To establish an in vivo radiation carcinogenesis model using glutathione S-transferase placental form positive (GST-P+) hepatic foci, newborn rats were irradiated once by 0.5 Gy and 2 Gy of gamma ray or 0.15 Gy and 0.6 Gy of neutron with or without 0.05% phenobarbital (PB). When the rats were sacrificed at the 12th or 21st week, the incidence of GST-P+ foci induction by radiation alone was very low. The neutron was more sensitive than the gamma ray at week 12 and the reverse phenomenon was observed in the groups at week 21. PB combination showed an increased incidence of GST-P+ foci in gamma ray irradiated groups. The neutron irradiation combined with PB did not show any significant difference compared with the corresponding PB untreated groups. We also investigated the combined effect of diethylnitrosamine (DEN) and 0.75 Gy of gamma ray irradiation. Intraperitoneal injection of 0.15 mumol/g body weight of DEN at 1 hour after gamma ray irradiation showed significantly increased the number and area of GST-P+ foci compared with those of DEN alone or DEN at 1 hour before gamma radiation (P < 0.001). From these data, after more defined experiments, an in vivo radiation carcinogenesis model will be established by radiation alone or a combination of radiation and carcinogens.
Animal ; Body Weight ; Diethylnitrosamine/*adverse effects ; Female ; Gamma Rays/adverse effects ; Glutathione Transferase/*drug effects/*radiation effects ; Liver/*drug effects/pathology/*radiation effects ; Liver Neoplasms/epidemiology/*etiology/pathology ; Neoplasms, Radiation-Induced/epidemiology/*etiology/pathology ; Neutrons/adverse effects ; Organ Weight ; Phenobarbital/*adverse effects ; Placenta/drug effects/radiation effects ; Pregnancy ; Radiation Dosage ; Rats ; Rats, Sprague-Dawley ; Time Factors

OBJECTIVETo investigate the effects of pentoxifylline (PTX) on radiation induced-cell cycle redistribution and radiosensitivity of human hepatocellular carcinoma cell line Hep3b.

METHODSMTT assay was performed to evaluate the cytotoxicity of PTX on p53-defective human hepatocellular carcinoma cell line Hep3b and clonogenic assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). Flow cytometry was performed to observe the cell cycle changes of Hep3b cells in response to X-ray irradiation and the interventional effect of PTX.

RESULTSThe cytotoxicity of PTX on the cells increased in a dose-dependent manner following a 48-hour treatment, with the optimal dose range of 1-5 mmol/L. A sub-toxic dose of PTX at 2 mmol/L was then used in subsequent experiments. Clonogenic survival assays up to 12 Gy demonstrated that p53-defective Hep3b cells (SER of 2.68+/-0.24) were sensitized by PTX (2 mmol/L). PTX (2 mmol/L) treatment following exposure to irradiation (6 Gy) resulted in abrogation of radiation-induced G(2)/M arrest of Hep3b cells, and the proportions of Hep3b cells in G(2)/M phase were 86.8% and 14.8% after exposure to 6 Gy alone and 6 Gy plus 2 mmol/L PTX, respectively.

CONCLUSIONRadiosensitization by PTX is possibly associated with the abrogation of G(2)/M arrest in Hep3b cells following radiation exposure, suggesting that potential clinical application of PTX may enhance the efficacy of radiotherapy against hepatocellular carcinoma.

Carcinoma, Hepatocellular ; drug therapy ; pathology ; radiotherapy ; Cell Cycle ; drug effects ; radiation effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; radiation effects ; Combined Modality Therapy ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Radiation ; Humans ; Liver Neoplasms ; drug therapy ; pathology ; radiotherapy ; Pentoxifylline ; pharmacology ; Radiation-Sensitizing Agents ; pharmacology ; X-Rays

We studied the effect of photodynamic therapy with phycobiliproteins on human liver cancer cells in vitro. With 3-(4, 5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT assay), we used two phycobiliproteins, R-phycoerythrin (R-PE) and C-phycocyanin (C-PC) prepared from Porphyra yezoensis, to determine the killing rates and apoptosis rates of human liver cancer cells (SMMC-7721) mediated by laser. When the concentration of R-PE was 120 mg/L, the survival rate of human liver cancer cells was 27% after treated by Argon laser with 100 J/cm2 doses, while the survival rate in the control group (without adding R-PE) was 65%. When the C-PC concentration was 120 mg/L, the survival cell rate was 47% after treated by He-Ne laser with 35 J/cm2 dose, while the survival rate in the control group (without adding C-PC) was 70%. After handled only with these two kinds of phycobiliproteins for 72 h, the growth of cancer cells presented significant inhibition. The maximal inhibition rates reached up to 31% with R-PE (120 mg/L concentration) and 27% with C-PC (250 mg/L concentration) respectively. After irradiated by laser for 8 h, the maximal cell apoptosis rates were 31.54% with R-PE and 32.54% with C-PC, respectively. It indicated that R-PE and C-PC extracted from Porphyra yezoensis could develop to new photosensitizers for cancer photodynamic therapy.
Apoptosis ; drug effects ; radiation effects ; Cell Line, Tumor ; Humans ; Lasers ; Liver Neoplasms ; pathology ; Photochemical Processes ; Photochemotherapy ; methods ; Phycobiliproteins ; isolation & purification ; pharmacology ; Phycoerythrin ; isolation & purification ; pharmacology ; Porphyra ; chemistry

OBJECTIVETo study the inhibitory effect of Ganoderma lucidum, the extract of chloroform, the extract of ethyl acetate and the remains after two-time extraction on BEL-7402 and MGC-803 cells and their protective effects on HL-7702 cells pre-and post-exposed to cisplatin (DDP) and various doses of 60Co gamma irradiation.

METHODThe antitumor activity and protective effects on damaged HL-7702 cells induced by radiotherapy and chemotherapy of ganoderma lucidum were determined by MTT technique.

RESULTThe anticancer activity of the extract of chloroform Ganoderma lucidum was the best: at the concentration of 0.125 mg x mL(-1), the inhibitory rate was over 50%. To the HL-7702 cells damaged by DDP, four kinds of extracts didn't exert restoring effect, but the pretreatment with the extract of chloroform reduced the damaged degree significantly. To the 60Co gamma irradiated HL-7702 cells, only the extract of chloroform exerted restoring effect to some extent when exposed to middle or high dose of irradiation. The pre-administration of four kinds of extracts reduced the damaged degree by radiation.

CONCLUSIONThe extract of chloroform exerts notable antitumor effects on cancer cells and protective effects on damaged normal cells induced by radiotherapy and chemotherapy.

Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; radiation effects ; Cisplatin ; adverse effects ; Cobalt Radioisotopes ; adverse effects ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Humans ; Liver Neoplasms ; pathology ; Radiation-Protective Agents ; isolation & purification ; pharmacology ; Reishi ; chemistry ; Stomach Neoplasms ; pathology

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines. METHODS: Western blotting was used to measure P53 expression. The effects of radiotherapy with iodine-131 were assessed by using the clonogenic assay to evaluate cell survival. Flow cytometry was carried out to examine the effects of iodine-131 on cell death, oxidative stress, reduced intracellular glutathione expression, the mitochondrial membrane potential, and the cell cycle. RESULTS: The P53 protein was not expressed in Hep3B2.1-7 cells, was expressed at normal levels in HepG2 cells, and was overexpressed in HuH7 cells. P53 expression in the HuH7 and HepG2 cell lines increased after internal and external irradiation with iodine-131. Irradiation induced a decrease in cell survival and led to a decrease in cell viability in all of the cell lines studied, accompanied by cell death via late apoptosis/necrosis and necrosis. Irradiation with 131-iodine induced mostly cell-cycle arrest in the G0/G1 phase. CONCLUSIONS: These results suggest that P53 plays a key role in the radiotherapy response of HCC.
Apoptosis/*radiation effects ; Blotting, Western ; Carcinoma, Hepatocellular/metabolism/pathology/radiotherapy ; Cell Line, Tumor ; Cell Survival/drug effects ; G1 Phase Cell Cycle Checkpoints/radiation effects ; *Gamma Rays ; Glutathione/metabolism ; Hep G2 Cells ; Humans ; Iodine Radioisotopes/chemistry/pharmacology/therapeutic use ; Liver Neoplasms/metabolism/pathology/radiotherapy ; Phosphorylation ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/*metabolism

PURPOSE: Sorafenib is an effective systemic agent for advanced hepatocellular carcinoma. To increase its efficacy, we evaluated the feasibility and benefit of sorafenib combined with radiotherapy. MATERIALS AND METHODS: From July 2007 to July 2011, 31 patients were treated with a daily dose of 800 mg of sorafenib and radiotherapy. Among them, 13 patients who received radiotherapy on the bone metastasis were excluded. Thirteen patients received 30-54 Gy of radiotherapy on the primary tumor (primary group) and 5 patients received 30-58.4 Gy on the measurable metastatic lesions (measurable metastasis group). Tumor responses at 1 month after the completion of radiotherapy and overall survival were evaluated. RESULTS: The in-field response rate was 100% in the primary group and 60% in the measurable metastasis group. A decrease of more than 80% in the tumor marker alpha-fetoprotein was observed in 7 patients in the primary group (54%). Toxicities of grades 3-4 were hand-foot syndrome in 3 (17%) patients, duodenal bleeding in 1 (6%) patient, thrombocytopenia in 3 (17%) patients and elevation of aspartate transaminase in 1 (6%) patient. The median overall survival was 7.8 months (95% confidence interval, 3.0-12.6). CONCLUSION: The combined treatment of sorafenib and radiotherapy was feasible and induced substantial tumor responses in the target lesions. The results of this study emphasize the importance of individualized approach in the management of advanced hepatocellular carcinoma and encourage the initiation of a controlled clinical trial.
Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/pathology/*radiotherapy ; Chemotherapy, Adjuvant ; Feasibility Studies ; Female ; Humans ; Liver Neoplasms/drug therapy/pathology/*radiotherapy ; Male ; Niacinamide/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/administration & dosage/adverse effects/*therapeutic use ; Radiation Dosage ; Radiotherapy/adverse effects

OBJECTIVETo study the protective effect of an extract of Guipi Pill () against radiation-induced damage.

METHODSA total of 100 Kunming mice were randomly divided into normal group, model group, positive drug group (treated with radioprotective agent "523", 5 mg/kg at 24 h before irradiation) and two treatment groups, with 20 mice in each group. The extract of water extraction-alcohol precipitation (WAP) from Guipi Pill were administered orally to the mice in the two treatment groups at the dose of 500 and 1,000 mg/kg, respectively, for 6 days prior to whole body radiation (8 Gy). Fifty mice with 10 in each group were used to observe the survival rate 30 days after radiation. The other 50 mice with 10 in each group were sacrificed on day 10 after radiation (6 Gy) in order to take blood, liver and unilateral femur.

RESULTSPretreatment prior to irradiation with WAP resulted in a significantly higher 30-day survival rate of mice after exposure to a potentially lethal dose of 8-Gy radiation. WAP could significantly increase the total white blood cell count and DNA content of bone marrow, and it also increased the activity of various antioxidant enzymes, such as superoxide dismutase, catalase, total antioxidant capacity and glutathione peroxidase in liver tissue of mice, which were reduced by radiation treatment. Maleic dialdehyde level and bone marrow micronucleus rate were significantly reduced by WAP, which were increased after 6-Gy radiation.

CONCLUSIONWAP of Guipi Pill could increase the 30-day survival rate and the antioxidant capacity as well as protect bone marrow in mice. WAP of Guipi Pill is an effective radioprotective agent.

Animals ; Antioxidants ; metabolism ; Bone Marrow ; pathology ; Chemical Precipitation ; DNA ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Leukocyte Count ; Liver ; metabolism ; pathology ; radiation effects ; Male ; Mice ; Micronuclei, Chromosome-Defective ; Phytotherapy ; Plant Extracts ; pharmacology ; therapeutic use ; Protective Agents ; pharmacology ; therapeutic use ; Radiation Injuries, Experimental ; blood ; drug therapy ; prevention & control ; Survival Analysis ; Water