• Title, Summary, Keyword: Breast cancer

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Estrogeicity of Genistein and Bisphenol A (콩류식품의 주성분인 Genistein과 식품포장재 및 용기에 사용되는 Bisphenol A의 에스트로젠 효과에 관한 연구)

  • 강경선;이영순;신광순
    • Journal of Food Hygiene and Safety
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    • v.13 no.2
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    • pp.106-111
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    • 1998
  • This study has been focused on both estrogenic and proliferating activity of genistein (GEN) and bisphenol A (BPA). GEN and BPA enhance the proliferation of estrogen-dependent MCF-7 human breast cancer cells at concentrations as low as 100 nM of GEN and 8 ng/ml of BP A achieving similar effect to that of estradiol at 1 nM. Expression of the estrogen responsive gene, pS2 was also induced in MCF-7 cells by treatment with genistein at dose as low as 1 nM and BPA at dose as low as 4 ng/ml. Using 21 day-old ovariectomized nude mice, we examined end-bud formation and mammary gland development after treatment with bisphenol A or genistein. Compared with untreated control, mammary gland development and end-bud formation were significantly increased in mice fed genistein or bisphenol A (p<0.05). Taken together, it is concluded that GEN and BP A can act as an estrogen agonist resulting in cell proliferation and induction of the estrogen responsive pS2 gene in MCF-7 cells in vitro and in athymic mice in vivo, respectively. Therefore, it is suggested that GEN and BP A might modulate human endocrine system and these compounds might be considered as a endocrine modulator at the low levels of doses.

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Colony Size Distributions according to in vitro Aging in Human Skin Fibroblasts (피부 섬유모세포 노화에 따른 세포집락 크기의 분포)

  • Kim, Jun-Sang;Kim, Jae-Sung;Cho, Moon-June;Park, Jeong-Kyu;Park, Tae-Hyun
    • Radiation Oncology Journal
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    • v.17 no.2
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    • pp.158-165
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    • 1999
  • Purpose : To investigate the percentage of colonies wi1h16or more cells distribution of human skin fibroblast according to in vitro aging, and to evaluate the relationship between percentage of colonies with 10 or more cells and in vivo donor age in human skin fibroblast culture. Material and Method : C1, C2, C3a, and C3b human skin fibroblast samples from three breast cancer patients were used as subjects. The C1, C2, and C3a donor were 44, 54, and 55 years old, respectively. C3a and C3b cells were isolated from the same person. Single cell suspension of skin fibroblasts was prepared with primary explant technique. One hundred cells are plated into 100m1 tissue culture flask and cultured for two weeks. The colony size was defined as colonies with 16 or more cells. The cultured cell was stained with crystal violet, and number of cells in each colony was determined with stereo microscope at $\times$10 magnification. Passage number of C1, C2, C3a and C3b skin fibroblast were 12th, 17th, and 14th, respectively. Results : Percentage of colonies with 16 or more cells of skin fibroblast samples decreased with increasing in vitro passage number. In contrast, cumulative population doublings of skin fibroblast sample increased with increasing in vitro passage number. Percentage of colonies with 16 or more cells also decreased with increasing population doublings in human skin fibroblast culture. There was strong correlation with percentage of colonies with 16 or more cells and population doublings En C3a skin fibroblast sampie. At the same point of population doublings, the percentage of colonies with 16 or more cells of the young C1 donor was higher level than the old C3a donor. Conclusion : The population doublings increased with increasing in vitro passage number but percentage of colonies with 16 or more cells decreased. The results of this study imply that percentage of colonies with 16 or more cell is useful as a indicator of in vitro human skin fibroblast aging and may estimate the in vivo donor age.

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Effect of Genistein on the Onset of Puberty in Female Rats (암컷 흰쥐의 사춘기 개시에 미치는 Genistein의 효과)

  • Lee, Kyeung-Yeup;Lee, Sung-Ho
    • Development and Reproduction
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    • v.10 no.1
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    • pp.55-61
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    • 2006
  • There is growing concern that dietary soy intake is associated with protection of breast cancer. However, questions persist on the potential adverse effects of the main soy constituent genistein(GS) on female reproductive physiology. In this study, we examined whether prepubertal exposure to GS affected on the onset of puberty and the associated reproductive parameters such as hormone receptor expressions in female rats. GS(100mg/kg/day) was administrated daily from postnatal day 25(PND 25) to the day when the first vaginal opening(VO) was observed, and the animals were sacrificed on the day after VO occurred. Gross anatomy and tissue weight were compared to test the GS's effect on the cell proliferation. Furthermore, histological studies were performed to assess the structural alterations in tissues. Specific radioimmunoassay(RIA) were carried out to measure serum LH levels. To determine the transcriptional changes in progesterone receptors(PR), total RNAs were extracted from ovary and uterus and were applied to semi-quantitative reverse transcription polymerase chain reaction(RT-PCR). As a results, advanced VO was shown in the GS group(PND $31.2{\pm}0.6$) compared to the vehicle group (PND $35.3{\pm}0.7$). GS treatment significantly increased wet weight of ovaries and uteri compared to the vehicle group. Increased serum LH levels were also shown in the GS group. Graafian follicles and corpora lutea(CL) were observed only in the ovaries from GS treated animals. Similarly, hypertrophy of luminal and glandular uterine epithelium were found only in the GS group. Collectively, these effects were probably due to the estrogenic effects of GS. In the semi-quantitative RT-PCR studies, the transcriptional activities of PR in both ovary and uterus from GS-treated group were significantly higher than those from the vehicle group. The present studies demonstrated that acute exposure to GS, at levels comparable to the ranges of human exposure, during the critical period of prepubertal stage activates the reproductive system resulting precocious puberty in immature female rats.

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The Study on the Correlation of the Ejection Fraction of Multi Gated Blood Pool Scan and Echocardiography According to the Condition of Cardiac Function (심장기능상태의 분류에 따른 게이트심장혈액풀 검사와 심장초음파의 심박출계수 상관관계에 관한 고찰)

  • Lee, Dong Hun;Park, Jang Won;Nam, Ki Pyo
    • The Korean Journal of Nuclear Medicine Technology
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    • v.19 no.1
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    • pp.57-61
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    • 2015
  • Purpose We considered the correlation of Ejection Fraction (EF) which was analyzed by Multi Gated Blood Pool Scan (MUGA) and Echocardiography (ECHO) for the patients who were classified according to the condition of cardiac function. Materials and Methods We analyzed the patients (female 60) who were diagnosed with breast cancer and were examined by both MUGA and ECHO. The 30 patients (age: $58.27{\pm}13.48$) who were analyzed into less than 50% to 70% of EF were categorized as normal group and the other 30 patients (age: $53.70{\pm}8.45$) who were analyzed into less than 50% of EF were categorized as abnormal group. Statistical analysis with SPSS ver. 18 was applied. Results Each of the value of mean and standard deviation of normal group was $66.43{\pm}5.80$ (MUGA), $60.50{\pm}4.93$ (ECHO). There was a significant difference (p<0.001). Each of the value of mean and standard deviation of abnormal group was $41.93{\pm}7.58$ (MUGA), $41.70{\pm}11.49$ (ECHO). There was no significant difference (p>0.001). In the result, all 30 cases of normal group showed the same reading. 8 out of 30 cases in abnormal group showed inconsistency of the reading. Conclusion We could confirm the correlation of the EF in MUGA and ECHO statistically. There was difference between abnormal groups from the result of reading. If we are aware of the result according to the different cardiac function categorization, MUGA and ECHO can be used as even more accurate interchangeable test.

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Consideration of Standardized Uptake Value (SUV) According to the Change of Volume Size through the Application of Astonish TF Reconstruction Method (Astonish TF 재구성 기법의 적용을 통한 체적 크기의 변화에 따른 표준섭취계수(SUV)에 관한 고찰)

  • Lee, Juyoung;Nam-Kung, Sik;Kim, Ji-Hyeon;Park, Hoon-Hee
    • The Korean Journal of Nuclear Medicine Technology
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    • v.18 no.1
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    • pp.115-121
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    • 2014
  • Purpose: In addition to improving the quality of the PET image, through much research, the development of various programs are performed. Astonish TF reconstruction techniques by Philips can confirm the improved contrast of the lesion. Also, It's image reconstruction of 2 mm is possible with rapid reconstruction rate than conventional. In this study, we compared and evaluated Standardized Uptake Value (SUV) in accordance with the 2 mm reconstruction techniques and traditional 4 mm from the $^{18}F-FDG$ PET whole body image. Materials and Methods: In the phantom experiment, NEMA IEC body phantom (sphere: 10, 13, 17, 22, 28, 37 mm) was used to obtain images by using GEMINI TF 64 PET/CT (Philips, Cleveland, USA). Also, In the clinical images, we performed $^{18}F-FDG$ PET/CT examination to 30 women (age: $55.1{\pm}11.3$, BMI: $24.1{\pm}2.9$) with a diagnosis of breast cancer. After that, we reconstructed images in 2 mm and 4 mm respectively. The region of interest was drawn to acquired images. Since then, we measured SUV and statistically analyzed with SPSS ver.18 by using EBW (Extended Brilliance Workstation) NM ver.1.0. Results: After analyzing the result of the phantom study, there was a tendency that the bigger hot sphere size, the higher SUV. If you compared the 2 mm reconstruction techniques to 4 mm, it increased 95.78% in 10 mm, 50.60% in 13 mm, 25.00% in 17 mm, 30.04% in 22 mm, 31.81% in 28 mm, and 27.84% in 37 mm. Through the result of the analysis of the 2 mm reconstruction techniques and 4 mm in clinical images, it appeared that SUV of 2 mm was higher than that of 4 mm. Also the smaller the volume was, the more the change rate increased. Conclusion: After analyzing the result of the clinical picture and phantom experiments applied by Astonish TF reconstruction techniques, as the size of the volume was small, the change rate of the SUV increased. Therefore, it was necessary to further research about the SUV correction for accurate and active utilization of 2 mm reconstruction techniques which had excellent lesion discrimination ability and contrast in clinic.

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Neuroprotective effects of geneticin (G418) via apoptosis in perinatal hypoxic-ischemic brain injury (주산기 저산소성 허혈성 뇌손상에서 항고사를 통한 geneticin (G418)의 신경보호 효과)

  • Ju, Mi;Lee, Hyun Ju;Lee, Sun Ju;Seo, Eo Su;Park, Hye Jin;Lee, Kye Yang;Lee, Gyeong Hoon;Choi, Eun Jin;Kim, Jin Kyung;Lee, Jong Won;Chung, Hai Lee;Kim, Woo Taek
    • Clinical and Experimental Pediatrics
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    • v.51 no.2
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    • pp.170-180
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    • 2008
  • Purpose : Some antibiotics were known to exert neuroprotective effects in the animal model of hypoxic-ischemic (H-I) brain injury, but the mechanism is still unclear. A recent study reported that geneticin (G418), an aminoglycoside antibiotic, increased survival of human breast cancer cells by suppressing apoptosis. We investigated the neuroprotective effects of systemically administrated geneticin via anti-apoptosis following the H-I brain injury Methods : Seven-day-old Sprague-Dawley rat pups were subjected to unilateral (left) common carotid artery occlusion followed by 2.5 hours of hypoxic exposure and the cortical cell culture of rat brain was done under a hypoxic incubator. Apoptosis was measured in the injured hemispheres 7 days after H-I insult and in the injured cells from hypoxic chamber using morphologic analysis by Terminal dUTP Nick-end Labeling(TUNEL) assay and immunohistochemistry for caspase-3, and cytologic analysis by western blot and real time PCR for bax, bcl-2, and caspase-3. Results : The gross appearance and hematoxylin and eosin stain revealed increased brain volume in the geneticin-treated animal model of perinatal H-I brain injury. The TUNEL assay revealed decreased apoptotic cells after administration of geneticin in the cell culture model of anoxia. Immunohistochemistry showed decreased caspase-3 expression in geneticin-treated cortical cell culture. Western blot and real-time PCR showed decreased caspase-3 expression and decreased ratio of Bax/Bcl-2 expression in geneticin-treated animal model. Conclusion : Geneticin appears to exert a neuroprotective effect against perinatal H-I brain injury at least via anti-apoptosis. However, more experiments are needed in order to demonstrate the usefulness of geneticin as a preventive and rescue treatment for H-I brain injuries of neonatal brain.

Physiological Activities of Ginkgo biloba Sarcotesta Extract with Heat Treatment (열처리에 따른 은행 외종피 추출물의 생리활성)

  • Kim, Sung Tae;Lee, Ji Hyun;Lee, Sang Hoon;Jang, Gwi Yeong;Li, Meishan;Kim, Min Young;Yoon, Nara;Lee, Junsoo;Jeong, Heon Sang
    • The Korean Journal of Food And Nutrition
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    • v.28 no.3
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    • pp.369-375
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    • 2015
  • This study was performed to investigate the physiological activities of Ginkgo biloba sarcotesta extracts before and after heat treatment. G. biloba sarcotesta was heated at $130^{\circ}C$ for 2 h and extracted with water, 70% ethanol and 80% methanol. ABTS and DPPH radical scavenging activities increased after heating in the water (14.95 mg AAE/g and 7.36 mg TE/g) and ethanol extracts (12.20 mg AAE/g and 6.23 mg TE/g). ${\alpha}$-Glucosidase inhibitory activity decreased after heating in all but the water extract. Angiotensin converting enzyme I inhibitory activities decreased after heating in all extracts. Nitric oxide production inhibitory activity increased from 12.40~44.55% of the raw sample to 40.76~72.39% of the heated sample at a concentration of $200{\mu}g/mL$. Lipid accumulation inhibitory activities were similar before and after heat treatment. The highest antiproliferative effects on MCF-7 human breast cancer cell lines were observed in 80% methanol extract in the heated sample. Cell viability at concentrations of 25, 50, 100, and $200{\mu}g/mL$ measured 34.88, 17.58, 8.44 and 10.48%, respectively. From the results, the antioxidant and antiproliferative activities of G. biloba sarcotesta extracts increased with heat treatment, and research on the identification of the structure for the active compounds are needed in further studies.

H2AX Directly Interacts with BRCA1 and BARD1 via its NLS and BRCT Domain Respectively in vitro (H2AX의 BRCA1 NLS domain과 BARD1 BRCT domain 각각과의 in vitro 상호 결합)

  • Bae, Seung-Hee;Lee, Sun-Mi;Kim, Su-Mi;Choe, Tae-Boo;Kim, Cha-Soon;Seong, Ki-Moon;Jin, Young-Woo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.4
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    • pp.403-409
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    • 2009
  • H2AX, a crucial component of chromatin, is implicated in DNA repair, cell cycle check point and tumor suppression. The aim of this study was to identify direct binding partners of H2AX to regulate cellular responses to above mechanisms. Literature reviews and bioinformatical tools were attempted intensively to find binding partners of H2AX, which resulted in identifying two potential proteins, breast cancer-1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1). Although it has been reported in vivo that BRCA1 co-localizes with H2AX at the site of DNA damage, their biochemical mechanism for H2AX were however only known that the complex monoubiquitinates histone monomers, including unphosphorylated H2AX in vitro. Therefore, it is important to know whether the complex directly interacts with H2AX, and also which regions of these are specifically mediated for the interaction. Using in vitro GST pull-down assay, we present here that BRCA1 and BARD1 directly bind to H2AX. Moreover, through combinational approaches of domain analysis, fragment clonings and in vitro binding assay, we revealed molecular details of the BRCA1-H2AX and BARD1-H2AX complex. These data provide the potential evidence that each of the BRCA1 nuclear localization signal (NLS) and BARD1 BRCA1 C-terminal (BRCT) repeat domain is the novel mediator of H2AX recognition.

Inhibitory Mechanisms of Cell Cycle Regulation Induced by Indole-3-carbinol in Hepatocellular Carci-noma HepG2 Cells. (간암 세포주에서의 Indole-3-Carbinol에 의해 유도되는 세포주기 억제 기전)

  • 김동우;이광수;김민경;조율희;이철훈
    • Microbiology and Biotechnology Letters
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    • v.29 no.3
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    • pp.181-185
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    • 2001
  • The naturally occurring chemical indole-3-carbinol (13C), found in vegetables of the Brassica genus, is a promising anticancer agent that was shown previ- ously to induce a Gl cell cycle arrest of human breast cancer cell lines, independent of estrogen receptor signaling. The anticancer activity of 13C and the possible mechanisms of its action were explored in a human hepatocellular carcinoma cell line, HepG2. Treatment of HepG2 cells with 13C suppressed the growth of the cells. The growth sup- pression caused by 13C ($IC_{50}$/: 444$\mu$M) was found to be partially due to its ability to stop the cell cycle in HepG2 cells. Western blot analysis for the Gl phase artiest demonstrated that the expression-levels of cyclin-dependent kinase (Cdk4, Cdk6) and cyclic D were reduced strongly after treatment of Hep72 cells with 13C (4007M) for 24- 72 hrs. Furthermore, I3C selectively abolished the expression of Cdk6 in a dose- and time-dependent manner, and accordingly, inhibited the phosphorylation of retinoblastoma. Interestingly, after the HepG2 cells reached their max- imal growth arrest, the level of the p21, a well-known Cdk inhibitor, increased significantly. Therefore, it could be considered that the Gl arrest of HepG2 cells treated with 13C was due to the indirect inhibition of Cdk4/6 activities by p21 Western blot analysis for G2/M phase arrest of demonstrated the levels of Cdc2 and cyclin Bl werer reduced dramatically after the treatment of HepG2 cells with 13C ($40\mu$M) for 24-72 hrs. flow cytometry of propidium iodide-stained HepG2 cells revealed that 13C induces a Gl (53%,72hr incubation) and G2 (25%,24hr incubation) cell cycle arrest. Thus, our observations have uncovered a previously undefined antiproliferative pathway for r3C that implicates Cdk4/6 and Cdc2 as a target for cell cycle control in human HepG2 cells. However, the 13C-medi- ated cell cycle arrest and repression of Cdk4/6 production did not affect the apoptotic induction of HepG2 cell.

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Antimutagenic and Cytotoxic Effects of Acer ginnala Max. Bark Extracts (신나무 껍질 추출물의 항돌연변이원성 및 세포독성 효과)

  • Oh Heung-Seok;Cui Cheng-Bi;Choi Hyung-Taek;Kim Soo-Hyun;Jeon Mi-Sun;Ham Seung-Shi
    • Korean Journal of Food Preservation
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    • v.11 no.4
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    • pp.550-556
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    • 2004
  • In the present study, we investigated the antimutagenic and cytotoxic effects of Acer ginnala Max. bark extract on S. typhimurium TA98, TA100 and cancer cell lines with Ames test and SRB assay, respectively. They were extracted with methanol and then fractionated using hexane, chloroform, ethyl acetate, butanol, and water to obtain the fractions. The inhibition rate of methanol ($200\;{\mu}g/plate$) of Acer ginnala Max. bark extract in the Salmonella typhimurium TA100 strain showed $83.3\%$ against the mutagenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). In addition, the suppression of methanol extract with same concentration of in the Salmonella typhimurium TA98 and TA100 strains showed $80.3\%\;and\;92.7\%$ inhibition against 3-amino-1,4-dimethyl-5H-pyrido-(4,3-b)indol (Trp-P-1), respectively. The cytotoxicity effects of Acer ginnala Max. bark extract against the cell lines with human lung carcinoma (A549), human gastric carcinoma (AGS), human hepatocellular carcinoma (Hep3B) and human breast adenocarcinoma (MCF-7) were inhibited with the increase of the extract concentration. The treatment of 1.0 mg/mL Acer ginnala Max. bark methanol extract of methanol showed strong cytotoxicities of $77.3\%,\;90.4\%,\;88.9\%,\;and\;83.7\%$ against A549, AGS, Hep3B and MCF-7, respectively.