• Tuberculosis and Respiratory Diseases
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• v.82 no.3
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• pp.179-189
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• 2019

Although recent advances in molecular targeted therapy and immuno-oncology have revolutionized the landscape of lung cancer therapeutics, cytotoxic chemotherapy remains an essential component of lung cancer treatment. Extensive evidence has demonstrated the clinical benefit of chemotherapy, either alone or in combination with other treatment modalities, on survival and quality of life of patients with early and advanced lung cancer. Combinational approaches with other classes of anti-neoplastic agents and new drug-delivery systems have revealed promising data and are areas of active investigation. Chemotherapy is recommended as a standard of care in patients that have progressed after tyrosine kinase inhibitors or immune checkpoint inhibitors. Chemotherapy remains the fundamental means of lung cancer management and keeps expanding its clinical implication. This review will discuss the current position and future role of chemotherapy, and specific consideration for its clinical application in the era of precision medicine.

• Biomedical Science Letters
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• v.25 no.3
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• pp.201-210
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• 2019

The oncolytic viruses selectively infect and destroy cancer cells, not harming normal cells. The cancer cell materials released by oncolysis, like tumor antigens, stimulate host antitumor immune responses, which is a long-lasting antitumor immunity removing cancer cells in remote parts of the body by a systemic response. Oncolytic viruses armed with transgenes such as cytokines or other immune stimulating factors enhance the immune responses. The first oncolytic virus approved by US-FDA is $Imlygic^{(R)}$ targeting for melanoma. The oncolytic virus is considered as a revolutionary immunotherapy for tumors together with immune checkpoint inhibitors. A variety of oncolytic viruses are under research in the treatment of kidney cancer, liver cancer, breast cancer, and many others solid tumors. Clinical trials have shown promising results in different types of cancers. Here, we present a brief introduction of various aspects of oncolytic virus, and a review of the current status of oncolytic virus therapy development.

• BMB Reports
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• v.54 no.1
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• pp.21-30
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• 2021

Clinical trials have demonstrated that an increased number of effector cells, especially tumor-specific T cells, is positively linked with patients' prognosis. Although the discovery of checkpoint inhibitors (CPIs) has led to encouraging progress in cancer immunotherapy, the lack of either T cells or targets for CPIs is a limitation for patients with poor prognosis. Since interleukin (IL)-2 and IL-7 are cytokines that target many aspects of T-cell responses, they have been used to treat cancers. In this review, we focus on the basic biology of how these cytokines regulate T-cell response and on the clinical trials using the cytokines against cancer. Further, we introduce several recent studies that aim to improve cytokines' biological activities and find the strategy for combination with other therapeutics.

• BMB Reports
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• v.54 no.1
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• pp.70-88
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• 2021

Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resistance to immunotherapy, to expand our knowledge of advances in biomarker and therapeutics development, and to help to find the most appropriate option or a way of overcoming the resistance for cancer patients.

• Journal of Microbiology and Biotechnology
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• v.31 no.2
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• pp.171-180
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• 2021

Caffeine, a methylxanthine analog of purine bases, is a compound that is largely consumed in beverages and medications for psychoactive and diuretic effects and plays many beneficial roles in neuronal stimulation and enhancement of anti-tumor immune responses by blocking adenosine receptors in higher organisms. In single-cell eukaryotes, however, caffeine somehow impairs cellular fitness by compromising cell wall integrity, inhibiting target of rapamycin (TOR) signaling and growth, and overriding cell cycle arrest caused by DNA damage. Among its multiple inhibitory targets, caffeine specifically interacts with phosphatidylinositol 3-kinase (PI3K)-related kinases causing radiosensitization and cytotoxicity via specialized intermediate molecules. Caffeine potentiates the lethality of cells in conjunction with several other stressors such as oxidants, irradiation, and various toxic compounds through largely unknown mechanisms. In this review, recent findings on caffeine effects and cellular detoxification schemes are highlighted and discussed with an emphasis on the inhibitory interactions between caffeine and its multiple targets in eukaryotic microorganisms such as budding and fission yeasts.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.439-446
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• 2022

The antitumoral effects of valdecoxib (Val), an United States Food and Drug Administration-approved anti-inflammatory drug that was withdrawn due to the side effects of increased risk of cardiovascular adverse events, were investigated in hypopharyngeal squamous cell carcinoma cells by performing a cell viability assay, transwell assay, immunofluorescence imaging, and Western blotting. Val markedly inhibited cell viability with an IC50 of 67.3 µM after 48 h of treatment, and also downregulated cell cycle proteins such as Cdks and their regulatory cyclin units. Cell migration and invasion were severely suppressed by inhibiting integrin α4/FAK expression. In addition, Val activated the cell cycle checkpoint CHK2 in response to excessive DNA damage, which led to the activation of caspase-3/9 and induced caspase-dependent apoptosis. Furthermore, the signaling cascades of the PI3K/AKT/mTOR and mitogen-activated protein kinase pathways were significantly inhibited by Val treatment. Taken together, our results indicate that Val can be used for the treatment of hypopharyngeal squamous cell carcinoma.

• Genomics & Informatics
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• v.18 no.4
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• pp.35.1-35.7
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• 2020

Identifying the patterns of gene expression in breast cancers is essential to understanding their pathophysiology and developing anticancer drugs. Breast cancer is a heterogeneous disease with different subtypes determined by distinct biological features. Luminal breast cancer is characterized by a relatively high expression of estrogen receptor (ER) and progesterone receptor (PR) genes, which are expressed in breast luminal cells. In ~25% of invasive breast cancers, human epidermal growth factor receptor 2 (HER2) is overexpressed; these cancers are categorized as the HER2 type. Triple-negative breast cancer (TNBC), in which the cancer cells do not express ER/PR or HER2, shows highly aggressive clinical outcomes. TNBC can be further classified into specific subtypes according to genomic mutations and cancer immunogenicity. Herein, we discuss the brief history of TNBC classification and its implications for promising treatments.

• International Journal of Internet, Broadcasting and Communication
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• v.14 no.3
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• pp.8-16
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• 2022

In this paper, we propose a method of reconstructing the file system to obtain digital forensics information from the APFS file system when meta information that can know the structure of the file system is deleted due to partial damage to the disk. This method is to reconstruct the tree structure of the file system by only retrieving the B-tree node where file/directory information is stored. This method is not a method of constructing nodes based on structural information such as Container Superblock (NXSB) and Volume Checkpoint Superblock (APSB), and B-tree root and leaf node information. The entire disk cluster is traversed to find scattered B-tree leaf nodes and to gather all the information in the file system to build information. It is a method of reconstructing a tree structure of a file/directory based on refined essential data by removing duplicate data. We demonstrate that the proposed method is valid through the results of applying the proposed method by generating numbers of user files and directories.

• International Journal of Internet, Broadcasting and Communication
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• v.14 no.1
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• pp.10-18
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• 2022

Since High Sierra, APFS has been used as the main file system. It is a well-established file system that has been used stably thus far. From the perspective of digital forensics, there are still many areas to be investigated. Apple File System Reference is provided to the apple developer site, but it is not satisfactory to fully analyze APFS. Researchers know more about the structure of APFS than before, but they have not yet fully analyzed its structure to a perfect level about it. In this paper, we develop APFS object identification tool for digital forensics. The most basic and essential object identification and analysis of the APFS filesystem will be conducted with the tool. The analysis in this study serves as the background for an analysis of the checkpoint operation principle and structure, including the more complex B-tree structure of APFS. There are several options for the developed tool, but the results of two use cases will be shown here. Based on the implemented tool, it is hoped that more functions will be added to make APFS a useful tool for faster and more accurate analyses.

• Molecules and Cells
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• v.45 no.8
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• pp.513-521
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• 2022

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an immune checkpoint molecule that is mainly expressed on activated T cells and regulatory T (Treg) cells that inhibits T-cell activation and regulates immune homeostasis. Due to the crucial functions of CTLA-4 in T-cell biology, CTLA-4-targeted immunotherapies have been developed for autoimmune disease as well as cancers. CTLA-4 is known to compete with CD28 to interact with B7, but some studies have revealed that its downstream signaling is independent of its ligand interaction. As a signaling domain of CTLA-4, the tyrosine motif plays a role in inhibiting T-cell activation. Recently, the lysine motif has been shown to be required for the function of Treg cells, emphasizing the importance of CTLA-4 signaling. In this review, we summarize the current understanding of CTLA-4 biology and molecular signaling events and discuss strategies to target CTLA-4 signaling for immune modulation and disease therapy.