• Journal of Microbiology and Biotechnology
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• 제31권7호
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• pp.933-941
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• 2021

Ginsenoside Rg4 is a rare ginsenoside that is naturally found in ginseng, and exhibits a wide range of biological activities including antioxidant and anti-inflammatory properties in several cell types. The purpose of this study was to use an in vivo model of hair follicle (HF)-mimic based on a human dermal papilla (DP) spheroid system prepared by three-dimensional (3D) culture and to investigate the effect of Rg4 on the hair-inductive properties of DP cells. Treatment of the DP spheroids with Rg4 (20 to 50 ㎍/ml) significantly increased the viability and size of the DP spheres in a dose-dependent manner. Rg4 also increased the mRNA and protein expression of DP signature genes that are related to hair growth including ALP, BMP2, and VCAN in the DP spheres. Analysis of the signaling molecules and luciferase reporter assays further revealed that Rg4 induces the activation of phosphoinositide 3-kinase (PI3K)/AKT and the inhibitory phosphorylation of GSK3β, which activates the WNT/β-catenin signaling pathway. These results correlated with not only the increased nuclear translocation of β-catenin following the treatment of the DP spheres with Rg4 but also the significant elevation of mRNA expression of the downstream target genes of the WNT/β-catenin pathway including WNT5A, β-catenin, and LEF1. In conclusion, these results demonstrated that ginsenoside Rg4 promotes the hair-inductive properties of DP cells by activating the AKT/GSK3β/β-catenin signaling pathway in DP spheres, suggesting that Rg4 could be a potential natural therapy for hair growth.

• 대한방사성의약품학회지
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• 제8권1호
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• pp.9-15
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• 2022

Anti-cancer and therapeutic effects using therapeutic radioisotopes have been demonstrated by various studies, and it is well-known that therapeutic radioisotopes are useful in cancer treatment. Recently, one of the therapeutic radioisotopes, scandium is emerging as a radioisotope applicable to PET imaging (⁴³Sc, ⁴⁴Sc) and therapy (⁴⁷Sc) in cancer theranostic approach. However, ⁴⁷Sc has little known radiobiological and therapeutic efficacy compared to other therapeutic radioisotopes. Here, we investigated the quality and therapeutic efficacy of ⁴⁷Sc radioisotope produced by our production/isolation technology at the research reactor 'HANARO' in KAERI (Korea Atomic Energy Research Institute). We showed that the therapeutic efficacy of ⁴⁷Sc, produced by our production/isolation technology, effectively suppressed epidermal growth factor receptor (EGFR)-targeted non-small cell lung cancer (NSCLC) cells. Consequently, these results suggest that the high quality of the produced ⁴⁷Sc by our production/isolation technology enables the development of therapeutic strategies for cancer treatment and radiopharmaceuticals using ⁴⁷Sc.

• Journal of Gastric Cancer
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• 제19권3호
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• pp.235-253
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• 2019

Gastric cancer (GC) is one of the deadliest malignancies in the world. Currently, clinical treatment decisions are mostly made based on the extent of the tumor and its anatomy, such as tumor-node-metastasis staging. Recent advances in genome-wide molecular technology have enabled delineation of the molecular characteristics of GC. Based on this, efforts have been made to classify GC into molecular subtypes with distinct prognosis and therapeutic response. Simplified algorithms based on protein and RNA expressions have been proposed to reproduce the GC classification in the clinical field. Furthermore, a recent study established a single patient classifier (SPC) predicting the prognosis and chemotherapy response of resectable GC patients based on a 4-gene real-time polymerase chain reaction assay. GC patient stratification according to SPC will enable personalized therapeutic strategies in adjuvant settings. At the same time, patient-derived xenografts and patient-derived organoids are now emerging as novel preclinical models for the treatment of GC. These models recapitulate the complex features of the primary tumor, which is expected to facilitate both drug development and clinical therapeutic decision making. An integrated approach applying molecular patient stratification and patient-derived models in the clinical realm is considered a turning point in precision medicine in GC.

• BMB Reports
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• 제54권1호
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• pp.31-43
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• 2021

Dendritic cells (DC), which consist of several different subsets, specialize in antigen presentation and are critical for mediating the innate and adaptive immune responses. DC subsets can be classified into conventional, plasmacytoid, and monocyte-derived DC in the tumor microenvironment, and each subset plays a different role. Because of the role of intratumoral DCs in initiating antitumor immune responses with tumor-derived antigen presentation to T cells, DCs have been targeted in the treatment of cancer. By regulating the functionality of DCs, several DC-based immunotherapies have been developed, including administration of tumor-derived antigens and DC vaccines. In addition, DCs participate in the mechanisms of classical cancer therapies, such as radiation therapy and chemotherapy. Thus, regulating DCs is also important in improving current cancer therapies. Here, we will discuss the role of each DC subset in antitumor immune responses, and the current status of DC-related cancer therapies.

• BMB Reports
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• 제57권3호
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• pp.155-160
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• 2024

Lung cancer carries one of the highest mortality rates among all cancers. It is often diagnosed at more advanced stages with limited treatment options compared to other malignancies. This study focuses on calnexin as a potential biomarker for diagnosis and treatment of lung cancer. Calnexin, a molecular chaperone integral to N-linked glycoprotein synthesis, has shown some associations with cancer. However, targeted therapeutic or diagnostic methods using calnexin have been proposed. Through 1D-LCMSMS, we identified calnexin as a biomarker for lung cancer and substantiated its expression in human lung cancer cell membranes using Western blotting, flow cytometry, and immunocytochemistry. Anti-calnexin antibodies exhibited complement-dependent cytotoxicity to lung cancer cell lines, resulting in a notable reduction in tumor growth in a subcutaneous xenograft model. Additionally, we verified the feasibility of labeling tumors through in vivo imaging using antibodies against calnexin. Furthermore, exosomal detection of calnexin suggested the potential utility of liquid biopsy for diagnostic purposes. In conclusion, this study establishes calnexin as a promising target for antibody-based lung cancer diagnosis and therapy, unlocking novel avenues for early detection and treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제16권5호
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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.

• 대한치과의사협회지
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• 제48권8호
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• pp.576-586
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• 2010

Recent advancement in molocular biology enhanced further understanding of the carcinogenesis of oral cancer and its relation with various genetic backgrounds. Familial risk factors includes similar habits of the family and polymorphic variations of the genes. Recently, human papilloma virus has been suggested to be linked with oral cancer progression. Enhancement of understanding of the damage or alteration in molecular pathway in various cellular response of oral cancer progression would lead the targeted therapy or precise early diagnosis of the oral cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제17권7호
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• pp.3025-3033
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• 2016

Chronic myeloid leukaemia (CML) is a clonal myeloproliferative hematopoietic stem cell disorder. Deregulated BCR-ABL fusion tyrosine kinase activity is the main cause of CML disease pathogenesis, making BCR-ABL an ideal target for inhibition. Current tyrosine kinase inhibitors (TKIs) designed to inhibit BCR-ABL oncoprotein activity, have completely transformed the prognosis of CML. Interruption of TKI treatment leads to minimal residual disease reside (MRD), thought to reside in TKI-insensitive leukaemia stem cells which remain a potential reservoir for disease relapse. This highlights the need to develop new therapeutic strategies for CML either as small molecule master TKIs or phytopharmaceuticals derived from nature to achieve chronic molecular remission. This review outlines the past, present and future therapeutic approaches for CML including coverage of relevant mechanisms, whether ABL dependent or independent, and epigenetic factors responsible for developing resistance against TKIs. Appearance of mutant clones along the course of therapy either pre-existing or induced due to therapy is still a challenge for the clinician. A proposed in-vitro model of generating colony forming units from CML stem cells derived from diagnostic samples seems to be achievable in the era of high throughput technology which can take care of single cell genomic profiling.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4915-4918
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• 2014

Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

• 대한방사성의약품학회지
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• 제9권1호
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• pp.49-55
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• 2023

Tumors are encircled by various non-cancerous cell types in the extracellular matrix, including fibroblasts, endothelial cells, immune cells, and cytokines. Fibroblasts are the most critical cells in the tumor stroma and play an important role in tumor development, which has been highlighted in some epithelial cancers. Many studies have shown a tight connection between cancerous cells and fibroblasts in the last decade. Regulatory factors secreted into the tumor environment by special fibroblast cells, cancer-associated fibroblasts (CAFs), play an important role in tumor and vessel development, metastasis, and therapy resistance. This review addresses the development of FAP inhibitors, emphasizing the first, second, and latest generations. First-generation inhibitors exhibit low selectivity and chemical stability, encouraging researchers to develop new scaffolds based on preclinical and clinical data. Second-generation enzymes such as UAMC-1110 demonstrated enhanced FAP binding and better selectivity. Targeted treatment and diagnostic imaging have become possible by further developing radionuclide-labeled fibroblast activation protein inhibitors (FAPIs). Although all three FAPIs (01, 02, and 04) showed excellent preclinical and clinical findings. The final optimization of these FAPI scaffolds resulted in FAPI-46 with the highest tumor-to-background ratio and better binding affinity.