• Molecules and Cells
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• v.37 no.5
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• pp.383-388
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• 2014

Renal cell carcinoma (RCC) is associated with a high frequency of metastasis and only few therapies substantially prolong survival. Honokiol, isolated from Magnolia spp. bark, has been shown to exhibit pleiotropic anticancer effects in many cancer types. However, whether honokiol could suppress RCC metastasis has not been fully elucidated. In the present study, we found that honokiol suppressed renal cancer cells' metastasis via dual-blocking epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) properties. In addition, honokiol inhibited tumor growth in vivo. It was found that honokiol could upregulate miR-141, which targeted ZEB2 and modulated ZEB2 expression. Honokiol reversed EMT and suppressed CSC properties partly through the miR-141/ZEB2 axis. Our study suggested that honokiol may be a suitable therapeutic strategy for RCC treatment.

• Radiation Oncology Journal
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• v.36 no.3
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• pp.172-181
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• 2018

Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

• BMB Reports
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• v.52 no.11
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• pp.625-634
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• 2019

Severe combined immunodeficiency (SCID) is a group of inherited disorders characterized by compromised T lymphocyte differentiation related to abnormal development of other lymphocytes [i.e., B and/or natural killer (NK) cells], leading to death early in life unless treated immediately with hematopoietic stem cell transplant. Functional NK cells may impact engraftment success of life-saving procedures such as bone marrow transplantation in human SCID patients. Therefore, in animal models, a T cell-/B cell-/NK cell＋ environment provides a valuable tool for understanding the function of the innate immune system and for developing targeted NK therapies against human immune diseases. In this review, we focus on underlying mechanisms of human SCID, recent progress in the development of SCID animal models, and utilization of SCID pig model in biomedical sciences. Numerous physiologies in pig are comparable to those in human such as immune system, X-linked heritability, typical T-B＋NK- cellular phenotype, and anatomy. Due to analogous features of pig to those of human, studies have found that immunodeficient pig is the most appropriate model for human SCID.

• Biomedical Science Letters
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• v.24 no.4
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• pp.426-429
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• 2018

Chronic eosinophilic leukemia (CEL) is characterized by eosinophilia and organ damage. Imatinib is widely used for treating CEL, chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Unfortunately, the cancer cells gain resistance against the drug after prolonged molecular-targeted therapies. Imatinib-resistant EoL-1 (EoL-1-IR) cells were produced from chronic eosinophilic leukemia cells (EoL-1) after treatment with imatinib for a long duration. Two-dimensional electrophoresis (2-DE) analysis revealed numerous protein variations in the EoL-1 and EoL-1-IR sub-types. Compared to the EoL-1 cells, expression levels of TIP49, RBBP7, ${\alpha}$-enolase, adenosine deaminase, C protein, galactokinase, eukaryotic translation initiation factor, $IFN-{\gamma}$, and human protein homologous to DROER were increased, whereas core I protein, proteasome subunit p42, heterogeneous ribonuclear particle protein, chain B, and nucleoside diphosphate were decreased in the EoL-1-IR cells. Taken together, these results contribute to understanding the pathogenic mechanism of drug-resistant diseases.

• Journal of Genetic Medicine
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• v.21 no.1
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• pp.14-21
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• 2024

Infantile nystagmus syndrome (INS) refers to congenital forms of nystagmus that are present at birth or during infancy. This syndrome may be caused by afferent visual system disorders or abnormal development of the ocular motor system. INS is a genetically heterogeneous disorder for which there are more than 100 causative genes. Since applying clinical tests for the differential diagnosis of INS can be challenging in early infancy and children, genetic testings such as next-generation sequencing are becoming more important for achieving accurate diagnoses. An improved understanding of the molecular mechanisms of INS may also lead to the development of gene-based therapies for INS. These advantages of genetic testing have the potential to change the diagnostic paradigm of patients with INS. However, the diagnostic pathway based on genetic testing still has several limitations in terms of the therapeutic effect and methodology. This review summarizes genetic and clinical features of INS, and discusses the promise and pitfalls of genetic testing in INS.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3849-3856
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• 2015

Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. Materials and Methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-${\alpha}$ and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. Results: After comparing the proteomics profile of TNF-${\alpha}$ induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-${\alpha}$ stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-${\alpha}$. Conclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.601-605
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• 2007

The cure rate of acute lymphoblastic leukemia (ALL) in children dramatically improved over past 5 decades from zero to about 80%. The main cause of improvement is owing to the development of chemotherapy by multicenter clinical trial of large study groups with the understanding of leukemia biology. Recently, pediatric ALL protocols were applied to the treatment of adolescent and even adult ALL patients. For nearly 30 years, clinical factors have been used to risk-stratify therapy for children with ALL, so that the most intensive therapies are reserved for those patients at the highest risk of relapse. The risk groups of ALL are divided as standard- (low- plus intermediate-), high- and very high-risk group according to the prognostic factors, and treatment results improved by this risk based treatment. The factors used to risk-stratify therapy include age, gender, presenting leukocyte count, immunophenotype, cytogenetic aberrations including ploidy and translocations, and initial response after 1 to 2 weeks of therapy. But treatment efficacy is the most important determinant and can abolish the clinical significance of most, if at all, prognostic factors. Today, in the era of intensive, multiagent regimens, there is increasing evidence that we have reached the limits of prognostic significance of currently applied clinical risk factors in childhood ALL. As the cure rate of ALL is about 80%, introducing new prognostic factors such as new molecular prognostic markers, new methods of assessment about minimal residual disease, and pharmacogenetic study, with the development of stem cell transplantation and molecular targeted therapy are needed to cure residual 20% of childhood ALL patients without short and long term complications.

• BMB Reports
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• v.55 no.12
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• pp.645-650
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• 2022

Epithelial-to-mesenchymal transition (EMT)-subtype gastric cancers have the worst prognosis due to their higher recurrence rate, higher probability of developing metastases and higher chemo-resistance compared to those of other molecular subtypes. Pharmacologically actionable somatic mutations are rarely found in EMT-subtype gastric cancers, limiting the utility of targeted therapies. Here, we conducted a high-throughput chemical screen using 37 gastric cancer cell lines and 48,467 synthetic small-molecule compounds. We identified YK-135, a small-molecule compound that showed higher cytotoxicity toward EMT-subtype gastric cancer cell lines than toward non-EMT-subtype gastric cancer cell lines. YK-135 exerts its cytotoxic effects by inhibiting mitochondrial complex I activity and inducing AMP-activated protein kinase (AMPK)-mediated apoptosis. We found that the lower glycolytic capacity of the EMT-subtype gastric cancer cells confers synthetic lethality to the inhibition of mitochondrial complex I, possibly by failing to maintain energy homeostasis. Other well-known mitochondrial complex I inhibitors (e.g., rotenone and phenformin) mimic the efficacy of YK-135, supporting our results. These findings highlight mitochondrial complex I inhibitors as promising therapeutic agents for EMT-subtype gastric cancers and YK-135 as a novel chemical scaffold for further drug development.

• Journal of Gastric Cancer
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• v.23 no.2
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• pp.340-354
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• 2023

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5405-5408
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• 2012

Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride ($CCL_4$) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% $CCL_4$ twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.