Chang-Hwan Yeom

Background: Vitamin C is a potent antioxidant and is also known as a neuromodulator of dopaminergic neurons. This study investigated the association between SVCT2 expression levels in peripheral lymphocytes and the stage of Parkinson's disease. Methods: From November 1, 2023, to November 30, 2025, a total of 144 patients with Parkinson's disease (mean age: 67 ± 8.1 years) who were treated at YCH Hospital were enrolled in the study. The Hoehn-Yahr scale was used to classify the severity of Parkinson's disease. SVCT2 levels in lymphocytes were also measured through blood tests. The association between the SVCT2 levels and Parkinson's disease severity was analyzed using ordinal logistic regression analysis, including confounding variables. Results: Patients were divided into two groups based on the Hoehn-Yahr scale: early-stage (scale 1, 48 patients) and advanced-stage (scales 2–4, 96 patients). SVCT2 expression in lymphocytes of patients with severe Parkinson's disease was significantly lower than in patients with mild disease (p < 0.01). Linear regression analysis revealed that SVCT2 expression decreased significantly with each one-point increase in the H-Y scale (β = -1.25, p < 0.01). Additionally, ordinal logistic regression analysis revealed that a one-point increase in SVCT2 expression was associated with a significantly higher likelihood of being in a lower H-Y stage. Conclusions: These results suggest that SVCT2 levels in peripheral blood lymphocytes may serve as a useful biomarker for predicting the progression of Parkinson's disease. Furthermore, enhancing SVCT2 levels may not only attenuate disease progression but also potentially alleviate Parkinsonian symptoms.

Background: Globally, the incidence of prostate cancer is estimated to increase by approximately 80% by 2040 compared to 2018. Bone is the most common metastatic site in prostate cancer and accurate prediction of bone metastasis in prostate cancer is crucial for deciding treatment decisions. The aim of this study is to evaluate the potential of G6PD activity level as a biomarker for predicting bone metastasis in patients with prostate cancer. Methods: A total of 56 patients participated in this study and participants included in the study were prostate cancer patients aged 19 years or older who visited YCH Hospital. We compared G6PD activity levels according to presence of bone metastasis. Also, ROC analysis was conducted to evaluate the predictive performance of G6PD activity level for bone metastasis. Optimal cutoff value of G6PD activity level was determined using Youden’s index and corresponding sensitivity and specificity were calculated. Results: The median G6PD activity was significantly higher in the group with bone metastasis than in the group without bone metastasis. According to ROC curve analysis, the area under the curve (AUC) was 0.78 (95% CI, 0.66–0.90). The optimal cutoff value of G6PD activity level for predicting bone metastasis was determined to be 11.5 U/g Hb. At this cutoff value, sensitivity and specificity were 0.81 and 0.73, respectively. Conclusions: G6PD activity is a complementary non-invasive biomarker for predicting bone metastasis in patients with prostate cancer.

Background: Gastric cancer is the fifth most prevalent cancer diagnosed worldwide, and approximately 40% of patients who experience recurrence within five years develop hematogenous metastasis. Given that early prediction of recurrence may improve overall survival, there is a need for a biomarker that allows for repeated measurements and can accurately predict cancer stage. This study aimed to evaluate the potential of glucose-6-phosphate dehydrogenase activity, which is a factor associated with cancer progression, as a biomarker for predicting the stage of gastric cancer. Methods: This cross-sectional study retrospectively analyzed the medical records of patients with gastric cancer. Patients were classified into early-stage (Stage I–II) and advanced-stage (Stage III–IV) groups, and serum G6PD activity was compared between the two groups. Receiver operating characteristic (ROC) curve analysis was conducted to calculate the area under the curve (AUC), identifying the optimal cutoff value, and to determine the corresponding sensitivity and specificity. Results: Serum G6PD activity was significantly higher in the advanced-stage group compared to the early-stage group. Moreover, ROC curve analysis yielded an AUC of 0.70, indicating fair diagnostic performance. The optimal G6PD cutoff point was determined to be 12.05 U/g Hb, corresponding to a sensitivity of 0.59 and a specificity of 0.78. Conclusions: This study demonstrated the clinical utility of serum G6PD activity in predicting the stage of gastric cancer. As the test requires only a single drop of blood and provides rapid results, the test could be a practical tool for monitoring of recurrence in gastric cancer follow-up settings.

This case study explores the effectiveness of autologous cytokine-induced killer (CIK) cell-based immunotherapy in a 49-year-old male patient with inoperable stage IIIb cholangiocarcinoma, characterized by high levels of the sodium-dependent vitamin C transporter-2 (SVCT2) in immune cells. Despite an initial lack of tumor reduction following chemotherapy, the patient showed a significant decrease in tumor markers and stabilization of the tumor after undergoing radiation and proton therapy. Subsequently, CIK cell therapy, combined with high-dose vitamin C, was administered 52 times over 6 years. The patient’s tumor size reduced, and no cancer activity was detected for 7 years and 10 months post-diagnosis, indicating a successful long-term outcome without recurrence. This study suggests that CIK cell therapy, particularly in patients with elevated SVCT2 levels, may offer a promising adjuvant treatment for cholangiocarcinoma and potentially other cancers. Further research is needed to validate SVCT2 as a biomarker for the effectiveness of CIK cell therapy.

_L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of _L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of _L-ascorbic acid. In this study, we demonstrate that _L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of _L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose _L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of _L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that _L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

There is an ongoing interest in cellular antioxidants and oxidants as well as cellular mechanisms underlying their effects. Several reports suggest that vitamin C (L-ascorbic acid) functions as a pro-oxidant with selective toxicity against specific types of tumor cells. In addition, reduced glutathione plays an emerging role in reducing oxidative stress due to xenobiotic toxins such as metals and oxidants associated with diseases such as cancer, cardiovascular disease, and stroke. High-dose intravenous vitamin C and intravenous glutathione have been used as complementary, alternative, and adjuvant medicines. Here, we review the molecular mechanisms underlying the regulation of oxidation/reduction systems, focusing on the altered metabolomics profile in cancer cells following treatment with pharmacological vitamin C. This review focuses on the role of vitamin C in energy metabolism in terms of adenosine triphosphate, cysteine, and reduced glutathione levels, affecting cancer cell death.

Oxaliplatin, a platinum-based anti-cancer drug, induces peripheral neuropathy as a side effect and causes cold hyperalgesia in cancer patients receiving anti-cancer chemotherapy. In oxaliplatin-treated mice, aluminum was accumulated in the dorsal root ganglia (DRG), and accumulated aluminum in DRG or other organs aggravated oxaliplatin-induced neuropathic pain. To investigate whether aluminum oxalate, which is the compound of aluminum and oxaliplatin, might be the peripheral neuropathy inducer, the withdrawal responses of mice to coldness, the expression of transient receptor potential ankyrin 1 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays in DRG were analyzed in mice administered with aluminum oxalate. In addition, the concentrations of aluminum in aluminum oxalate-treated mice were significantly increased compared to those of mice treated with aluminum chloride. To alleviate neuropathic pain, glutathione (GSH), known as an antioxidant and a metal chelator, was injected into oxaliplatin-treated mice. The concentrations of aluminum in the DRG were decreased by the chelation action of GSH. Taken together, behavioral and molecular analyses also supported that aluminum accumulation on the DRG might be a factor for neuropathic pain. This result also suggested that the aluminum chelation by GSH can provide an alleviatory remedy of neuropathic pain for cancer patients with oxaliplatin-induced neuropathic pain.

Exosomes are small membrane vesicles between 30 and 100 nm in diameter secreted by many cell types, and are associated with a wide range of physiological and/or pathological processes. Exosomes containing proteins, lipids, mRNA, and microRNA contribute to cell-to-cell communication and cell-to-environment regulation, however, their biological functions are not yet fully understood. In this report, exosomes in the glioblastoma cell line, U-87MG, were isolated and the proteome was investigated. In addition, exosome proteome changes in U-87MG cells exposed to a low temperature were investigated to elucidate whether the exosome proteome could respond to an external stimulus. Cell culture medium was collected, and exosomes were isolated by continuous centrifugation eliminating cell debris, nucleic acids, and other particles. The morphology of exosomes was observed by cryo-tunneling electron microscopy. According to 2-dimensional electrophoresis and matrix-assisted laser desorption ionization time-of-flight mass spectrometry, certain proteins including collagen type VI alpha 1, putative RNA-binding protein 15B chain A, substrate induced remodeling of the active site regulates HTRA1, coatomer protein complex-subunit beta 2, myosin-heavy chain 1, and keratin-type I cytoskeletal 9 showed differences between the control proteome and the low temperature-exposed proteome.

Oxaliplatin is a platinum-based anticancer drug used to treat metastatic colorectal, breast, and lung cancers. While oxaliplatin kills cancer cells effectively, it exhibits several side effects of varying severity. Neuropathic pain is commonly experienced during treatment with oxaliplatin. Patients describe symptoms of paresthesias or dysesthesias that are triggered by cold (acute neuropathy), or as abnormal sensory or motor function (chronic neuropathy). In particular, we found that aluminum levels were relatively high in some cancer patients suffering from neuropathic pain based on clinical observations. Based on these findings, we hypothesized that aluminum accumulation in the dorsal root ganglion (DRG) in the course of oxaliplatin treatment exacerbates neuropathic pain. In mice injected with oxaliplatin (three cycles of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest), we detected cold allodynia using the acetone test, but not heat hyperalgesia using a hot plate. However, co-treatment with aluminum chloride (AlCl_3∙6H₂O; 7 mg/kg i.p. for 14 days: equivalent 0.78 mg/kg of elemental Al) and oxaliplatin (1 cycle of 3 mg/kg i.p. daily for 5 days, followed by 5 days of rest) synergistically induced cold allodynia as well as increased TRPAl mRNA and protein expression. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) analysis showed a significant increase in aluminum concentrations in the DRG of mice treated with aluminum chloride and oxaliplatin compared to aluminum chloride alone. Similarly, in a mouse induced-tumor model, aluminum concentrations were increased in DRG tissue and tumor cells after oxaliplatin treatment. Taken together, these findings suggest that aluminum accumulation in the DRG may exacerbate neuropathic pain in oxaliplatin-treated mice.