To evaluate the effect of wild-type p53 gene on the growth and radiotherapeutic sensitivity of human glioma cells, plasmid PC53-SN3 carrying wild-type p53 gene was transfected into U251 cells. p53 gene expression in transfected cells was detected by RT-PCR, and the cell growth inhibition and apoptosis in the absence or presence of irradiation were assessed by MTT and flow cytometry. The transfection of p53 gene into U251 cells was confirmed by RT-PCR. MTT showed that p53 gene alone induced strong inhibitory effect on the growth of U251 cells (inhibition rate (IR), (79.60 +/- 5.69)%). The killing effect of irradiation alone on U251 cells was not strong (IR: (17.06 +/- 4.35)% (17.39 +/- 1.67)% (18.73 +/- 4.68)%) and increased with the irradiation doses (3, 6, 9 Gy). When combined treatment of wild-type p53 gene transfection and irradiation was used, the effect was significantly increased (IR:(80.60 +/- 5.35)%. (90.30 +/- 1.67)%, (91.30 +/- 2.01)%). The apoptosis rate of U251 cells induced by p53 gene transfection was 17.38%. The rate induced by irradiation increased (4.61%, 4.84%, 5.40%) with the irradiation doses (3, 6, 9 Gy). The apoptosis rate was also significantly increased (17.80%, 20.03%, 22.34%) after combined treatment of p53 and irradiation with different doses (3, 6, 9 Gy). It is concluded that wild-type p53 gene and irradiation could result in synergistic inhibitory effect on the growth of human glioma cells.
Apoptosis/*radiation effects ; Brain Neoplasms/genetics ; Brain Neoplasms/*pathology ; Genes, p53/*radiation effects ; Glioma/genetics ; Glioma/*pathology ; Transfection ; Tumor Cells, Cultured

OBJECTIVETo study the radiosensitization on the cells of colorectal cancer transfected with recombinant adenovirus vector-mediated wild-type p53.

METHODSSW480 cells transfected by wild-type p53 were treated with 4 Gy and 6 Gy radiation. The expression of recombinant adenovirus vector-mediated wild-type p53 gene was detected by Western blotting. The inhibition rate of SW480 cells was examined by MTT, apoptotic rate by TdT-mediated dUTP nick end labeling (TUNEL) and proliferating cell nuclear antigen (PCNA) by immunohistochemical method.

RESULTSSW480 cells transfected by wild-type p53 were inhibited significantly by 4 Gy and 6 Gy radiation. The level of apoptosis increased and the expression of PCNA decreased.

CONCLUSIONCells of colorectal carcinoma transfected with wild-type p53 increases their radiation sensitivity.

Adenoviridae ; genetics ; Colorectal Neoplasms ; genetics ; pathology ; radiotherapy ; Genes, p53 ; radiation effects ; Genetic Vectors ; Humans ; Mutation ; Radiation Tolerance ; Transfection ; Tumor Cells, Cultured

INTRODUCTIONSensori-neural hearing loss (SNHL) is a frequent complication of conventional radiotherapy for head and neck tumours, especially nasopharyngeal carcinoma. To manage radiation-induced ototoxicity appropriately, an understanding of the cellular and molecular basis of this complication is necessary.

MATERIALS AND METHODSA medline search of relevant literature was done, focusing on the radiation-induced cellular and molecular processes that lead to hair cell death in the cochlea.

RESULTSRadiation-induced SNHL occurs in the cochlea, with the retro-cochlear pathways remaining functionally intact. By simulating radiotherapy regimes used clinically, radiation-induced cochlear cell degeneration in the absence of damage to the supporting structures and blood vessels has been demonstrated in animals. This could be due to apoptotic cochlear cell death, which has been shown to be associated with p53 upregulation and intra-cellular reactive oxygen species (ROS) generation. Oxidative stress may initiate the upstream processes that lead to apoptosis and other cell death mechanisms.

CONCLUSIONSA model of radiation-induced SNHL based on a dose and ROS-dependent cochlear cell apoptosis, is proposed. This model supports the feasibility of cochlear implantation, should one be clinically indicated. It can explain clinical observations such as radiation-induced SNHL being dose-dependent and affects the high frequencies more than the lower frequencies. It also opens up the possibility of preventive strategies targeted at different stages of the apoptotic process. Antioxidants look promising as effective agents to prevent radiation-induced ototoxicity; they target upstream processes leading to different cell death mechanisms that may co-exist in the population of damaged cells.

Animals ; Cell Death ; Cell Line ; Cochlea ; radiation effects ; Genes, p53 ; Hair Cells, Auditory ; radiation effects ; Hearing Loss, Sensorineural ; etiology ; genetics ; physiopathology ; Humans ; Mice ; Radiation Injuries ; complications ; Reactive Oxygen Species ; metabolism

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage

Following improvements in therapy for childhood malignancies, the striking increase in survival rate over the past 30 years has led to the increase risk of developing second malignant neoplasms (SMNs). We report a case of colorectal carcinoma as a SMN, following treatment for rhabdomyosarcoma. The patient was diagnosed with rhabdomyosarcoma of the urinary bladder at his age of three years, and developed adenocarcinoma in the colon 13 years later. Histologic examination of the surgical specimen revealed adenocarcinoma involving the rectosigmoid area with radiation colitis in its background. The tumor cells showed strong immunoreactivity for p53 protein, suggesting the role of irradiation and p53 mutation in carcinogenesis. This case emphasizes the need for dose observation in survivors of early childhood malignancies treated with radiation and multiagent chemotherapy.
Adenocarcinoma/pathology ; Adenocarcinoma/genetics ; Adenocarcinoma/etiology+ACo- ; Adolescence ; Antineoplastic Agents, Combined/therapeutic use ; Antineoplastic Agents, Combined/adverse effects+ACo- ; Bladder Neoplasms+ACo-/radiotherapy ; Bladder Neoplasms+ACo-/drug therapy ; Case Report ; Colitis/pathology ; Colitis/etiology ; Colorectal Neoplasms/pathology ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/etiology+ACo- ; Combined Modality Therapy ; Cyclophosphamide/adverse effects ; Cyclophosphamide/administration +ACY- dosage ; Doxorubicin/adverse effects ; Doxorubicin/administration +ACY- dosage ; Genes, p53 ; Human ; Male ; Neoplasm Proteins/analysis ; Neoplasms, Radiation-Induced/pathology ; Neoplasms, Radiation-Induced/genetics ; Neoplasms, Radiation-Induced/etiology+ACo- ; Neoplasms, Second Primary/etiology+ACo- ; Protein p53/analysis ; Radiation Injuries/pathology ; Radiation Injuries/etiology ; Radiotherapy/adverse effects+ACo- ; Rhabdomyosarcoma+ACo-/radiotherapy ; Rhabdomyosarcoma+ACo-/drug therapy ; Sigmoid Neoplasms/pathology ; Sigmoid Neoplasms/genetics ; Sigmoid Neoplasms/etiology ; Time Factors ; Vincristine/adverse effects ; Vincristine/administration +ACY- dosage

OBJECTIVETo investigate the effect of HER2/neu overexpression on the wild p53 gene expression, cell proliferation and sensitivity to gamma-irradiation via phosphatidylinositol 3-kinase (PI3K) pathway in human breast cancer cell MCF7.

METHODSLipofectin-mediated gene transfection method was used to transfer HER2/neu into MCF7 cells. Expression of HER2/neu, p53, Akt and p-Akt protein after PI3K pathway inhibitor LY294002 treatment was determined by Western blot. Cell proliferation and cell surviving fraction after gamma-irradiation treatment were assayed by MTT.

RESULTSEighteen of HER2/neu stably transfected MCF7 cell clones were established, one of them was HER2/neu overexpressing. HER2/neu overexpressing MCF7 cells showed higher p-Akt expression and lower p53 expression than those of parental MCF7 cells, which could be abrogated by LY294002. HER2/neu overexpressing MCF7 cells had higher proliferation rate and lower sensitivity to gamma-irradiation than those of parental MCF7 cells, which could be opposed by LY294002.

CONCLUSIONOverexpression of HER2/neu induces reduced expression of wild-type p53 protein, relatively high cell proliferation and low sensitivity to gamma-irradiation in breast cancer cell MCF7 by activating PI3K/Akt pathway, which may contribute to therapeutic resistance in some breast cancer patients with wild-type p53 gene status.

Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cesium Radioisotopes ; Chromones ; pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Genes, erbB-2 ; Humans ; Morpholines ; pharmacology ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Radiation Tolerance ; Receptor, ErbB-2 ; biosynthesis ; genetics ; Signal Transduction ; Transfection ; Tumor Suppressor Protein p53 ; metabolism