• Bulletin of the Korean Chemical Society
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• v.34 no.11
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• pp.3345-3349
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• 2013

Hsp90 shows great promise as a therapeutic target due to its potential to disable multiple signaling pathways simultaneously. In this study, we discovered that a natural product, butein moderately inhibited the growth of drug-resistant cancer cells (A2780cis and H1975), and brought about the degradation of oncogenic Hsp90 client proteins. The study demonstrated that butein would be a therapeutic lead to circumvent drug-resistance in cancer chemotherapy. The structure-based screening, synthesis, and biological evaluation of butein are described herein.

• Development and Reproduction
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• v.27 no.4
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• pp.167-174
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• 2023

Development of hepatocellular carcinoma (HCC) is driven by a multistep and long-term process. Because current therapeutic strategies are limited for HCC patients, there are increasing demands for understanding of immunotherapy, which has made technological and conceptual innovations in the treatment of cancer. Here, I discuss HCC immunotherapy in the view of interaction between liver resident cells and immune cells.

• Journal of the Korea Society of Computer and Information
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• v.21 no.3
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• pp.65-71
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• 2016

To reduce the expenses for development a novel drug, systems biology has been studied actively. Target prediction, a part of systems biology, contributes to finding a new purpose for FDA(Food and Drug Administration) approved drugs and development novel drugs. In this paper, we propose a classification model for predicting novel target genes based on relation between target genes and disease related genes. After collecting known target genes from TTD(Therapeutic Target Database) and disease related genes from OMIM(Online Mendelian Inheritance in Man), we analyzed the effect of target genes on disease related genes based on PPI(Protein-Protein Interactions) network. We focused on the distinguishing characteristics between known target genes and random target genes, and used the characteristics as features for building a classifier. Because our model is constructed using information about only a disease and its known targets, the model can be applied to unusual diseases without similar drugs and diseases, while existing models for finding new drug-disease associations are based on drug-drug similarity and disease-disease similarity. We validated accuracy of the model using LOOCV of ten times and the AUCs were 0.74 on Alzheimer's disease and 0.71 on Breast cancer.

• Journal of Life Science
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• v.28 no.6
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• pp.753-763
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• 2018

Cysteine cathepsins are lysosomal enzymes that belong to the papain family and can induce the degradation of damaged proteins through the endo-lysosomal pathway. It is highly upregulated in many cancers by regulating gene amplification and transcriptional, translational, and post-transcriptional modifications. Cathepsin S is part of the cysteine cathepsin family. Many studies have demonstrated that cathepsin S not only plays a specific role in MHC class II antigen presentation but also plays a crucial role in cancers. Cathepsin S is more stable at a neutral pH compared to other cysteine cathepsins, which supports the importance of cathepsin S in disease microenvironments. Therefore, the dysregulation of cathepsin S has participated in a variety of pathological processes, including cancer, arthritis, and cardiovascular disease. Furthermore, a decrease or depletion in the expression of cathepsin S has been implicated in the processes of tumor growth, invasion, metastasis, and angiogenesis. Taken together, cathepsin S has been suggested as an attractive therapeutic target for cancer therapy. In this review, the known involvement of cathepsin S in diseases, particularly with respect to recent work indicating its role in cancer therapy, is examined. An overview of current literature on the inhibitors of cathepsin S as a therapeutic target for cancer is also provided.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9459-9465
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• 2014

Background: Structural maintenance of chromosomes 4 (SMC-4) is a chromosomal ATPase which plays an important role in regulate chromosome assembly and segregation. However, the role of SMC-4 in the incidence of malignancies, especially colorectal cancer is still poorly understood. Materials and Methods: We here used quantitative PCR and Western blot analysis to examine SMC-4 mRNA and protein levels in primary colorectal cancer and paired normal colonic mucosa. SMC-4 clinicopathological significance was assessed by immunohistochemical staining in a tissue microarray (TMA) in which 118 cases of primary colorectal cancer were paired with noncancerous tissue. The biological function of SMC-4 knockdown was measured by CCK8 and plate colony formation assays. Fluorescence detection has been used to detect cell cycling and apoptosis. Results: SMC-4 expression was significantly higher in colorectal cancer and associated with T stage, N stage, AJCC stage and differentiation. Knockdown of SMC-4 expression significantly suppressed the proliferation of cancer cells and degraded its malignant degree. Conclusions: Our clinical and experimental data suggest that SMC-4 may contribute to the progression of colorectal carcinogenesis. Our study provides a new therapeutic target for colorectal cancer treatment.

• Molecules and Cells
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• v.41 no.6
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• pp.591-602
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• 2018

Gastric cancer is the fifth most common type of malignancy worldwide, and the survival rate of patients with advanced-stage gastric cancer is low, even after receiving chemotherapy. Here, we validated neurotensin receptor 1 (NTSR1) as a potential therapeutic target in gastric cancer. We compared NTSR1 expression levels in sixty different gastric cancer-tissue samples and cells, as well as in other cancer cells (lung, breast, pancreatic, and colon), by assessing NTSR1 expression via semi-quantitative real-time reverse transcription polymerase chain reaction, immunocytochemistry and western blot. Following neurotensin (NT) treatment, we analyzed the expression and activity of matrix metalloproteinase-9 (MMP-9) and further determined the effects on cell migration and invasion via wound-healing and transwell assays. Our results revealed that NTSR1 mRNA levels were higher in gastric cancer tissues than non-cancerous tissues. Both of NTSR1 mRNA levels and expression were higher in gastric cancer cell lines relative to levels observed in other cancer-cell lines. Moreover, NT treatment induced MMP-9 expression and activity in all cancer cell lines, which was significantly decreased following treatment with the NTSR1 antagonist SR48692 or small-interfering RNA targeting NTSR1. Furthermore, NT-mediated metastases was confirmed by observing epithelial-mesenchymal transition markers SNAIL and E-cadherin in gastric cancer cells. NT-mediated invasion and migration of gastric cancer cells were reduced by NTSR1 depletion through the Erk signaling. These findings strongly suggested that NTR1 constitutes a potential therapeutic target for the inhibition of gastric cancer invasion and metastasis.

• BMB Reports
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• v.57 no.4
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• pp.188-193
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• 2024

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.439-448
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• 1993

The B-type gamma knife unit was installed at Kyung-Hee University Hospital in March 1992. The selective beam plugging method can be used to reduce the low percentage isodose profiles of normal sensitive organ and to modify the isodose curves of treatment volume for better shaping of the target volume. For representing the changes of the low percentage isodose profiles, the variations of dose distribution for several cases were discussed in this paper. The film dosimetry was peformed for the evaluation of calculated isodose profiles predicted by KULA dose planning system. The results were verified by RFA-3 automatic densitometry. The clinical application of selective beam shielding method was peformed in 17 patients in 100 patients who have undergone gamma knife radiosurgery for a year. The calculated and the measured isodose profiles for the high percentage regions were well consistent with each other. When the target of pituitary tumor is macro-size, the selective beam shielding method is the most applicable method. When the target size, however, is small, the correct selection of the proper helmet size is very important. All patients were exposed almost about 3~12 Gy for brain stem, and 3~11.2 Gy for optic apparatus. It is recommended that the same or other plugging patterns with multiple isocenters should be used for protection of the radiosensitive normal structures with precise treatment of CNS lesions.

• BMB Reports
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• v.52 no.12
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• pp.712-717
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• 2019

Translocase of outer mitochondrial membrane 20 (TOMM20) plays an essential role as a receptor for proteins targeted to mitochondria. TOMM20 was shown to be overexpressed in various cancers. However, the oncological function and therapeutic potential for TOMM20 in cancer remains largely unexplored. The purpose of this study was to elucidate the underlying molecular mechanism of TOMM20's contribution to tumorigenesis and to explore the possibility of its therapeutic potential using colorectal cancer as a model. The results show that TOMM20 overexpression resulted in an increase in cell proliferation, migration, and invasion of colorectal cancer (CRC) cells, while siRNA-mediated inhibition of TOMM20 resulted in significant decreases in cell proliferation, migration, and invasion. TOMM20 expression directly impacted the mitochondrial function including ATP production and maintenance of membrane potential, which contributed to tumorigenic cellular activities including regulation of S phase cell cycle and apoptosis. TOMM20 was overexpressed in CRC compared to the normal tissues and increased expression of TOMM20 to be associated with malignant characteristics including a higher number of lymph nodes and perineural invasion in CRC. Notably, knockdown of TOMM20 in the xenograft mouse model resulted in a significant reduction of tumor growth. This is the first report demonstrating a relationship between TOMM20 and tumorigenesis in colorectal cancer and providing promising evidence for the potential for TOMM20 to serve as a new therapeutic target of colorectal cancer.

• Biomolecules & Therapeutics
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• v.32 no.3
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• pp.281-290
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• 2024

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.