• Journal of Chest Surgery
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• v.37 no.10
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• pp.817-826
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• 2004

Background: Several studies have demonstrated that conventional hypothermic cardiopulmonary bypass (CPB) causes cellular injury, abnormal responses in peripheral vascular beds and increased postoperative bleeding, whereas normothermic CPB provides protection of the hypothermic-induced effects and better cardiac recovery. The present study was prospectively performed to compare the effects of normothermic CPB to those of hypothermic CPB on the inflammatory and hematologic responses during cardiac surgery. Material and Method: Thirty-four adult patients scheduled for elective cardiac surgery were randomly assigned to hypothermic CPB (nasopharyngeal temperature $26～28^{\circ}C,$ n=17) or normothermic CPB (nasopharyngeal $temperature>35.5^{\circ}C,$ n=17) group. In both groups, cold $(4^{\circ}C)$ crystalloid cardioplegia was applied for myocardial protection. Blood samples were drawn from radial artery before (Pre-CPB), 10 minutes after starting (CPB-10) and immediately after ending (CPB-OFF) CPB. Total leukocyte and platelet counts, interleukin-6 (IL-6) level(expressed as percent to the baseline of Pre-CPB), D-dimer level, protein C and protein S activity were measured with the blood samples. The amount of bleeding for postoperative 24 hours and blood transfusion after operation were also assessed. All parameters were compared between the two groups. Result: The total leukocyte counts $(10,032\pm65/mm^3)$ and the increased ratio of IL-6 $(353\pm7.0%)$ at CPB-OFF in the normothermic group were higher than that $(7,254\pm48/mm^3$ and $298\pm7.3%)$ of the hypothermic group(p=0.02 and p=0.03). In the normothermic group, protein C activity $(32\pm3.8%)$ and protein S activity $(35\pm4.1%)$ at CPB-OFF were significantly lower than that $(45\pm4.3%$ and $51\pm3.8%)$ of the hypothermic group (p=0.04 and p=0.009). However, there were no differences in platelet counts and D-dimer concentration. In the normothermic group, the amount of bleeding for postoperative 24 hours $(850\pm23.2$ mL) and requirements for blood transfusion after operation such as packed cell $(1,402\pm20.5$ mL), fresh frozen plasma $(970\pm20.8$ mL) and platelet $(252\pm6.4$ mL) were higher than that $(530\pm21.5$ mL, $696\pm15.7$ mL, $603\pm18.2$ mL and $50\pm0.0$ mL) of the hypothermic group. Conclusion: These results indicate that normothermic CPB with cold crystalloid cardioplegia was associated with higher increase in inflammatory response, hemostatic abnormalities and postoperative bleeding problem than moderate hypothermic CPB.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.332-342
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• 2000

Background : The importance of pro-inflammatory cytokines, especially tumor necrosis factor $\alpha$ (INF-$\alpha$) and interleukin-1$\beta$ (IL-1$\beta$), have been extensively documented in the generation of inflammatory lung disease. Lung epithelial cells are also actively involved in initiating and maintaining inflammation by producing pro-inflammatory mediators. Understanding the mechanism of pro-inflammatory cytokine expression in lung epithelial cells is crucial to the development of new therapeutic modalities for inflammatory lung disease. Transcription of most pro-inflammatory cytokines is dependent on the activation of NF-${\kappa}B$. However, the relationship between pro-inflammatory cytokine expression and NF-${\kappa}B/I{\kappa}B$ pathway in lung epithelial cells is not clear. Methods : BEAS-2B, A549, Na-H157, NCI-H719 cells were stimulated with IL-$1{\beta}$ or TNF-$\alpha$ at various times, and then IL-8 and TNF-$\alpha$mRNA expressions were assayed by Northern blot analysis. IL-$1{\beta}$ or TNF-$\alpha$-induced NF-${\kappa}B$ activation was assessed by the nuclear translocation of p65 NF-${\kappa}B$ subunit. The degradation of $I{\kappa}B{\alpha}$ and $I{\kappa}B{\beta}$ by IL-$1{\beta}$ or TNF-$\alpha$stimulation was assayed by Western blot analysis. The phosphorylation of $I{\kappa}B{\alpha}$ was evaluated by Western blot analysis after pre-treating cells with proteasome inhibitor followed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation. The basal level of IKK $\alpha$ expression was evaluated by Western blot analysis. Results: $I{\kappa}B{\alpha}$ and $I{\kappa}B{\alpha}$ was rapidly degraded after 5 minutes of incubation with IL-$1{\beta}$ or TNF-$\alpha$ in BEAS-2B, A549, and NCI-H157 cells. The activation of NF-${\kappa}B{\alpha}$ and the induction of IL-8 and TNF-$\alpha$ mRNA expression were observed by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in these cells. In contrast, neither the changes in NF-${\kappa}B/I{\kappa}B$ pathway nor IL-8 and TNF-$\alpha$mRNA expression was induced by IL-$1{\beta}$ or TNF-$\alpha$ stimulation in NCI-H719 cells. IL-$1{\beta}$ and TNF-$\alpha$-induced $I{\kappa}B$ phosphorylation was observed in BEAS-2B, A549, and NCI-H157 cells, but not in NCI-H719 cells. The basal level of IKK$\alpha$ expression was not different between cell. Conclusion : NF-${\kappa}B/I{\kappa}B$ pathway plays an important role in the expression of pro-inflammatory cytokine in most lung epithelial cells. The absence of the effect on NF-${\kappa}B/I{\kappa}B$ pathway in NCI-H719 cells sæms to be due to the defect in the intracellular signal transduction pathway upstream to IKK.

• Tuberculosis and Respiratory Diseases
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• v.49 no.4
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• pp.441-452
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• 2000

Background : It is well known that the prevalence of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) patients than in the general population. This high prevalence is explained by the concept of 'scar carcinoma'. There have been several reports on the prevalence of histologic typo of lung cancer in IPF with conflicting results. Despite of the high smoker rate in almost all previous reports, none considered the smoking history of patients. Therefore we performed a separate studies on fibrosis associated lung cancer and smoking associated lung cancer. The purpose of this study is to investigate the proportion of lung cancer in IPF that is fibrosis associated and to determine the most common histologic type in fibrosis associated lung cancer in IPF. Method : A retrospective review of medical records and radiologic studies was performed for cases of lung cancer with IPF. We investigated smoking history, sequence of diagnosis of lung cancer and IPF, histologic type of lung cancer and the cancer location, especially whether the location is associated with fibrosis. To evaluate the proportion of fibrous associated lung cancer, the lung cancer in IPF were categorized according to the presence of fibrosis at cancer location. Results : Fifty seven patients were subjects for this analysis. Six (11%) cases were diagnosed as lung cancer during follow-up for IPF, and both diseases were diagnosed simultaneously in the others. Ninety four percent of patients were smokers and the average smoking amount was 47.1$\pm$21.9 pack-year. Among the patients with IPF and lung cancer, 42(80.8%) cases were considered as "fibrosis associated". The remainder was "not fibrosis associated" and probably was due to smoking etc. Although the most frequent histologic type was squamous cell carcinoma as a whole, adenocarcinoma was the prominent histologic type in "fibrosis associated lung cancer." Conclusion : Considering the proportion of "fibrosis not associated lung cancer" in the patients with IPF and lung cancer, significant proportion of lung cancer in IPF may not be fibrosis induced. This may influence the distribution of histologic type of lung cancer in IPF.

• Journal of Periodontal and Implant Science
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• v.32 no.3
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• pp.457-473
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• 2002

The purposes of this study is to evaluate the combination effects of TGF-${\beta}_1$ and PDGF-BB on the periodontal ligament cells to use as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM/100% FBS at the $37^{\circ}C$, 5% $CO_2$ incubator. Authors measured the DNA synthesis, total protein, collagen and noncollagenous protein synthesis according to the concentration of TGF-${\beta}_1$,(1,5ng/ml) and PDGF-BB (1,10 ng/ml) in combination. To explore further this delayed effect of TGF-${\beta}_1$, we preincubated human periodontal ligament cells with TGF-${\beta}_1$ for 4 or 24 hours before PDGF-BB stimulation. The results were as follows: The DNA synthetic activity was increased dose dependently by TGF-${\beta}_1$, PDGF-BB. The combination of TGF-${\beta}_1$ and PDGF-BB consistently enhanced the DNA synthetic activity to PDGF-BB alone. The ability of TGF-${\beta}_1$ to enhance DNA synthetic activity in PDGF-BB treated periodontal ligament cells was dose dependent. The maximum mitogenic effect was at the 5ng/ml of TGF-${\beta}_1$ and l0ng/ml of PDGF-BB. Preincubation of cell with TGF-${\beta}_1$ resulted in significantly greater response to PDGF-BB at all TGF-${\beta}_1$ concentration studied, and may be useful for clinical application in periodontal regenerative procedures. The total protein, collagen and noncollagen synthesis was increased dose pendently by TGF-${\beta}_1$, PDGF-BB. The % of collagen was slightly decreased according to the concentration of TGF-${\beta}_1$, PDGF-BB. The effect of TGF-${\beta}_1$, PDGF-BB were not specific for collagen synthesis since it also increased noncollagenous protein synthesis. This study demonstrates that PDGF-BB is major mitogens for human periodontal ligament cells in vitro, and supports a role for TGF-${\beta}_1$ as a regulation of the mitogenic and total protein formation to PDGF-BB in these cells.

• Korean Journal of Animal Reproduction
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• v.26 no.1
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• pp.1-7
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• 2002

The present study was carried out to investigate the effects of maturation media on penetrability of pig oocytes by liquid boar sperm coincubated with different sperm concentrations in a modified Tris­buffered medium (mTBM). Follicular oocytes collected from ovaries of prepubertal gilts were matured in a modified TCM-199 (mTCM-199) medium, modified Waymouth MB 752/1 (mWaymouth MB 752/1) medium or NCSU-23 medium. Oocytes (30~40) were transferred into each well of a Nunc 4-well multidish containing 0.5 $m\ell$ maturation medium. The sperm­ich portion of ejaculates with greater than 90% motile sperm were used in the experiment. The semen was cooled 22 to 24$^{\circ}C$ over 2 h period. The semen was diluted with Beltsville Thawing Solution (BTS) extender at room temperature to give 2$\times$10$^{8}$ sperm/$m\ell$ in 100 $m\ell$ plastic bottle. Liquid boar semen of 30 $m\ell$ in 100 $m\ell$ plastic bottle was kept at 17$^{\circ}C$ far 5 days. The sperm with greater than 70% motility after day 5 of storage were used for in-vitro fertilization (IVF). After 44 h maturation of immature oocytes in 5% $CO_2$in air at 38.5$^{\circ}C$, cumulus cells were removed and oocytes (30~40) were coincubated for 6 h in 0.5 $m\ell$ mTBM fertilization medium with five different (1$\times$10$^{6}$ , 2$\times$10$^{6}$ , 4$\times$10$^{6}$ , 6$\times$10$^{6}$, 10$\times$10$^{6}$ $m\ell$) sperm concentrations. At 6 h after IVF, oocytes were transferred into 0.5 $m\ell$ NCSU-23 culture medium fur further culture of 6 h. At 12 h after IVF, sperm penetration, polyspermy and male pronuclear formation of oocytes were evaluated. Oocytes of NCSU-23 maturation medium decreased polyspermy and increased male pronuclear formation compared to those of mTCM­199 and mWaymouth MB 752/1 maturation media. Of oocytes matured in NCSU-23 medium and inseminated in mTBM medium with 2~4$\times$10$^{6}$ $m\ell$ sperm concentrations, 50.8~50.9% showed sperm penetration, 13.3~19.5% polyspermy and 43.9~45.4% male pronuclear formation. In conclusion, we found out that oocytes matured in NCSU­23 medium and inseminated in mTBM medium showed superior in­vitro fertilization compared to those matured in mTCM­199 and mWaymouth MB 752/1 maturation media and inseminated in mTBM medium. The optimum sperm concentrations for in-vitro fertilization of oocytes matured in NCSU-23 medium by liquid boar semen stored at 17$^{\circ}C$ for 5 days were 2~4$\times$10$^{6}$ $m\ell$.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.91-99
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• 1999

Propose : This study was performed to find out the prognostic factors affecting local control, survival and disease free survival rate in nasopharyngeal carcinomas treated with chemotherapy and radiation therapy. Materials and Methods : We analysed 47 patients of nasopharyngeal carcinomas, histologically confirmed and treated at Chonnam University Hospital between July 1986 and June 1996, retrospectively. Range of patients' age were from 16 to 80 years (median; 52 years). Thirty three (70$\%$) patients was male. Histological types were composed of 3 (6$\%$) keratinizing, 30 (64$\%$) nonkeratinizing squamous cell carcinoma and 13 (28$\%$) undifferentiated carcinoma. Histoiogicai type was not known in 1 patient (2$\%$). We restaged according to the staging system of 1997 American Joint Committee on Cancer Forty seven patients were recorded as follows: 71: 11 (23$\%$), T2a; 6 (13$\%$), T2b; 9 (19$\%$), 73; 7 (15$\%$), 74: 14 (30$\%$), and NO; 7 (15$\%$), Nl: 14 (30$\%$), N2; 21 (45%), N3: 5 (10%). Clinical staging was grouped as follows: Stage 1; 2 (4$\%$), IIA: 2 (4$\%$), IIB; 10 (21$\%$), III; 14 (30$\%$), IVA; 14 (30$\%$) and IVB; 5 (11$\%$). Radiation therapy was done using 6 MV and 10 MV X- ray of linear accelerator. Electron beam was used for the Iymph nodes of posterior neck after 4500 cGy. The range of total radiation dose delivered to the primary tumor was from 6120 to 7920 cGy (median; 7020 cGy). Neoadjuvant chemotherapy was performed with cisplatin +5-fluorouracil (25 patients) or cisplatin+pepleomycin (17 patients) with one to three cycles. Five patients did not received chemotherapy. Local control rate, survival and disease free suwival rate were calculated by Kaplan-Meier method. Generalized Wilcoxon test was used to evaluate the difference of survival rates between groups. multivariate analysis using Cox proportional hazard model was done for finding prognostic factors. Results: Local control rate was 81$\%$ in 5 year. Five year survival rate was 60$\%$ (median survival; 100 months). We included age, sex, cranial nerve deflicit, histologic type, stage group, chemotherapy, elapsed days between chemotherapy and radiotherapy, total radiation dose, period of radiotherapy as potential prognostic factors in multivariate analysis. As a result, cranial none deficit (P=0.004) had statistical significance in local control rate. Stage group and total radiation dose were significant prognostic factors in survival (P=0.000, P=0.012), and in disease free survival rates (P=0.003, P=0.008), respectively. Common complications were xerostomia, tooth and ear problems. Hypothyroidism was developed in 2 patients. Conclusion : In our study, cranial none deficit was a significant prognostic factor in local control rate, and stage group and total radiation dose were significant factors in both survival and disease free survival of nasopharyngeal carcinoma. We have concluded that chemotherapy and radiotherapy used in our patients were effective without any serious complication.

• Journal of Nutrition and Health
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• v.41 no.8
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• pp.701-710
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• 2008

The wild simulated ginseng (WSG) has been effectively used in folk medicine as a remedy against hepatic disease, hypertension and arthritic disease. However, there is still lack of scientific proof about its antioxidant capability. The present study has been conducted to evaluate the protective role of the WSG ethanol extract in the CCl4-induced oxidative stress and resultant hepatic disfunction in ICR mice. The electron donating abilities and IC50 of WSG etnanol extract were 76.86 ${\pm}$ 1.06% and 33.3 ${\mu}g$/mL (that of ascobic acid was 16.5 ${\mu}g$/mL), respectively. Total antioxidant status of WSG extract was 2.13 ${\pm}$ 0.06 mmoL/mg, while the values of ascorbic acid and BHT were 3.63 ${\pm}$ 0.06 and 3.12 ${\pm}$ 0.02, respectively. ICR mice (aged 3weeks) were fed for 4 weeks on AIN-93M diet and had free access to food and water. The animals were divided into three groups: normal group (intraperitoneally (i.p) injected with PBS at 100 ${\mu}L$/mouse), group C; CCl4-induced and without any treatment. (i.p injected only PBS, 100 ${\mu}L$ /mice), group G; CCl4-induced and treated with WSG (i.p injected with 5 mg WSG extract per mouse, suspended in 100 ${\mu}L$ phosphate buffer). After the i.p. injection of WSG or PBS (5 times for 7weeks), all mice were administered CCl4 in olive oil at the last day of the experiment, except for normal group. The normal group was administered only olive oil. Determination of plasma triglyceride, total cholersterol, fasting glucose and GPT activity was performed using automatic blood analyzer. To evaluate the protective effect against the oxidative stress, DNA fragmentation and TBARS were determined in blood leucocytes and RBC and hepatocyte, respectively. Body and organs weights and food intake did not show significant differences among the groups. Blood total cholesterol of group G was similar to that of normal group, which was the lowest in group C. The fasting blood glucose level was the highest in normal group (205.20 ${\pm}$ 135.24), which were decreased in group C (134.2 ${\pm}$ 79.31) and group G (126.48 ${\pm}$ 77.05). TBARS values in a red blood cell and hepatic tisuue homogenate were lower in group G comparing to the group C. DNA% in tail, tail length (TL) and tail moment (TM) of blood leucoocytes showed the highest values in group C (20.11 ${\pm}$ 2.47, 17.36 ${\pm}$ 2.58, 94.11 ${\pm}$ 12.29) and they were significantly diminished in group G (9.63 ${\pm}$ 1.19, 7.04 ${\pm}$ 1.50, 38.64 ${\pm}$ 7.60). In conclusion, wild simulated ginseng might be a protective agent against the oxidative stress.

• Journal of Aquaculture
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• v.11 no.4
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• pp.529-546
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• 1998

Gonadal part that developed by indifferentiation period for 6 months after hatching is made as gonad and fat body. These gonad are thin semi-transparant and undistinguished germ cell. Germinal epithelium is distinguished by development of gonad epithelial tissue from 7 months after hatching. Sex differentiation is begun by oogonia develoment at 8 months after hatching. Primary oocytes grow over germinal epithelium of gonadal cavity, at 9 months after hatching, gonadal cavity become ovarian cavity as they increasing. As soon as oocytes at 13 months after hatching are filled with the whole part of gonad, degeneration of oocyte is begun. And then, gonad has cavity tissue, a small number of oocyte are located in gonadal cavity. At 15 months after hatching, new primary oocyte develop and cavity of ovarian tissue in the central of ovarian cavity. Spermatogonia multiplicate and cavity tissue consist of testicular tissue. These gonad become hermaphrodite and then ditermine the sex of female and male. These results show the red sea bream is juvenile hermaphrodite and undif-ferentiated gonochoristic teleost. Male and female differentiation type of gonad is divided in undifferentiation stage, oogonia-like stage, ovary-like stage, ovary development stage, hermaphroditic testis stage, hermaphroditic ovary stage, and testis development stage. Undifferentiation stage is continued total lenth 18cm at 13 months after hatching. ovary-like stage is continued total length 11~18cm at 13 months after hatching. Ovary-like stage is continued total length 14~26cm at 10~14 months after hatching. Ovary development stage begins from total length 20cm, 14 months after hatching. At 20 months after hatching, 44 percent of total sampled individuals had ovary. Hermaphroditic ovary stage first begins total length 19~20 cm at 15 months after hatching, but it is not observed total length 28~29cm at 20months after hatching. Hermaphroditic testis stage first begins total length 21~22cm at 20months after hatching and is continued for 20months. Testis development stage first begins total length 20~21cm at 20 months after hatching, and is occupied 33 percent total length 28~29cm at 20 months. The beginning of sex differentiation more than 50 percent is from total length 16cm at 11 months after hatching. Sex determination begins total length 20cm, 14months after hatching in female and total length 20cm, 15 months after hatching in male. Sex determination more than 50 percent begins total length 23cm,, 17 months after hatching. Undifferentiated gonadal part of red sea bream consist gonad and fat body. As differentiation is going on and gonad is growing, fat body shrinks. This appearence is showed the same tendency in 3-year old red sea bream. 1.9mm larvae after hatching grow about 19mm larvae for 47 days. The relationship between the total length and body weight of larvae and juveniles in $BW=4.45{\times}10^{-6}TL^{3.4718}$ r=0.9820. Fishes in cage culture grow to maximum total length 28.4cm. The relationship between the total length and body weight of these fishes is $BW=2.36{\times}10^{-2}TL^{2.9180}$, r=0.9971. Undifferentiated gonadal part of red sea bream consist gonad and fat body. As differentiation is going on and gonad is growing, fat body shrinks.

• Korean Journal of Weed Science
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• v.6 no.2
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• pp.174-190
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• 1986

A series of laboratory and greenhouse experiments were conducted to find out the possibility of tissue culture and cell culture methods as a tool to study herbicidal behaviour and herbicide tolerance screening from 1985 to 1986 at the Yeongnam Crop Experiment Station. For dehulled-rice culture, pure agar medium was the most appropriate in rice growth campared to other media used for plant tissue culture method. All the media but the pure agar medium resulted in growth retardance by approximately 50% and this effect was more pronounced to root growth than shoot growth. Herbicidal phytotoxicity was enhanced under light condition for butachlor, 2.4-D, and propanil while this effect was reversed for DPX F-5384 and CGA 142464, respectively. And also, herbicides of butachlor, chlornitrofen, oxadiazon, and BAS-514 resulted in more phytotoxic effect when shoot and root of rice were exposed to herbicide than root exposure only while other used herbicides exhibited no significant difference between two exposure regimes. Similar response was obtained from Echinochloa crusgalli even though the degree of growth retardance was much greater. Particularly, butachlor, 2.4-D, chlornitrofen, oxadiaxon, pyrazolate and BAS-514 totally inhibited chlorophyll biosynthesis even at the single contact of root. Apparent cultivar differences to herbicide were observed at the young seedling culture method and dehulled rice cultivars were more tolerant in DPX F-5384, NC-311, pyrazolate and pyrazoxyfen, respectively. For derant than other types or rice cultivar in butachlor, pretilachlor, perfluidone and oxadiazon while Tongil-type rice cultivars were more tolerant in DPXF-5384, NC-311, Pyrazolate and Pyrazoxyfen, respectively. For dehulled rice culture, on the other hand, Japonica-type rice cultivar was less tolerant to herbicides of butachlor, propanil, chlornitrofen and oxadiazon that was reversed trend to young seedling culture test. Cultivar differences were also exhibited within same cultivar type. In general, relatively higher tolerant cultivars were Milyang 42, Cheongcheongbyeo, Samgangbyeo, Chilseoungbyeo for Tongil-type, Somjinbyeo for Japonica-type and IR50 for Indica-type, respectively. The response of callus growth showed similar to dehulled rice culture method in all herbicides regardless of property variables. However, concentration response was much sensitive in callus response. The concentration ranges of $10^{-9}M-10^(-8)M$ were appropriate to distinguish the difference between herbicides for E. crusgalli callus growth. Among used herbicides, BAS-514 was the most effective to E. crusgalli callus growth. Based on the above results, tissue culture method could be successfully used as a tool for studying herbicidal behaviour and tolerance screening to herbicide.

• Journal of Life Science
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• v.23 no.10
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• pp.1230-1238
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• 2013

The regulatory effect of the tumor-suppressor protein p53 on the apoptogenic activity of $17{\alpha}$-estradiol ($17{\alpha}-E_2$) was compared between HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells. When the HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells were treated with $2.5{\sim}10{\mu}M$ $17{\alpha}-E_2$ for 48 h or with $10{\mu}M$for various time periods, cytotoxicity and an apoptotic sub-$G_1$ peak were induced in the HCT116 ($p53^{+/+}$) cells in a dose- and time-dependent manner. However, the HCT116 ($p53^{-/-}$) cells were much less sensitive to the apoptotic effect of $17{\alpha}-E_2$. Although $17{\alpha}-E_2$ induced aberrant mitotic spindle organization and incomplete chromosome congregation at the equatorial plate, $G_2/M$ arrest was induced to a similar extent in both cell types. In addition, $17{\alpha}-E_2$-induced activation of Bak and Bax, ${\Delta}{\Psi}m$ loss, and PARP degradation were more dominant in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells. In accordance with enhancement of p53 phosphorylation (Ser-15) and p53 levels, p21 and Bax levels were elevated in the HCT116 ($p53^{+/+}$) cells treated with $17{\alpha}-E_2$. The HCT116 ($p53^{-/-}$) cells exhibited barely or undetectable levels of p21 and Bax, regardless of $17{\alpha}-E_2$ treatment. On the other hand, although the level of Bcl-2 was slightly lower in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells, it remained relatively constant after the $17{\alpha}-E_2$ treatment. Together, these results show that among the components of the $17{\alpha}-E_2$-induced apoptotic-signaling pathway, which proceeds through mitotic spindle defects causing mitotic arrest, subsequent activation of Bak and Bax and the mitochondria-dependent caspase cascade, leading to PARP degradation, $17{\alpha}-E_2$-induced activation of Bak and Bax is the upstream target of proapoptotic action of p53.