• Biomolecules & Therapeutics
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• 제22권5호
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• pp.371-383
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• 2014

The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the formation of cancer.

• Journal of Gastric Cancer
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• 제13권3호
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• pp.129-135
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• 2013

Gastric cancer is the second leading cause of cancer-related deaths worldwide. In advanced and metastatic gastric cancer, the conventional chemotherapy with limited efficacy shows an overall survival period of about 10 months. Patient specific and effective treatments known as personalized cancer therapy is of significant importance. Advances in high-throughput technologies such as microarray and next generation sequencing for genes, protein expression profiles and oncogenic signaling pathways have reinforced the discovery of treatment targets and personalized treatments. However, there are numerous challenges from cancer target discoveries to practical clinical benefits. Although there is a flood of biomarkers and target agents, only a minority of patients are tested and treated accordingly. Numerous molecular target agents have been under investigation for gastric cancer. Currently, targets for gastric cancer include the epidermal growth factor receptor family, mesenchymal-epithelial transition factor axis, and the phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathways. Deeper insights of molecular characteristics for gastric cancer has enabled the molecular classification of gastric cancer, the diagnosis of gastric cancer, the prediction of prognosis, the recognition of gastric cancer driver genes, and the discovery of potential therapeutic targets. Not only have we deeper insights for the molecular diversity of gastric cancer, but we have also prospected both affirmative potentials and hurdles to molecular diagnostics. New paradigm of transdisciplinary team science, which is composed of innovative explorations and clinical investigations of oncologists, geneticists, pathologists, biologists, and bio-informaticians, is mandatory to recognize personalized target therapy.

• BMB Reports
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• 제51권7호
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• pp.315-316
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• 2018

Genome engineering with clustered regularly interspaced short palindromic repeats (CRISPR) system can be used as a tool to correct pathological mutations or modulate gene expression levels associated with pathogenesis of human diseases. Owing to well-established local administration methods including intravitreal and subretinal injection, it is relatively easy to administer therapeutic genome engineering machinery to ocular tissues for treating retinal diseases. In this context, we have investigated the potential of in vivo genome engineering as a therapeutic approach in the form of ribonucleoprotein or CRISPR packaged in viral vectors. Major issues in therapeutic application of genome engineering include specificity and efficacy according to types of CRISPR system. In addition to previous platforms based on ribonucleoprotein and CRISPR-associated protein 9 derived from Campylobacter jejuni, we evaluated the therapeutic effects of a CRISPR RNA-guided endonuclease derived from Lachnospiraceae bacterium ND2006 (LbCpf1) in regulating pathological angiogenesis in an animal model of wet-type age-related macular degeneration. LbCpf1 targeting Vegfa or Hif1a effectively disrupted the expression of genes in ocular tissues, resulting in suppression of choroidal neovascularization. It was also notable that there were no significant off-target effects in vivo.

• 대한방사성의약품학회지
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• 제8권2호
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• pp.139-150
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• 2022

Theranostics, a composite word of therapy and diagnosis, is known as personalized medicine and the concept of diagnosis and treatment at the same time. In nuclear medicine, it means performing both therapeutic and diagnostic radioisotope therapy using the same target molecule. The increased production and utilization of ⁶⁴Cu opens a new era of theranostics. The studies introduced here have shown that ⁶⁴CuCl₂ and various compounds or biomolecules labeled with ⁶⁴Cu are unique radiopharmaceuticals with physiological properties suitable for use as diagnostic and therapeutic agents. So far, these two abilities have been described only for radioactive iodine. Although ⁶⁴Cu has complex chemical properties compared to other PET radioisotopes such as ⁶⁸Ga, it has an appropriate half-life and enables high-quality PET images similar to ¹⁸F, which is an advantage in terms of diagnosis. In addition, since it also has therapeutic properties through the release of β^- particles and Auger electrons by electron capture, radiopharmaceuticals using ⁶⁴Cu stand for innovative radiopharmaceuticals for theranostic purposes. Therefore, based on the initial results obtained using ⁶⁴Cu as a therapeutic agent, it is expected that additional research on the application of ⁶⁴Cu will lead to a new era in the theranostics field.

• BMB Reports
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• 제56권7호
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• pp.374-384
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• 2023

Fibrosis is a pathological condition that is characterized by an abnormal buildup of extracellular matrix (ECM) components, such as collagen, in tissues. This condition affects various organs of the body, including the liver and kidney. Early diagnosis and treatment of fibrosis are crucial, as it is a progressive and irreversible process in both organs. While there are certain similarities in the fibrosis process between the liver and kidney, there are also significant differences that must be identified to determine molecular diagnostic markers and potential therapeutic targets. Long non-coding RNAs (lncRNAs), a class of RNA molecules that do not code for proteins, are increasingly recognized as playing significant roles in gene expression regulation. Emerging evidence suggests that specific lncRNAs are involved in fibrosis development and progression by modulating signaling pathways, such as the TGF-β/Smad pathway and the β-catenin pathway. Thus, identifying the precise lncRNAs involved in fibrosis could lead to novel therapeutic approaches for fibrotic diseases. In this review, we summarize lncRNAs related to fibrosis in the liver and kidney, and propose their potential as therapeutic targets based on their functions.

• 대한의생명과학회지
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• 제29권4호
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• pp.336-343
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• 2023

Lung cancer is one of the cancers with high mortality and incidence rates worldwide. Although, various anticancer research efforts are underway to completely treat cancer, the challenge against it remains in the inability to eliminate cancer stem cells (CSCs), leading to difficulties in curing the cancer and resulting in recurrence. As a result, there is a growing interest in the discovery of new biomarkers and therapeutic molecules that can simultaneously target both cancer cells and CSCs. From this point of view, we focused on fibronectin leucine rich transmembrane protein 3 (FLRT3), one of the genes known to be present in human lung cells and the discovery from our previous cancer proteomic analysis study. This study aimed to evaluate the potential of FLRT3 as a specific therapeutic biomarker for lung cancer and Lung Cancer-derived-Stem Cells (LCSC). Also, to estimate the biological function of FLRT3 in cancer and LCSC, short hairpin RNA (shRNA) was generated and showed the ability of the decreased-cell migration and cell proliferation of lung cancer through ERK signaling pathway when FLRT3 was knock-downed. In conclusion, our study is the first to report that FLRT3 has the potential as therapeutic biomarker for the treatment of lung cancer and LCSC.

• Journal of Microbiology and Biotechnology
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• 제30권2호
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• pp.306-312
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• 2020

Despite the importance of brown adipocytes as a therapeutic target for the prevention and treatment of obesity, the molecular mechanism underlying brown adipocyte differentiation is not fully understood. In particular, the role of post-translational modifications in brown adipocyte differentiation has not been extensively studied. Histidine phosphorylation is increasingly recognized an important process for protein post-translational modifications. In this study, we show that histidine phosphorylation patterns change during brown adipocyte differentiation. In addition, the expression level of protein histidine phosphatase 1 (PHPT1), a major mammalian phosphohistidine phosphatase, is reduced rapidly at the early phase of differentiation and recovers at the later phase. During white adipocyte differentiation of 3T3-L1 preadipocytes, however, the expression level of PHPT1 do not significantly change. Knockdown of PHPT1 promotes brown adipocyte differentiation, whereas ectopic expression of PHPT1 suppresses brown adipocyte differentiation. These results collectively suggest that histidine phosphorylation is closely linked to brown adipocyte differentiation and could be a therapeutic target for obesity and related metabolic diseases.

• 통합자연과학논문집
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• 제8권3호
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• pp.164-175
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• 2015

CXCR3 is a C-X-C chemokine receptor type 3 also known as GPR9 and CD183. CXCR3 is a G-Protein coupled chemokine receptor which interacts with three endogenous interferon inducible chemokine's (CXCL9, CXCL10 and CXCL11) and is proved to play a vital role in the Th1 inflammatory responses. CXCR3 has been implicated to be associated with various disease conditions like inflammatory diseases, autoimmune diseases, type I diabetes and acute cardiac allograft rejection. Therefore CXCR3 receptor is found to be an attractive therapeutic target for the treatment of inflammatory diseases. Inorder to decipher the biological function of a CXCR3, 3D structure is of much important but the crystal structure for CXCR3 has not yet been resolved. Hence, in the current study Homology modeling of CXCR3 was performed against various templates and validated using different parameters to suggest the best model for CXCR3. The reported best model can be used for further studies such as docking to identify the important binding site residues.

• 대한핵의학회지
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• 제38권2호
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• pp.171-174
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• 2004

Angiogenesis, the formation of new capillaries from existing vessels, increases oxygenation and nutrient supply to ischemic tissue and allows tumor growth and metastasis. As such, angiogenesis targeting provides a novel approach for cancer treatment with easier drug delivery and less drug resistance. Therapeutic anti-angiogenesis has shown impressive effects in animal tumor models and are now entering clinical trials. However, the successful clinical introduction of this new therapeutic approach requires diagnostic tools that can reliably measure angiogenesis in a noninvasive and repetitive manner. Molecular imaging is emerging as an exciting new discipline that deals with imaging of disease on a cellular or genetic level. Angiogenesis imaging is an important area for molecular imaging research, and the use of radiotracers offers a particularly promising technique for its development. While current perfusion and metabolism radiotracers can provide useful information related to tissue vascularity, recent endeavors are focused on the development of novel radioprobes that specifically and directly target angiogenic vessels. Presently available proges include RGD sequence containing peptides that target ${\alpha}_v\;{\beta}_3$ integrin, endothelial growth factors such as VEGF or FGF, metalloptoteinase inhibitors, and specific antiangiogenic drugs. It is now clear that nuclear medicine techniques have a remarkable potential for angiogenesis imaging, and efforts are currently continuing to develop new radioprobes with superior imaging properties. With future identification of novel targets, design of better probes, and improvements in instrumentation, radiotracer angiogenesis imaging promises to play an increasingly important role in the diagnostic evaluation and treatment of cancer and other angiogenesis related diseases.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4147-4156
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• 2015

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.