• Title/Summary/Keyword: Mitotic Activity

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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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    • v.11 no.3
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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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    • v.47 no.11
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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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    • v.46 no.6
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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.

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

  • Kim, Jung-Hee;Kim, Keun;Choi, Yong-Keel
    • Korean Journal of Microbiology
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    • v.32 no.4
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    • pp.271-279
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    • 1994
  • To develop a yeast strain which stably secretes both $\alpha$-amylase and glucoamylase and therefore is able to convert starch directly to ethanol, a mouse salivary $\alpha$-amylase cDNA gene with a yeast alcohol dehydrogenase I promoter has been introduced into the cell of a Saccharomyces diactaticus hybrid strain secreting only glucoamylase. To secrete both enzymes more stably without loss of the $\alpha$-amylase gene during a cell-multiplication, an integrating plasmid vector containing $\alpha$-amylase gene was constructed and introduced into the yeast cell. The results showed that the linearized form of the integrating vector was superior in the transformation efficiency and the rate of the expression of the $\alpha$-amylase gene than the circular type of the vector. The yeast transformant having a linearized plasmid vector exhibited higher mitotic stability than the yeast transformant habouring episomat plasmid vector. The transformant containing the linearized vector producing both $\alpha$-amylase and glucoamylase exhibited 2-3 times more amylolytic activity than the original untransformed strain secreting only glucoamylase.

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Motility Contrast Imaging for Drug Screening Applications

  • Jeong, Kwan
    • Journal of the Optical Society of Korea
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    • v.19 no.4
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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

  • Ju, Hyun-Hee;Ghil, Sung-Ho
    • Biomedical Science Letters
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    • v.14 no.2
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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
    • Environmental Mutagens and Carcinogens
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    • v.15 no.2
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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
    • Proceedings of the Korean Society of Veterinary Pathology Conference
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    • 2001.09a
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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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A Case of Epithelioid Hemangioendothelioma on the Choana (후비공에 발생한 상피모양 혈관내피종 1예)

  • Sohn, Jung Heob;Cho, Kyoung Rai
    • Journal of Rhinology
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    • v.25 no.2
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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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    • v.8 no.5
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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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