• Journal of Life Science
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• v.27 no.11
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• pp.1245-1255
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• 2017

Most cancer cells produce ATP predominantly through glycolysis instead of through mitochondrial oxidative phosphorylation, even in the presence of oxygen. The phenomenon is termed the Warburg effect, or the glycolytic switch, and it is thought to increase the availability of biosynthetic precursors for cell proliferation. EMTs have critical roles in the initiation of the invasion and metastasis of cancer cells. The glycolytic switch and EMT are important for tumor development and progression; however, their correlation with tumor progression is largely unknown. The Snail transcription factor is a major factor involved in EMT. The Snail expression is regulated by distal-less homeobox 2 (Dlx-2), a homeodomain transcription factor that is involved in embryonic and tumor development. The Dlx-2/Snail cascade is involved in Wnt-induced EMTs and the glycolytic switch. This study showed that in response to Wnt signaling, the Dlx-2/Snail cascade induces the expression of PFKFB2, which is a glycolytic enzyme that synthesizes and degrades fructose 2, 6-bisphosphate (F2,6BP). It also showed that PFKFB2 shRNA prevents Wnt-induced EMTs in the breast-tumor cell line MCF-7. The prevention indicated that glycolysis is linked to Wnt-induced EMT. Additionally, this study showed PFKFB2 shRNA suppresses in vivo tumor metastasis and growth. Finally, it showed the PFKFB2 expression is higher in breast, colon and ovarian cancer tissues than in matched normal tissues regardless of the cancers' stages. The results demonstrated that PFKFB2 is an important regulator of EMTs and metastases induced by the Wnt, Dlx-2 and Snail factors.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.33 no.5
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• pp.431-438
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• 2000

To clarify the annual reproductive cycle in a rockfish, Sebastes schlegeli, monthly changes in gonadosomatic index (GSI), hepatosomatic index (HSI) and histological feature of gonads and plasma levels of sex steroid hormones ($estradiol-l7{\beta},\;17{\alpha},\;20{\beta}-dihydroxy-4-pregnen-3-one,\;testosterone\;and\;11-ketotestosterone$) were investigated. The annual reproductive cycle in females could be divided into 5 periods as follows: 1) recovery period (June to September): serum level of $estradiol-l7{\beta}$ increased gradually; 2) vitellogenesis period (Septemer to february) : vitellogenic oocytes were obsewed, GSI sustained high value, and serum level of $estradiol-l7{\beta}$ increased; 3) gestation period (February-April): developing larva showed in the ovary, and serum levels of $17{\alpha},\;20{\beta}-dihydroxy-4-pregnen-3-one$ and testosterone increased; 4) partrition period (April to May) : larva were delivered, and value of GSI and serum levels of hormones decreased rapidly; 5) resting period (May to June) : value of GSI and serum levels of $estradiol-l7{\beta}$ and testosterone remained low. The annual reproductive cycle in males could be divided into 6 periods; 1) early maturation period (April to June): value of GSI and serum levels of hormones incresed gradually, cyst of spermatogonia incresed in number, and a small number of cyst of spermatocyte was observed; 2) mid-maturation perid (June to September); value of GSI and serum levels of hormones increased, and germ cells in many cysts were undergoing active sperrnatogenesis; 3) late maturation period (September to November) : value of GSI and serum levels of hormones remained high and spermatozoa were released into the lumina of the seminal lobules; 3) spermatozoa dischaging period (Nobember to December) : the lumina of the seminal lobules were enlarged and filled with mature spermatozoa; 4) degeneration period (December to Februauy)i value of GSI decresed and cyst of spermatocyte were decresed in number; 5) resting period (December to April) : no histological changes of testes were observed, and value of GSI and serum levels of hormones remained low. In November, the lumina of the seminal lobules were filled with mature spermatozoa and sperm masses were present in the ovarian cavity. Thus, copulation in this species occurred in November and December.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.71-78
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• 1997

This study was designed to investigate the number of the growing and mature follicles following gonadotrophin treatments for superovulation in mature rats. Eighteen mature rats (Sprague-Duwely, initially 190~230gm) were randomly alloted into 3 groups. One group was control group, another FSH-treated group was injected intramuscularly with 0.5 units of follicular stimulating hormone (FSH) / rat, and third PMS and HCG-treated group was intramuscularly injected with 20~25IU of pregnant mare serum (PMS) / rat and then at the 48 hrs later, with 20~25IU of human chorionic gonadotrophin (HCG) / rat. The uteri and ovaries of rats were collected and then were observed grossly and serial sections of paraffin embedding ovaries were stained with H-E. Number of ovarian follicles by following 3 grades of large, middle and small follicles from secondary and tertiary follicles were investigated by LM photography of preparations. Small follicles were classified as secondary follicles of preantral follicles with more than 2 layers of granulosa cells surrounding the oocyte and middle follicles were classified as secondary follicles with early signs of antral cavity or with more than one small cavity on either side of the oocytes and large follicles were classified as tertiary follicles with a single medium sized antral cavity or large well-formed antral cavity. In gross findings, the uteri were slightly swelling in FSH-treated group and markedly swelling or filled with fluid in the uterine lumen in PMS and HCG-treated group. In histological findings, the shape and size of the follicles were diverse in middle and large follicles of FSH-treated group and PMS and HCG-treated group, and proportion of atretic follicles was increased in FSH-treated group and PMS and HCG-treated group than those in control group. The uteri of FSH-treated group and PMS and HCG-treated group were hypertropied or filled with fluid in the lumens and walls of uteri. The wall tissue layers were flattened and their blood and lymph vessels were dilated. The mean number of follicle per ovary in control group were appeared to be $17.1{\pm}5.6$($14.0%{\pm}4.6%$), $37.8{\pm}9.1$($30.9{\pm}7.4%$) and $67.6{\pm}30.1$($55.2{\pm}24.6%$) respectively at large, middle and small follicles and total number of these 3 grade follicles were appeared to be $122.5{\pm}40.0$. The mean number of follicle per ovary in FSH-treated group were appeared to be $22.8{\pm}7.0$($17.4%{\pm}5.3%$), $43.4{\pm}6.6$($33.2{\pm}5.1%$) and $64.5{\pm}13.0$($49.3{\pm}9.9%$) respectively at large, middle and small follicles and total number of these 3 grade follicles were appeared to be $130.7{\pm}16.6$. The mean number of follicle per ovary in PMS and HCG-treated group were appeared to be $29.7{\pm}11.0$($16.3%{\pm}6.0%$), $61.9{\pm}17.2$($33.9{\pm}9.4%$) and $91.1{\pm}28.2$($49.9{\pm}15.4%$) respectively at large, middle and small follicles and total number of these 3 grade follicles were appeared to be $182.6{\pm}32.7$. The above findings reveal that large follicles were increased 29.8% in FSH-treated group and 73.7% in PMS and HCG-treated group than those in control group and in histologic findings, proportion of atretic follicles were more increased in ovaries with more number of more developing follicles.

• Radiation Oncology Journal
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• v.16 no.3
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• pp.225-231
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• 1998

Purpose : To determine whether TNF-$\alpha$ increases the antitumor effect of radiotherapy in murine syngeneic tumor system. Materials and Methods : Syngeneic murine tumors of MCa-K or MCa-4 (mammary carcinoma), OCa-I (ovarian carcinoma), or HCa-I(hepatocarcinoma were grown in hind legs of C3Hf/HeJ mice. When tumors were grown to 6 mm in mean diameter mice were treated with TNF-$\alpha$, radiation, or combination of the both. Gamma-radiation was given as a single dose of 30 Gy for HCa-I and 15 Gy for other tumors using Cobalt-60 teletherapy unit. A novel TNF-$\alpha$ mutein developed in Korea, was intraperitoneally administered daily at a dose of 10 ug per mouse for 7 days. In combination of radiation and TNF-$\alpha$, the drug was started 1 hour after radiation. Tumor growth delay assay was used to measure the tumor response to the treatment. Results : Among 4 tested tumors, TNF-$\alpha$ alone showed significant antitumor activity in MCa-K and OCa-I tumors, which showed absolute growth delay (AGD) of 5.0 days and 6.5 days, respectively. In combination with radiation, TNF-$\alpha$ showed significant delay of AGD (41.1 days) in OCA-I compared to AGDs of TNF-$\alpha$ alone and radiation, i.e., 6.5 days and 26.9 days, respectively(p<0.05). Enhancement factor was 1.29 in OCa-I, which showed supraadditive effect. TNF-$\alpha$ did not show significant delay of AGDs in the remaining 3 tumors compared to AGDs of TNF-$\alpha$ alone and radiation. Conclusions: TNF-$\alpha$ alone showed antitumor effects in MCa-K and OCa-I. In combination with radiation, TNF-$\alpha$ acted in supraadditive way in OCa-I only. The results of this study imply that the combination of TNF-$\alpha$ and radiation has different therapeutic potential depending on tumor model and further study is advocated.

• Clinical and Experimental Pediatrics
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• v.53 no.3
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• pp.420-427
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• 2010

Purpose : Several complications can occur in patients who received bone marrow transplantation (BMT) during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. Methods : One hundred patients (61 males, 39 females) were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD), growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. Results : Height standard deviation score (SDS) at BMT, after 1 year of BMT, and at the last visit were $0.08{\pm}1.04$, $-0.09{\pm}1.02$, and $-0.27{\pm}1.18$, respectively (P =0.001). Height SDS significantly decreased in patients who received total body irradiation (TBI) (P =0.017). One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9%) of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P =0.025). Of the 32 patients (17 males, 15 females) who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females) had increased luteinizing hormone (LH) or follicle-stimulating hormone (FSH). Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P =0.001). Conclusion : The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.4
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• pp.657-661
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• 2001

Osteoporosis that is associated with ovarian hormone deficiency following menopause (postmenopausal osteoporosis) is by far the most common cause of age-related bone loss. Isoflavone has been reported as a natural substance that possibly minimizes bone loss in postmenopausal women. This study was conducted to investigate the preventing, treating effects of isoflavone on bone loss in ovariectomized rats. 120 Sprague Dawley rats of 13 week-old were devided into 2 groups, a treatment group and prevention group. Each group was consisted of six subgroups; control (CON), sham operated (SH) or ovariectomized (OVX) and isoflavone supplemented goups: OVX+0.25mg isoflavone/kg diet (OL), OVX+0.8mg isoflavone/kg diet(OM) and OVX+2.5mg isoflavone/kg diet(OH). to study the preventing effects of isoflavone on bone loss, OL, OM and OH groups were fed with isoflavone from 4 days after ovariectomization. Treating effects of isoflavone on bone metabolism were investigated with OL, OM, OH groups supplemented with isoflavone from 8 weeks after ovariectomization. Isoflavone supplementation continued for 8 weeks. At 8 weeks after ovariectomization significant increase in alkaline phosphatase occurred comparing with CON and SH group. By isoflavone supplementation from 4 days after ovariectomy alkaline phosphatase and urinary hydroxyproline were lowered and bone mineral density, bone strength of the femur and tibia and bone dry weight were slightly enhanced with no significant difference. Isoflavone supplemented group at the level of 0.8mg/kg diet (OM group) had significantly lower serum alkaline phosphatase, urinary hydroxyproline, and higher strength of femur than OVX group. Groups with isoflavone supplementation fro 8 weeks after ovariectomy had lower level of serum alkaline phosphatase, urinary hydroxyproline than OVX group. Bone mineral density, bone dry weight and bone strength of the femur and tibia were slightly enhanced by isoflavone supplementation. However there was no significanct difference between OVS ad isoflavone supplementation groups. The results suggest that isoflavone might have potential role for preventing postmenopausal bone loss. Isoflavone supplementation at early stage of postemenopause may be beneficial to age-related bone health.

• Journal of Aquaculture
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• v.8 no.1
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• pp.31-46
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• 1995

Gonadal maturation and annual reproductive cycle in ovoviviparous oblong rockfish, Sebastes oblangus on the basis of monthly gonadosomatic indices (GSI), hepatosomatic indices (HSI) and histological observations of gonadal tissues. GSI values of female were in a wide range from $0.l5\pm0.0l\;(July)\;to\;58.54\pm3.86$ (December) and began to increase in August and reached the maxium in December, then decreased rapidly thereafter. Male GSI values were in a range from $0.08\pm0.03$ (July) to $1.55\pm0.27$ (September) and began to increase rapidly in July and reached the maximum in September, then decreased gradually, thereafter. Female HSI was in a range from $0.89\pm0.12$ (December) to $3.73\pm0.15$ (October), and male's was from $2.09\pm0.76$ (October) to $3.62\pm0.48$ (August). HSI reached the maximum values one or two months before GSI reached their maxium values in both sex, and then decreased rapidly thereafter. Mature oocytes began to appear in late October as being oocytes began to mature in August, and the type of oocyte development is categorized in the roup-synchronous oocyte development'. Ovulation and fertilization of ripe oocytes occurred in November, and hatched larvae were born from December to January. Maturation of testis was progressed in short term from August to October and spermatozoa were released in October. Sperm balls consisted of many spermatozoa were preserved in ovarian cavity of female after copulation. These results may suggest that the annual reproductive cycle of oblong rockfish could be divided into the following successive stages: growing (August and September), mature (September and October), gestation (November and December), parturition (December and January) and resting (February to July) in female, and growing (August and September), mature (September and October), copulation (October) and resting (November to July) in male.

• Clinical and Experimental Reproductive Medicine
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• v.13 no.1
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• pp.11-19
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• 1986

Follicular flxid (FF) and their matched oocytes were obtained from 58 follicles of 27 women who underwent an in vitro fertilization (IVF) procedure with ovarian hyperstimulation by clomiphene citrate(n=8), hMG(n=9),FSH/hMG(n=10). Follicular aspiration was performed 36 hours after human chorionic gonadotropin administration. The concentcation of androstendione (ADD), testosterone (T) was correlated with hyperstimulation regimens, the morphology of the oocyte-corona-cumulus complex (OCCC), oocyte fertilization, and the incidence of pregnancy after embryo transfer. The results were as follows. 1. According to hyperstimulation regimens, there was no significant differance in FF ADD and T concentrations of the similar morphology of OCCC. 2. In clomiphene-treated and FSH/hMG-treated cycles, FF ADD concentrations of preovulatory oocytes were 43.09${\pm}$9.53 ng/ml and 59.46${\pm}$9.09 ng/ml, those of immature occytes were 96.98${\pm}$16.55 ng/ml and 116.13${\pm}$36.81 ng/ml, those of atretic oocytes were 246.5 ${\pm}$9.25 ng/ml and 634.25${\pm}$9.25 ng/ml respectively, reflecting the significant relationship between FF ADD level and morphologic maturity of OCCC (p<0.05). But in hMG-treated cycles, such relationship was not found (p>0.1). In clomiphene-treated and FSH/hMG-treated cycles, FF T concentrations of preovulatory oocytes were 11.37${\pm}$2.38 ng/ml and 11.68${\pm}$1.73 ng/ml respectively which were significantly lower than those of atretic oocytes (25.1${\pm}$7.50 ng/ml and 23.25${\pm}$0.95 ng/ml respectively) (p<0.05). But in all cycles, FF T concentrations of immature oocytes were not significantly different from those of preovulatory oocytes, artetic oocytes (p>0.1). 3. In hMG-treated and FSH/hMG-treated cycles, FF ADD concentrations of fertilized oocytes were 32.43${\pm}$4.09 ng/ml and 42.61${\pm}$4.82 ng/ml respectively which were significantly lower than those of non-fertilized oocytes (72.18${\pm}$17.31 ng/ml and 108.09${\pm}$17.32 ng/ml respectively) (p<0.05), but in clomiphene-treated cycles there was no significant difference (p>0.1). In FSH/hMG-treated cycles, FF T concentration of fertilized oocytes was 7.33${\pm}$1.06 ng/ml which was significantly lower than that of non-fertilized oocytes (20.3${\pm}$6.21 ng/ml) (p>0.02), but in clomiphne-treated and hMG-treated cycles there was no significant difference (p>0.1). 4. In all cycles FF ADD and T concentrations did not correlated with the success of pregnancy after embryo transfer. Above results suggested that FF ADD and T may play an important role in oocyte maturation and fertilization, but their relationship with the success of psegnancy was not found.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.1
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• pp.41-48
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• 2010

Objectives: The aim of this study was to assess appropriate time to convert intramuscular progesterone support to oral administration for luteal phase support in in vitro fertilization (IVF). Methods: Seventy-six cycles of IVF in which fetal heart beat was identified after treatment were included. Patients underwent controlled ovarian hyperstimulation with GnRH agonist long protocol (n=7) or GnRH antagonist protocol (n=66). Cryopreserved embryo transfer was performed in three cycles. Luteal support was initiated by daily intramuscular injection of progesterone, and after confirmation of fetal heart beat, converted to oral micronized progesterone (Utrogestan, Laboratoires Besins International, France) 300 mg daily before or after 8 gestational weeks. The oral progesterone was continued for 11 weeks. Results: Overall clinical abortion rate was 3.9% (3/76) and mean time to conversion was $8^{+4}$ gestational weeks ($46{\pm}5.8$ days after oocytes retrieval). The abortion rate was 5.6% (1/17) and 3.4% (2/59) in patients with conversion before 7 weeks and after 8 weeks, respectively, which were not statistically significant (p=0.678). The miscarriages were occurred at $9^{+4}$ weeks, $11^{+3}$ weeks and $11^{+4}$ weeks. Conclusion: Sequential luteal support using intramuscular and oral progesterone yields a relatively low clinical abortion rate. If fetal heart beat confirmed, sequential regimen appears to be safe and convenient method to reduce patients' discomfort induced by multiple injections.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.2
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• pp.131-141
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• 2008

Objective: To compare the outcomes of intracytoplasmic sperm injection (ICSI) with fresh and cryopreserved-thawed testicular spermatozoa in patients with azoospermia. Methods: One hundred and nine cycles (66 couples) where ICSI was planned with fresh or cryopreserved-thawed testicular spermatozoa were included in this study; Ninety two cycles (61 couples) with fresh testicular spermatozoa (fresh group) and seventeen cycles (13 couples) with cryopreserved-thawed testicular spermatozoa (cryopreserved-thawed group). We compared ICSI outcomes such as fertilization rate, implantation rate, pregnancy rate and miscarriage rate, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: In 9 out of the 92 cycles where ICSI was planned with fresh testicular spermatozoa, testicular spermatozoa could not be retrieved. Fertilization rate tended to be higher in the fresh group than in the cryopreserved-thawed group ($58.0{\pm}27.8%$ vs. $45.9{\pm}25.0%$, p=0.076). The number of high quality embryos was significantly higher in the fresh group ($0.9{\pm}1.2$ vs. $0.2{\pm}0.5$, p=0.002). However, there were no significant differences in clinical pregnancy rate, implantation rate and miscarriage rate between the two groups. Conclusion: The results of this study suggest that although the use of cryopreserved-thawed testicular sperm for ICSI in patients with azoospermia may reduce fertilization capacity and embryo quality, it may not affect pregnancy rate, implantation rate and miscarriage rate. If testicular sperm can be obtained before ICSI procedure, the use of cryopreserved-thawed testicular sperm may also avoid unnecessary controlled ovarian hyperstimulation and cancellation of oocyte retrieval when spermatozoa cannot be retrieved as well as damage on testicular function by repeated TESE.