• 제목/요약/키워드: NeuN

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CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients

  • Yazdi, Mohammad Forat;Rafieian, Shiva;Gholi-Nataj, Mohsen;Sheikhha, Mohammad Hasan;Nazari, Tahereh;Neamatzadeh, Hossein
    • Asian Pacific Journal of Cancer Prevention
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    • 제16권15호
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    • pp.6783-6787
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    • 2015
  • Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer. Materials and Methods: A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3. Results: The mean age of the patients with the disease recurrence was $50.8{\pm}6.4$ and in non recurrent patients was $48.2{\pm}6.8$. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen-treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence. Conclusions: This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.

Neuronal differentiation and developmental characteristics in the dentate gyrus of staggerer mutant mice

  • Yi, Sun-Shin;Hwang, In-Koo;Shin, Jae-Hoon;Baek, Sung-Hee;Yoon, Yeo-Sung;Seong, Je-Kyung
    • BMB Reports
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    • 제43권2호
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    • pp.122-126
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    • 2010
  • Homozygous staggerer ($RORa^{sg/sg}$) mice showed a severe ataxia caused by cerebellum degeneration. Decreased and dysfunctional Rora is a main cause of this neurologic phenotype. The phenotype of staggerer mice has been well known in cerebellum. However, there has been rarely reported about cerebrum even though of staggerer is expressed in merely cerebellum but hippocampus, thalamus, cortex, and olfactory bulb. The expressions of Ki67, doublecortin (DCX), and NeuN, which are cell proliferation, neuronal differentiation and mature neuron markers, respectively, were measured with immunohistechemistry in dentate gyrus in staggerer mice in order to uncover whether staggerer can affect the change in dentate gyrus. The immunoreactivities of DCX and NeuN were significantly reduced in the dentate gyrus of staggerer mice than normal control, while Ki67 were rarely unchanged in staggerer mice. These results suggest that staggerer mutation has an influence on the neuronal differentiation and development not only in cerebellum but also in dentate gyrus.

Effect of Single Growth Factor and Growth Factor Combinations on Differentiation of Neural Stem Cells

  • Choi, Kyung-Chul;Yoo, Do-Sung;Cho, Kyung-Sock;Huh, Pil-Woo;Kim, Dal-Soo;Park, Chun-Kun
    • Journal of Korean Neurosurgical Society
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    • 제44권6호
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    • pp.375-381
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    • 2008
  • Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

둥근성게, Strongylocentrotus nudus 배에 존재하는 Polysialyltransferase의 특성 및 발현 조절에 관한 연구 (Characterization and Developmental Regulation of Polysialyltransferase from Embryos of Strongylocentrotus nudus)

  • 남지흔;김영대;박영제;조진원
    • 한국발생생물학회지:발생과생식
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    • 제2권2호
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    • pp.149-155
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    • 1998
  • 폴리시알린산 (polysialic acid)은 미생물로부터 인간에 이르기까지 다양한 세포의 세포 표면 복합당사슬에 공유 결합하는 당사슬의 일종이다. 최근 성게 난자의 젤리층과 성게 난자의 표면에서 폴리시알린산이 연결된 당단백질이 발견됨으로써 폴리시알린산의 생합성과 그 기능에 대한 의문이 제기되었다. 둥근성게의 난자와 배에서 추출한 효소액과 CMP-[$^{14}$ C]Neu5Ac를 기질로 사용하여 Neu5Ac를 endogenous acceptor에 전달하는 CMP-Neu5Ac:poly-$\alpha$2, 8 sialosyl sialyltransferase (polyST)를 발견하였다. polyST는 20mM MOPS (pH 7.0), 2$0^{\circ}C$에서 최적 활성을 나타냈다. 10 mM $Mg^2$$^{+}$를 효소 반응액에 첨가하면 polyST의 황성은 2.7배 증가하였다. poiyST는 또한 포유류의 gang1ioside인 GD3에 폴리시알린산을 합성할 수 있었다. 이와 같은 폴리시알린산이 존재하는 ganglioside가 현재까지 자연계에서 알려진 바가 없다는 사실은 하나의 polyST가 endogenous acceptor와 ganglioside에 폴리시알린산을 합성했다고 결론지을 수 있다. 과량의 GD3를 exogenous acceptor로 사용하여 둥근성게에 존재하는 polyST의 활성을 조사한 결과 mesenchyme 포배기 때부터 그 활성이 급격히 증가하고 낭배기 때에 최고에 도달했다. 성게의 배발생 때에 polyST의 활성이 조절된다는 것은 낭배기 때에 일어나는 세포나 조직 사이에 일어나는 변화와 초기 단계 spicule 형성에 어떤 중요한 기능을 담당하고 있을 가능성이 있다.

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Survival of Triple Negative versus Triple Positive Breast Cancers: Comparison and Contrast

  • Negi, Preety;Kingsley, Pamela Alice;Jain, Kunal;Sachdeva, Jaineet;Srivastava, Himanshu;Marcus, Sudeep;Pannu, Aman
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권8호
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    • pp.3911-3916
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    • 2016
  • Background: Triple negative (TN) and triple positive (TP) breast cancers both are aggressive types but TN generally has a shorter survival. Objectives: To compare the clinical characteristics and treatment outcomes for patients with TN versus TP breast cancer and to assess various prognostic factors affecting overall survival. Materials and Methods: A retrospective audit of 85 breast cancer patients was conducted in the Department of Radiation Oncology and Medical Oncology on patients from 2006 to 2013 for whom IHC for ER, PgR and Her-2 neu were available. The patients were stratified into: ER-, PR- and Her-2 neu- (Arm A, n=47) and ER+, PgR+ and Her-2 neu+ (Arm B, n=38). Results: TN subtype had higher numbers of premenopausal and advanced stage patients as compared to TP subtype. The locoregional recurrence (LRR) and distant metastatic rate was also higher in TN subtype but there was no definite pattern in both the arms. Among the prognostic factors, patients with premenopausal status and advanced stage in TN breast cancer had inferior survival (P=0.07) whereas for those with postmenopausal status and early stage there was no survival difference between the two arms. Conclusions: TN subtype tends to be more aggressive in terms of younger age and advanced stage at presentation, higher tumour grade, LRR and metastasis, suggesting need for future research efforts on providing aggressive treatment to these patients. We could attribute better outcome for TP subtype to receptor positivity enabling role of hormonal treatment and targeted therapy, although less number of patients received targeted therapy.

Purification and Properties of Non-Cariogenicity Sugar Produced by Alkalophilic Bacillus sp. S-1013

  • Ryu, Il-Hwan;Kim, Sun-Sook;Lee, Kap-Sang
    • Journal of Microbiology and Biotechnology
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    • 제14권4호
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    • pp.751-758
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    • 2004
  • The NCS(Non-Cariogenicity Sugar) from Bacillus sp. S-1013 was purified by cold acetone and methanol precipitation, and DEAE-cellulose ion-exchange and Sephadex G-100 column chromatographies, to yield an amorphous yellow syrup. The melting point and $[\alpha]_D^{20}$ were 155-$157^{\circ}C$ and +53, respectively. Instrumental analyses such as FT-IR, $^1H-NMR, and ^{13}C-NMR$ showed that the NCS contained an O-H group, C-H, C=O, $NH_2$, anomeric carbon, anomeric proton, N-acetylgalactose, fucose, and neuramic acid, thus, the NCS was determined to be a trisaccharide of Fuc($1\longrightarrow4$)GalNAc($2\longrightarrow6$) NeuAc.

Comparative N-Linked Glycan Analysis of Wild-Type and α1,3-Galactosyltransferase Gene Knock-Out Pig Fibroblasts Using Mass Spectrometry Approaches

  • Park, Hae-Min;Kim, Yoon-Woo;Kim, Kyoung-Jin;Kim, Young June;Yang, Yung-Hun;Jin, Jang Mi;Kim, Young Hwan;Kim, Byung-Gee;Shim, Hosup;Kim, Yun-Gon
    • Molecules and Cells
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    • 제38권1호
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    • pp.65-74
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    • 2015
  • Carbohydrate antigens expressed on pig cells are considered to be major barriers in pig-to-human xenotransplantation. Even after ${\alpha}1,3$-galactosyltransferase gene knock-out (GalT-KO) pigs are generated, potential non-Gal antigens are still existed. However, to the best of our knowledge there is no extensive study analyzing N-glycans expressed on the GalT-KO pig tissues or cells. Here, we identified and quantified totally 47 N-glycans from wild-type (WT) and GalT-KO pig fibroblasts using mass spectrometry. First, our results confirmed the absence of galactose-alpha-1,3-galactose (${\alpha}$-Gal) residue in the GalT-KO pig cells. Interestingly, we showed that the level of overall fucosylated N-glycans from GalT-KO pig fibroblasts is much higher than from WT pig fibroblasts. Moreover, the relative quantity of the N-glycolylneuraminic acid (NeuGc) antigen is slightly higher in the GalT-KO pigs. Thus, this study will contribute to a better understanding of cellular glycan alterations on GalT-KO pigs for successful xenotransplantation.

세 가지 균주 유래의 N-acetylneuraminate lyase 비교; Escherichia coli, Haemophilus influenzae, Clostridium perfringens.

  • 이정호;김병기
    • 한국생물공학회:학술대회논문집
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    • 한국생물공학회 2000년도 추계학술발표대회 및 bio-venture fair
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    • pp.575-578
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    • 2000
  • pNAN15b와 E. coli BL21(${\lambda}DE3$)를 써서 클로닝한 E. coli 유래의 NALase는 높은 수준으로 발현이 되었다. Escherichia coli, Haemophilus influenzae, Clostridium perfringens 세 가지 균주 유래의 NALase를 비교해본 결과 E. coli 유래의 NALase가 발현이 잘되어 전체 활성도는 높았지만 활성저해를 받는 경향이나 pH 11에서의 안정성을 보면 H. influenzae 유래의 NALase가 Neu5Ac 합성에 더 유리한 특성을 갖고 있어서 H. influenzae 유래의 NALase를 E. coli에서 충분히 발현할 수 있다면 H. influenzae 유래의 NALase가 더 효과적이라고 할 수 있다.

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신경 분화 유도한 인체 지방조직 유래 간질세포의 신경 표현형과 유전자 발현 (Neuronal Phenotypes and Gene Expression Profiles of the Human Adipose Tissue-Derived Stromal Cells in the Neuronal Induction)

  • 심수경;오득영;전영준;이백권;안상태;이종원
    • Archives of Plastic Surgery
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    • 제34권1호
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    • pp.1-7
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    • 2007
  • Purpose: Human adipose tissue-derived stromal cells(hADSCs) can be expanded in vitro and induced to differentiate into multiple mesenchymal cell types. In this study we have examined various neuronal phenotypes and gene expression profiles of the hADSCs in the neuronal induction. Methods: The hADSCs were isolated from human adipose tissue and they were characterized by the flow cytometry analysis using CD13, CD29, CD34, CD45, CD49d, CD90, CD105 and HLA-DR cell surface markers. We differentiated the hADSCs into the neuronal lineage by using chemical induction medium and observed the cells with contrast microscopy. The immunocytochemistry and western blotting were performed using the NSE, NeuN, Trk-A, Vimentin, N-CAM, S-100 and ${\beta}$-Tubulin III antibodies. Results: The hADSCs were positive for CD13($90.3{\pm}4%$), CD29($98.9{\pm}0.7%$), CD49d($13.6{\pm}6%$), CD90 ($99.4{\pm}0.1%$), CD105($96%{\pm}2.8%$) but negative for CD34, CD45 and HLA-DR. The untreated cultures of hADSCs predominately consisted of spindle shaped cells and a few large, flat cells. Three hours after the addition of induction medium, the hADSCs had changed morphology and adopted neuronal-like phenotypes. The result of immunocytochemistry and western blotting showed that NSE, NeuN, Trk-A, Vimentin, N-CAM, S-100 and ${\beta}$-Tubulin III were expressed. However, NSE, NeuN, Vimentin were weakly expressed in the control. Conclusion: Theses results indicate that hADSCs have the capabillity of differentiating into neuronal lineage in a specialized culture medium. hADSCs may be useful in the treatment of a wide variety of neurological disorders.