence does not affect the outcome.

Objective: To investigate the efficacy and toxic reaction of the accelerated hyperfraction radiotherapy for esophageal carcinoma. Methods: Eighty patients with esophageal carcinoma were randomized into the conventional fraction group (CF,40 cases) and the accelerated hyperfraction group (AHF,40 cases) from January 1994 to May 1995. CF group received a fraction dose of 2 Gy once a day, 5 times a week and to a total dose of 70 Gy. AHF group received the same dose as the CF group during the first two thirds of the therapeutic course(40 Gy),then followed by a fraction dose of 1.5 Gy one time twice a day, with an interval of more than 6 hours, and to a total dose of 30 Gy. The total dose of 2 stages was 70 Gy. The same 10 mV linear accelerator X ray radiotherapy was used in both groups. Results: The 3 year actual survival and tumor local control rates in the group AHF were significantly improved compared with group CF, being 42.5% vs 25% and 52.5% vs 25% respectively. There were no significant differences in radiation reactions and complications between 2 groups. The radiation treatment could be completed without any break. Conclusion: The accelerated hyperfraction radiotherapy can improve the tumor local control and survival rates in esophageal carcinoma. The radiation reactions and complications with the AHF radiotherapy are not significantly greater than with the CF radiotherapy. The patients can tolerate the AHF radiotherapy. [

Objective To delineate and measure the left anterior descending coronary artery (LAD) on CT angiography (CTA) and evaluate the dose delivered to LAD by different radiotherapy techniques for left-sided breast cancer.Methods Twenty-nine left-side breast cancer women with mean age of 54.71 years (range:30-80 years) were included.CTA was performed, and LAD was contoured and the distances were measured between LAD and chest wall (posteroanterior diameter,PD), between LAD and internal mammary artery (horizontal diameter,HD), between LAD and interventricular groove (oblique diameter,OD) at the level of T7-T8,T8-T9,T9-T10 and at level of nipple and lower boundary of the breast.The dose delivered to LAD was calculated on three-dimensional plans for two patients with mastectomy whose chest wall and internal mammary chain (IMC) were irradiated and one patient with breast-conserving surgery who received whole breast irradiation.Results The LAD arose at the level of the third rib in 40% of patients and at the fourth rib in 60% of patients.The mean length of LAD was 7.49±0.58 cm.At the level of T7-T8,T8-T9,T9-T10,the mean PD were 2.99±1.11 cm, 1.26±0.65 cm,0.68±0.39 cm, the mean HD were 2.27±0.84 cm, 2.81±0.65 cm, 3.37±1.21 cm, and the mean OD were 0.47±0.25 cm,0.38±0.21 cm,0.42±0.19 cm respectively.At the level of the breast nipple and the lower boundary of the breast, the mean PD were 2.94±1.06 cm, 0.79±0.46 cm, the mean HD were 2.45±0.89 cm, 3.31±1.22 cm,and the mean OD were 0.56±0.30 cm,0.57±0.24 cm respectively.The mean dose to the LAD was 5 Gy and 14 Gy for patients with mastectomy whose IMC was irradiated with 9 MeV electron and whose IMC was irradiated with 6 MV photon tangential beams.The mean dose to the LAD was 26 Gy for patients with breast conserving surgery.Conclusions To contour the LAD, the interventricular groove could be the reference point.Tangential technique can be giving a higher dose of LAD when compared with other radiation techniques

Objective To evaluate the effect of preoperative radiotherapy and postoperative brachy radiotherapy (POBRT) on patients with primary liver cancer(PLC). Methods 50 patients with PLC were randomly divided into 2 groups:(1)Radiotherapy group, 25 patients who underwent preoperative radiotherapy 14～17 days before hepatectomy and POBRT 3～10 days after hepatectomy ;(2)Control group,25 cases who underwent hepatectomy only. In radiotherapy group, before heptectomy, the single-dose 6Gy per time and 3 sessions were given to each patient. 3～6 ductus were placed for POBRT during operation,and 10Gy of POBRT per time and 2～4 sessions were given postoperatively. In control group,no radio cherapy was given before and after hepatectomy. Results In radiotherapy group, the cancer shrank significantly after preoperative radiotherapy (P

OBJECTIVETo explore the combined anti-tumor effect of radiation therapy and gene-targeted suppression of tumor neovasculature in lung adenocarcinoma in vivo, and to explore the feasibility of micro-PET/CT in dynamic evaluation of treatment effectiveness.

METHODSThirty 5-6-week old male BALB/c nude mice were used in this study. The mouse models of xenotransplanted human lung adenocarcinoma were divided into 5 groups at random, six mice in each group: the control group, radiation treatment alone group and three groups of recombinant baculovirus plus radiation treatment (intratumoral injection, tail vein injection, and intramuscular injection). The tumor volume was measured every 2 days. Growth delay time (GD) and growth inhibition rate was calculated. FDG metabolism was evaluated by micro-PET-CT before and after treatment. The expressions of VEGF, CD31 and Ki-67 were detected by immunohistochemistry (IHC).

RESULTSThe tumor growth delay was >12 days, and the tumor inhibition rate was >45% in the recombinant baculovirus combined with radiotherapy groups, significantly higher than that of the radiotherapy alone group (P < 0.05). Immunohistochemical analysis showed that the expressions of VEGF, CD31 and Ki-67 were significantly lower than that in other groups (P < 0.05). The micro-PET-CT assessment showed that the FDG-metabolism in the recombinant baculovirus combined with radiotherapy groups was significantly reduced (P < 0.05), and the SUVmax (FDG metabolism) of transplanted tumors after treatment was also markedly decreased in comparison with that of the control group. The tumor volume after treatment was significantly correlated with SUVmax in the recombinant baculovirus intratumoral injection + radiotherapy group(r = 0.976), recombinant baculovirus intravenous injection + radiotherapy group (r = 0.954), recombinant baculovirus intramuscular injection + radiotherapy group (r = 0.929), and radiotherapy alone group (r = 0.871, P < 0.05).

CONCLUSIONSThe recombinant baculovirus containing Egr1 promoter and K5 gene combined with radiotherapy enhances the suppressing effect on the growth of lung adenocarcinoma in the tumor-bearing nude mice. The inducibility of Egr1 promoter by radiation allows the targeting and controllability of treatment. Micro-PET-CT results have a good correlation with the treatment effectiveness. Therefore, it can be used in real-time evaluation of tumor metabolic function in vivo.

Adenocarcinoma ; metabolism ; pathology ; radiotherapy ; Animals ; Baculoviridae ; genetics ; Cell Line, Tumor ; Combined Modality Therapy ; Early Growth Response Protein 1 ; genetics ; physiology ; Fluorodeoxyglucose F18 ; Genetic Therapy ; Genetic Vectors ; Humans ; Ki-67 Antigen ; metabolism ; Lung Neoplasms ; metabolism ; pathology ; radiotherapy ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Targeted Therapy ; Neoplasm Transplantation ; Peptide Fragments ; genetics ; physiology ; Plasminogen ; genetics ; physiology ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Positron-Emission Tomography ; Promoter Regions, Genetic ; Random Allocation ; Recombinant Proteins ; genetics ; Tomography, X-Ray Computed ; Tumor Burden ; Vascular Endothelial Growth Factor A ; metabolism