• Journal of Yeungnam Medical Science
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• v.37 no.3
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• pp.230-235
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• 2020

Systemic therapy for metastatic triple-negative breast cancer (TNBC) still remains challenging because there are no targeted agents or endocrine therapies currently available. The present case report documents the successful use of cisplatin monotherapy to manage a heavily pretreated TNBC patient showing poor response to therapy. The patient was a 51-year-old woman who had already undergone several lines of systemic chemotherapy for widespread TNBC. Although the mutation analysis performed on DNA isolated from blood cells and progressed lesion samples confirmed the tumor to be germline BRCA wild-type, cisplatin monotherapy was administered based on the increasing evidence of safety and efficacy of platinum for breast cancer. After three cycles of cisplatin treatment, the patient's metastatic lesions dramatically improved without any major toxicity, and she completed 17 cycles with good response. This case study indicates that patients with heavily pretreated TNBC can potentially achieve a good response to cisplatin monotherapy.

• Journal of Microbiology and Biotechnology
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• v.29 no.4
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• pp.571-576
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• 2019

Microenvironmental stress, which is naturally observed in solid tumors, has been implicated in anticancer drug resistance. This tumor-specific stress causes the degradation of topoisomerase $II{\alpha}$, rendering cells resistant to topoisomerase $II{\alpha}$-targeted anticancer agents. In addition, microenvironmental stress can induce the overexpression of 78kDa glucose regulated protein (GRP78), which can subsequently block the activation of apoptosis induced by treatment with anticancer agents. Therefore, inhibition of topoisomerase $II{\alpha}$ degradation and reduction in GRP78 expression may be effective strategies for inhibiting anticancer drug resistance. In this study, we investigated the active compound arctigenin, which inhibited microenvironmental stress-induced etoposide resistance in HT-29 cells. Arctigenin was also highly toxic to etoposide-resistant HT-29 cells, with an $IC_{50}$ value of $10{\mu}M$ for colony formation. We further showed that arctigenin inhibited the degradation of topoisomerase $II{\alpha}$ and reduced the expression of GRP78. Thus, these results suggest that arctigenin is a novel therapeutic agent that inhibits resistance to etoposide associated with microenvironmental stress conditions.

• IMMUNE NETWORK
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• v.22 no.1
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• pp.10.1-10.17
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• 2022

Systemic autoimmune diseases arise from loss of self-tolerance and immune homeostasis between effector and regulator functions. There are many therapeutic modalities for autoimmune diseases ranging from conventional disease-modifying anti-rheumatic drugs and immunosuppressants exerting nonspecific immune suppression to targeted agents including biologic agents and small molecule inhibitors aiming at specific cytokines and intracellular signal pathways. However, such current therapeutic strategies can rarely induce recovery of immune tolerance in autoimmune disease patients. To overcome limitations of conventional treatment modalities, novel approaches using specific cell populations with immune-regulatory properties have been attempted to attenuate autoimmunity. Recently progressed biotechnologies enable sufficient in vitro expansion and proper manipulation of such 'tolerogenic' cell populations to be considered for clinical application. We introduce 3 representative cell types with immunosuppressive features, including mesenchymal stromal cells, Tregs, and myeloid-derived suppressor cells. Their cellular definitions, characteristics, mechanisms of immune regulation, and recent data about preclinical and clinical studies in systemic autoimmune diseases are reviewed here. Challenges and limitations of each cell therapy are also addressed.

• Korean Circulation Journal
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• v.52 no.3
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• pp.173-197
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• 2022

Treatment options for patients with heart failure (HF) with reduced ejection fraction (HFrEF) have expanded considerably over the past few decades. Whereas neurohormonal modulation remains central to the management of patients with HFrEF, other pathways have been targeted with drugs that have novel mechanisms of action. The angiotensin receptor-neprilysin inhibitors (ARNIs) which enhance levels of compensatory molecules such as the natriuretic peptides while simultaneously providing angiotensin receptor blockade have emerged as the preferred strategy for inhibiting the renin angiotensin system. Sodium glucose cotransporter 2 (SGLT2) inhibitors which were developed as hypoglycemic agents have been shown to improve outcomes in patients with HF regardless of their diabetic status. These agents along with beta blockers and mineralocorticoid receptor antagonists are the core medical therapies for patients with HFrEF. Additional approaches using ivabradine to slow heart rate in patients with sinus rhythm, the hydralazine/isosorbide dinitrate combination to unload the heart, digoxin to provide inotropic support and vericiguat to augment cyclic guanosine monophosphate production have been shown in well-designed trials to have beneficial effects in the HFrEF population and are used as adjuncts to the core therapies in selected patients. This review provides an overview of the medical management of patients with HFrEF with focus on the major developments that have taken place in the field. It offers prospective of how these drugs should be employed in clinical practice and also a glimpse into some strategies that may prove to be useful in the future.

• Journal of the Economic Geographical Society of Korea
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• v.22 no.4
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• pp.381-404
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• 2019

The paper aims to identify how North Korean various economic agents respond to the economic crisis in North Korea, and how these multiple practices are entangled with its spatiality by through the questionnaire survey and in-depth interview targeted at North Korean refugees. The paper argues that it needs to examine the marketization in North Korea in terms of the domesticating recently debated in economic geography. In this perspective, the marketization in North Korea could be explained not as a grand project 'out there' with hegemonic power, but as various economic agents within their space are constantly (re)constructed through everyday life practices. Economic agents' responses to economic crisis, economic rupture, and economic marginalization could be identified in terms of articulation between economic and non-economic factors. More specifically, the paper emphasizes everyday life responses are over-determined by their economic and non-economic factors and its effectiveness is differentiated by their power relations.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7261-7266
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• 2015

Breast cancer, the most common cancer in the women, is the leading cause of death. Necrotic signaling pathways will enable targeted therapeutic agents to eliminate apoptosis-resistant cancer cells. In the present study, the effect of shikonin on the induction of cell necroptosis or apoptosis was evaluated using the T-47D breast cancer cell line. The cell death modes, caspase-3 and 8 activities and the levels of reactive oxygen species (ROS) were assessed. Cell death mainly occurred through necroptosis. In the presence of Nec-1, caspase-3 mediated apoptosis was apparent in the shikonin treated cells. Shikonin stimulates ROS generation in the mitochondria of T-47D cells, which causes necroptosis or apoptosis. Induction of necroptosis, as a backup-programmed cell death pathway via ROS stimulation, offers a new strategy for the treatment of breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1693-1698
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• 2015

The heterogeneous nature of lung cancer has become increasingly apparent since introduction of molecular classification. In general, advanced lung cancer is an aggressive malignancy with a poor prognosis. Activating alterations in several potential driver oncogenic genes have been identified, including EGFR, ROS1 and ALK and understanding of their molecular mechanisms underlying development, progression, and survival of lung cancer has led to the design of personalized treatments that have produced superior clinical outcomes in tumours harbouring these mutations. In light of the tsunami of new biomarkers and targeted agents, next generation sequencing testing strategies will be more appropriate in identifying the patients for each therapy and enabling personalized patients care. The challenge now is how best to interpret the results of these genomic tests, in the context of other clinical data, to optimize treatment choices. In genomic era of cancer treatment, the traditional one-size-fits-all paradigm is being replaced with more effective, personalized oncologic care. This review provides an overview of lung cancer genomics and personalized treatment.

• Toxicological Research
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• v.17
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• pp.89-96
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• 2001

Recently, considerable attention has been focused on the role of cyclooxygenase-2 (COX-2) in the carcinogenesis as well as in inflammation. Improperly overexpressed COX-2 has been observed in many types of human cancers and transformed cells in culture. Thus, it is conceivable that targeted inhibition of abnormally or improperly up-regulated COX-2 provides one of the most effective and promising strategies for cancer prevention. A ubiquitous eukaryotic transcription factor, NF-kB is considered to be involved in regulation of COX-2 expression. Furthermore, extracellular-regulated protein kinase and p38 mitogen-activated protein (MAP) kinase appear to be key elements of the intracellular signaling cascades involved in NF-kB activation in response to a wide array of external stimuli. Certain chemopreventive phytochemicals suppress activation of NF-kB by blocking one or more of the MAP kinases, which may contribute to their inhibitory effects on COX-2 induction. One of the plausible mechanisms by which chemopreventive phytochemicals inhibit NF-kB activation involves suppression of degradation of the inhibitory unit I kB, which hampers subsequent translocation of p65, the functionally active subunit of NF-kB.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.4843-4847
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• 2015

To date, cytotoxic effects of flavonoids in various cancer cells are well accepted. However, the intracellular signaling cascades triggered by these natural compounds remain largely unknown and elusive. In this mini-review, the multiplicity of molecular targets of flavonoids in blood cancer cells is discussed by demonstrating the involvement of various signaling pathways in induction of apoptotic responses. Although these data reveal a great potential of flavonoids for the development of novel agents against different types of hematological malignancies, the pleiotropic nature of these compounds in modulation of cellular processes and their interactions certainly need unraveling and further investigation.

• Proceedings of the Materials Research Society of Korea Conference
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• 2012.05a
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• pp.55.1-55.1
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• 2012

In the first part of this talk, I will introduce an effort to use gold nanoparticles and UO22+ (uranyl) specific DNAzyme for development of highly sensitive and selective colorimetric uranyl sensors. In addition, I will discuss how DNA aptamers can be delivered by nanoparticles to cancer cell nucleus and released by ultrafast femtosecond pulsed laser for targeted cancer therapy. Finally, I will show how proteins such as streptavidin and myoglobin, or nanoparticles can be precisely aligned on DNA with nanometer resolution via backbone-modified phosphorothioate DNA and bifunctional linkers. These interesting functional and structural properties of DNA can provide new opportunities to develop dynamic DNA structures for potential use as intracellular sensors and drug delivery agents.