• Tuberculosis and Respiratory Diseases
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• 제43권1호
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• pp.63-68
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• 1996

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 electrophoresis 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(dimethylthiazolyl diphenyltetrazolium bromide) bioassay. Also, after we treated A549 with 100 units/mi 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.

• Clinical and Experimental Pediatrics
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• 제51권10호
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• pp.1112-1117
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• 2008

Purpose : We intended to observe cell death and apoptotic changes in neurons in organotypic hippocampal slice cultures following oxygen-glucose deprivation (OGD), using propidium iodide (PI) uptake, Fluoro-Jade (FJ) staining, TUNEL staining and immunofluorescent staining for caspase-3. Methods : The hippocampus of 7-day-old rats was cut into $350{\mu}m$ slices. The slices were cultured for 10 d (date in vitro, DIV 10) and and exposed to OGD for 60 min at DIV 10. They were then incubated for reperfusion under normoxic conditions for an additional 48 h. Fluorescence of PI uptake was observed at predetermined intervals, and the cell death percentage was recorded. At 24 h following OGD, the slices were Cryo-cut into $15{\mu}m$ thicknesses, and Fluoro-Jade staining, TUNEL staining, and immunofluorescence staining for caspase-3 were performed. Results : 1) PI uptake was restricted to the pyramidal cell layer and DG in the slices after OGD. The fluorescent intensities of PI increased from 6 to 48 h during the reperfusion stage. The cell death percentage significantly increased time-dependently in CA1 and DG following OGD (P<0.05). 2) At 24 h after OGD, many FJ positive cells were detected in CA1 and DG. Some neurons had distinct nuclei and processes while others had fragmented nuclei and disrupted processes in CA1. TUNEL and immunofluorescent staining for caspase-3 showed increased expression of TUNEL labeling and caspase-3 in CA1 and DG at 24 h after OGD. Conclusion : The numerous dead cells in the slice cultures after OGD tended to display apoptotic changes mediated by the activation of caspase-3.

• Journal of Yeungnam Medical Science
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• 제14권2호
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• pp.293-313
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• 1997

이상에서 고찰하였듯이 현재까지는 어느 하나로 결정할 만한 선별 검사 방법이 없지만, 그 중에서 경질 초음파 검사와 color-flow Doppler 초음파 검사가 시행하기가 쉬우면서 민감하고 비교적 특이도가 높은 방법이라고 할 수 있다. 그러나 역학적인 면에서 조기 진단 혹은 선별 검사의 효율은 검사의 시행과 그에 따른 처치에 의해 사망률이 실제로 감소되었을 때 유의하다고 할 수 있으며, 이런 면에서 아직까지 난소암으로 인한 사망률을 감소시킬 만한 결정적인 선별 검사 방법은 알려져 있지 않다. 사망률이 1/3 감소되었음을 확인하는데 100,000명의 선별 검사자와 100,000명의 대조군이 필요하므로 앞으로 보다 많은 인구를 대상으로 한 역학적인 연구가 필요하다. 앞으로의 선별 검사에는 보다 특이도가 높은 종양 표지 물질의 개발, 초음파를 비롯한 진단 기기의 혁신적인 발달이 필요하며 이는 현재까지의 발전 상황으로 보아 실제로 가능할 것으로 생각된다. 이와 더불어 돌연변이를 일으킨 난소 상피 세포가 수 차례의 분열만 일으키더라도 그 유전자 산물을 검색해 낼 수 있고, 나아가서는 DNA 진단까지 가능한 분자 생물학적 혹은 세포 유전학전 진단 방법의 개발과 이용도 기대된다.

• Radiation Oncology Journal
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• 제20권4호
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• pp.367-374
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• 2002

Purpose : To investigate the growth inhibitory effects, and the underlying mechanism of human colon cancer cell (HT-29) death, induced by a new synthetic bile acid derivative (HS-1200). Materials and Methods : Human colon cancer cells (HT-29), in exponential growth phase, were treated with various concentrations of a new synthetic bile acid derivative (HS-1200). The growth inhibitory effects on HT-29 cells were examined using a frypan blue exclusion assay. The extent of apoptosis was determined using agarose gel electrophoresis, TUNEL assays and Hoechst staining. The apoptotic cell death was also confirmed by Western blotting of PARP, caspase-3 and DNA fragmentation factor (DFF) analysis. To investigate the involvement of mitochondria, we employed immunofluorescent staining of cytochrome c and mitochondrial membrane potential analyses. Results : The dose required for the half maximal inhibition $(IC_{50})$ of the HT-29 cell growth was $100\~150\;{\mu}M$ of HS-1200. Several changes, associated with the apoptosis of the HT-29 cells, were reveal by the agarose gel eletrophoresis, TUNEL assays and Hoechst staining, following their treatment with $100\;{\mu}M$ of HS-1200. HS-1200 treatment also induced caspase-3, PARP and DFF degradations, and the western blotting showed the processed caspase-3 p20, PARP p85 and DFF p30 and p11 cleaved products. Mitochondrial events were also demonstrated. The cytochrome c staining indicated that cytochrome c had been released from the mitochondria in the HS-1200 treated cells. The mitochondrial membrane potential $(\Delta\Psi_m)$ was also prominently decreased in the HS-1200 treated cells. Conclusion : These findings suggest that the HS-1200 - induced apoptosis of human colon cancer cells (HT-29) is mediated via caspase and mitochondrial pathways.

• Journal of Chest Surgery
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• 제42권6호
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• pp.725-731
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• 2009

Background: Lobectomy and more extended anatomic resection are regarded as standard treatment for stage Ia non-small cell lung cancer, but approximately 15~40% of patients suffer from treatment failures such as cancer recurrence or death. The authors analyzed types and causes of treatment failures in surgically treated cases of stage Ia non small cell lung cancer. Material and Method: We retrospectively reviewed the medical records of 156 patients who had undergone complete resection for stage Ia NSCLC between Jan 1992 and Aug 2005. Patients were divided into two different treatment failure groups: cancer-related deaths and non-cancer-related deaths. Risk factors were analyzed in each group by the Kaplan-Meyer survival method and the Cox proportional hazard model. Result: Among the 156 patients, 93 were males; the mean age was 61. The median follow-up period was 33.8 months. The 5 year survival rate was 87.6%. Microscopic lympho-vascular permeation was reported in 10 patients. Recurrence was reported in 19 patients and 12 patients died due to recurrent lung cancer. Noncancer related deaths occurred in 16 patients. Risk factors for cancer recurrence and cancer related death were microscopic lympho-vascular permeation (HR=6.81, p=0.007, HR=7.81, p<0.001); for non-cancer related death, risk factors were pneumonectomy (HR=25.92, p=0.001) and postoperative cardiopulmonary complications (HR=29.67, p=0.002). Conclusion: After complete resection of stage Ia non small cell lung cancer patients, mortality includes not only cancer related deaths but also cancer unrelated deaths. Adjuvant chemotherapy is advised for patients who show microscopic lympho-vascular permeation, which is a risk factor for recurrence and for cancer related death. Patients who had pneumonectomy or who suffered from cardiac or respiratory complications need meticulous care in order to reduce comorbidity-induced death.

• KSBB Journal
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• 제10권3호
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• pp.323-334
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• 1995

The effects of glucose on cell growth kinetics, monoclonal antibody productivity, and cell metabolism or hybridoma cells were investigated. The mouse-mouse hybridoma cell line VIII H-8 producing mouse IgG2a was used as a modal system. Glucose showed substrate inhibition type dependence on specific growth raie. The maximum cell density increased as initial glucose concentration increased up to 4 g/$\ell$. Glucose showed a strong influence on cell death kinetics, and an inverse relationship between specific death rate and glucose concentration was found. Cell viability and monoclonal antibody production increased as initial glucose concentration increased. The specific glucose consumption rate increased with glucose concentration, and cumulative specific lactate production rate increased with increasing initial glucose concentration. The overall kinetics of ammonium ion production was almost invariant with respect to initial glucose concentration, while the cumulative specific ammonium ion production rate was dependent on initial glucose concentration.

• The Science & Technology
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• 제29권11호통권330호
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• pp.80-81
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• 1996

우리나라 여성들에게서 발병 사망률이 높은 자궁경부암의 세포주를 배양하여 암의 발생원인 특성을 밝혀낸 가톨릭대 의대 김진우교수. 김교수는 난소암 자궁내막암 세포배양에도 성공하여 앞으로 임상실험을 하기 위한 재료확보와 암의 항원 전체구조를 파악하는 연구를 계속할 것이라고 한다.

• Korean Journal of Biological Psychiatry
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• 제5권2호
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• pp.219-226
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• 1998

Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

• Journal of Life Science
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• 제18권11호
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• pp.1485-1492
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• 2008

Prostaglandin $A_2$ ($PGA_2$), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. $PGA_2$-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas $H_2O_2$-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by $PGA_2$. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that $PGA_2$ induces both apoptosis and HO-1 expression, which are critically related to the thiol- reactivity of $PGA_2$, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by $PGA_2$ without contribution to apoptosis progression.

• Journal of Chest Surgery
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• 제32권8호
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• pp.757-760
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• 1999

A rare small cell carcinoma of the trachea was managed in a 59 year old female patient. The diagnosis was confirmed by histopathological and immunohistochemical studies. Surgical resection and adjuvant chemotherapy were done. The patient died 6 months later due to multiple metastasis.