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Glycoantigen Biosyntheses of Human Hepatoma and Colon Cancer Cells are Dependent on Different N-Acetylglucosaminyltransferase-III and -V Activities

  • Kim, Cheorl-Ho
    • Journal of Microbiology and Biotechnology
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    • v.14 no.5
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    • pp.891-900
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    • 2004
  • UDP-N-Acetylglucosamine(GlcNAc):$\beta$1,4-D-mannoside$\beta$-l ,4N-acetylglucosaminyltransferase-III (GnT-III) and UDP-N-GlcNAc:$\alpha$-6-D-mannosid$\beta$-1,6N-acetylglucosaminyltransferase-V(GnT - V) activities were determined in human hepatoma cell lines and metastatic colon cancer cells, and their activities were compared with those of normal liver cells and fetal hepatocytes. GnT-III activities were higher than those of GnT-V in hepatic carcinoma cells. When the two enzyme activities were assayed in highly metastatic colon cancer cells, GnT - V activities were much higher than those of GnT-III. When GlcN, GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzymes displayed different kinetic properties between hepatic and colon cancer cells, depending on their metastatic potentials. Normal cells of two origins had characteristically very low levels of GnT-III and -V activities, whereas hepatoma and colon cancer cells contained high levels of activities. These data were supported by RT-PCR and Northern blot analyses, showing that the expression of GnT-III and -V mRNAs were increased in proportion to the enzymatic activities. The increased GnT-III, md -V activities were also correlated with increased glycosylation of the cellular glycoproteins in hepatoma and colon cancer cells, as examined by lectin blotting analysis by using wheat germ glutinin (WGA), erythroagglutinating phytohemagglutinin (E-PHA), leukoagglutinating phytohemagglutinin (L-PHA), and concanavalin A (Con A). Treatment with retinoic acid, a differentiation agent, resulted in decreases of both GnT-III and -V activities of HepG2 and HepG3 cells. In colon carcinoma cells, however, treatment with retinoic acid resulted in a reduction of GnT-V activity, but not with GnT-III activity. Although the mechanism underlying the induction of these mzymes is unclear, oligosaccharides in many glycoproteins have been observed of cancer cells.

Gonadotropin-releasing Hormone and Its Receptor as a Therapeutic Concept in the Progression of Epithelial Ovarian Cancer

  • Kim, Ki-Yon;Choi, Kyung-Chul
    • Journal of Embryo Transfer
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    • v.24 no.1
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    • pp.1-14
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    • 2009
  • Ovarian cancer is a significant cause of cancer-related death in women, but the main biological causes remain open questions. Hormonal factors have been considered to be an important determinant causing ovarian cancer. Recent studies have shown that gonadotropin-releasing hormone (GnRH)-I and its analogs have clinically therapeutic value in the treatment of ovarian cancer. In addition, numerous studies have shown that the potential of GnRH-II in normal reproductive system or reproductive disorder. GnRH-I receptors have been detected in approximately 80% of ovarian cancer biopsy specimens as well as normal ovarian epithelial cells and immortalized ovarian surface epithelium cells. GnRH-II receptors have also been found to be more widely expressed than GnRH-I receptors in mammals, suggesting that GnRH receptors may have additional functions in reproductive system including ovarian cancer. The signal transduction pathway following the binding of GnRH to GnRH receptor has been extensively studied. The activation of protein kinase A/C (PKA/PKC) pathway is involved in the GnRH-I induced anti-proliferative effect in ovarian cancer cells. In addition, GnRH-I induced mitogen-activated protein kinase (MAPK) activation plays a role in anti-proliferative effect and apoptosis in ovarian cancer cells and the activation of transcriptional factors related to cellular responses. However, the role of GnRH-I and II receptors, there are discrepancies between previous reports. In this review, the role of GnRH in ovarian cancer and the mechanisms to induce anti-proliferation were evaluated.

Interfacial Durability and Acoustic Properties of Transparent xGnP/PVDF/xGnP Graphite Composites Film for Acoustic Actuator (음향 작동기를 위한 투명한 xGnP/PVDF/xGnP 그래핀 복합재료 필름의 계면 내구성 및 음향 특성)

  • Gu, Ga-Young;Wang, Zuo-Jia;Kwon, Dong-Jun;Park, Joung-Man
    • Composites Research
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    • v.25 no.3
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    • pp.70-75
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    • 2012
  • Interfacial durability and electrical properties of CNT, ITO or xGnP coated PVDF nanocomposites were investigated for acoustic actuator applications. The xGnP coated PVDF nanocomposite exhibited better electrical conductivity than CNT and ITO case due to the unique electrical property of xGnP, and this nanocomposite also showed good sound characteristics. Interfacial adhesion durability between either neat CNT or plasma treated CNT and plasma treated PVDF were measured by static contact angle, surface energy, work of adhesion, and spreading coefficient tests. The optimum acoustic actuation performance of xGnP coated PVDF nanocomposite was measured using sound level meter with changing radius of curvature and coating conditions. As compared to CNT and ITO, the xGnP was known as more appropriate acoustic actuator due to the characteristic electrical property. It is the most appropriate condition when the radius of curvature is 15 degree. Although sound characteristics were different with various coating thicknesses, it is possible to manufacture transparent actuator with good sound quality.

The Comparison of Clinical Outcomes between GnRH Agonist Long Protocol and GnRH Antagonist Short Protocol in Oocyte Donation Cycles (난자공여를 통한 체외수정 시술에서 성선자극호르몬 유리호르몬 효능제 장기요법과 길항제 단기요법 사이의 임상 결과 비교)

  • Rhee, Jeong-Ho;Park, Joon-Chul;Kim, Jong-In
    • Clinical and Experimental Reproductive Medicine
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    • v.30 no.1
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    • pp.95-103
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    • 2003
  • Objective : To assess and compare the clinical outcomes between GnRH agonist long protocol and GnRH antagonist short protocol in oocyte donation program. Materials and Methods: Of total 18 oocyte donation cycles, controlled ovarian hyperstimulation (COH) were performed with GnRH agonist long protocol and GnRH antagonist short protocol in initial 9 cycles and later 9 cycles, respectively. Oral estradiol valerate and progesterone in oil we re administrated to all recipients for endometrial preparation. Oral estradiol administration was started from donor cycle day 1 after full shut down of gonadal axis with GnRH agonist in patients with ovarian function. Progesterone was injected from oocyte retrieval day of donor initially, then continuously till pregnancy 12 weeks if pregnancy was ongoing. We compared the parameters of clinical outcomes, such as number of the retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate, COH duration, total gonadotropin dose for COH between GnRH agonist long protocol group and GnRH antagonist group. Statistical analysis was performed using Mann-Whitney test, p<0.05 was considered as statistically significant. Results: The number of retrieved oocytes, fertilization rate, high grade embryo production rate, clinical pregnancy rate, implantation rate, ongoing pregnancy rate were $14.89{\pm}7.83$, 81%, 64%, 78%, 31%, 78%, respectively in GnRHa long protocol group and $11.22{\pm}8.50$, 79%, 64%, 67%, 34%, 56%, respectively in GnRH antagonist group. There was no significant differences in parameters of clinical outcomes between 2 groups (all p value >0.05). Duration and total gonadotropin dose for COH were $10.94{\pm}1.70$ days and $43.78{\pm}6.8$ vials in 18 cycles, $12.00{\pm}1.73$ days and $48.00{\pm}6.93$ vials in agonist group, $9.88{\pm}0.78$ days and $39.55{\pm}3.13$ vials in antagonist group, respectively. In GnRH agonist long protocol group, significantly longer duration and higher gonadotropin dose for COH were needed (p=0.012). Conclusion: In oocyte donation program, clinical outcomes from controlled ovarian hyperstimulation with GnRH antagonist were comparable to those from GnRH agonist long protocol group, so controlled ovarian hyperstimulation with GnRH antagonist may be effective as GnRH agonist long protocol. At least there may not be harmful effects of GnRH antagonist on oocyte development and quality.

STATISTICAL CORRELATION ANALYSIS OF CVM, SMI AND MANDIBULAR LENGTH WITH NORMAL OCCLUSION IN GROWING CHILDREN (소아청소년기 정상 교합 아동에서 경추골 및 수완부골 성숙도에 대한 하악골 성장의 연관성)

  • Kim, Soo-Yung;Yang, Kyu-Ho;Choi, Nam-Ki;Kim, Seon-Mi
    • Journal of the korean academy of Pediatric Dentistry
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    • v.39 no.4
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    • pp.357-365
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    • 2012
  • There are orthodontic treatment which involves tooth movements and orthopedic treatment which involves skeletal movement. In childhood and adolescence, especially for the treatment of orthopedic treatment, the evaluation of bone maturity and growth potential is very important. The purpose of this study is to assess the developmental stage and to compare the amount of mandibular growth with cephalometric radiographs and hand-wrist radiograph in 6 to 13-year-old children with normal occlusion. The results are as follows : SMI and CVM showed a significant correlation (p < 0.05). Ar-Go, Co-Go, N-Go, S-Gn, N-Me, Co-Gn, Go-Me, Go-Gn increased with increasing maturity of hand-wrist and Ar-Go, Co-Go, N-Go, S-Gn, N-Me, Co-Gn, Go-Me, Go-Gn increased with increasing maturity of cervical vertebrae maturation. Also Ar-Go, Co-Go, N-Go, S-Gn, N-Me, Co-Gn, Go-Me, Go-Gn showed a significant correlation with each of the cervical vertebrae maturation stages and hand-wrist maturation stages (p < 0.05). These results suggested that mandibular growth had a significant correlation with cervical vertebrae maturation stages and hand-wrist maturation stages.

The inhibitory effects of gonadotropin-releasing hormone(GnRH) agonist on ovarian functions in immature rats pretreated with pregnant mare serum gonadotropin(PMSG)

  • Yun, Young-won;Yun, Sang-keun;Yu, Wook-joon
    • Korean Journal of Veterinary Research
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    • v.39 no.2
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    • pp.276-286
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    • 1999
  • In the present study, to understand how gonadotropin-releasing hormone (GnRH) affects ovarian functions in superovulated rats, we examined the effects of GnRH agonist on the ovulatory response, the morphological normality and nuclear maturation of ovulated oocytes, the ovarian weight, the ovarian histology, and the circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in immature rats pretreated with 30IU pregnant mare serum gonadotropin (PMSG) and supplemented with 10IU human chorionic gonadotropin(hCG). GnRH agonist was intravenously injected via jugular vein catheter every 20min for 4hrs in early follicular phase (from 6hr after PMSG) of superovulated rats. In addition, GnRH antagonist, Antide, was intravenously injected in combination with GnRH agonist to verify the effects of GnRH agonist on ovarian functions. All animals were sacrificed at 72hr after PMSG administration. The administration with GnRH agonist in early follicular phase of superovulated rats caused inhibition of ovulatory response, increased the proportion of abnormal appearing oocytes(especially, in the rats of the group treated with 500ng GnRH agonist), decreased ovarian weight and promote follicular atresia, compared to those from the rats of control regimen that were not treated with GnRH agonist. In addition, the treatment with GnRH agonist in the superovulated rat distinctly decreased serum steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in preovulatory phase. On the other hand, the inhibitory effects of GnRH agonist treatment in superovulation-pretreated rats on ovarian functions were totally reversed by the combination with GnRH antagonist, Antide. The nuclear maturation of oocytes recovered from the oviducts in immature rats treated with GnRH agonist and/or GnRH antagonist was characterized by prematurity and asynchronization in early follicular phase, which was similar to control group. The overall results of this study indicate that GnRH agonist disturbs directly ovarian function in early follicular phase of superovulated immature rats in terms of ovulatory response and morphological normality of ovulated oocytes. This concept has been further evidenced by the findings of a great decrease in ovarian weight, a marked increase in follicular and a distinct decrease circulating steroid hormone ($17{\beta}$-estradiol, progesterone and testosterone) levels in GnRH agonist treatment regimen in early follicular phase.

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Comparison between GnRH Antagonist and Agonist Long Protocols in Poor Responders (불량반응군에서 GnRH Antagonist와 Agonist Long Protocol의 비교)

  • Choi, Ji-Young;Ku, Seung-Yup;Kim, Hoon;Jee, Byung-Chul;Suh, Chang-Suk;Kim, Seok-Hyun;Choi, Young-Min;Kim, Jung-Gu;Moon, Shin-Yong
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.3
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    • pp.239-244
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    • 2010
  • Objective: The objective of this retrospective study was to compare the in vitro fertilization (IVF) outcomes of gonadotropinreleasing hormone (GnRH) agonist and GnRH antagonist protocols in poor responders. Methods: A total of 172 cycles in subjects with less than 5 oocytes retrieved treated with either GnRH agonist long protocols or antagonist protocols were included. The outcome variables such as numbers of growing follicles and retrieved oocytes, and the fertilization rate were evaluated as the main outcome measures. Results: There was no difference in regard to the numbers of growing follicles and oocytes, and fertilization rate between the two groups. $E_2$ level on Day 7/8, mean gonadotropin dose, and the days of stimulation were shown to be statistically different (p<0.01, respectively). Conclusion: Considering that similar results were observed with less time and gonadotropin dose, GnRH antagonist protocol may be considered as a preferable choice over GnRH agonist protocols in poor responders.

Involvement of Amino Acids Flanking Glu7.32 of the Gonadotropin-releasing Hormone Receptor in the Selectivity of Antagonists

  • Wang, Chengbing;Oh, Da Young;Maiti, Kaushik;Kwon, Hyuk Bang;Cheon, Jun;Hwang, Jong-Ik;Seong, Jae Young
    • Molecules and Cells
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    • v.25 no.1
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    • pp.91-98
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    • 2008
  • The Glu/$Asp^{7.32}$ residue in extracellular loop 3 of the mammalian type-I gonadotropin-releasing hormone receptor (GnRHR) interacts with $Arg^8$ of GnRH-I, conferring preferential ligand selectivity for GnRH-I over GnRH-II. Previously, we demonstrated that the residues (Ser and Pro) flanking Glu/$Asp^{7.32}$ also play a role in the differential agonist selectivity of mammalian and non-mammalian GnRHRs. In this study, we examined the differential antagonist selectivity of wild type and mutant GnRHRs in which the Ser and Pro residues were changed. Cetrorelix, a GnRH-I antagonist, and Trptorelix-2, a GnRH-II antagonist, exhibited high selectivity for mammalian type-I and non-mammalian GnRHRs, respectively. The inhibitory activities of the antagonists were dependent on agonist concentration and subtype. Rat GnRHR in which the Ser-Glu-Pro (SEP) motif was changed to Pro-Glu-Val (PEV) or Pro-Glu-Ser (PES) had increased sensitivity to Trptorelix-2 but decreased sensitivity to Cetrorelix. Mutant bullfrog GnRHR-1 with the SEP motif had the reverse antagonist selectivity, with reduced sensitivity to Trptorelix-2 but increased sensitivity to Cetrorelix. These findings indicate that the residues flanking $Glu^{7.32}$ are important for antagonist as well as agonist selectivity.

Long-term effects of gonadotropin-releasing hormone analogs in girls with central precocious puberty

  • Kim, Eun Young
    • Clinical and Experimental Pediatrics
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    • v.58 no.1
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    • pp.1-7
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    • 2015
  • Gonadotropin-releasing hormone analogs (GnRHa) are widely used to treat central precocious puberty (CPP). The efficacy and safety of GnRHa treatment are known, but concerns regarding long-term complications are increasing. Follow-up observation results after GnRHa treatment cessation in female CPP patients up to adulthood showed that treatment (especially <6 years) was beneficial for final adult height relative to that of pretreated or untreated patients. Puberty was recovered within 1 year after GnRHa treatment discontinuation, and there were no abnormalities in reproductive function. CPP patients had a relatively high body mass index (BMI) at the time of CPP diagnosis, but BMI standard deviation score maintenance during GnRHa treatment seemed to prevent the aggravation of obesity in many cases. Bone mineral density decreases during GnRHa treatment but recovers to normal afterwards, and peak bone mass formation through bone mineral accretion during puberty is not affected. Recent studies reported a high prevalence of polycystic ovarian syndrome in CPP patients after GnRHa treatment, but it remains unclear whether the cause is the reproductive mechanism of CPP or GnRHa treatment itself. Studies of the psychosocial effects on CPP patients after GnRHa treatment are very limited. Some studies have reported decreases in psychosocial problems after GnRHa treatment. Overall, GnRHa seems effective and safe for CPP patients, based on long-term follow-up studies. There have been only a few long-term studies on GnRHa treatment in CPP patients in Korea; therefore, additional long-term follow-up investigations are needed to establish the efficacy and safety of GnRHa in the Korean population.

A Study of Clinical Efficacy of GnRH Antagonist (Cetrorelix) Single and Multiple Dose Protocol for Controlled Ovarian Hyperstimulation (과배란유도에서 GnRH Antagonist (Cetrorelix) Single 및 Multiple Dose Protocol의 임상적 효용성에 관한 연구)

  • Ko, Sang-Hyeon;Kim, Dong-Ho;Bae, Do-Hwan;Lee, Sang-Hoon
    • Clinical and Experimental Reproductive Medicine
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    • v.29 no.4
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    • pp.259-267
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    • 2002
  • Objective: This study was performed to compare the clinical outcomes of GnRH antagonist (Cetrorelix) single dose and multiple dose protocols for controlled ovarian hyperstimulation with GnRH agonist long protocol. Materials and Method: From September 2001 to March 2002, 48 patients (55 cycles) were performed controlled ovarian hyperstimulation for ART using by either GnRH antagonist and GnRH agonist. Single dose of 3 mg GnRH antagonist was administered in 15 patients (17 cycles, single dose group) at MCD #8 and multiple dose of 0.25 mg of GnRH antagonist was administered in 15 patients (18 cycles, multiple dose group) from MCD #7 to hCG injection day. GnRH agonist was administered in 18 patients (20 cycles, control group) by conventional GnRH agonist long protocol. We compared the implantation rate, number of embryos, and clinical pregnancy rate among three groups. Student-t test and Chi-square were used to determine statistical significance. Statistical significance was defined as p<0.05. Results: There were no significant differences in ampules of used gonadotropins, number of mature oocytes, obtained embryos between single and multiple dose group, but compared with control group, ampules of used gonadotropins, number of mature oocytes, obtained embryos were decreased significantly in both groups. Clinical pregnancy rate and implantation rate were not different in three groups. There were no premature LH surge and ovarian hyperstimulation syndrome in three groups. Multiple pregnancy were occurred 1 case in multiple dose group and 2 case in control group. Conclusions: GnRH antagonist is a safe, effective, and alternative method in the controlled ovarian hyperstimulation compared with GnRH agonist. Clinical outcomes and efficacy of both single and multiple dose protocol are similar between two groups.