BACKGROUND: Tumor necrosis factor(TNF) has been considered as an important candidate for cancer gene therapy based on it9 potent anti-tumor activity. However, since the efficiency of current techniques of gene transfer is not satisfactory, the majorities of current protocols is aiming the in vitro gene transfer to cancer cells and re-introducing genetically modified cancer cells to host In previous study, it was shown that TNF-sensitive cancer cells transfected with TNF-α CDNA would become highly resistant to TNF. Understanding the mechanisms of TNF-resistance in TNF-α gene transfected cancer cells would be an important step for improving the efficacy of cancer gene therapy as we]1 as for better understandings of tumor biology. This study was designed to evaluate the role of new protective protein synthesis in the acquired resistance to TNF of TNF-α gene transfected cancer cells. METHOD: We transfected TNF-α c-DNA to WEHI l64, a murine fibrosarcoma cell line, using retroviral vector (pLT12SN(TNF)) and confirm the expression of TNF with PCRf ELISA, MTT assay. Then we determined the TNF resistance of TNF gene transfected cells(WEHI 164-TNF) and the changes of TNF sensitivities after treatments with actinomycin D(transcription inhibitor) and cycloheximide(translation inhibitor). RESULTS: WEHI 164 which was sensitive to TNF became resistant to TNF after being trsnsfected with TNF-α gene and the resistance to TNF was partially reversed after treatment with actinomycin D, but not with cycloheximide. CONCLUSION: The acquired resistance to TNF after TNF-α gene transfection may be associated with synthesis of some protective proteins.
Biology ; Cell Line ; Cycloheximide ; Dactinomycin ; DNA, Complementary ; Enzyme-Linked Immunosorbent Assay ; Fibrosarcoma ; Genes, Neoplasm ; Necrosis ; Transfection ; Tumor Necrosis Factor-alpha* ; Zidovudine*

No abstract available.
Transplants*

BACKGROUND: Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts proteolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell in vitro was evaluated for the future purpose of gene therapy against lung cancer. METHODS: Recombinant adenvirus-TIMP-2(Ad-TIMP-2) was generated by homologeous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate mathod. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-β-gal. An-chorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. RESULTS: Ad-TIMP-2 transduced calu-6 cells produced bilolgically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorgenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. CONCLUSION: Even though TIMP-2 gene transfer did not inhibit in vitr tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.
Adenoviridae* ; Agar ; Calcium ; Genetic Therapy ; Humans ; Lung Neoplasms* ; Lung* ; Parents ; Peptide Hydrolases ; Recombination, Genetic ; Tissue Inhibitor of Metalloproteinase-2*

Surgical resection of esophageal cance has played a prominent role in both cure and palliation. The radiologic evaluation of postesophagectomy patients is directed at the detection of normal and pathological appearances after surgical resection. Since early detection of recurrent tumor is important in the management of patients who have undergone esophagectomy, we undertook a retrospective study to evaluate the findings of recurrence on CT in postesophagectomy patients. Between January 1988 and July 1991, 26 patients who had undergone transthoracic esophagectomy with esophagogastrostomy for epidermoid carcinoma of the esophagus with following reoccurance were examined by chest CT. The group included 25 male and one female patients were aged 45-71 years(mean, 53). All patients had studies done immediate post operative 7-10 days. The CT were performed with a CT 9800 scanner (GE Medical System, Milwaukee) after administration of oral contrast media and intravenous injection of contrast media. The findings seen on CT were cnfirmed by biopsy in five cases and by clinical, radiological follow-up manifestation in 21 cases. The abnormalities that were demonstrated on follow-up CT were adenopathy-mediastinal node(ten cases) or abdominal node(five cases), local recurrence-previous tumor site (five case), anastomotic siteI(two cases) or thoracases), peicardial effusion(two cases). Our results indicate that serial chest CT play an important role in the evaluation of the patients after transthoracic esophagectomy with esophagogastrotomy.
Biopsy ; Carcinoma, Squamous Cell ; Contrast Media ; Esophageal Neoplasms* ; Esophagectomy* ; Esophagus ; Female ; Follow-Up Studies ; Humans ; Injections, Intravenous ; Male ; Recurrence ; Retrospective Studies ; Thorax* ; Tomography, X-Ray Computed*

No abstract available.
Erythromycin*

PURPOSE: p53 mutations are one of the most common genetic alterations in human lung cancer. Although the prognostic value of mutant p53 is still debated, it is widely accepted as a relatively early genetic event in the development and progression of lung cancer. Moreover, there are growing reports about an association between smoking and p53 mutation, suggesting that the p53 gene could be a target of the smoking associated carcino- genesis in the lung cancer. MATERIALS AND METHODS: Surgically resected 89 primary non-small cell lung cancers were obtained from May of 1995 to May of 1997. p53 expression and Ki-67 expression were measured by immunohistochemistry, and each p53 expression and smoking amount were compared with Ki-67 expression and other clinical prognostic factors. RESULTS: Positive p53 expressions were found in 52 (58%) specimens, including 38 (69%) squamous cell carcinomas, 11 (39%) adenocarcinomas, and 3 (50%) large cell carcinomas, and closely associated with male and squamous cell carcinoma. Also close correlation was observed between smoking amount and p53 expression by the regression analysis. But p53 and Ki-67 expression showed no associations in pathologic stage and survival, and there was no association between p53 expression and survival after adjuvant radiotherapy. CONCLUSION: Smoking seems to affect p53 mutations in non-small cell lung cancer, and additional efforts are needed to evaluate the carcinogesis of lung cancer.
Adenocarcinoma ; Carcinoma, Large Cell ; Carcinoma, Non-Small-Cell Lung ; Carcinoma, Squamous Cell ; Genes, p53 ; Humans ; Immunohistochemistry ; Lung Neoplasms ; Male ; Radiotherapy, Adjuvant ; Small Cell Lung Carcinoma* ; Smoke* ; Smoking*

BACKGROUND: Smoking and high-risk occupation have been known to be the risk factors of lung cancer. The carcinogen-metabolizing enzymes in human body such as glutathione S-transferase M1, T1 and N-acetyltransferase 1 have also been regarded as risk factors in many cancers, because the activities of those enzymes play a role in metabolizing the carcinogen. A case-control study was conducted to evaluate the genetic polymorphism of GSTM1, T1 and NAT1 in lung carcinogenesis in Korean men. METHODS: The histologically proven lung cancer cases were recruited from Seoul National University Hospital. The patients of more than 40-year-old with the nonmalignant urinary tract diseases were recruited as controls from the same hospitals. The informations of demographical characteristics and smoking were obtained by interview or chart review and the genetic polymorphisms of GSTM1, T1 and NAT1 were determined by PCR-based assay. The statistical analyses were performed by linear logistic regression. RESULTS: The number of case-control was 118 and 150, respectively. The smoking history was significantly higher in the lung cancer patients than the controls. The prevalence of GSTM1 null-type was statistically higher(OR=2.25 ; 95% C I=1.12-4.51) in squamous cell carcinoma than other genotypes, but other histologic types were not. The prevalence of GSTT1 null-type were not statistically higher than other genotypes in all histologic types. The fast acetylator of NAT1 was more prevalent than normal(OR-2.13 ; 95% C I=1.04-4.40) in all lung cancer patients. CONCLUSION: The null-type of GSTM1 and fast acetylator of NAT1 are associated with development of lung cancer in Korean men.
Adult ; Carcinogenesis ; Carcinoma, Squamous Cell ; Case-Control Studies ; Genotype ; Glutathione Transferase* ; Glutathione* ; Human Body ; Humans ; Logistic Models ; Lung Neoplasms* ; Lung* ; Male ; Occupations ; Polymorphism, Genetic* ; Prevalence ; Risk Factors ; Seoul ; Smoke ; Smoking ; Urologic Diseases

BACKGROUND: Interferon-gamma has various biologic effects, including antiviral effect, antitumor proliferative effect, activation of macrophage and B lymphocyte, and increased expression of major histocompatibility complex. Especially, antitumor proliferative effect of interferon-gamma has already been proved to be important in vivo as well as in vitro. And, clinical studies of interferon-gamma have been tried in lung cancer patients. However, the mechanism of antitumor effect of interferon-gamma has not yet been established despite of many hypotheses. "Necrosis" is a type of cell death which is well known to occur in the circumstances of severe stresses. In contrast, "apoptosis" is another type of cell death which occurs in such biological circumstances as embryonic development, regression of organs, and self-tolerance of lymphocytes. And, apoptosis is an active process of cell death in which cells are dying with fragmentations of their cytoplasms and nuclei. And, in the process of apoptosis the DNAs of cells are cleaved between nucleosomes by unidentified endonuclease and therefore DNAs of apoptotic cells result in a typical electorphoresis pattern known as DNA ladder pattern. Recently it has been suggested that cytotoxic effect of interferon-gamma occurs via apoptosis. To elucidate the mechanism of antitumor cytotoxic effect of interferon-gamma, we microscopically observed a lung cancer cell line, A549 which was treated with interferon-gamma. We observed A545 treated with interferon-gamma was dying fragmented. And so, we performed this study to find out that the mechanism of antitumor cytotoxic effect of interferon-gamma be apoptosis. METHOD: We treated A549, human lung cancer cell line with various concentration of interferon-gamma and quantified its cytotoxic effect of various periods, 24 hours, 72 hours and,, 120 hours by MTT(dimethylthiazoly1 diphenyltetrazolium bromide) bioassay. Also, after we treated A549 with 100 units/ml of interferon-gamma for 120 hours, we observed the pattern of cell death with inverted microscope and we extracted DNAs from the dead A549 cells and observed the pattern of 1.5% agarose gel electrophoresis with ethidium bromide staining. RESULT: 1) Cytotoxic effect of interferon-gamma on A549: For the first 24 hours, threre was little cytotoxic effect and for between 24 hours and 72 hours, there was the beginning of cytotoxic effect and for 120 hours there was increased cytotoxic effect. 2) Pattern of A549 cell death by interferon-gamma: We observed with inverted microscope that A549 cells were dying fragmented. 3) DNA ladder pattern of gel electrophoresis: We observed DNA ladder pattern of gel electrophoresis of extracted DNAs from dead A549 cells. CONCLUSION: We concluded that the mechanism of interferon-gamma induced cytotoxicity on lung cancer cell line, A549 be via apoptosis.
Apoptosis ; Biological Assay ; Cell Death ; Cell Line* ; Cytoplasm ; DNA ; Electrophoresis ; Electrophoresis, Agar Gel ; Embryonic Development ; Ethidium ; Female ; Humans ; Interferon-gamma* ; Lung Neoplasms* ; Lung* ; Lymphocytes ; Macrophages ; Major Histocompatibility Complex ; Nucleosomes ; Pregnancy

OBJECTIVE: The aim of this study is to describe the clinical characteristics and outcome of cancer diagnosed during pregnancy. METHODS: This is a retrospective cohort study of women who were diagnosed with cancer during pregnancy at a tertiary academic hospital between 1995 and 2013. Maternal characteristics, gestational age at diagnosis, and type, stage, symptoms and signs of cancer for each patient were retrieved from the medical records. The cancer treatment, pregnancy management and the subsequent perinatal and maternal outcomes for each cancer were assessed. RESULTS: A total of 87 women were diagnosed with cancer during pregnancy (172.6 cases per 100,000 deliveries). The most common cancer was breast cancer (n=20), followed by gastrointestinal (n=17), hematologic (n=13), thyroid (n=11), central nervous system (n=7), cervical (n=7), ovarian (n=5), lung (n=3), and other cancers (n=4). Eighteen (20.7%) patients terminated their pregnancies. In the 69 (79.3%) patients who maintained their pregnancies, one patient miscarried and 34 patients delivered preterm. Of the preterm babies, 24 (70.6%) were admitted to the neonatal intensive care unit and 3 (8.8%) of those expired. The maternal mortality rate was 31.0%, with highest rate seen with lung cancers (66.7%), followed by gastrointestinal (50.0%), central nervous system (50.0%), hematologic (30.8%), breast (25.0%), ovarian (20.0%) cervical (14.3%), and thyroid cancers (0%). CONCLUSION: The clinical characteristics and outcome of cancer during pregnancy were highly variable depending on the type of cancer. However, timely diagnosis and appropriate management of cancer during pregnancy may improve both maternal and neonatal outcome.
Breast ; Breast Neoplasms ; Central Nervous System ; Cohort Studies ; Diagnosis ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Intensive Care, Neonatal ; Lung ; Lung Neoplasms ; Maternal Mortality ; Medical Records ; Pregnancy Outcome ; Pregnancy* ; Retrospective Studies ; Thyroid Gland

PURPOSE: In the pediatric patients who have medically intractable epilepsy the callosotomy is useful to prevent the propagation of seizure from one hemisphere to the other. The indications of callosotomy are drop attack, life threatening primarily or secondarily generalized seizure, medically refractory mixed seizure types such as Lennox-Gastaut syndrome. In addition, the retarded children are not contraindicated. The anterior callosotomy is used to perform to control medically intractable epilepsy which is believed to have some advantages to total callosotomy. But, we propose that the anterior callosotomy does not seem to be superior to total callosotomy for the prevention of the propagation of seizure or complication. We describe a series of 21 patients with medically intractable epilepsy who underwent total callosotomy in one stage. METHODS: The diagnoses in these patients included Lennox-Gastaut syndrome, atonic seizure, infantile hemiplegia, and no obvious solitary seizure focus on chronic video/EEG monitoring to characterize seizures, electrographic activity, and postictal behaviors. Preoperatively 16 patients suffered from disabling drop attacks or intense head drop seizures which caused frequent physical injuries. Other types of seizures are 12 generalized tonic-clonic seizures, 7 complex partial seizures, 1 absence seizure, and 7 myoclonic seizures. Male:Female=14:7, Age: 2-22 years (Mean: 9.4 years). The follow-up period ranged from 0.8 to 3.8 years (median 2.4 years). Seizure outcome, parental assessment of daily function, and parental satisfaction with outcome were assessed postoperatively. RESULTS: Drop attacks disappeared completely during the entire follow-up period in 13 patients and decreased to less than 10% of baseline in five. The corpus callosum of the one patient were not completely sectioned in Diffusion Tensor Image, tractography. Other types of seizures resolved completely in 14 patients and decreased in 7. 2 patients experienced a transient disconnection syndrome, but completely resolved within four weeks. Overall daily function improved and parents were satisfied with the surgical outcome in all patients except three who experienced recurrent of drop attacks after operation. There was no sign of significant and persistent neurological deficits in any case. CONCLUSION: Results of total callosotomy in patients with medically intractable epilepsy with diffuse epileptic foci were favorable in most cases. The procedure was particularly effective against drop attacks causing physical injuries and impaired quality of life in these patients.
Child ; Corpus Callosum ; Diagnosis ; Diffusion ; Epilepsy* ; Epilepsy, Absence ; Follow-Up Studies ; Head ; Hemiplegia ; Humans ; Parents ; Quality of Life ; Seizures ; Syncope