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A Novel Chenodeoxycholic Derivative HS-1200 Enhances Radiation-induced Apoptosis in Human MCF-7 Breast Cancer Cells (담즙산 합성유도체(HS-1200)가 인체 유방암 세포주(MCF-7)에서 유도하는 방사선 감작 효과)

  • Lee Hyung Sik;Choi Young Min;Kwon Hyuk Chan;Song Yeon Suk
    • Radiation Oncology Journal
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    • v.22 no.2
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    • pp.145-154
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    • 2004
  • Purpose : To examine whether a synthetic bile acid derivatives (HS-1200) sensitizes the radiation-induced apoptosis in human breast cancer cells (MCF-7) and to investigate the underlying mechanism. Materials and Methods : Human breast cancer cells (MCF-7) in exponential growth phase were treated with HS-1200 for 24 hours at 37$^{\circ}C$ with 5$\%$ CO$_{2}$ in air atmosphere. After removal of HS-1200, cells were irradiated with 2$\~$8 Gy X-ray, and then cultured Ii drug-free media for 24-96 hours. The effect of radiation on the clonogenicity of MCF-7 cells was determined with clonogenic cell survival assay with 16$\mu$M of HS-1200. The induction of apoptosis was determined using agarose gel electrophoresis and Hoechst staining. The expression level of apoptosis-related molecules, such as PARP, Bax, Bcl-2, Bak and AIF, were assayed by Western blotting analysis with 40$\mu$M of HS-1200 combined with 8 Gy irradiation. To examine the cellular location of cytochrome c, bax and AIF immunofluorescent stainings were undertaken. Results : Treatment of MCF-7 cells with 40$\mu$M of HS-1200 combined with 8 Gy irradiation showed several changes associated with enhanced apoptosis by agarose gel electrophoresis and Hoechst staining. HS-1200 combined with 8 Gy irradiation treatment also enhanced production of PARP cleavage products and increased Bax/Bcl-2 ratio by Western blotting. Loss of mitochondrial membrane potential ($\Delta$$\psi$$_{m}$) and increased cytochrome c staining indicated that cytochrome c had been released from the mitochondria in HS-1200 treated cells. Conclusion : We demonstrated that combination treatment with a synthetic chenodeoxycholic acid derivative HS-1200 and irradiation enhanced radiation-induced apoptosis of human breast cancer cells (MCF-7). We suggest that the increased Bax/Bcl-2 ratio In HS-1200 co-treatment group underlies the increased radio sensitivity of MCF-7 cells. Further futures studies are remained elusive.

The Significance of Ku70 Expression in Patients with Nasopharyngeal Carcinoma (비인강암에서 방사선치료의 예측인자로써 Ku70 발현의 의의)

  • Song Si Yeol;Lee Sang-wook;Yu Eunsil;Cho Kyung-Ja;Park Jin-hong;Kim Sang Yoon;Nam Soon Yuhl;Lee Bong-Jae;Kim Sung Bae;Choi Seung-Ho;Ahn Seung Do;Shin Seong Soo;Choi Eun Kyung
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.1-8
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    • 2005
  • Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.

Arm Morbidity after Breast Cancer Treatments and Analysis of Related Factors (유방암 환자의 상지 부작용과 관련 요인)

  • Chun Mi Son;Moon Seong Mi;Lee hye Jin;Lee Eun-Hyun;Song Yeoung Suk;Chung Yong Sik;Park Hee Bung;Kang Seung Hee
    • Radiation Oncology Journal
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    • v.23 no.1
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    • pp.32-42
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    • 2005
  • Purpose : To evaluate the incidence of arm morbidity following breast cancer surgery including axillary dissection and to identify related factors. Materials and Methods : One hundred and fifty nine patients were studied using a self-report questionnaire and a clinical examination. Lymphedema, reduction of range of motion in shoulder joint and subjective symptoms (pain, impaired arm movement, numbness, stiffness) were evaluated. As related factors, demographic, oncologic characteristics and types of treatment were analysed. Results : The incidence of lymphedema ($\geqq$2 cm difference comparing to unaffected arm) was $6.3\%$, $10.7\%$, $22.5\%$ and $23.3\%$ at each 10 cm, 20 cm, 30 cm, and 40 cm from wrist. Reduction of range of motion in shoulder joint ($\geqq$ 20 degree difference comparing to unaffected arm) was noted In more than 1/3 patients for flexion, abduction and internal rotation. Especially the reduction of range of motion in internal rotation was severe ($>50\%$ reduction) in 1/3 patients. Approximately 50 to $60\%$ of patients complained impaired arm movement, numbness, stiffness and pain. Body mass index (BMI) was the significant risk factor for lymphedema. Conclusion : Lymphedema was present in 1/3 of patients and the common sites of edema were 30 cm 40 cm proximal from the wrist. Also most severe reduction of range of motion in shoulder joint was with internal rotation. There needs weight control for lymphedema because BMI was the significant risk factor for lymphedema. Also rehabilitation program for range of motion especially internal rotation In shoulder joint should be developed.

Efficacy of Transcervical Fallopian Tube Catheterization in Infertility Patients with Fallopian Tube Occlusion (난관 폐쇄에 기인한 불임 환자에서 난관 개통술의 효용성)

  • Park, Chan-Woo;Cha, Sun-Hwa;Yang, Kwang-Moon;Han, Ae-Ra;Yoo, Ji-Hee;Song, In-Ok;Kim, Hye-OK;Kang, Inn-Soo;Koong, Mi-Kyoung;Lee, Kyung-Sang
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.4
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    • pp.321-327
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    • 2010
  • Objective: To evaluate the significance and efficacy of trans-cervical fallopian tube catheterization (TFTC) in diagnosis and optimal treatment modality for tubal blockage. Methods: The retrospective study was performed in those underwent TFTC from January 2005 to December 2009. A total of 342 fallopian tubes in 215 patients which showed tubal blockage in hysterosalpingography (HSG), were subjected to TFTC. Recanalization rate (RR) was compared according to portion of tubal blockage; proximal, isthmic and distal portion and blockage type; tapering, concave, and convex type. Results: In total, RR was 72.5% (248/342 tube). According to the portion of tubal blockage, RR was 83.8% in proximal, 45.6% in isthmic and 100% in distal portion. RR was 92.3% in tapering, 80.2% in concave and 25.5% in convex type, respectively. There were 98 pregnancies in 156 patients after successful recanalization, which shows 62.7% pregnancy rate. Conclusio: TFTC were capable of recanalizing tubal blockage in 248 of 342 tubes in 156 of 215 patients (72.5%). The RR was increased with proximal portion and tapering type tubal blockage.

Effect of Cholesterol Supplementation in Freezing Medium on the Survival and Integrity of Human Sperm after Cryopreservation (콜레스테롤이 동결-해동 후 인간정자의 생존과 기능보존에 미치는 영향)

  • Lim, Jung-Jin;Sung, Su-Ye;Kim, Kye-Seong;Song, Seung-Hon;Lee, Woo-Sik;Yoon, Tae-Ki;Lee, Dong-Ryul
    • Clinical and Experimental Reproductive Medicine
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    • v.35 no.3
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    • pp.203-212
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    • 2008
  • Objective: During cryopreservation process, cold shock and cryo-injury affect the fertilizing capacity of the sperm by damaging cell membranes with loss of functional integrity. A longstanding concept for preventing the cryo-damage is to stabilize the plasma membrane by incorporating cholesterol. This study was to determine the effects of cholesterol in freezing media on the motility and functional integrity of human sperm after cryopreservation. Methods: Control group (non-cholesterol treated) and different concentrations of cholesterol-treated sperm (14 healthy males) were frozen and thawed. After freezing and thawing of sperm, the quality of sperm was evaluated by sperm analysis, acrosome reaction test and sperm chromatin structure assay. Results: When human sperm were incubated in sperm freezing medium (SFM) containing $0.5{\mu}g$ cholesterol and then freezing/thawing, the motility of sperm have significantly improved compared to those untreated cholesterol ($33.46{\pm}1.48%$ vs. $30.10{\pm}1.07%$, p<0.05). The rate of calcium ionophore-induced acrosome reactions in post-thawed sperm was significantly higher than that ($53.60{\pm}1.60%$ vs. $47.40{\pm}1.86%$, p<0.05) in SFM containing cholesterol. Sperm chromatin structure assay revealed that DNA damage to the sperm in the cholesterol-treated group was lower than that of non-treated group. Conclusion: These results suggest that increased cholesterol content of sperm plasma membrane by supplementation of cholesterol in SFM improves sperm motility, capacitation status, and DNA integrity. Therefore, addition of cholesterol into SFM could be a useful for protecting human sperm from cold shock and cryo-injury during cryopreservation.

Predictor of IVF Outcomes Following Single Embryo Transfer in Poor Responder Patients (저반응군의 체외수정에서 한 개의 배아 이식 시 임신에 영향을 주는 요인)

  • Kim, Hye-Ok;Kim, Min-Ji;Yeon, Myeong-Jin;Cha, Sun-Wha;Koong, Mi-Kyoung;Song, In-Ok
    • Clinical and Experimental Reproductive Medicine
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    • v.35 no.3
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    • pp.213-221
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    • 2008
  • Objective: To evaluate predictor of IVF outcomes following single embryo transfer in patients with decreased ovarian reserve. Methods: A retrospective review was performed in 919 IVF cycles with elevated basal serum FSH (${\geq}12\;mIU/mL$), the number of retrieved oocytes ${\geq}4$ and serum $E_2$ concentration on hCG day <500 pg/ml between Jan. 1996 and Dec. 2006. Two hundred thirty five IVF cycles following single embryo transfer were included. Pregnancy rates and live birth rates was evaluated according to maternal age, serum $E_2$ on hCG day, basal FSH level, the number of blastomere on day 3 ET, stimulation protocol, the number of cycles of ET. Statistical analysis was used SPSS 12.0 program. Results: OPU cancellation rates were 25.6% (235 cycles), OPU failure rates were 18.5% (170 cycles), embryo transfer cancellation rates were 14.0% (129 cycles). Pregnancy rates following single embryo transfer was 8.1% (19 cycles) and live birth rates was 4.7% (11 cycles). Pregnancy rates and live birth rates of women under 35 years old was statistically higher than those of women above 35 years old (20% vs. 3.5% (p<0.0001), 12.3% vs. 1.8%, (p=0.002)). There was no difference in basal FSH, serum $E_2$ on hCG day, and the number of blastomere on ET, and stimulation protocol. Cumulative pregnancy rates according to the number of cycles of ET were $1^{st}$ 8.1%, $2^{nd}$ 9.2%, $3^{rd}$ 9.7%, $4^{th}$ 9.0%, and $5^{th}$ 9.5%. Conclusion: Pregnancy rates and live birth rates of IVF-ET cycles following single embryo transfer in patients with decreased ovarian reserve are statistically increased in women under 35 yrs old. There is no difference in cumulative pregnancy rates. These data may be helpful for counseling women with decreased ovarian reserve in attempting IVF with their own eggs or when choosing donor oocytes.

The effectiveness of earlier oocyte retrieval in the case of a premature luteinizing hormone surge on hCG day in in vitro fertilization-embryo transfer cycles

  • Choi, Min Hye;Cha, Sun Hwa;Park, Chan Woo;Kim, Jin Young;Yang, Kwang Moon;Song, In Ok;Koong, Mi Kyoung;Kang, Inn Soo;Kim, Hye Ok
    • Clinical and Experimental Reproductive Medicine
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    • v.40 no.2
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    • pp.90-94
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    • 2013
  • Objective: To evaluate the efficacy of earlier oocyte retrieval in IVF patients with a premature LH surge on hCG day. Methods: One hundred forty IVF patients (164 cycles) with premature LH surge on hCG day were included, retrospectively. We divided them into 2 study groups: LH surge with timed ovum pick-up (OPU) 36 hours after hCG injection (group B, 129 premature cycles), and LH surge with earlier OPU within 36 hours after hCG injection (group C, 35 cycles). Control groups were tubal factor infertility without premature LH surge (group A, 143 cycles). Results: The mean age (year) was statistically higher in group C than in groups A or B ($38.2{\pm}5.4$ vs. $36.2{\pm}4.2$ vs. $36.8{\pm}4.9$, respectively; p=0.012). The serum LH levels (mIU/mL) on hCG day were significantly higher in group B and C than in group A ($22.7{\pm}14.9$ vs. $30.3{\pm}15.9$ vs. $3.2{\pm}2.9$, respectively; p>0.001). Among groups A, B, and C, 4.9%, 31.7%, and 51.4% of the cycles, respectively, had no oocytes, and the overall rates of cycle cancellation (OPU cancellation, no oocyte, or no embryos transferrable) were 15.4%, 65.9%, and 74.3%, respectively. The fertilization rate (%) was significantly higher in group B than in group C ($73.2{\pm}38.9$ vs. $47.8{\pm}42.9$, p=0.024). The clinical pregnancy rate was significantly higher in group C than in groups A and B (44.4% vs. 27.3% vs. 9.1%, respectively, p=0.021). However, the miscarriage rate was also higher in group C than in group B (22% vs. 0%, respectively, p=0.026). Conclusion: Earlier OPU may not be effective in reducing the risk of cycle cancellation in patients with premature LH surge on hCG day. A larger scale study will be required to reveal the effectiveness of earlier ovum retrieval with premature LH surge.

Can high serum anti-M${\ddot{u}}$llerian hormone levels predict the phenotypes of polycystic ovary syndrome (PCOS) and metabolic disturbances in PCOS patients?

  • Hwang, Yu Im;Sung, Na Young;Koo, Hwa Seon;Cha, Sun Hwa;Park, Chan Woo;Kim, Jin Yeong;Yang, Kwang Moon;Song, In Ok;Koong, Mi Kyoung;Kang, Inn Soo;Kim, Hye Ok
    • Clinical and Experimental Reproductive Medicine
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    • v.40 no.3
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    • pp.135-140
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    • 2013
  • Objective: To evaluate correlations between serum anti-M${\ddot{u}}$llerian hormone (AMH) levels, phenotypes of polycystic ovary syndrome (PCOS), obesity, and metabolic parameters in patients with PCOS. Methods: A total of 175 patients with PCOS were diagnosed according to the Rotterdam Consensus were included. Exclusion criteria were age over 40, FSH>25 mIU/mL, and 17a-OHP>1.5 ng/mL. The Phenotypes of PCOS were divided into a severe form (oligo-anovulation, ANOV/hyperandrogenism/polycystic ovary morphology [PCOM]; n=59) and a mild form without HA (ANOV/PCOM, n=105). The serum AMH levels were classified into 3 groups (<5 vs. 5-10 vs. >10 ng/mL). Obesity was defined as body mass index (BMI) ${\geq}25kg/m^2$ (n=34). Results: The mean age was $25.9{\pm}5.7$ year and mean AMH level was $10.1{\pm}5.4$ ng/mL. The BMI ($kg/m^2$) was higher in group 1 ($24.2{\pm}6.3$) than in group 2 ($21.9{\pm}4.3$, p=0.046) or group 3 ($21.6{\pm}3.3$, p=0.019). There was no difference among the three groups in age, menstrual interval, antral follicle counts, androgens, or other metabolic parameters. The obesity group showed significantly lower AMH ($7.7{\pm}3.9$ ng/mL vs. $10.7{\pm}5.6$ ng/mL), p=0.004) and low-density lipoprotein levels ($93.1{\pm}21.2$ mg/dL vs. $107.5{\pm}39.3$ mg/dL, p=0.031), and showed higher total T ($0.74{\pm}0.59$ L vs. $0.47{\pm}0.36$ ng/mL, p=0.001), free T ($2.01{\pm}1.9$ vs. $1.04{\pm}0.8$ pg/mL, p=0.0001), and free androgen index ($6.2{\pm}7.9$ vs. $3.5{\pm}3.0$, p=0.003). After controlling for age factors and BMI, the serum AMH levles did not show any significant correlations with other hormonal or metabolic parmeters. Conclusion: For PCOS patients under the age 40, serum AMH is not negatively correlated with age. High serum AMH levels can not predict the phenotype of PCOS and metabolic disturbances in PCOS patients in the non-obese group. Further study might be needed to define the relation more clearly.

The Geochemical Characteristics and Environmental Factors on the Marine Shellfish Farm in Namhae-po Tidal Flat of Taean (태안 남해포 갯벌 패류양식해역의 환경특성)

  • Choi, Yoon Seok;Park, Kwang Jae;Yoon, Sang Pil;Chung, Sang Ok;An, Kyoung Ho;Song, Jae Hee
    • The Korean Journal of Malacology
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    • v.29 no.1
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    • pp.51-63
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    • 2013
  • To assess the effect of environmental factors on the sustainability of cultured production shellfish, we investigated the habitat characteristics of tidal flat (Namhae-po in Taean). We measured the physiochemical parameters (temperature, salanity, pH, dissolved oxygen and nutrients) and the geochemical characteristics (chemical oxygen demand, ignition loss, C/N ratio and C/S ratio). Surface sediments were collected from several site of tidal flat to examine the geochemical characteristics of both the benthic environment and heavy metal pollution. The grain size for research area of tidal flat were similar at the ratio of silt and clay in comparison with the other site of it. The C/N ratio was more than 5.0, reflecting the range arising from the mix of marine organism and organic matter. The C/S ratio (about 2.8) showed that survey area had anoxic or sub-anoxic bottom conditions. The enrichment factor (Ef) and index of accumulation rate (Igeo) of the metals showed that those research areas can be classified as heavily polluted, heavily to moderately polluted, or more or less unpolluted, respectively. Adult surf clam (Mactra veneriformis) density was highest at St. 2 (middle part of the Namhae-po), on the other hand, surf clam spat density was highest at St. 3 (lower part of the Namhae-po). Heavy rain, terrigenous suspended clay with fresh water from neighboring agricultural land, and severe high air temperature during summer could be thought as detrimental causes of spat and adult mortality in Namhae-po tidal flat. We suggested that the growth of shellfish in the tidal flat was effected by the various environmental conditions, so an improvement in the cultured method was needed.

Effects of Sodium and Gallium on Characteristics of CIGS Thin Films and CdS/CIGS Solar Cells by Co-evaporation Method (Na확산과 Ga첨가에 따른 동시진공증발법으로 제조된 CIGS 박막과 CdS/CIGS 태양전지의 특성)

  • Kwon, S.H.;Lee, J.C.;Kang, K.H.;Kim, S.K.;Yoon, K.H.;Song, J.S.;Lee, D.Y.;Ahn, B.T.
    • Solar Energy
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    • v.20 no.2
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    • pp.43-54
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    • 2000
  • We prepared and characterized $Cu(In_{1-x}Ga_x)Se_2$(CIGS) films using a elemental co-evaporation method for absorbing layer of high efficiency thin film solar cells. The CIGS films deposited on a soda-lime glass exhibited low resistivity because of higher carrier concentration. Na was accumulated at the CIGS surface and the 0 and Se were also accumulated at the surface, suggesting that oxidation is a driving force of Na accumulation. The structure of CIGS film was modified or a secondary phase was formed in the Cu-poor CIGS bulk films probably due to the incorporation of Na into Cu vacancy sites. As the Ga/(In+Ga) ratio increased, the diffraction peaks of $Cu(In_{1-x}Ga_x)Se_2$ films were shifted to larger angle and splitted, and the grain size of $Cu_{0.91}(In_{1-x}Ga_x)Se_2$ films became smaller. All $Cu_{0.91}(In_{1-x}Ga_x)Se_2$ films showed the p-type conductivity regardless of the Ga/(In+Ga) ratio. Ag/n-ZnO/i-ZnO/CdS/$Cu_{0.91}(In_{0.7}Ga_{0.3})Se_2$/Mo solar cells were fabricated. The currently best efficiency in this study was 14.48% for $0.18cm^2$ area ($V_{oc}=581.5mV,\;J_{sc}=34.88mA$, F.F=0.714).

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