OBJECTIVETo investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice.

METHODSFemale Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor β1 (TGF-β1) were analyzed by western blot.

RESULTSCompared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-β1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-β1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-β1 and the difference was marked as compared with the untreated and negative control groups (P<0.05).

CONCLUSIONHJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Animals ; Biological Products ; pharmacology ; therapeutic use ; Cell Proliferation ; drug effects ; radiation effects ; Cobalt Radioisotopes ; Dermatitis ; complications ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fibroblast Growth Factor 2 ; genetics ; metabolism ; Fibroblasts ; drug effects ; pathology ; radiation effects ; Gamma Rays ; Humans ; L-Lactate Dehydrogenase ; metabolism ; Malondialdehyde ; metabolism ; Mice ; Mitochondria ; drug effects ; metabolism ; radiation effects ; Ointments ; Oxidative Stress ; drug effects ; radiation effects ; Pharmaceutical Preparations ; Radiation Injuries ; complications ; drug therapy ; pathology ; Superoxide Dismutase ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism ; Up-Regulation ; drug effects ; radiation effects

OBJECTIVETo evaluate the therapeutic effect of Liujunzi decoction combined with Zuojin pills in treating the radioactive duodenitis and their mechanism, and compare with clinical routine acid suppressants combined with mucous membrane protective preparations to study the mechanism of their efficacy.

METHODAccording to the study of Williams J P and characteristics of duodenitis, and by reference to the radiation enteritis modeling standard, we took the lead in establishing the mouse radioactive duodenal injury model. The model mice were randomly divided into the control group (n = 26), traditional Chinese medicine (TCM) group (n = 16) and the western medicine (oral administration with famotidine 0.5 mL + almagate suspension 0.3 mL per mouse, once a day) group (n = 16). After the standard administrating, such objective indexes as general condition, weight, changes in health score, pathology and expression of inflammatory factors were observed to evaluate the efficacy.

RESULTThe radioactive duodenitis model of mice was successfully established with 12 Gy. Mice in the control group suffered from weight loss, anorexia, low fluid intake, loose stools, and occasionally mucous bloody stool, poor spirit, dim fur, lack of exercise and arch back. Mice in drug intervention groups were generally better than those in the pure irradiation group. The IL-6, IL-1beta, TNF-alpha mRNA expressions in spleen and mesenteric lymph node tissues in TCM and western medicine groups showed a declining trend compared with the control group. Their concentrations in peripheral blood serum also slightly changed. The TCM group revealed notable advantage in reducing inflammatory factors. The microscopic observation showed that a better mucosa repair in intervention groups than the pure irradiation group. The improved Chiu's scoring method showed a statistical significance in the difference between TCM and western medicine groups (P < 0.05).

CONCLUSIONLiujunzi decoction combined with Zuojin pills could treat acute radiation enteritis, regulate organic immunity, and inhibit acute injury, promote local tissue repair, with the potential to resist such adverse effects as radiation intestinal fibrosis. The regulation of inflammatory factor release is one of efficacy generation mechanisms.

Animals ; Cobalt Radioisotopes ; adverse effects ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Duodenitis ; blood ; drug therapy ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Mice ; Mice, Inbred BALB C ; Mucous Membrane ; drug effects ; radiation effects ; Radiation Injuries, Experimental ; blood ; drug therapy ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the effect of pretreatment with apoptotic donor spleen cells on spleen lymphocyte function of recipient rats undergoing islet transplantation to explore new approaches to prolong islet graft survival.

METHODSApoptotic spleen cells from donor rats were obtained by exposure to γ-ray irradiation from (60)Co. Diabetic SD rat models were randomly divided into 4 groups to receive tail vein injections with saline (group A), normal cells (group B), apoptotic donor cells (group C), or necrotic donor cells (group D). One week later, orthotopic transplantation of islets under the renal capsule was performed. Before and at 1 and 2 weeks after islet transplantation, the recipient rats were examined for proliferative activity of spleen lymphocytes with CFSE cell staining and for IL-2 and IL-10 expressions in the cells using ELISA.

RESULTSPretreatment with donor apoptotic cells significantly suppressed the proliferative activity of recipient spleen lymphocytes before and at 1 and 2 weeks after islet transplantation as compared with the other three groups (P<0.05). The level of IL-2 was significantly decreased while IL-10 increased in apoptotic donor cell pretreatment group compared with those in the other 3 groups at each time point of observation.

CONCLUSIONThe effect of pretreatment with apoptotic donor cells on recipient spleen lymphocytes suggest an important role of apoptotic donor spleen cells in immune tolerance of grafts.

Animals ; Apoptosis ; immunology ; Cell Proliferation ; Cobalt Radioisotopes ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; surgery ; Gamma Rays ; Graft Survival ; Immune Tolerance ; Interleukin-10 ; metabolism ; Interleukin-2 ; metabolism ; Islets of Langerhans Transplantation ; Lymphocyte Transfusion ; Lymphocytes ; metabolism ; pathology ; radiation effects ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Spleen ; cytology ; metabolism ; radiation effects

OBJECTIVE: To explore the anti-radiation protective effect of resveratrol (RES). METHODS: (60)Co-γ irradiated injury model was established. A total of 200 Kunming mice were randomly divided into 4 groups (50 in each group): Group I, II, III, and IV. Each group was sub-divided into 5 groups: a normal control (n=10), an irradiated model control group (n=10) and 3 treatment groups of RES (50, 100, and 300 mg/kg RES treatment groups, 10 in each group). RES was orally administered daily for 30 d in the RES treatment groups and 1% sodium carboxymethylcellulose was orally administered in the normal control and irradiated model group. Thereafter, except the normal control group, the mice in other groups were exposed to different dosages of (60)Co-γ once, and the gavage was continued until the end of different experimental periods. Peripheral leucocytes, nucleated bone marrow cells were counted; superoxide dismutase (SOD) activity and hemolysin in the serum were determined at different time. RESULTS: Under the different dosages of (60)Co-γ irradiation and the provisions of the experimental conditions, the leucocyte count was (1.69±0.82)× 10(9) and (1.61±0.51)× 10(9)/L in the 100 and 300 mg/kg RES treatment groups, which was significantly increased, when compared with the irradiated model control group [(0.73±0.69)× 10(9)/L] ( P<0.05, P<0.01 respectively). The number of nucleated bone marrow cells was (17.5±4.8) and (17.1±4.7)× 10(5)/mL in the 100 and 300 mg/kg RES treatment groups respectively, which significantly increased when compared with the irradiated model control group [(7.3±2.2)× 10(5)/mL ] ( P<0.01 ). The SOD activity was (110.41±17.04) U/ mL in the 100 mg/kg RES treatment group, which was significantly increased when compared with the irradiated model control group [(95.80±10.42) U/mL ] ( P<0.05 ). There was no significant difference in the serum hemolysin in all RES treatment groups (all P>0.05). CONCLUSION At 100 and 300 mg/kg, RES has good anti-radiation effect.
Animals ; Cobalt Radioisotopes ; Gamma Rays ; Mice ; Plant Extracts ; therapeutic use ; Radiation Injuries, Experimental ; drug therapy ; metabolism ; prevention & control ; Radiation-Protective Agents ; therapeutic use ; Resveratrol ; Stilbenes ; therapeutic use ; Superoxide Dismutase ; metabolism

OBJECTIVEWe identify ionizing radiation-induced mitochondrial DNA (mtDNA) deletions in human lymphocytes and their distribution in normal populations.

METHODSLong-range polymerase chain reactions (PCR) using two pairs of primers specific for the human mitochondrial genome were used to analyze the lymphoblastoid cell line following exposure to 10 Gy (60)Co γ-rays. Limited-condition PCR, cloning and sequencing techniques were applied to verify the mtDNA deletions detected with long-range PCR. Human peripheral blood samples were irradiated with 0, 2 and 6 Gy (60)Co γ-rays, and real-time PCR analysis was performed to validate the mtDNA deletions. In order to know the distribution of mtDNA deletions in normal population, 222 healthy Chinese adults were also investigated.

RESULTSTwo mtDNA deletions, a 7455-bp deletion (nt475-nt7929 in heavy strand) and a 9225-bp deletion (nt7714 -nt369 in heavy strand), occurring between two 8-bp direct repeats, were identified in lymphoblastoid cells using long-range PCR, limited-condition PCR and sequencing. These results were also observed for (60)Co γ-rays irradiated human peripheral blood cells.

CONCLUSIONTwo novel mtDNA deletions, a 7455-bp deletion and a 9225-bp deletion, were induced by ionizing radiation. The rate of the mtDNA deletions within a normal population was related to the donors' age, but was independent of gender.

Cell Line ; Cloning, Molecular ; Cobalt Radioisotopes ; DNA Damage ; genetics ; radiation effects ; DNA, Mitochondrial ; genetics ; radiation effects ; Gene Deletion ; Genetic Markers ; Humans ; Lymphocytes ; radiation effects ; Radiation, Ionizing ; Real-Time Polymerase Chain Reaction

OBJECTIVETo investigate the prognosis of adenoid cystic carcinoma (ACC) in minor salivary glands and its influencing factors.

METHODSClinical data of 52 patients with ACC in minor salivary glands were reviewed. The distribution of stage was as follows: stage I (6%), stage II (21%), stage III (27%) and stage IV (46%). Counting data was analyzed by χ(2) test or Fisher's exact. Survival rates were calculated by Kaplan-Merier method. Statistical significance of differences in the cumulative survival curves was evaluated using the Log-rank test. Multivariate analysis was performed by Cox proportional hazard model.

RESULTSAll patients underwent primary tumor radical resection, 39 patients (75%) received postoperative radiation. The regional recurrence rate was 37% and distant metastasis rate was 21%. The 5-, 10-year cumulative local control rate were 68% and 63% respectively. The 5-, 10-year cumulative distant control rate were 86%, 68% respectively. The 5-, 10-year tumor specific survival rates were 70% and 54% respectively. Multivariate analysis showed that T stage, lymph node metastasis and perineural invasion were relevant to the tumor specific survival of ACC in minor salivary glands.

CONCLUSIONSRecurrence and metastasis were the main cause of treatment failure of ACC in minor salivary glands. T stage, lymph node metastasis and perineural invasion were the independent prognostic factors of ACC in minor salivary glands. Radical surgery and reasonably postoperative radiotherapy were the main treatment strategy.

Adult ; Aged ; Carcinoma, Adenoid Cystic ; pathology ; radiotherapy ; secondary ; surgery ; Cobalt Radioisotopes ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Particle Accelerators ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Salivary Gland Neoplasms ; pathology ; radiotherapy ; surgery ; Salivary Glands, Minor ; Survival Rate ; Young Adult

OBJECTIVETo compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy.

METHODSOne hundred and sixty two cases with primary cervical carcinoma diagnosed and treated in the Jiangxi Maternal and Children Hospital between January 2008 and November 2009 were enrolled in this randomized controlled trial. Seventy one cases were included in the paclitaxel group and 91 in the paclitaxel liposome group. The chemotherapy doses were as followings: paclitaxel liposome and paclitaxel 135 mg/m(2); cisplatin 80 mg/m(2) or carboplatin AUC 4 - 6, repeated every 21 days for two or three times. Radical radiotherapy was given to both groups at the same time. The efficacy was evaluated by the tumor regression and the patients were followed-up for six months.

RESULTSThe overall response rates of paclitaxel group and paclitaxel liposome group were 90.1% and 89.0%, respectively (P > 0.05). The 1-year cumulative survival rate was 91.4% for the paclitaxel group and 89.2% for the paclitaxel liposom group (P > 0.05). The incidence rate of adverse effects such as rash, gastrointestinal toxicity, bone marrow suppression and muscle/joint pain in the paclitaxel liposome group was significantly lower than that in the paclitaxel group (P < 0.05), while there was no significant difference regarding the hair loss, liver damage, and peripheral neuritis (P > 0.05).

CONCLUSIONSPaclitaxel liposome plus platinum is a safe and effective therapeutic regimen for stage IIa-IV cervical carcinoma. However, the long-term efficacy of this regimen should be further observed.

Adenocarcinoma ; pathology ; therapy ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Brachytherapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Squamous Cell ; pathology ; therapy ; Chemoradiotherapy ; Cisplatin ; administration & dosage ; adverse effects ; Cobalt Radioisotopes ; therapeutic use ; Exanthema ; chemically induced ; Female ; Follow-Up Studies ; Gastrointestinal Diseases ; chemically induced ; Humans ; Iridium Radioisotopes ; therapeutic use ; Liposomes ; administration & dosage ; adverse effects ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Remission Induction ; Survival Rate ; Uterine Cervical Neoplasms ; pathology ; therapy

Postoperative radiotherapy (PRT) is widely advocated for patients with squamous cell carcinomas of the head and neck that are considered to be at high risk of recurrence after surgical resection. The aims of this study were to evaluate the treatment outcomes of PRT for patients with laryngeal carcinoma and to identify the value of several prognostic factors. We reviewed the records of 256 patients treated for laryngeal squamous cell carcinoma between January 1993 and December 2005. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Log-rank test was employed to identify significant prognostic factors for DFS and OS. The Cox proportional hazards model was applied to identify covariates significantly associated with the aforementioned endpoints. Our results showed the 3-, 5-, and 10-year DFS for all patients were 69.9%, 59.5%, and 34.9%, respectively. The 3-, 5-, and 10-year OS rates were 80.8%, 68.6%, and 38.8%, respectively. Significant prognostic factors for both DFS and OS on univariate analysis were grade, primary site, T stage, N stage, overall stage, lymph node metastasis, overall treatment times of radiation, the interval between surgery and radiotherapy, and radiotherapy equipment. Favorable prognostic factors for both DFS and OS on multivariate analysis were lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment. In conclusion, our data suggest that lower overall stage, no cervical lymph node metastasis, and using 60Co as radiotherapy equipment are favorable prognostic factors for DFS and OS and that reducing the overall treatment times of radiation to 6 weeks or less and the interval between surgery and radiotherapy to less than 3 weeks are simple measures to remarkably improve treatment outcome.
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; surgery ; Cobalt Radioisotopes ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Laryngeal Neoplasms ; pathology ; radiotherapy ; surgery ; Laryngectomy ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Postoperative Period ; Proportional Hazards Models ; Radioisotope Teletherapy ; Retrospective Studies ; Survival Rate ; Young Adult

BACKGROUND AND OBJECTIVECombined hypoxic cytotoxic drugs and chemoradiotherapy is an important mean of oncotherapy, and Tirapazamine (TPZ) is one of the most remarkable drugs. It has been shown that TPZ has a synergistic effect with radiotherapy on tumor cells, but whether TPZ would down-regulate the expression of the hypoxia-induced genes has not been reported. This study was to investigate the hypoxia-induced mRNA expressions of hypoxia inducible factor-1alpha (HIF-1alpha) and osteopontin (OPN) in human nasopharyngeal carcinoma HNE-1 and CNE-1 cells and the radiosensitization of TPZ, a hypoxia-specific drug, on HNE-1 and CNE-1 cells in vitro.

METHODSThe IC50 values of TPZ for HNE-1 and CNE-1 cells were measured using MTT assay, and the mRNA expressions of HIF-1alpha and OPN in HNE-1 and CNE-1 cells was determined using RT-PCR under aerobic and hypoxic conditions, respectively. The survival rates of HNE-1 and CNE-1 cells treated with or without TPZ at IC10 in the presence or absence of oxygen for 6 h were determined using colony formation assay following exposure to 1-6 Gy of 60Co radiation. The dose-survival curves were plotted and the values of D0, Dq and SER were calculated as a single-hit multitarget model.

RESULTSThe IC50 values of TPZ were 34.81 μmol/L and 35.02 μmol/L in HNE-1 and CNE-1 cells under aerobic condition, and 30.20 μmol/L and 28.48 μmol/L under hypoxic condition, respectively. The expressions of HIF-1alpha and OPN mRNA were reduced by TPZ in HNE-1 cells, but not in CNE-1 cells under hypoxic condition. For the HNE-1 cells, the respective values of D0 and Dq were 0.89 Gy and 0.28 Gy following normoxic irradiation versus 1.47 Gy and 0.44 Gy following hypoxic irradiation. For the CNE-1 cells, the respective values of D0 and Dq were 0.72 Gy and 0.68 Gy following normoxic irradiation versus 0.95 Gy and 0.56 Gy following hypoxic irradiation. The values of D0 and Dq for HNE-1 and CNE-1 cells treated with TPZ under hypoxic condition following irradiation were 0.66 Gy, 0.21 Gy and 0.85 Gy, 0.79 Gy, respectively.

CONCLUSIONTPZ can down-regulate hypoxia-induced expression of HIF-1alpha and OPN mRNA of HNE-1 cells and radiosensitize the HNE-1 cells but not CNE-1 cells, and act as a hypoxia modifier.

Antineoplastic Agents ; pharmacology ; Cell Hypoxia ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Cobalt Radioisotopes ; Down-Regulation ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Inhibitory Concentration 50 ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Osteopontin ; genetics ; metabolism ; RNA, Messenger ; metabolism ; Radiation Tolerance ; drug effects ; Radiation-Sensitizing Agents ; pharmacology ; Triazines ; pharmacology

BACKGROUND AND OBJECTIVEThe level-Ib lymph node metastasis is rare in nasopharyngeal carcinoma (NPC). When and how this level should be irradiated with precise radiotherapy remains controversial. This study evaluated the prevalence and prognostic significance of level-Ib lymphadenopathy on the prognosis of NPC patients.

METHODSFrom January 1990 and December 1999, 933 newly diagnosed patients with NPC treated at Sun Yat-sen University Cancer Center were randomly selected, examined with computed tomography (CT) imagining for evidence of level-Ib lymphadenopathy before treatment. All patients received radical radiotherapy with or without chemotherapy. The relationship between level-Ib lymphadenopathy and post-treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier methods. The Cox proportional hazards regression model was used to adjust for other prognostic factors.

RESULTSOf the 933 patients, 55 (5.9%) were found to have level-Ib lymphadenopathy, which was associated with carotid sheath involvement, oropharynx involvement and levels, and lateral cervical lymph node involvement. In the subgroup with carotid sheath involvement, with multivariate analysis accounting for all previously known prognostic factors, level-Ib lymphadenopathy was still associated with a risk of decreased OS (RR, 2.124; P<0.001), DMFS (RR, 2.168; P<0.001), and LRFS (RR, 1.989; P=0.001).

CONCLUSIONLevel-Ib lymphadenopathy in the patients with carotid sheath involvement is an independent prognostic factor.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; diagnostic imaging ; drug therapy ; pathology ; radiotherapy ; Chemotherapy, Adjuvant ; Child ; Cobalt Radioisotopes ; therapeutic use ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; diagnostic imaging ; drug therapy ; pathology ; radiotherapy ; Neck ; pathology ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Particle Accelerators ; Pharynx ; pathology ; Prognosis ; Proportional Hazards Models ; Radiography ; Radioisotope Teletherapy ; Retrospective Studies ; Survival Rate ; Young Adult