• 제목/요약/키워드: Triple negative

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Anticancer Effects of the Hsp90 Inhibitor 17-Demethoxy-Reblastatin in Human Breast Cancer MDA-MB-231 Cells

  • Zhao, Qing;Wu, Cheng-Zhu;Lee, Jae Kyoung;Zhao, Su-Rong;Li, Hong-Mei;Huo, Qiang;Ma, Tao;Zhang, Jin;Hong, Young-Soo;Liu, Hao
    • Journal of Microbiology and Biotechnology
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    • v.24 no.7
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    • pp.914-920
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    • 2014
  • Triple-negative breast cancer (TNBC) possesses a higher rate of distant recurrence and a poorer prognosis than other breast cancer subtypes. Interestingly, most of the heat shock protein 90 (Hsp90) client proteins are oncoproteins, and some are closely related to unfavorable factors of TNBC patients. 17-Demethoxy-reblastatin (17-DR), a novel non-benzoquinone-type geldanamycin analog, exhibited potent Hsp90 ATPase inhibition activity. In this study, the anticancer effects of 17-DR on TNBC MDA-MB-231 cells were investigated. These results showed that 17-DR inhibited cell proliferation, induced apoptosis, and suppressed cell invasion and migration in the MDA-MB-231 cells. Down-regulation of the key Hsp90-dependent tumor-driving molecules, such as RIP1 and MMP-9, by 17-DR may be related to these effects. Taken together, our results suggest that 17-DR has potential as a therapeutic agent for the treatment of TNBC.

All rants and no substance?: A new framework for studying the rationality of cyberspace

  • Soon, Carol;How, Tan Tarn
    • Journal of Contemporary Eastern Asia
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    • v.16 no.2
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    • pp.20-43
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    • 2017
  • While the Internet has been used to galvanise people for the collective good, many have voiced concerns over the noise and vitriol present online and polarisation. In Singapore where the government regulates traditional mainstream media such as print and broadcast, the online space has been described as a "Wild Wild West" rife with rumours, untruths and misinformation. Such developments do not only exert a potential negative effect on the deliberative nature of public discourse but also skew bias towards the online space, affecting the ability of online users to communicate with authority and power. This study seeks to examine the rationality of the cyberspace through using a new "rationality" framework to analyse political discourse online. Comprising objectivity, emotionality and partisanship, the rationality framework was applied to a content analysis of 197 blogs with political content in 2014. The analysis indicated that the online political space was not the Wild Wild West that it was touted to be with significant levels of objectivity and non-partisanship. There was a stark absence of emotional discourse, and relationships were observed between bloggers' anonymity and rationality. Cognisant of academia's and policymakers' interest on the quality and effects of online discourse, the proposed analytical framework and the study findings hold implications for both developed and developing countries.

Backbone NMR Assignments of an Uncharacterized Protein, SF1002 from Shigella flexneri 5a M90T

  • Lee, Yoo-Sup;Yoon, Won-Su;Chung, Il;Chung, Ka Young;Won, Hyung-Sik;Seo, Min-Duk
    • Journal of the Korean Magnetic Resonance Society
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    • v.19 no.1
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    • pp.36-41
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    • 2015
  • The causative agent of shigellosis, Shigella flexneri, is a Gram-negative anaerobic bacterial pathogen that causes one of the most infectious bacterial dysenteries in humans. It originates infection by invading cells of the colonic epithelium using a type III secretion system. Despite S. flexneri is closely linked with the human disease, structural study is very deficient. Here, we have initiated NMR study of SF1002 which is the uncharacterized protein from S. flexneri strain 5a M90T. Based on a series of triple resonance spectra, sequence-specific assignments of the backbone amide resonances of SF1002 could be completed. This NMR study would contribute to the structural genomics of S.flexneri.

Framing North Korea on Twitter: Is Network Strength Related to Sentiment?

  • Kang, Seok
    • Journal of Contemporary Eastern Asia
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    • v.20 no.2
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    • pp.108-128
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    • 2021
  • Research on the news coverage of North Korea has been paying less attention to social media platforms than to legacy media. An increasing number of social media users post, retweet, share, interpret, and set agendas on North Korea. The accessibility of international users and North Korea's publicity purposes make social media a venue for expression, news diversity, and framing about the nation. This study examined the sentiment of Twitter posts on North Korea from a framing perspective and the relationship between network strengths and sentiment from a social network perspective. Data were collected using two tools: Jupyter Notebook with Python 3.6 for preliminary analysis and NodeXL for main analysis. A total of 11,957 tweets, 10,000 of which were collected using Python and 1,957 tweets using NodeXL, about North Korea between June 20-21, 2020 were collected. Results demonstrated that there was more negative sentiment than positive sentiment about North Korea in the sampled Twitter posts. Some users belonging to small network sizes reached out to others on Twitter to build networks and spread positive information about North Korea. Influential users tended to be impartial to sentiment about North Korea, while some Twitter users with a small network exhibited high percentages of positive words about North Korea. Overall, marginalized populations with network bonding were more likely to express positive sentiment about North Korea than were influencers at the center of networks.

Indirubin-3-monoxime Prevents Tumorigenesis in Breast Cancer through Inhibition of JNK1 Activity

  • Kim, Mi-Yeon;Jo, Eun-Hye;Kim, Yong-Chul;Park, Hee-Sae
    • Biomedical Science Letters
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    • v.27 no.3
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    • pp.134-141
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    • 2021
  • c-Jun N-terminal kinases (JNKs) have a Janus face, regulating both cell apoptosis and survival. The present study focused on understanding the function of JNK in tumor development and the chemoresistance underlying JNK-mediated cancer cell survival. We identified an inhibitor of JNK1, an important regulator of cancer cell survival. Kinase assay data showed that JNK1-dependent c-Jun phosphorylation was inhibited by indirubin derivatives. In particular, indirubin-3-monoxime (I3M) directly inhibited the phosphorylation of c-Jun in vitro, with a half inhibition dose (IC50) of 10 nM. I3M had a significant inhibitory effect on JNK1 activity. Furthermore, we carried out assays to determine the viability, migration, and proliferation of breast cancer cells. Our results demonstrated that cell growth, scratched wound healing, and colony forming abilities were inhibited by the JNK inhibitor SP600125 and I3M. The combination of SP600125 and I3M significantly decreased cancer cell proliferation, compared with either SP600125 or I3M alone. Our studies may provide further support for JNK1-targeting cancer therapy using the indirubin derivative I3M in breast cancer.

Anti-cancer Effect of Apigenin on Human Breast Carcinoma MDA-MB-231 through Cell Cycle Arrest and Apoptosis

  • Lee, Hwan Hee;Cho, Hyosun
    • Microbiology and Biotechnology Letters
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    • v.47 no.1
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    • pp.34-42
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    • 2019
  • Apigenin, a common natural product that is found in many plants and vegetables, has been reported to have many biological activities, including antioxidative, anti-inflammatory, and anticancer effects. The triple-negative breast carcinoma cell line MDA-MB-231 is known to be highly invasive and resistant to chemotherapy. In this study, we investigated the anticancer effect of apigenin on human MDA-MB-231 cells. First, the cytotoxicity of apigenin toward MDA-MB-231 cells was analyzed by MTT assay. Then, the cell cycle and apoptotic effects of apigenin were examined, and the molecular mechanism underlying its anticancer activity was explored. Apigenin inhibited the growth of the cells in a dose-dependent manner, correlating with the cell cycle arrest at the G2-M phase as well as an increase of early apoptosis. The cell-cycle inhibitory effect was highly associated with the increased expression of p21 and decreased expression of CDK6, cyclin D1, and cyclin B1. The induction of apoptosis by apigenin was associated with the upregulated expression of cleaved PARP and cleaved caspase-3, -7, and -9.

Breast Tumor Cell Nuclei Segmentation in Histopathology Images using EfficientUnet++ and Multi-organ Transfer Learning

  • Dinh, Tuan Le;Kwon, Seong-Geun;Lee, Suk-Hwan;Kwon, Ki-Ryong
    • Journal of Korea Multimedia Society
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    • v.24 no.8
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    • pp.1000-1011
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    • 2021
  • In recent years, using Deep Learning methods to apply for medical and biomedical image analysis has seen many advancements. In clinical, using Deep Learning-based approaches for cancer image analysis is one of the key applications for cancer detection and treatment. However, the scarcity and shortage of labeling images make the task of cancer detection and analysis difficult to reach high accuracy. In 2015, the Unet model was introduced and gained much attention from researchers in the field. The success of Unet model is the ability to produce high accuracy with very few input images. Since the development of Unet, there are many variants and modifications of Unet related architecture. This paper proposes a new approach of using Unet++ with pretrained EfficientNet as backbone architecture for breast tumor cell nuclei segmentation and uses the multi-organ transfer learning approach to segment nuclei of breast tumor cells. We attempt to experiment and evaluate the performance of the network on the MonuSeg training dataset and Triple Negative Breast Cancer (TNBC) testing dataset, both are Hematoxylin and Eosin (H & E)-stained images. The results have shown that EfficientUnet++ architecture and the multi-organ transfer learning approach had outperformed other techniques and produced notable accuracy for breast tumor cell nuclei segmentation.

C-Reactive Protein Signaling Pathways in Tumor Progression

  • Eun-Sook Kim;Sun Young Kim;Aree Moon
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.473-483
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    • 2023
  • Many cancers arise from sites of chronic inflammation, which creates an inflammatory microenvironment surrounding the tumor. Inflammatory substances secreted by cells in the inflammatory environment can induce the proliferation and survival of cancer cells, thereby promoting cancer metastasis and angiogenesis. Therefore, it is important to identify the role of inflammatory factors in cancer progression. This review summarizes the signaling pathways and roles of C-reactive protein (CRP) in various cancer types, including breast, liver, renal, and pancreatic cancer, and the tumor microenvironment. Mounting evidence suggests the role of CRP in breast cancer, particularly in triple-negative breast cancer (TNBC), which is typically associated with a worse prognosis. Increased CRP in the inflammatory environment contributes to enhanced invasiveness and tumor formation in TNBC cells. CRP promotes endothelial cell formation and angiogenesis and contributes to the initiation and progression of atherosclerosis. In pancreatic and kidney cancers, CRP contributes to tumor progression. In liver cancer, CRP regulates inflammatory responses and lipid metabolism. CRP modulates the activity of various signaling molecules in macrophages and monocytes present in the tumor microenvironment, contributing to tumor development, the immune response, and inflammation. In the present review, we overviewed the role of CRP signaling pathways and the association between inflammation and cancer in various types of cancer. Identifying the interactions between CRP signaling pathways and other inflammatory mediators in cancer progression is crucial for understanding the complex relationship between inflammation and cancer.

Emodin Attenuates Inflammasome Activation Induced by Helicobacter pylori Infection through Inhibition of VacA Translocation

  • Thach Phan Van;Anh Duy Do
    • Microbiology and Biotechnology Letters
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    • v.51 no.4
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    • pp.507-516
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    • 2023
  • Eradication of Helicobacter pylori infection is an essential strategy to decrease the risk of developing gastric cancer. However, the standard triple therapy has negative aspects associated with side effects and the emergence of antibiotic resistance. Therefore, alternative therapies are required to enhance the management of H. pylori infection effectively. In this study we examined the effect of emodin on the amelioration of inflammatory response due to H. pylori infection. Our results indicated that emodin treatment effectively decreased the expression of virulence genes, including sabA, vacA, cagL, cagA, sabA, and suppressed the adhesion ability of H. pylori to AGS cells. Emodin has been shown inhibitory effects on the inflammasome pathway through reductions in VacA translocation, lowering ROS stress, cleaved Caspase-1, NLRP3, and cleaved Gasdermin D levels, thereby lowered pyroptosis in infected cells. In summary, our study demonstrated that emodin has the ability to attenuate inflammation caused by H. pylori by modulating virulence gene expression and decreasing VacA translocation. Further study is required to evaluate the therapeutic efficacy of emodin in treating H. pylori infection and better understand the underlying mechanisms.

A Study on BRCA1/2 Mutations, Hormone Status and HER-2 Status in Korean Women with Early-onset Breast Cancer (젊은 한국인 유방암 환자에서 BRCA1/2 돌연변이와 호르몬 수용체, HER-2 상태에 관한 연구)

  • Choi, Doo-Ho;Jin, So-Young;Lee, Dong-Wha;Kim, Eun-Seog;Kim, Yong-Ho
    • Radiation Oncology Journal
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    • v.26 no.1
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    • pp.65-73
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    • 2008
  • Purpose: Women with breast cancer diagnosed at an age of 40 years or younger have a greater prevalence of germline BRCA1 and BRCA2 mutations than the prevalence of women with breast cancer diagnosed at older ages. Several immunohistochemical characteristics have been identified in breast cancers from studies of Caucasian women with BRCA1/2 mutations having familial or early-onset breast cancers. The aim of this study is to determine whether early-onset breast cancer in BRCA1 or BRCA2 mutation carriers, who were not selected from a family history, could be distinguished by the use of immunohistochemical methods and could be distinguished from breast cancer in women of a similar age without a germline BRCA1 or BRCA2 mutation. We also analyzed the prognostic difference between BRCA1/2 related and BRCA1/2 non-related patients by the use of univariate and multivariate analysis. Materials and Methods: Breast cancer tissue specimens from Korean women with early-onset breast cancers were studied using a tumor tissue microarray. Immunohistochemical staining of estrogen receptor(ER), progesterone receptor(PR) and HER-2, as well as the histology and grade of these specimens, were compared. The prognostic impact of immunohistochemical and histological factors as well as the BRCA1/2 mutation status was investigated separately. Results: There were 14 cases and 16 deleterious BRCA1/2 mutations among 101 patients tested. A family history(4/14) and bilateral breast cancers(3/9) were high risk factors for BRCA1/2 mutations. BRCA1/2-associated cancers demonstrated more expression of ER-negative(19.4% versus 5.1%, p=0.038) and HER-2 negative than BRCA1/2 negative tumors, especially for tumors with BRCA1 tumors The BRCA1/2 mutation rate for patients with triple negative tumors(negative expression of ER, PR and HER-2) was 24.2%. Tumor size, nodal status, and HER-2 expression status were significantly associated with disease free survival, as determined by univariate and multivariate analysis, but the BRCA1/2 status was not a prognostic factor. Conclusion: Breast cancer that occurs in women with a germline BRCA1 or BRCA2 mutations have recognizable immunohistochemical features, which may be useful in identifying individuals that are more likely to carry germline mutations. Although the BRCA1/2 mutation status was not a prognostic factor in Korean women with early-onset breast cancer, more cases with a longer follow-up period are needed for further study.