BACKGROUND: Two tumor suppressor genes, p53 and p16, which have different roles in controlling the cell cycle and inducing apoptosis, are frequently inactivated during carcinogenesis including lung cancer. Single tumor suppressor gene therapies using tither with p53 or p16 have been studied extensively. However, there is a paucity of reports regarding a combined gene therapy using these two genes. METHODS: The combined effect of p53 and p16 gene transfer by the adenoviral vector on the growth of lung cancer cell lines and its interactive mechanism was investigated. RESULTS: An isobologram showed that the co-transduction of p53 and p16 exhibited a synergistic growth inhibitory effect on NCI H358 and an additive effect on NCI H23. Cell cycle analysis demonstrated the induction of a synergistic G1/S arrest by a combined p53 and p16 transfer. This synergistic interaction was again confirmed in a soft agar clonogenic assay. CONCLUSION: These observations suggest the potential of a p53 and p16 combination gene therapy as another potent strategy in cancer gene therapy.
Adenoviridae ; Agar ; Apoptosis ; Carcinogenesis ; Cell Cycle ; Cell Line* ; Genes, Neoplasm ; Genes, p16 ; Genes, Tumor Suppressor ; Genetic Therapy ; Lung Neoplasms* ; Lung*

PURPOSE: Although Pokeweed intoxication is relatively less severe, thereis little data onthe clinical presentation ofPokeweed intoxication in Korea. This study examined the clinical aspectsto providebasic data for evaluating Pokeweed intoxication. METHODS: A retrospective study by a chart review was performedon 19 patients who ingested Pokeweed and presented to anacademic emergency department with an annual census of 40,000 between March 2012 and May 2012. RESULTS: Nineteen patients were identified. All patients wereintoxicated unintentionally. The most common symptoms were vomiting with diarrhea and abdominal pain. The onset time varied, but occurs 30 minutes to 5 hours post ingestion of Pokeweed. All patients were discharged without fatal complications. CONCLUSION: Compared to previous reports, mostpokeweed poisoning patients complain of gastrointestinal symptoms. Supportive care is the mainstay of the management of pokeweed intoxication. All symptoms were resolved over a 24 to 48 hour period.
Abdominal Pain ; Censuses ; Diarrhea ; Eating ; Emergencies ; Humans ; Korea ; Phytolacca americana ; Plant Poisoning ; Retrospective Studies ; Vomiting

BACKGROUND: Some chemotherapeutic drugs induce NF-κB activation by degrading the IκBα protein in cancer cells which contributes to anticancer drug resistance. We hypothesized that inhibiting IκBα degradation would block NF-κB activation and result in increased tumor cell mortality in response to chemotherapy. METHODS: The "superrepressor" form of the NF-κB inhibitor was transferred by an adenoviral vector (Ad-IκBα-SR) to the human lung cancer cell lines (NCI H157 and NCI H460). With a MTT assay, the level of sensitization to cisplatin and paclitaxel were measured. To confirm the mechanism, an EMSA and Annexin V assay were performed. RESULTS: EMSA showed that IκBα-SR effectively blocked the NF-κB activation induced by cisplatin. Transduction with Ad-IκBα-SR resulted in an increased sensitivity of the lung cancer cell lines to cisplatin and paclitaxel by a factor of 2~3 in terms of IC50. Annexin-V analysis suggests that this increment in chemosensitivity to cisplatin probably occurs through the induction of apoptosis. CONCLUSION: The blockade of chemotherapeutics induced NF-κB activation by inducing Ad-IκBα-SR, increased apoptosis and increasing the chemosensitivity of the lung cancer cell lines tested, subsequently. Gene transfer of IκBα-SR appears to be a new therapeutic strategy of chemosensitization in lung cancer.
Adenoviridae ; Annexin A5 ; Apoptosis ; Cell Line* ; Cisplatin ; Drug Resistance ; Drug Therapy ; Humans* ; Inhibitory Concentration 50 ; Lung Neoplasms* ; Lung* ; Mortality ; Paclitaxel*

Various cell types in higher multicellular organisms are genetically homogenous, but are functionally and morphologically heterogeneous due to the differential expression of genes during development, which appears to be controlled by epigenetic mechanisms. However, the exact molecular mechanisms that govern the tissue-specific gene expression are poorly understood. Here, we show that dynamic changes in histone modifications and DNA methylation in the upstream coding region of a gene containing the transcription initiation site determine the tissue-specific gene expression pattern. The tissue-specific expression of the transgene correlated with DNA demethylation at specific CpG sites as well as significant changes in histone modifications from a low ratio of methylated H3- lysine 4 or acetylated H3-lysine 9, 14 to acetylated H4 to higher ratios. Based on the programmed status of transgene silenced in cloned mammalian ear-derived fibroblasts, the transgene could be reprogrammed by change of histone modification and DNA methylation by inhibiting both histone deacetylase and DNA methylation, resulting in high expression of the transgene. These findings indicate that dynamic change of histone modification and DNA methylation is potentially important in the establishment and maintenance of tissue-specific gene expression.
Transgenes/*genetics ; Swine ; Organ Specificity/genetics ; Methylation ; Lysine/*metabolism ; Histones/*metabolism ; Histone Deacetylases/metabolism ; Gene Silencing ; *Gene Expression ; Fibroblasts ; Ear ; *DNA Methylation ; Cells, Cultured ; Animals, Genetically Modified ; Animals ; Acetylation

PURPOSE: To evaluate the effect of the simulation method on recurrence among the patients who received radiotherapy after breast-conserving surgery (BCS) for early breast carcinoma. METHODS AND MATERIALS: Between 1995 and 2000, 70 patients with stage I-II breast carcinoma underwent breast-conserving surgery and adjuvant radiotherapy. Twenty nine patients (41.4%) were simulated with the 2D contour-based method (September 1995 to August 1997) and 41 patients (58.6%) were simulated with the 3D CT-based method (September 1997 to February 2000). To analyze the effect of the simulation method, the patient and treatment characteristics were compared. RESULTS: The characteristics were similar for the patients between the 2D contour-based simulation group and the 3D CT-based simulation group. During a median follow-up period of 75 months, 4 (13.8%) of 29 patients who were treated with 2D simulation and 1 (2.4%) of 41 patients who were treated with 3D simulation group devel-oped treatment failure. The five-year survival rates were 89.2% and 95.1% between the 2D and 3D simulation groups (p=0.196). The five-year disease free survival (DFS) rates were 86.2% and 97.5% between the 2D and 3D simulation groups (p=0.0636). On univariate analysis, age > 40 (p= 0.0226) and the number of dissected axillary lymph node > or = 10 (p=0.0435) were independent predictors of improved 5-year DFS. CONCLUSIONS: Although our data showed marginal significance for the DFS between the two groups, it is insufficient, due to the small number of patients in our study, to prove whether 3D CT-based simulation might improve the DFS and reduce the risk of recurrence when compared with 2D contour-based simulation. Further study is needed with a larger group of patients.
Breast Neoplasms ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Lymph Nodes ; Mastectomy, Segmental* ; Radiotherapy* ; Radiotherapy, Adjuvant ; Recurrence* ; Survival Rate ; Treatment Failure

PURPOSE: Breast-conserving therapy (BCT) is a practical alternative to mastectomy for treating ductal carcinoma in situ (DCIS). We reviewed our experience for treating patients with DCIS of the breast to evaluate the outcome after performing breast-conserving surgery plus radiotherapy (BCS-RT). MATERIALS AND METHODS: Between January 1983 and December 2002, 25 patients with clinically or mammographically detected DCIS were treated by BCS-RT. One patient was diagnosed with bilateral DCIS. Thirteen cases (50%) had symptomatic lesions at presentation. All 26 cases of 25 patients underwent BCS such as lumpectomy, partial mastectomy or quadrantectomy. All of them received whole breast irradiation to a median dose of 50.4 Gy. Twenty-four cases (92.3%) received a boost to the tumor bed for a median total dose of 59.4 Gy. The median follow up period was 67 months (range: 38 to 149 months). RESULTS: Two cases (7.7%) experienced ipsilateral breast tumor recurrence (IBTR) after BCS-RT. The histology results at the time of IBTR showed invasive ductal carcinoma (IDC), and the median time to IBTR was 25.5 months. On the univariate analysis, there were no significant factors associated with IBTR in the DCIS patients. The three-year local recurrence free survival rate was 96.0% and the overall survival rate was 96.3%. CONCLUSION: After the treatment for DCIS, the IBTR rate in our study was similar to other previous studies. Considering that we included patients who had many symptomatic lesions, close or positive margins and less that complete early data, our result is comparable to the previous studies. We could not find the prognostic significant factors associated with IBTR after BCS-RT. A longer follow up period with more patients would be required to evaluate the role of any predictive factors and to confirm these short-term results.
Breast Neoplasms ; Breast* ; Carcinoma, Ductal* ; Carcinoma, Intraductal, Noninfiltrating* ; Follow-Up Studies ; Humans ; Mastectomy ; Mastectomy, Segmental* ; Radiotherapy* ; Recurrence ; Survival Rate