• 제목/요약/키워드: mitotic activity

검색결과 83건 처리시간 0.03초

Role of $^{18}F$-fluoro-2-deoxyglucose Positron Emission Tomography in Gastric GIST: Predicting Malignant Potential Pre-operatively

  • Park, Jeon-Woo;Cho, Chang-Ho;Jeong, Duck-Su;Chae, Hyun-Dong
    • Journal of Gastric Cancer
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    • 제11권3호
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    • pp.173-179
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    • 2011
  • Purpose: It is difficult to obtain biopsies from gastrointestinal stromal tumors (GISTs) prior to surgery because GISTs are submucoal tumors, despite being the most common nonepithelial neoplasms of the gastrointestinal tract. Unlike anatomic imaging techniques, PET-CT, which is a molecular imaging tool, can be a useful technique for assessing tumor activity and predicting the malignant potential of certain tumors. Thus, we aimed to evaluate the usefulness of PET-CT as a pre-operative prognostic factor for GISTs by analyzing the correlation between the existing post-operative prognostic factors and the maximum SUV uptake (SUVmax) of pre-operative 18F-fluoro-2-deoxyglucose (FDG) PET-CT. Materials and Methods: The study was conducted on 26 patients who were diagnosed with gastric GISTs and underwent surgery after being examined with pre-operative FDG PET-CT. An analysis of the correlation bewteen (i) NIH risk classification and the Ki-67 proliferation index, which are post-operative prognostic factors, and (ii) the SUVmax of PET-CT, which is a pre-operative prognostic factor, was performed. Results: There were significant correlations between (i) SUVmax and (ii) Ki-67 index, tumor size, mitotic count, and NIH risk group (r=0.854, 0.888, 0.791, and 0.756, respectively). The optimal cut-off value for SUVmax was 3.94 between "low-risk malignancy" and "high-risk malignancy" groups. The sensitivity and specificity of SUVmax for predicting the risk of malignancy were 85.7% and 94.7%, respectively. Conclusions: The SUVmax of PET-CT is associated with Ki-67 index, tumor size, mitotic count, and NIH classification. Therefore, it is believed that PET-CT is a relatively safe, non-invasive diagnostic tool for assessing malignant potential pre-operatively.

Aurora-A kinase-inactive mutants disrupt the interaction with Ajuba and cause defects in mitotic spindle formation and G2/M phase arrest in HeLa cells

  • Bai, Meirong;Ni, Jun;Shen, Suqin;Huang, Qiang;Wu, Jiaxue;Le, Yichen;Yu, Long
    • BMB Reports
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    • 제47권11호
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    • pp.631-636
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    • 2014
  • Aurora-A is a centrosome-localized serine/threonine kinase that is overexpressed in multiple human cancers. We previously reported an intramolecular inhibitory regulation of Aurora-A between its N-terminal regulatory domain (Nt, amino acids [aa] 1-128) and the C-terminal catalytic domain (Cd, aa 129-403). Here, we demonstrate that although both Aurora-A mutants (AurA-K250G and AurA-D294G/Y295G) lacked interactions between the Nt and Cd, they also failed to interact with Ajuba, an essential activator of Aurora-A, leading to loss of kinase activity. Additionally, overexpression of either of the mutants resulted in centrosome amplification and mitotic spindle formation defects. Both mutants were also able to cause G2/M arrest and apoptosis. These results indicate that both K250 and D294/Y295 are critical for direct interaction between Aurora-A and Ajuba and the function of the Aurora-A complex in cell cycle progression.

Microtubule Acetylation-Specific Inhibitors Induce Cell Death and Mitotic Arrest via JNK/AP-1 Activation in Triple-Negative Breast Cancer Cells

  • Suyeon Ahn;Ahreum Kwon;Youngsoo Oh;Sangmyung Rhee;Woo Keun Song
    • Molecules and Cells
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    • 제46권6호
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    • pp.387-398
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    • 2023
  • Microtubule acetylation has been proposed as a marker of highly heterogeneous and aggressive triple-negative breast cancer (TNBC). The novel microtubule acetylation inhibitors GM-90257 and GM-90631 (GM compounds) cause TNBC cancer cell death but the underlying mechanisms are currently unknown. In this study, we demonstrated that GM compounds function as anti-TNBC agents through activation of the JNK/AP-1 pathway. RNA-seq and biochemical analyses of GM compound-treated cells revealed that c-Jun N-terminal kinase (JNK) and members of its downstream signaling pathway are potential targets for GM compounds. Mechanistically, JNK activation by GM compounds induced an increase in c-Jun phosphorylation and c-Fos protein levels, thereby activating the activator protein-1 (AP-1) transcription factor. Notably, direct suppression of JNK with a pharmacological inhibitor alleviated Bcl2 reduction and cell death caused by GM compounds. TNBC cell death and mitotic arrest were induced by GM compounds through AP-1 activation in vitro. These results were reproduced in vivo, validating the significance of microtubule acetylation/JNK/AP-1 axis activation in the anti-cancer activity of GM compounds. Moreover, GM compounds significantly attenuated tumor growth, metastasis, and cancer-related death in mice, demonstrating strong potential as therapeutic agents for TNBC.

전분발효 효모에서의 외래 $\alpha$-Amylase 유전자의 세포분열시 안정성 증진 (Mitotic Stability of Heterologous $\alpha$-Amylase Gene in Starch-Fermenting Yeast)

  • 김정희;김근;최영길
    • 미생물학회지
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    • 제32권4호
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    • pp.271-279
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    • 1994
  • ${\alpha}$-Amylase와 glucoamylase를 동시에 안정하게 분비하여 전분을 일단계로 직접 에탄올로 발효시킬수 있는 효모 균주를 개발하기 위하여 glucoamylase를 분비하는 Saccharomyces diastaticus hybrid 균주에 쥐의 침샘 유래의 ${\alpha}$-amylase cDNA 유전자를 plasmid vector를 이용하여 도입하였다. 이 균주로부터 효소생산에 필요한 유전자를 잃어버림이 없이 안정하게 분비할 수 있도록 하기 위하여 $\alpha$-amylase 유전자를 효모의 염색체에 삽입시키기 위한 integrating plasmid vector인 YIpMS$\Delta$R(LEU2)를 제작하였다. 이 vector의 효모형질전환에 있어 원형(circular)상태와 제한 효소 XbaI으로 처리된 직선화된(linearized) 상태의 두가지 형태를 비교한 결과 형질전환 효율에서나 형질전환체내의 $\alpha$-amylase 유전자 보유정도가 모두 직선화된 형태의 경우가 원형상태의 경우보다 높았다. Linearized vecotr를 가진 효모 형질전환체에서의 유전자 발현 안정도는 세포분열을 거듭할수록 episomal vecotr에 의한 효모 형질전환체에서의 발현 안정도보다 우수하게 나타났다. 또한 이 linearized vector를 가진 형질전환체는 $\alpha$-amylase와 glucoamylase를 동시에 분비하여 glucoamylase만 분비하는 원균주보다 2배 이상의 전분분해력을 보였다.

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Motility Contrast Imaging for Drug Screening Applications

  • Jeong, Kwan
    • Journal of the Optical Society of Korea
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    • 제19권4호
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    • pp.382-389
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    • 2015
  • Motility contrast imaging is a coherence-domain imaging technique that uses cellular motility as a fully endogenous imaging contrast agent. Motility is measured inside tissue using a digital holographic coherence gate that extracts dynamic speckle from fixed depths. The dynamic speckle arises from the normal organelle motion inside cells, and from the movement of the cellular membranes driven by the cytoskeleton. It measures cellular activity and the effects of temperature and osmolarity. Motion is sensitive to cytoskeletal drugs, such as the antimitotic drugs used for cancer chemotherapy, and the effects of drug combinations also can be monitored. Motility contrast imaging is a potential tissue-based assay platform for highthroughput screening of pharmaceuticals.

Protein Kinase A Increases DNA-Binding Activity of Testis-Brain RNA-Binding Protein

  • ;길성호
    • 대한의생명과학회지
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    • 제14권2호
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    • pp.77-81
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    • 2008
  • Testis brain RNA-binding protein (TB-RBP) is a DNA/RNA binding protein. TB-RBP is mainly expressed in testis and brain and highly conserved protein with several functions, including chromosomal translocations, DNA repair, mitotic cell division, and mRNA transport, stabilization, and storage. In our previous study, we identified TB-RBP as an interacting partner for the catalytic subunit $(C{\alpha})$ of protein kinase A(PKA) and verified their interaction with several biochemical analyses. Here, we confirmed interaction between $C{\alpha}$. and TB-RBP in mammalian cells and determined the effect of $C{\alpha}$. on the function of TB-RBP. The activation of $C{\alpha}$. increased the TB-RBP function as a DNA-binding protein. These results suggest that the function of TB-RBP can be modulated by PKA and provide insights into the diverse role of PKA.

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Genotoxicity of Capsaicin in Cultured Human Lymphocytes

  • Lee, Sang-Sup;Park, Young-Ho;Sohn, Yeowon;Ryu, Soo-Jung;Surh, Young-Joon
    • 한국환경성돌연변이발암원학회지
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    • 제15권2호
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    • pp.81-87
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    • 1995
  • The clastogenic activity of capsaicin, a major pungent and irritating constituent of hot chili pepper, was evaluated in cultured human lymphocytes. Capsaicin (125, 250, and 500 $\mu$M) caused cytogenetic damage as determined by increased frequency of chromosome/chromatid aberrations compared to the solvent control. The mitotic indices were also decreased in a concentration-related manner in capsaicin-treated cells. Moreover, capsaicin suppressed [$^3$]thymidine incorporation into lymphocytes. The clastogenicity and cytotoxicity of capsaicin towards human lymphocytes were evident without an external metabolic activation system. Taken together, these findings suggest that capsaicin is a genotoxic agent and may thus represent a potential health hazard in humans.

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Ductular mammary carcinoma in a lioness

  • L Kolodzieyski;Lim, C-W;Kim, Y-J;Rim, B-M
    • 한국수의병리학회:학술대회논문집
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    • 한국수의병리학회 2001년도 추계학술대회 및 정기총회
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    • pp.29-29
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    • 2001
  • Well bordered solid enlarged 16.7x9.7x8 cm in the size neoplasma was found in a 7-year-old lioness without any clinical signs of diseases in Chonju city zoo and surgically removed. Simple lobes were separated by pale gray yellowish fibrous tissue. The tumor parenchyma was yellowish with numerous cysts, necrotic foci and hemorrhages. Histologically neoplasma was composed of cell nests different in the size and shape with high mitotic activity. Slow invasive spreading on the border was observed. Formation of the narrow ductular lumina bordered the flattened cells leading to keratinization was seen in some places. It was noted by supplemental clinical investigations, that the tumor did not metastasized to other organs. This tumor is considered to be a sample of a malignant tumor without metastatic spreading and was note described in literature yet.

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후비공에 발생한 상피모양 혈관내피종 1예 (A Case of Epithelioid Hemangioendothelioma on the Choana)

  • 손정협;조경래
    • Journal of Rhinology
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    • 제25권2호
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    • pp.118-122
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    • 2018
  • Epithelioid hemangioendothelioma is a rare vascular tumor with intermediate malignity and metastasis risk. It presents epithelioid cells with intracytoplasmic vacuoles and low mitotic activity. Its vascular nature can be confirmed by immunohistochemical studies (vimentin, CD31, CD34, and factor VIII). It is extremely rare in the nasal cavity, with only one case reported on the middle turbinate in Korea. The authors present a case of epithelioid hemangioendothelioma on the choana with a size of 2mm, which easily coult have been misdiagnosed as a blood clot.

Development of Cellobiose-utilizing Recombinant Yeast for Ethanol Production from Cellulose Hydrolyzate

  • Pack, Seung-Pil;Cho, Kwang-Myung;Kang, Hyen-Sam;Yoo, Young-Je
    • Journal of Microbiology and Biotechnology
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    • 제8권5호
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    • pp.441-448
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    • 1998
  • A cellobiose-utilizing recombinant yeast having $\beta$-glucosidase activity was developed for ethanol production from a mixture of glucose and cellobiose. Using $\delta$-sequences of Tyl transposon of yeast as target sites for homologous recombination, a heterologous gene of $\beta$-glucosidase was integrated into the chromosome of Saccharomyces cerevisiae. The $\delta$-integrated recombinant yeast, Saccharomyces cerevisiae L2612 (Pb-BGL), showed perfect mitotic stability even in nonselective media and showed ca. 1.5 fold higher $\beta$-glucosidase activity than the recombinant yeast harboring the $2\mu$-based plasmid vector system. A mathematical model was developed to describe the $\beta$-glucosidase formation and ethanol production from the Saccharomyces cerevisiae L2612 ($p\delta-BGL$). The model newly described that the heterologous $\beta$-glucosidase production mediated by ADH1 promoter is regulated by glucose and repressed by ethanol.

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