• BMB Reports
• /
• v.51 no.7
• /
• pp.319-326
• /
• 2018

Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differentiated bulk tumor cells, and these specific metabolic activities directly participate in the process of CSC transformation or support the biological processes that enable tumor progression. Exploring the role of CSC metabolism and the mechanism of the metabolic plasticity of CSCs has become a major focus in current cancer research. The targeting of CSC metabolism may provide new effective therapies to reduce the risk of recurrence and metastasis. In this review, we summarize the most significant discoveries regarding the metabolism of CSCs and highlight recent approaches in targeting CSC metabolism.

• Journal of Ginseng Research
• /
• v.48 no.2
• /
• pp.129-139
• /
• 2024

Liver diseases are a significant global health burden and are among the most common diseases. Ginssennoside Rg3 (Rg3), which is one of the most abundant ginsenosides, has been found to have significant preventive and therapeutic effects against various types of diseases with minimal side effects. Numerous studies have demonstrated the significant preventive and therapeutic effects of Rg3 on various liver diseases such as viral hepatitis, acute liver injury, nonalcoholic liver diseases (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). The underlying molecular mechanism behind these effects is attributed to apoptosis, autophagy, antioxidant, anti-inflammatory activities, and the regulation of multiple signaling pathways. This review provides a comprehensive description of the potential molecular mechanisms of Rg3 in the development of liver diseases. The article focuses on the regulation of apoptosis, oxidative stress, autophagy, inflammation, and other related factors. Additionally, the review discusses combination therapy and liver targeting strategy, which can accelerate the translation of Rg3 from bench to bedside. Overall, this article serves as a valuable reference for researchers and clinicians alike.

• Biomolecules & Therapeutics
• /
• v.26 no.1
• /
• pp.45-56
• /
• 2018

Cancer is the leading cause of human deaths worldwide. Understanding the biology underlying the evolution of cancer is important for reducing the economic and social burden of cancer. In addition to genetic aberrations, recent studies demonstrate metabolic rewiring, such as aerobic glycolysis, glutamine dependency, accumulation of intermediates of glycolysis, and upregulation of lipid and amino acid synthesis, in several types of cancer to support their high demands on nutrients for building blocks and energy production. Moreover, oncogenic mutations are known to be associated with metabolic reprogramming in cancer, and these overall changes collectively influence tumor-microenvironment interactions and cancer progression. Accordingly, several agents targeting metabolic alterations in cancer have been extensively evaluated in preclinical and clinical settings. Additionally, metabolic reprogramming is considered a novel target to control cancers harboring un-targetable oncogenic alterations such as KRAS. Focusing on lung cancer, here, we highlight recent findings regarding metabolic rewiring in cancer, its association with oncogenic alterations, and therapeutic strategies to control deregulated metabolism in cancer.

• Journal of Society of Preventive Korean Medicine
• /
• v.22 no.3
• /
• pp.83-89
• /
• 2018

Objectives : The aim of this study was to investigate expert opinions on the questions contained in a questionnaire for diagnosing blood stasis accompanying metabolic disorders. Methods : Two rounds of Delphi survey were conducted online targeting on one hundred Korean medicine doctors. Respondents rated the appropriateness of the 30 questions in diagnosing metabolic disorder on a five-point scale, anchored at '5 = very appropriate', '4 = appropriate', '3 = somewhat appropriate', '2 = inappropriate', and '1 = very inappropriate'. Results : The mean score on 30 questions of first and second Delphi survey was 3.26 points and 3.31 points, respectively. The ranking of the top 10 questions that were rated as appropriate for diagnosing blood stasis accompanying metabolic disorder were 'sublingual varices', 'reddish black tongue', 'reddish black gum', 'reddish black lips', ''dark purple palatal mucosa and venous edema', 'night pain, 'ecchymosis of the tongue', 'piercing pain', 'ecchymosis of the skin' and 'prolonged numbness'. Conclusions : The experts agreed that three of the most typical symptoms of blood stasis and the conditions of capillary vessels in the tongue or the oral cavity were highly associated with metabolic disorder, whereas the questions related to abdominal pain lacked an association with metabolic disorders.

• Biomolecules & Therapeutics
• /
• v.31 no.6
• /
• pp.583-598
• /
• 2023

Dementia is a clinical syndrome characterized by progressive impairment of cognitive and functional abilities. As currently applied treatments for dementia can only delay the progression of dementia and cannot fundamentally cure it, much attention is being paid to reducing its incidence by preventing the associated risk factors. Cardiovascular and metabolic diseases are well-known risk factors for dementia, and many studies have attempted to prevent dementia by treating these risk factors. Growing evidence suggests that sex-based factors may play an important role in the pathogenesis of dementia. Therefore, a deeper understanding of the differences in the effects of drugs based on sex may help improve their effectiveness. In this study, we reviewed sex differences in the impact of therapeutics targeting risk factors for dementia, such as cardiovascular and metabolic diseases, to prevent the incidence and/or progression of dementia.

• Biomolecules & Therapeutics
• /
• v.26 no.1
• /
• pp.29-38
• /
• 2018

During cancer progression, cancer cells are repeatedly exposed to metabolic stress conditions in a resource-limited environment which they must escape. Increasing evidence indicates the importance of nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis in the survival of cancer cells under metabolic stress conditions, such as metabolic resource limitation and therapeutic intervention. NADPH is essential for scavenging of reactive oxygen species (ROS) mainly derived from oxidative phosphorylation required for ATP generation. Thus, metabolic reprogramming of NADPH homeostasis is an important step in cancer progression as well as in combinational therapeutic approaches. In mammalian, the pentose phosphate pathway (PPP) and one-carbon metabolism are major sources of NADPH production. In this review, we focus on the importance of glucose flux control towards PPP regulated by oncogenic pathways and the potential therein for metabolic targeting as a cancer therapy. We also summarize the role of Snail (Snai1), an important regulator of the epithelial mesenchymal transition (EMT), in controlling glucose flux towards PPP and thus potentiating cancer cell survival under oxidative and metabolic stress.

• Journal of Ginseng Research
• /
• v.45 no.3
• /
• pp.371-379
• /
• 2021

Mitochondrial dysfunction contributes to the pathogenesis and prognosis of many common disorders, including neurodegeneration, stroke, myocardial infarction, tumor, and metabolic diseases. Ginsenosides, the major bioactive constituents of Panax ginseng (P. ginseng), have been reported to play beneficial roles in the molecular pathophysiology of these diseases by targeting mitochondrial dysfunction. In this review, we first introduce the types of ginsenosides and basic mitochondrial functions. Then, recent findings are summarized on different ginsenosides targeting mitochondria and their key signaling pathways for the treatment of multiple diseases, including neurological disorders, cancer, heart disease, hyperglycemia, and inflammation are summarized. This review may explain the common targets of ginsenosides against multiple diseases and provide new insights into the underlying mechanisms, facilitating research on the clinical application of P. ginseng.

• Proceedings of the Korean Society of Medical Physics Conference
• /
• 2003.09a
• /
• pp.72-72
• /
• 2003

Purpose: To prove feasibility of proton chemical shift imaging (lH CSI) during stereotactic procedure, authors performed IH CSI in combination with a stereotactic headframe and selected targets according to local metabolic information, evaluated the pathologic results. Methods: The 1H CSI directed stereotactic biopsy was performed in five patients. 1H CSI was performed before conventional stereotactic MRI with gadolinium enhancement for stereotactic coordinates. The metabolite images expressed as integral ratios, Cho/Cr and Lac/Cr, were displayed in different colors. The stereotactic target coordinates were correlated with the coordinates from the 1H CSI images. Results: The final pathologic results obtained were concordant with the local metabolic information from 1H CSI. We believe that 1H CSI-directed stereotatic biopsy has the potential to significantly improve the accuracy of stereotactic biopsy targeting. Conclusions : Metabolic signals derived from 1H CSI could give us more direct clues for stereotactic target selection during the subsequent conventional stereotactic MR imaging. 1H CSI was feasible with the stereotatic headframe in place. The final pathologic results obtained were concordant with the local metabolic information from 1H CSI. Acknowledgement: This study was supported by a grant of the Center for Functional and Metabolic Imaging Technology, Ministry of Health & Welfare, Republic of Korea (02-PJ3-PG6-EV07-0002).

• IMMUNE NETWORK
• /
• v.23 no.1
• /
• pp.9.1-9.15
• /
• 2023

Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8⁺ T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8⁺ T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.10027-10031
• /
• 2014

Background: We investigated the risk of cancer mortality according to obesity status and metabolic health status using sampled cohort data from the National Health Insurance system. Materials and Methods: Data on body mass index and fasting blood glucose in the sampled cohort database (n=363,881) were used to estimate risk of cancer mortality. Data were analyzed using a Cox proportional hazard model (Model 1 was adjusted for age, sex, systolic blood pressure, diastolic blood pressure, total cholesterol level and urinary protein; Model 2 was adjusted for Model 1 plus smoking status, alcohol intake and physical activity). Results: According to the obesity status, the mean hazard ratios were 0.82 [95% confidence interval (CI), 0.75-0.89] and 0.79 (95% CI, 0.72-0.85) for the overweight and obese groups, respectively, compared with the normal weight group. According to the metabolic health status, the mean hazard ratio was 1.26 (95% CI, 1.14-1.40) for the metabolically unhealthy group compared with the metabolically healthy group. The interaction between obesity status and metabolic health status on the risk of cancer mortality was not statistically significant (p=0.31). Conclusions: We found that the risk of cancer mortality decreased according to the obesity status and increased according to the metabolic health status. Given the rise in the rate of metabolic dysfunction, the mortality from cancer is also likely to rise. Treatment strategies targeting metabolic dysfunction may lead to reductions in the risk of death from cancer.