• Title/Summary/Keyword: Cervical cancer

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S-allylcysteine-mediated Activation of Caspases and Inactivation of PARP to Inhibit Proliferation of HeLa (S-allylcysteine 매개 caspases의 활성화 및 PARP의 불활성화를 통한 HeLa 세포주의 증식 억제효과)

  • Kim, Hyun Hee;Kong, Il-Keun;Min, Gyesik
    • Journal of Life Science
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    • v.27 no.2
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    • pp.164-171
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    • 2017
  • Our previous study suggested that S-allylcysteine (SAC) inhibits the proliferation of the human cervical cancer cell line, HeLa, at least in part through the induction of apoptosis and cell cycle arrest. To further analyze the specific molecular mechanism(s) by which SAC mediates its antiproliferative effects, this study examined the role of SAC in regulating the protein expression of initiator caspase (caspase-9), effector caspases (caspase-3 and caspase-7), and poly-ADP-ribose polymerase (PARP) in HeLa. Western blot analysis showed that when cells were treated with 50 mM SAC for 48 hr, the expression of procaspase-3, -7, and -9 and PARP was reduced by 94%, 38%, 95%, and 64%, respectively, as compared to the untreated control. In contrast, the expression of caspase-3, -7, and -9 and cleaved-PARP was markedly increased by SAC treatment. The SAC-mediated changes in the expression of these proteins were correlated with the concomitant inhibition of cellular proliferation by SAC. The cell proliferation assay showed that HeLa treatment with more than 20 mM SAC for 6-48 hr resulted in both concentration- and time-dependent inhibition of cellular proliferation. These results indicate that the SAC-induced antiproliferative effect in HeLa may be mediated at least in part through the activation of caspase-9, followed by the activation of caspase-3 and caspase-7 as well as the inactivation of PARP, thus leading to cellular apoptosis.

Antiviral Effect of Retro-2.1 against Herpes Simplex Virus Type 2 In Vitro

  • Dai, Wenwen;Wu, Yu;Bi, Jinpeng;Wang, Jingyu;Wang, Shuai;Kong, Wei;Barbier, Julien;Cintrat, Jean-Christophe;Gao, Feng;Jiang, Zhengran;Gillet, Daniel;Su, Weiheng;Jiang, Chunlai
    • Journal of Microbiology and Biotechnology
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    • v.28 no.6
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    • pp.849-859
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    • 2018
  • Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

Studies on Antitumor Components of Collybia confluens (밀버섯의 항암성분에 관한 연구)

  • Kim, Sook-Hee;Kim, Jin-Sook;Jin, Mi-Rim;Kim, Ha-Won;Choi, Eung-Chil;Kim, Byong-Kak
    • Korean Journal of Pharmacognosy
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    • v.24 no.4
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    • pp.267-281
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    • 1993
  • To find antitumor components from higher fungi, the mycelia of Collybia confluens (Pers. ex Fr.) Kummer were cultured in artificial media. For efficient production of the mycelia, the influences of various modifications of culture conditions were examined. A water-soluble protein-bound polysaccharide fraction, Fr. A, was obtained from the mycelia by hot water extraction. When Fr. A was purified and fractionated by DEAE-cellulose and Sepbadex G-200 gel filtration chromatographies into four fractions which were designated B, C, C-I and C-II. The tumor inhibition ratios of these fractions ranged from 46% to 75% against the solid forms of sarcoma 180 in ICR mice at doses of 20 and 50 mg/kg/day when given intraperitoneally. Especially, Fr. C which was named Collyban(CB) exhibited a marked life-prolonging effect of the mice against ascitic forms of sarcoma 180 at a dose of 50 mg via i.p. administration. To extend spectra of the antitumor activities and eliminate the effects of allograft rejection, the characterization of antitumor effects of CB was performed in syngeneic host-tumor systems. It did not show any antitumor activity against L1210 murine leukemia in $CD_2Fl$ mice but prolonged their life span against ascitic forms of $MM_{46}$ carcinoma in $C_3H/He$ mice. Also it exhibited antitumor activity against human cervical cancer HeLa cells that were xenografted into nude mice having BALB/c genetic backgrounds by the i.p. injection at a dose of 100 mg/kg/day. In order to characterize the antitumor components, CB was examined by chemical analysis. It was acidic protein-bound polysaccharides composed of 31% polysaccharide, 27% protein and 3% hexosamine. CB was fractionated into two fractions, Fr. C-I(M.W.: 500 Kd) and Fr. C-II(M.W.:30 and 8 Kd) by Sephadex G-200 gel filtration chromatography.

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Health Educational Program for Women's Health in Women's Health Care Center (여성건강교육 프로그램 개발에 관한 연구 - 여성건강간호센터에서의 교육을 중심으로 -)

  • Lee, Eun-Hee;Choi, Sang-Soon;So, Ae-Young
    • Women's Health Nursing
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    • v.6 no.1
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    • pp.67-81
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    • 2000
  • The purpose of this study was to analyze women's health problems using Green & Kreuter's(1991) PRECEDE model and to develop health education program for women's health. The subjects were recruited women from Wonju city 18 years or older. 1. The results showed that about 50% of the women were satisfied with their lives as women, 23% of the sample felt there was a need for a women's health care center. The mean number of health problems was 3.1 and the prevalence rate, 44.4%. 2. We developed on educational program according to group differences related to health problems, diagnosis of disease, variables influencing health promotion behavior, and programs which each group wanted. Also we stressed self-efficacy and self-help group for the management of individual health to all groups. 3. The diagnoses of diseases that were experienced premarital over the past year were gastritis, bronchitis, spinal disk, and fracture, for the childbearing/rearing group, gastritis, vaginitis and cervicitis, cervical cancer and cystitis and nephritis and arthritis and for the middle-aged/elderly group arthritis, gastritis, vaginitis and cervicitis, and spinal disk. Of the sample 30.5% did not have a health exam in the past year, and only 10% of the premarital group, 12.5% of the childbearing/child-rearing group, and 18.3% of the middle aged-elderly group were concerned about their health and did something for their health. 4. The average score on the HPLP was 2.41. the HPLP was scores according to group were found to have significant differences. self-efficacy, family functions, health attention and were considered important variables in the premarital group, in the childbearing/child-rearing group self-efficacy, family functions, internal locus of control, health attention, and health perception and power others locus of control and then for the middle aged-elderly group self-efficacy, health attention, internal locus of control, family functions and health perception. 5. There are a few educational programs in the city provided by the Wonju Health Center and by community health nurse practitioners. The premarital group requested the educational programs on diet, health exercise, family health and stress management. Also the childbearing/child-rearing group wanted programs on diet, family health, stress management, and health exercise, and the middle-aged/elderly group wanted that of family health, diet, climacteric changes stress management and health exercise. The program suggested that this program should be applied to women in the community to insure adequate management of women's health. Follow-up research with PROCEED is needed to analyze health outcomes, also, a women's health nursing specialist system is required to develop health promotion, and improve the quality of life for women.

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Serial Determinations of Serum Squamous Cell Carcinoma Antigen (SCC) during Radiotherapy for Uterine Cervix Cancer (자궁경부암에서 방사선치료 중 혈중 Squamous Cell Carcinoma Antigen 값의 변화)

  • Yun, Hyong-Geun;Park, Seok-Kun
    • Radiation Oncology Journal
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    • v.19 no.2
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    • pp.136-141
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    • 2001
  • Purpose : To evaluate the significance of serum SCC for the monitoring of treatment response and the early detection of distant metastasis during radiotherapy (RT). Materials and Methods : In 13 patients with histologically proven primary squamous cell carcinoma of uterine cervix, serum SCC values were checked in pre-RT point, weekly during RT, and in post-RT point. Results : In 4 of 13 cases, metastasis appeared at the end of external RT, so that intracavitary radiation couldn't be peformed.01 these 4 cases,3 with elevated pre-RT SCC level, who resulted in lung metastasis on chest PA at the end of external RT showed decreased post-RT SCC value despite of metastasis. Of all 10 cases with elevated pre-RT SCC value (including 3 with metastasis at the end of external RT), SCC value was higher than pre-RT value in 7 at 9 Gy and the difference was statistically significant. At 18 Gy, SCC was higher in 4 and lower in 6 than pre-RT value. After 18 Gy, SCC value decreased continuously to the end of RT in all 10 cases. Conclusion : During RT, SCC value increased initially at 9 Gy. To 18 Gy, SCC value decreased to the nearly same with pre-RT value. After 18 Gy, to the end of RT, SCC value decreased continuously and normalized in completely responded cases. In cases with appearance of lung metastasis, SCC value also decreased with the disappearance of main mass of uterine cervix despite metastasis.

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Results of Postoperative Irradiation in Patients with Carcinoma of Uterine Cervix Stage IB and IIA (자궁경부암 IB와 IIA 환자의 수술후 방사선치료 결과)

  • Ahn Sung Ja;Nam Taek Keun;Chung Woong Ki;Nah Byung Sik;Choi Ho Sun;Byun Ji Soo
    • Radiation Oncology Journal
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    • v.13 no.1
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    • pp.41-48
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    • 1995
  • Purpose : The adjuvant postoperative radiotherapy has been usually applied to the patients with unfavorable prognostic factors after radical operation in early cervical cancer. We focused on the evaluation of the survival status and failure patterns of the patients with postoperative radiotherapy. Materials and Methods : We retrospectively analyzed ninety patients with FIGO stage IB and IIA cervix cancer who received postoperative pelvic irradiation at Chonnam University Hospital between August 1985 and December 1988, Seventy-eight patients had adequate follow-up information for survival analysis. Median follow-up time of these patients was 64 months. Results : The 5 year overall and disease free survival rate of ninety patients was $80.0\%$ and $80.2\%$, respectively. The prognostic significance to the survival was determined by multivariate analysis. Adequacy of resection margin(p=0.005) and lymph node status(p=0.005) appeared to be independent prognostic factors. Recurrence occurred in 13 patients, 5 in the pelvis and 8 at distant sites. The median time to recurrence was 19 months(range:3-39 months). The pelvic recurrence was more prevalent in the group of patients with adenocarcinoma, depth of stromal invasion more than 10mm and use of chemotherapy. The distant failure was more prevalent in the group of positive resection margin or positive lymph node with statistical significance. Conclusion : Patients with pelvic lymph node or surgical margin involvement clearly constitute a high risk group in this analysis and should be considered as candidates for some form of adjuvant therapy.

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Immunohistochemical and Immunogold Electron Microscopic Studies on Effects of Cis-platin on the Ciliogenesis of Rat Oviducts (Cis-Platin이 흰쥐 난관의 섬모형성에 미치는 영향에 대한 면역조직학적 및 면역도금법에 의한 전자현미경적 연구)

  • Kim, Jin-Kook;Kim, Won-Kyu;Paik, Doo-Jin;Chung, Ho-Sam
    • Applied Microscopy
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    • v.30 no.1
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    • pp.45-59
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    • 2000
  • Cis-platin is a widely used anticancer drug against certain solid tumors such as malignant ovarian tumor, malignant carcinoma of head and neck, bladder cancer and cervical cancer of uterus, and its major mechanism of action is inhibition of DNA synthesis of the tumor cell. To investigate the inhibitory effects of cis-platin on the ciliogensis of the ciliated cells in the mucosa of oviduct, the author pursued the alterations of $\alpha-tubulin$, which is the main constituent of the microtubles in cilia, after cis-platin treatment. To eliminate the possible variations due to ovarian cycle, female Spargue-Dawley rats ($150\sim200gm$ in B.W.) were pretreated with estradiol benzoate (20 mg/kg, once a day, for 4 consecutive days). Animals were administrated with cis-platin (6 mg/kg, i.p.) and sacrificed at 1day, 3days, 5days and 7days after treatment, respectively. Immunohistochemistry for $\alpha-tubulin$ using mouse anti-rat $\alpha-tubulin$ monoclonal antibody as primary antibody was done. Immunogold electronmicroscopy for intracellular distributions of $\alpha-tubulin$ was also performed with same primary antibody and Goat anti- mouse IgM which is preconjugated with gold particles of 15 nm as secondary antibody. The results obtained were as follows; 1. Strong immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1, 3 and 5 days after estradiol pretreatment. 2. Weak immunoreactivity of $\alpha-tubulin$ was observed in ciliated cells of oviducts at 1 and 3 days after cis-platin treatment but it was recovered to strong immunoreactivity in 5 days 3. In immunogold electronmicroscopy, density of gold particles for $\alpha-tubulin$ reactions was decreased in apical cytoplasm, but few changes were observed in basal body or cilia at 1 and 3 days after cis-platin treatment. From these above results, it is indicated that synthesis of $\alpha-tubulin$ in ciliated cells of rat oviduct is inhibited by cis-platin treatment.

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Effect of a Needle Aspiration in Patients with Lymphedema (암 수술 후 발생한 림프부종 환자의 바늘 흡인술 효과)

  • Yang, Gu-Hwan;Kwak, Sung-Wook;Kim, Sun-Hyn;Shin, Young-Tae;Hwang, Hee-Jin;Park, No-Hyeok;Yeom, Chang-Hwan
    • Journal of Hospice and Palliative Care
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    • v.12 no.1
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    • pp.27-31
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    • 2009
  • Purpose: Lymphedemas are tissue fluid swellings, usually on the arms or legs, and occur as a result of impaired lymphatic drainage. Presently, the most effective treatment available is complete decongestive physiotherapy (CDP). However, this therapy is ineffective in some patients and surgery may be indicated. Herein, we examined the efficacy of minimally invasive needle aspiration of the most enlarged areas in hypodermic adipose tissues, of patients who had failed CDP. Methods: We included 21 patients who were diagnosed with lymphedema stage II-III in the upper or lower extremities and visited the lymphedema clinic at a university hospital from September 1, 2003 to February 28, 2004. All patients had been treated with CDP at least once, but had failed to respond to the therapy for more than one year. Nine patients had breast cancer and 12 had cervical cancer. We identified the area with the most severe edema by using MRI and performed a 16-gauge angio-needle aspiration on the area. The patients were followed up for 3 months. Effectiveness of the treatment was evaluated by comparing the volume of edema before and after the treatment using Wilcoxon signed rank-test. Results: The mean reduction ratio of the volume of edema comparison normal volume was 41.1${\pm}$35.3% (P=0.001). There were no major or minor operative complications except localized hemorrhage. Conclusion: We conclude that a needle aspiration prior to other surgical treatments is relatively safe and effective for those patients who are unresponsive to CDP.

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Antimutagenic and Antitumor Effects of Adenophora triphylla Extracts (잔대 추출물들의 항돌연변이 및 항종양 효과)

  • Ham, Young-An;Choi, Hyun-Jin;Kim, Soo-Hyun;Chung, Mi-Ja;Ham, Seung-Shi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.38 no.1
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    • pp.25-31
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    • 2009
  • This study was carried out to investigate the mutagenic, antimutagenic, cytotoxicity and antitumor effects of Adenophora triphylla (AT). AT was extracted with 70% ethanol and then further fractionated to hexane, chloroform, ethyl acetate, butanol and water. Antimutagenic, cytotoxicity and antitumor effects of AT extracts were measured by using Ames test, SRB method, and the tumor growth inhibition test. AT extracts did not show any mutagenicity in the Ames test; however, 70% ethanol extracts and its fractions had strong antimutagenic effects against mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 4-nitroquinoline-1-oxide (4NQO). The ethyl acetate fraction of AT (200 ${\mu}g$/plate) showed approximately 66.5% inhibitory effect on the mutagenesis induced by 4NQO against TA98 strain, whereas 83.3% and 75.1% inhibitions were observed on the mutagenesis induced by MNNG and 4NQO against TA100 strain. In anticancer effects, the cytotoxicity of AT extract and its fractions against cancer cell lines including human cervical adenocarcinoma (HeLa), human hepatocellular carcinoma (Hep3B), human breast adenocarcinoma (MCF-7), human gastric carcinoma (AGS), human lung carcinoma (A549) and transformed primary human embryo kidney (293) were investigated. The treatment of 1 mg/mL AT ethyl acetate faction had the highest cytotoxicity of 79.9%, 74.9%, 66.0%, 71.0% and 74.3% against HeLa, Hep3B, MCF-7, AGS and A549 cells, respectively. In contrast, the extract and its fractions showed only $3{\sim}36%$ cytotoxicity for a normal human kidney cell line (293). In vivo anti-cancer effect of Adenophora triphylla extract was tested using Balb/c mice transplanted sarcoma-180 cells. Adenophora triphylla ethyl acetate fraction showed the highest inhibition rate of 37.2% at the 50 mg/kg concentration.

Radiotherapy Results of Carcinoma of the Cervix with Positive Resection Margin (절제연 양성 자궁경부암의 수술후 방사선치료)

  • Huh Seung Jae;Kim Won Dong;Wu Hong Gyun;Kim Dae Yong;Ha Sung Whan;Ahn Yong Chan;Kim Il Han;Park Charn Il
    • Radiation Oncology Journal
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    • v.14 no.4
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    • pp.317-322
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    • 1996
  • Purpose : Patients with cervical cancer who have positive resection margins after radical hysterectomy are at increased risk for local recurrence. The result of postoperative pelvic radiotherapy for cervix cancer with positive resection margins were analyzed to evaluate the role of radiotherapy. Materials and Methods : Between n 1979 and 1992, 60 patients of cervix carcinoma were treated with postoperative radiotherapy after radical hysterectomy and pelvic lymphadenectomy because of positive vaginal (48 patients) or parametrial resection margins (12 patients). Patients were treated with external beam radiation therapy (EBRT) alone (12 Patients) or EBRT plus vaginal ovoid irradiation (VOI) (48 patients). The median followup period was 55 months. Results : The 5-year actuarial disease free and overall survival rates for all patients were $75.2\%$, $84.1\%$, respectively. The overall recurrence rate was $23\%$ (14/60). In 48 patients with Positive vaginal resection margins, the pelvic recurrence was $8\%$ (4/48). Distant metastasis was $15\%$(7/48). Of the 43 patients with positive vaginal resection margins treated with EBRT and VOI, recurrence rate was $21\%$(9/43) , while recurrence rate was $40\%$(2/5) in the EBRT only treated group. In 12 patients with positive parametrial margins, three patients ($25\%$) had distant metastases. The most significant prognostic factor was lymph node metastasis. Complications resulting from radiotherapy occurred at a rate of $32\%$(19/60) and grade III complications occurred in three patients ($5\%$). Conclusion : Postoperative radiotherapy can produce excellent pelvic control rates in patients with positive resection margins. In patients with positive vaginal margins, whole pelvic EBRT and VOI is recommended.

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