• Radiation Oncology Journal
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• v.17 no.2
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• pp.113-119
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• 1999

Purpose : To evaluate possible acute toxicity and early response of concurrent radiation therapy and low dose daily cisplatin as a radiosensitizer in patients with locally advanced uterine cervical carcinomas. Materials and Method : From December 1996 to January 1999, 38 previously untreated Patients with locally advanced squamous cell carcinoma of the uterine cervix (from stage IIB to stage IIIB) were treated at Inha University Hospital. All patients underwent standard pretreatment staging Procedures after the initial evaluation by gynecologists and radiation oncologists. Sixteen Patients with huge cervical mass (>4 cm) were submitted to the group treated with concurrent radiation therapy and low dose daily cisplatin while the remainder was treated with radiation therapy alone. Radiation therapy consisted of 4500 cGy external beam irradiation to whole pelvis (midline block after 3000 cGy), 900$\~$1000 cGy boost to involved parametrium, and high dose-rate intracavitary brachytherapy (a total dose of 3000$\~$3500 cGy/500 cGy per fraction to point A, twice per week). In the group treated with low dose cisplatin concurrently, 10 mg of daily intravenous cisplatin was given from the 1st day of radiation therapy to the 20th day of radiation therapy. Acute toxicity was measured according to expanded common toxicity criteria of the NCI (C) Clinical Trials. Early response data were analyzed at minimum 4 weeks' follow-up after completion of the treatment protocol. Results: Hematolgic toxici쇼 was more prominent in patients treated with radiation therapy and cisplatin. Six of 16 patients (37.5$\~$) treated with radiation therapy and cisplatin and one of 22 patients (4.5$\~$) treated with radiation therapy alone experienced grade 3 leukopenia. In Fisher's exact test, there was statistically significant difference between two groups regarding leukopenia (P=0.030). There was no apparent difference in the frequency of gastrointestinal and genitourinary toxicity between two groups (P=0.066). Three of 16 patients (18.7$\~$) treated with radiation therapy and cisplatin and two of 22 patients (9.1$\~$) treated with radiation therapy alone experienced more than 5 kg weight loss during the treatment. There was no statistically significant difference on weight loss between two groups (P=0.63). Two patients on each group were not evaluable for the early response because of incomplete treatment. The complete response rate at four weeks' follow-up was 80$\~$(16/20) for the radiation therapy alone group and 78$\~$ (11/14) for the radiation therapy and cisplatin group. There was no statistically significant difference in early response between two treatment groups (P=0.126). Conclusion : This study led to the conclusion that the hematologic toxicity from the treatment with concurrent radiation therapy and low dose daily cisplatin seems to be more prominent than that from the treatment of radiation therapy alone. There was no grade 4 hematologic toxicity or mortality in both groups. The hematologic toxicity in both treatment groups seems to be well managable modically. Since the risk factors were not balanced between two treatment groups, the direct comparison of early response of both groups was not possible. However, preliminary results regarding early response for patients with bulky cervical tumor mass treated with radiation therapy and low dose daily cisplatin was encouraging. Longer follow-up is necessary to evaluate the survival data. A phase III study is needed to evaluate the efficacy of concurrent daily low dose cisplatin with radiation therapy in bulky cervical cancer.

• The Journal of Korean Obstetrics and Gynecology
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• v.30 no.4
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• pp.18-44
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• 2017

Purpose: The object of this study was to observe the anti-climacterium activity of Gagamguibiondam-tang (GGOT) on ovariectomized (OVX) rats, a well-documented rodent models resembles with women postmenopausal climacterium symptoms, as including cardiovascular diseases, obesity, hyperlipidemia, osteoporosis, organ steatosis and mental disorders. Methods: In this study, anti-climacteric effects were evaluated separated into three categories; 1) anti-obese, 2) anti-uterine atrophy and 3) anti-osteoporotic effects. Five groups were used (8 rats in each group); sham control, OVX control, GGOT 500, 250 and 125 mg/kg administered groups. Twenty-eight days after bilateral OVX surgery, GGOT were orally administered, once a day for 84 days, and then the changes on the body weight and gain during experimental periods, serum estradiol levels, abdominal fat pad and uterus weights with histopathology of abdominal fat pads (total thickness and mean adipocyte diameters) and uterus (total, epithelial and mucosal thickness, percentages of uterine gland regions) for anti-obese and estrogenic effects. In addition, femur, tibia and fourth or fifth lumbar vertebrae (L4 or L5) wet, dry and ash weights, mineral density (BMD), bone strength (failure load), serum osteocalcin and bone specific alkaline phosphatase (bALP) contents, histological and histomorphometrical analyses - bone mass and structure with bone resorption, were monitored for anti-osteoporosis activity. Results: As a result of OVX, noticeable increases of body weight and gains, food and water consumption, weights of abdominal fat pad deposited in dorsal abdominal cavity, serum osteocalcin levels were demonstrated in this experiment with decrease of uterus, femur, tibia and L5 weights, serum bALP and estradiol levels. In addition, marked hypertrophic changes of adipocytes located in deposited abdominal fat pads, uterine disused atrophic changes, decreases of bone mass and structures of femur, tibia and L4 were also observed in OVX control rats with dramatic increases of bone resorption markers, the Ocn and OS/BS at histopathological and histomorphometrical analysis in this study as compared with sham-operated control rats, suggesting the estrogen-deficient climacterium symptoms - obese and osteoporosis were induced by OVX, respectively. However, these estrogen-deficient climacterium symptoms induced by bilateral OVX in rats were significantly inhibited by 84 days of continuous oral treatment of GGOT 500, 250 and 125 mg/kg, respectively. Especially, GGOT 500, 250 and 125 mg/kg showed clear dose-dependent inhibitory activities on the OVX-induced climacterium signs. Conclusion: The results suggest that oral administration of GGOT 500, 250 and 125 mg/kg has clear dose-dependent favorable anti-climacterium effects - estrogenic, anti-obese and anti-osteoporotic activities in OVX rats in this experiment.

• Journal of Ginseng Research
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• v.44 no.3
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• pp.519-526
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• 2020

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

• Toxicological Research
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• v.33 no.1
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• pp.71-77
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• 2017

Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

• Korean Journal of Pharmacognosy
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• v.40 no.3
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• pp.218-223
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• 2009

The roots of Rumecis Radix have been used for the treatment of heat phlegm, jaundice, constipation, scabies and uterine hemorrhage. The aim of this study was to confirm whether Rumecis Radix water extract (RJWE) has a preventive effect on the development of atopic dermatitis (AD) in 2,4-dinitrochlorobenzene (DNCB)-applied BALB/c mice. Oral administration (12.5 mg/kg, 25 mg/kg) and topical application (0.5 mg/mouse, 1.0 mg/mouse) of RJWE decreased the development of AD-like skin lesions, ear swelling, spleen weight and total serum IgE. RJWE significantly also inhibited the infiltration of mast cells in the dorsal skin. Furthermore, the release of histamine from rat peritoneal mast cells (RPMCs) was suppressed significantly. These results suggest that the inhibitory effect of RJWE on AD might be associated with mast cells.

• Advances in Traditional Medicine
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• v.10 no.2
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• pp.103-110
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• 2010

The seed powder of Abrus precatorius L. has traditionally been used as oral contraceptive agent by the women in some rural areas in Bangladesh. The present study aimed to examine the antifertility activity of A. precatorius seed extracts in experimental female rats. Finely ground seeds were extracted with aqueous acetone followed by successive partitioning with n-hexane, ethyl acetate (EtOAc), methanol (MeOH) and water. Water suspended crude seed powder, organic fractions of acetone extract and a standard contraceptive drug ($Nordette^{(R)}28$) were separately administered orally to the female rats for 30 days. n-Hexane, EtOAc and MeOH solubles at the doses of 2, 4 and 6 mg/rat/day, respectively and crude seed powder at 100 mg/rat/day exhibited 100% antifertility activity with lowest levels of serum luteinizing hormone (LH), follicle stimulating hormone (FSH) and $17{\beta}$-estradiol. Histological study of ovary and uterus of these rats exhibited reduced number of developing follicles and increased number of atretic follicles in the ovary, and fewer uterine glands with shrunken morphology, reduced endometrial height, poor vascularity and compact stroma in uterus. However, the activities of serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase and the body weight of the rats remained almost unaffected in all the seed extract treated rats compared to control. These results suggest that A. precatorius seed extracts reduced the levels of serum FSH, LH and $17{\beta}$-estradiol probably by affecting hypothalamic-pituitary-gonadal axis. The reduced levels of these hormones might have affected the oestrous cycle, follicular development, and subsequently the establishment of pregnancy in treated rats.

• Journal of Life Science
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• v.21 no.3
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• pp.406-411
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• 2011

To investigate the effects of short-term treatment with tri-n-butyltin chloride (TBTCl) and bisphenol A (BPA) on the reproduction of striped field mice, the mice were intramuscularly injected with TBTCl or BPA immediately before the reproductive season and examined in the reproductive season after keeping them for 4 months. As a result, there were no differences between the control and the compound-treated groups regarding body weight in both sexes, the residual levels of the compounds in the adult males, and the gonadosomatic index (GSI) and the histological structures with LM and EM of the testes and epididymides in both the adult and young males. The infant mortality and abortion rate, however, were high in the TBTCl-treated groups and BPA-treated groups respectively, compared to the control group. Conclusively, it was suggested that short-term treatment with TBTCl or BPA in mice in the non-reproductive season might have inhibited the development of the uterine embryos or fetuses, although it did not induce accumulations of these compounds or affect the reproductive organs of adult and young (F1) males.

• Clinical and Experimental Reproductive Medicine
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• v.8 no.1
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• pp.23-34
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• 1981

In order to study twin pregnancies, a retrospective survey was carried out in Yonsei University, Severance Hospital. Twin deliveries during 1967-1976 numbered altogether 264, and their relative frequency was 1.30%. Clinical palpation in addition to auscultation and roentgenologic technique had been used in the twin diagnosis. The diagnosis was made prior to delivery in 93.18% of the cases. The deliveries took place in the 37.26th (S.D. 3.95) gestational weeks on an average. The mean weights of the infants were-A (first baby) 2416.03g. (S.D. 802.61), and B (second baby) 2299.81g. (S.D. 190.31). The most common manner of twin delivery was spontaneous vaginal delivery. Cesarean section was done in 14.39%, of which the most common indication was hypotonic uterine dysfunction (34.21 %). Low one minute Apgar scores occured more often in B twins than among A twins. Breech delivery gave low one minute Apgar scores more often than did spontaneous vertex delivery in both twins. Full term twins and infants weighing more than 2500g. had fewer low one minute Apgar scores than the preterm infants and those with low birth weight. Perinatal mortality (PNM) in the total series was 14.77% (A 12.50% and B17.05%). The most common cause of perinatal mortality was prematurity in 44.87%. The worst outcome was recorded for the age groups 15-19 and ${\geqq}$40, in which perinatal mortality were 50.00%, respectively. The perinatal mortality of both A and B infants was lowest in the group diagnosed early during antenatal care before delivery. On the basis of our findings, we wish to emphasize particularly the importance of the early diagnosis of twins.

• Korean Journal of Agricultural Science
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• v.36 no.1
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• pp.41-50
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• 2009

Fucoidan is a uniquely-structured sulfated fucose-rich polysaccharide derived from brown algae. Recently, the abalone glycosidase-digested fucoidan extract (fucoidan extract) derived from seaweed Cladosiphon novae-caledoniae Kylin (Mozuku) draws much attention because of its clinical anti-cancer effect in Japan. Here, we report the cancer cells-specific apoptosis inducing effects of the fucoidan extract. The fucoidan extract suppressed the growth of various anchorage-dependent and -independent cancer cells. The fucoidan extract contained low molecular weight components, which induced apoptosis of human leukemic HL 60 cells but not of human lymphocytes. It was shown that the fucoidan extract lead caspase 3/7 activation and loss of mitochondrial membrane potential in HL 60 cells. Another function of the fucoidan extract was also observed. It has been known that sugar chain expression on the surface of cancer cell membrane changes dependent on their malignancy. The analysis on sugar chain expression profiling using FITC-labeled lectins revealed that the expression of concanavalin A (Con A) binding sugar chain was enhanced by the treatment of human lung adenocarcinoma A549, human uterine carcinoma HeLa and human fibrosarcoma HT1080 cells with the fucoidan extract. Con A-induced apoptosis of cancer cells was stimulated in a dose-and time-dependent manner by the treatment with the fucoidan extract but not of human normal fibroblast TIG-1 cells.

• Development and Reproduction
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• v.24 no.3
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• pp.159-165
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• 2020

Previously, we reported adverse effects of low-dose nonylphenol (NP) exposure on the reproductive parameters of F1 female mice. In the present study we further investigated the pathohistological effect of NP exposure on the reproductive organs in F1 female mice. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 33 of F1 offspring for vaginal examination. Mice were sacrificed on PND 30 and the reproductive tissue weights were measured. The initial (at PND 21) body weights of the NP-50 group animals were significantly lower than those of control group animals, and the weight deficit were recovered when the terminal (PND 33) body weights were measured. Early vaginal opening was found in NP group animals (p<0.05). Pathohistological studies revealed that NP-treated F1 animals showed prominent increase in the ovarian follicle numbers (p<0.01), and decrease in the diameter of uterine myometrium (p<0.01), and increase in the diameter of luminal epithelium (p<0.05). The present study demonstrated that the subchronic low-dose NP exposure induced early beginning of puberty and pathohistological abnormalities in ovary and uterus of F1 mice. Further studies are needed to achieve a better understanding on the action mechanism of NP in pubertal onset and to find a way to avoid a hazardous situation provoked by NP exposure.