1.The Utility of Matrix Metalloproteinase-2 and TIMP-2 as tumor markers in cervical cancer.
Dong Choon PARK ; Jin Young YOO ; Young Ok LEW ; Dae Hoon KIM
Korean Journal of Obstetrics and Gynecology 2002;45(5):759-765
OBJECTIVE: The disintegration of extracellular matrix and basement membrane are important processes in the infiltration and metastasis of malignant tumors. We investigated the expressions of matrix metallo- proteinase-2 (MMP-2) and tissue inhibitors of metalloproteinases (TIMP-2) in tissues and sera from patients with cervical cancer, and compared the expressions of these enzymes with patient clinical status to determine the possibility of these enzymes being used as tumor biomarkers. METHODS : The expressions of MMP-2 and TIMP-2 were investigated in sixty cervical cancer tissues obtained from patients who were histologically confirmed having cervical cancer by immunohistochemical staining, and the expressions of the mRNAs of MMP-2 and TIMP-2 were confirmed by using RT-PCR. Also, the amounts of MMP-2 and TIMP-2 in sera obtained from each patient during treatment progress were measured using ELISA to determine the presence of a relationship between the expression levels of these enzymes and the clinical condition of the patient. RESULTS: In terms of the expression levels of MMP-2 and TIMP-2 by immunohistochemical staining, MMP-2 was shown to be positive in 46% (28/60) of the normal cervical tissues and in 75% (45/60) of the cervical cancer tissues, and the degree of expression of MMP-2 was also stronger in cervical cancer tissue than in normal cervical tissue. TIMP-2 was shown to be positive in 23% (14/60) and 27% (16/60) of normal cervical tissues and cervical cancer tissues, respectively, though these expressions were weak in nature. The mRNA of MMP-2 was more distinctly expressed in cervical cancer tissue than normal cervical tissue, but no difference could be seen in the case of TIMP-2. In terms of expressions as determined by ELISA, the positivity rate of MMP-2 in the normal control group and the cervical cancer group were 12% (7/54) and 76% (46/60), respectively, and the corresponding positivity rates of TIMP-2 were 22% (12/54) and 98% (59/60), respectively (p<0.05). MMP-2 expression reflected clinical condition in 57.5% of the patients, and TIMP-2 in 35%, however, MMP-2 expression increased in the presence of recurrent cervical cancer. CONCLUSIONS : MMP-2 and TIMP-2 are closely related with cervical cancer, and MMP-2 is believed a tumor biomarker that possibly reflects clinical status.
Basement Membrane
;
Biomarkers
;
Enzyme-Linked Immunosorbent Assay
;
Extracellular Matrix
;
Humans
;
Matrix Metalloproteinase 2*
;
Metalloproteases
;
Neoplasm Metastasis
;
RNA, Messenger
;
Tissue Inhibitor of Metalloproteinase-2*
;
Biomarkers, Tumor*
;
Uterine Cervical Neoplasms*
2.The Cytotoxic and Radiosensitizing Effects of Taxol in Uterine Sarcoma Cell Lines.
Hye Young LEE ; Dong Choon PARK ; Sung Whan KIM ; Young Ok LEW ; Dae Hoon KIM
Korean Journal of Obstetrics and Gynecology 2003;46(4):725-731
OBJECTIVE: The cytotoxic and radiosensitizing effects of Taxol in uterine sarcoma cell lines were investigated. METHODS: Two uterine sarcoma cell lines with different Taxol responses were used, namely, Taxol- sensitive and MDR gene negative MES-SA, and Taxol-resistant and MDR gene positive MES-SA/MX2 cells. These cells were treated with Taxol, radiation, or both, and cytotoxicities were compared by XTT assay and TUNEL staining. The cytotoxic mechanism was also studied by flow cytometry and by RT-PCR of the MDR gene expression. RESULTS: In Taxol-sensitive MES-SA cell lines, Taxol showed highly cytotoxic activity than radiation or the Taxol-radiation combined treatment. On the contrary, in Taxol-resistant MDR positive MES-SA/MX2 cell lines, Taxol significantly increased the sensitivity to radiation therapy, and increased cytotoxicity and apoptosis. Flow cytometry showed that treatment with Taxol alone produced the highest rate of cell cycle shifting to the G0/G1 phase in the MES-SA cell line. However, in the MES-SA/MX2 cell line, Taxol only treatment did not show significant cell cycle shifting compared to the control group. However, in cases of combined Taxolradiation treatment, the rate of cell cycle shifting was higher than for radiation treatment only. CONCLUSION: Taxol has cytotoxic and radiosensitizing effects on uterine sarcoma cell lines.
Apoptosis
;
Cell Cycle
;
Cell Line*
;
Flow Cytometry
;
Genes, MDR
;
In Situ Nick-End Labeling
;
Paclitaxel*
;
Radiation-Sensitizing Agents*
;
Sarcoma*
3.The Cytotoxic and Radiosensitizing Effects of Taxol in Uterine Sarcoma Cell Lines.
Hye Young LEE ; Dong Choon PARK ; Sung Whan KIM ; Young Ok LEW ; Dae Hoon KIM
Korean Journal of Obstetrics and Gynecology 2003;46(4):725-731
OBJECTIVE: The cytotoxic and radiosensitizing effects of Taxol in uterine sarcoma cell lines were investigated. METHODS: Two uterine sarcoma cell lines with different Taxol responses were used, namely, Taxol- sensitive and MDR gene negative MES-SA, and Taxol-resistant and MDR gene positive MES-SA/MX2 cells. These cells were treated with Taxol, radiation, or both, and cytotoxicities were compared by XTT assay and TUNEL staining. The cytotoxic mechanism was also studied by flow cytometry and by RT-PCR of the MDR gene expression. RESULTS: In Taxol-sensitive MES-SA cell lines, Taxol showed highly cytotoxic activity than radiation or the Taxol-radiation combined treatment. On the contrary, in Taxol-resistant MDR positive MES-SA/MX2 cell lines, Taxol significantly increased the sensitivity to radiation therapy, and increased cytotoxicity and apoptosis. Flow cytometry showed that treatment with Taxol alone produced the highest rate of cell cycle shifting to the G0/G1 phase in the MES-SA cell line. However, in the MES-SA/MX2 cell line, Taxol only treatment did not show significant cell cycle shifting compared to the control group. However, in cases of combined Taxolradiation treatment, the rate of cell cycle shifting was higher than for radiation treatment only. CONCLUSION: Taxol has cytotoxic and radiosensitizing effects on uterine sarcoma cell lines.
Apoptosis
;
Cell Cycle
;
Cell Line*
;
Flow Cytometry
;
Genes, MDR
;
In Situ Nick-End Labeling
;
Paclitaxel*
;
Radiation-Sensitizing Agents*
;
Sarcoma*
4.A Case of Adenoid Basal Carcinoma in Uterine Cervix.
Dong Choon PARK ; Jae Hoon KIM ; Hyung Gun LEE ; Dae Young CHUNG ; Jin Woo KIM ; Young Ok LEW ; Dae Hoon KIM ; Sung Eun NAMKOONG
Korean Journal of Obstetrics and Gynecology 1999;42(8):1823-1826
We report a rare case of adenoid basal carcinoma in uterine cervix. The patient was a 43-year-old Korean female. She received neoadjuvant chemotherapy with Quick Cis-VP16 (cisplatin and VP16 with 7-10 days interval), three times and radical hysterectomy with pelvic lymph nodes dissection under the diagnosis of cervical cancer stage IIa. After the neoadjuvant chemotherapy, the mass size was 3 x 2.5 Cm and which was protruded in exocervical region. Microscopically, scattered small nests of uniformed small cells with dark nuclei and scant cytoplasm were observed. Peripheral palisading as well as the formation of gland-like or acinar structures were noted. There were also foci of squamous differentiation in same portion of the small nests. The epithelial surface in other portions showed squamous cell carcinoma, large cell non-keratinizing cell type. Distribution between adenoid basal carcinoma of the cervix and other disease, such as adenoid cystic carcinoma and squamous cell carcinoma with basaloid features, is important for clinical management because the clinical behavior of adenoid basal carcinoma is less malignant than adenoid cystic carcinoma.
Adenoids*
;
Adult
;
Carcinoma, Adenoid Cystic
;
Carcinoma, Squamous Cell
;
Cervix Uteri*
;
Cytoplasm
;
Diagnosis
;
Drug Therapy
;
Etoposide
;
Female
;
Humans
;
Hysterectomy
;
Lymph Nodes
;
Uterine Cervical Neoplasms
5.Experimental animal model for preeclampsia by the infusion of nitric oxide synthase inhibitor and reverse of preeclampsia by high dose L-arginine infusion.
Hyung Gun LEE ; Jong Kun LEE ; Young Ok LEW ; Dae Young CHUNG ; Dong Choon PARK ; Jae Hoon KIM ; Jong Chul SHIN ; Dae Hoon KIM ; Soo Pyung KIM
Korean Journal of Obstetrics and Gynecology 1999;42(12):2768-2775
OBJECTIVES: To learn which inhibition of nitric oxide synthase with L-nitro arginine methylester(L-NAME) induces a preeclampsia-like syndrome in pregnant rabbits and high dose of L-arginine reverse the adverse changes induced by nitric oxide synthesis inhibition in pregnant rabbits. MTERIAL AND METHOD: Twenty Newzealand rabbits with 22-days of gestation were injected subcutaneously with 400mg of L-NAME for 7days and 100mg/kg L-arginine was also given intravenously 10 of 20 L-NAME injected pregnant rabbits. They are compared with the control group in which same volume of saline was subcutaneously injected to 5 rabbits with same condition. They were anesthesized by ketamine 50 mg/kg and roupum 2 mg/kg intramuscularly. Cutdown of femoral artery was performed and 22 gauge angioneedle was inserted. On manometer,three way catheter was connected, zeroed with saline, and blood pressure was read. Blood samples were taken from the vein of ear and checked for count of blood cells and bood chemistry (BUN/Cr, GOT/GPT, LDH, Uric acid). Urine protein was measured with nelaton catheterized urine. We injected drugs for 7 days begining on 22 days after mating and performed cesarian section to deliver fetus. To observe their effects on organs, lung, liver, placenta and kidney were taken and fixed with formalin. The sliced kidney tissue in thickness of 1 mm, was fixed with glutaraldehyde for electron microscopy and stored at 4degree C. Special staining was done for closed observation of pattern changes. For statistical analysis, mean+/-SEM was used. The control and experimental groups were compared by unpaired t-test and the differences were significant if probability level is less than 0.05(<0.05). RESULT: Mean blood pressure(MAP) in the experimental group I was significantly high compared to the control group(P<0.05). There was no significant differences in MAP between experimental group II and control group. Urine Protein, BUN, Cr, GOT/GPT, LDH, platelet count in the experimental group I was significantly high(p<0.05) compared to the control group. There was no significant difference between experimental group II and control group. In light microscopic examination, lung, liver, kidney, placenta showed specific finding in experimental group I. Misconstructive of glomerulus in the experimental kidney was well preserved under EM examination. Interstitium of kidney was widened by increase of mesangial matrix. Mild effacement of foot process and cytoplasm of proximal tubule containing electron dense myelin figure like structure were observed. CONCLUSION: Long term injection of L-arginine analogue produced preeclampsia like syndrome and pathologic changes of organ system in pregnant rabbits. Concurrent high dose of L-arginine reversed such chages.
Arginine*
;
Blood Cells
;
Blood Pressure
;
Catheters
;
Chemistry
;
Cytoplasm
;
Ear
;
Femoral Artery
;
Fetus
;
Foot
;
Formaldehyde
;
Glutaral
;
Ketamine
;
Kidney
;
Liver
;
Lung
;
Microscopy, Electron
;
Models, Animal*
;
Myelin Sheath
;
NG-Nitroarginine Methyl Ester
;
Nitric Oxide Synthase*
;
Nitric Oxide*
;
Placenta
;
Platelet Count
;
Pre-Eclampsia*
;
Pregnancy
;
Rabbits
;
Veins
6.Effects of Isoflavone on Surgically Menopaused Women.
Hyun Hee JO ; Mee Ran KIM ; Dong Jin KWON ; Jang Heub KIM ; Young Ok LEW ; Jin Hong KIM
Korean Journal of Obstetrics and Gynecology 2004;47(6):1223-1227
OBJECTIVE: To evaluate the effects of isoflavone intake on estrogen deprivated symptoms in surgically menopaused women. METHODS: Premenopausal women who took total hysterectomy with both adnexectomy were randomized into three groups. One group took conjugated equine estrogen 0.625 mg daily for 12 weeks after surgery, the second group took isoflavone 100 mg #3 daily for 12 weeks after surgery, and the third group took no medication for controlled group. Questionnaires about the acute menopausal symptoms, incontinence score, blood lipid profile, bone turnover marker were checked before and 12 weeks after surgery. RESULTS: Kupperman's index and insentience score were showed less increased rate than control group. Total cholesterol and triglyceride were increased in all groups and HDL cholesterol was increased in estrogen and isoflavone groups. Osteocalcin was decreased in estrogen and isoflavone groups, ICTP was decreased in estrogen group, and increased in the other groups. CONCLUSION: Isoflavone was effective to acute postmenopusal symptoms, urogenital atrophy and bone turnover.
Atrophy
;
Cholesterol
;
Cholesterol, HDL
;
Estrogens
;
Female
;
Humans
;
Hysterectomy
;
Osteocalcin
;
Surveys and Questionnaire
;
Triglycerides
7.Phase II trial of Neoadjuvant Paclitaxel and Cisplatin in Carcinoma of the Uterine Cervix.
Dong Choon PARK ; Jae Hoon KIM ; Young Ok LEW ; Dae Hoon KIM ; Sung Eun NAMKOONG
Korean Journal of Obstetrics and Gynecology 2002;45(4):682-686
OBJECTIVE: The toxicity and effectivity of intravenous paclitaxel and cisplatin as neoadjuvant chemotherapy were assessed in cervical cancer patients. METHODS: Thirty seven consecutive patients affected by FIGO stage IB2 to \\'a5\\'b1B were treated with paclitaxel 60 mg/m2 that was administered intravenously over a 3-hour period, followed by cisplatin 60 mg/m2, also administered intravenously. The chemotherapy was administered every 10 days and for three courses. The toxicity of the regimen in each cycle was determined according to the WHO toxicity criteria and in cases with grade 3 or 4 toxicity, chemotherapy was postponed for one week. The size of the tumor mass was measured prior to the neoadjuvant chemotherapy by means of pelvic examination and pelvic magnetic resonance imaging (MRI). The response to the treatment was determined 10 days after 3 cycles of chemotherapy by means of pelvic examination and pelvic MRI. Two weeks after the neoadjuvant chemotherapy was completed, the patients were either given an operation or radiation therapy, depending on their overall condition, the operational risks and personal willingness for an operation. RESULTS: A total of 37 patients were given a radical hysterectomy and enrolled in this study. Mild myalgia was the most common toxicity. Granulocytopenia was seen in four patients but there was no grade 3 or 4. Grade 1 neurotoxicities developed in four patients. Clinical responses occurred in 94.6% (35/37) of patients, including 35.1% (13/37) with a complete response, 10.8% (4/37) with a pathologically determined complete response, 59.5% (22/37) with a partial response, and 5.4% (2/37) showed stable disease. A down-staging response was seen in 75.7% (28/37) of those patients showing a response. CONCLUSIONS: The combination of paclitaxel with cisplatin for use in neoadjuvnant chemotherapy seems to be tolerated and very active in cervical cancer. Especially, every 10 days treatment did not delay the surgically or radologically optimal time. A larger number of cases need to be studied in order to confirm the efficacy of the treatment.
Agranulocytosis
;
Cervix Uteri*
;
Cisplatin*
;
Drug Therapy
;
Female
;
Gynecological Examination
;
Humans
;
Hysterectomy
;
Magnetic Resonance Imaging
;
Myalgia
;
Paclitaxel*
;
Uterine Cervical Neoplasms
8.The effect of Vitamin D(3)addition on bone mineral density in postmenopausal hormone replacement.
Sun Won YOO ; Hyun Hee JO ; Kyeong A YEO ; Young Ok LEW ; Dong Jin KWON ; Gi Wook CHUNG ; Jang Heub KIM ; Jin Hong KIM
Korean Journal of Obstetrics and Gynecology 2000;43(6):992-997
OBJECTIVE: To determine the effect of the addition of Vit. D3 (1,25-Dihydroxychole calciferol D3) to the conventional postmenopausal hormone replacement therapy on bone mineral density(BMD) DESIGN: A 2-year retrospective , randomized study Setting : Department of Obstetrics and Gynecology of Catholic university hospital Patients : 388 postmenopausal women were recruited and divided into 5 groups according to treatment regimen; A: conjugated estrogens only treated group(n=146), B : conjugated estrogens and progesterone treated group(n=103), C : conjugated estrogens and Vit.D3 treated group (n=36), D : conjugated estrogens, progesterone and Vit.D3 treated group (n=41), E : control group (n=60). METHODS: The bone mineral density of the lumbar spines and femoral neck were determined by dual-energy X-ray absorptiometry(DEXA) every 2 years. STATISTICS: The difference between before and after treatment was determined by paired t-test. The comparison among the groups were determined by one way ANOVA test and student's t-test. RESULTS: The addition of progesterone to estrogen showed insignificant increase in the lumbar and femoral neck BMD. The addition of Vit. D3 compared with conventional hormone replacement therapy insignificantly influened bone density in women with initially normal BMD, but definitely increase in women with initially osteopenic and osteoporotic BMD of femoral neck rather than lumar spine(p<0.05). CONCLUSIONS: The use of Vit. D3 combined with postmenopausal estrogen replacement effects the increase of BMD in low bone density than normal bone density, especially femoral neck.
Bone Density*
;
Estrogen Replacement Therapy
;
Estrogens
;
Estrogens, Conjugated (USP)
;
Female
;
Femur Neck
;
Gynecology
;
Hormone Replacement Therapy
;
Humans
;
Obstetrics
;
Progesterone
;
Retrospective Studies
;
Spine
;
Vitamins*
9.A Case of Ruptured Cornual Pregnancy in Adenomyosis Uterus at 29 Weeks' Gestation.
Chul Gu YOON ; Ok Kyung KIM ; Yoon Young LEE ; Hee Joong LEE ; Jae Hoon KIM ; Dong Jin KWON ; Tae Chul PARK ; Young Ok LEW ; Dae Hoon KIM
Korean Journal of Obstetrics and Gynecology 2004;47(6):1228-1231
A case of ruptured cornual pregnancy in adenomyosis uterus at 29 weeks' gestation is presented here. A cornual pregnancy occurs when the conceptus implants at the junction between the tube and the uterus rather than in main part of uterine cavity. It is relatively rare entity, but the rich vascularity of the uterus in this location makes rupture particularly dangerous. resulting in higher maternal mortality. The presented case was unique in continuing till the third trimester of pregnancy. We present a case of a ruptured cornual pregnancy in adenomyosis uterus at the third trimester of pregnancy with a brief review of literatures.
Adenomyosis*
;
Female
;
Humans
;
Maternal Mortality
;
Pregnancy Trimester, Third
;
Pregnancy*
;
Rupture
;
Uterus*
10.The significance of maternal serum and umbilical cord blood leptin concentration with intrauterine fetal growth restriction and/or preeclampsia.
Gui Se Ra LEE ; Ki Chul KIL ; Young LEE ; Hyun Young AHN ; Soo Young HUR ; Eun Young SHIN ; Jong Chul SHIN ; Young Ok LEW
Korean Journal of Obstetrics and Gynecology 2007;50(10):1336-1343
OBJECTIVE: To ascertain whether fetal growth restriction with or without preeclampsia is associated with alteration of leptin concentration in maternal and umbilical cord serum. METHODS: Maternal serum and umbilical cord blood leptin concentrations were determined by ELISA assay in 25 women with singletone pregnancies complicated by fetal growth restriction without preeclampsia (IUGR), in 11 women with singletone pregnancies complicated by fetal growth restriction with preeclampsia (IUGR+PE), in 9 women with singletone pregnancies complicated by preeclampsia without fetal growth restriction (PE), and in 13 women with uncomplicated singletone pregnancies (Control). RESULTS: Maternal weight and BMI before pregnancy and in delivery were significantly different among groups. The lowest weight and BMI before pregnancy and in delivery was group IUGR. Neonatal birth weight was significantly different among groups. The lowest birth weight was group IUGR+PE. Maternal serum leptin concentration and umbilical cord leptin concentration were not significantly different among groups. Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight. Umbilical cord blood leptin levels were significantly correlated with neonatal birth weight. CONCLUSION: Maternal serum leptin concentration and umbilical cord blood leptin levels were independent of presence of preeclampsia and/or IUGR. Umbilical cord blood leptin reflects neonatal birth weight.
Birth Weight
;
Enzyme-Linked Immunosorbent Assay
;
Female
;
Fetal Blood*
;
Fetal Development*
;
Fetal Growth Retardation
;
Humans
;
Leptin
;
Pre-Eclampsia*
;
Pregnancy
;
Umbilical Cord*