Seong Woo Yoon

Antiviral effect of Curcuma longa Linn extract against hepatitis B virus replication

ETHNOPHARMACOLOGICAL RELEVANCE A medicinal herb Curcuma longa Linn has been used for treating various liver diseases caused by hepatitis B virus (HBV) in Asia. AIM OF THE STUDY The study was performed in order to investigate the antiviral activity of Curcuma longa Linn against HBV replication in liver cells. MATERIALS AND METHODS Aqueous extract of Curcuma longa Linn (CLL) was prepared and used to analyze its antiviral activity against HBV replication in HepG 2.2.15 cells, which contain HBV genomes. The inhibitory effect of CLL on HBV replication was examined by testing the levels of secreted HBV surface antigens (HBsAg), HBV DNAs, and HBV RNAs in HepG 2.2.15 cells using ELISA, Southern blot, and Northern blot analyses. Cytotoxic activities of CLL extract on various liver cells were analyzed by MTT assay. To dissect the inhibitory mechanism of CLL extract on HBV replication, the levels of p53 protein and p53 mRNAs were analyzed by Western blot and RT-PCR in HepG 2.2.15 cells. The repression of CLL extract on HBV transcription was analyzed by RT-PCR and CAT assay. RESULTS CLL extract repressed the secretion of HBsAg from HepG 2.2.15 cells. CLL extract also suppressed the production of HBV particles and the level of intracellular HBV RNAs in HepG 2.2.15 cells, suggesting that CLL extract inhibits HBV replication. We found that the anti-HBV activity of CLL extract is mediated through enhancing the cellular accumulation of p53 protein by transactivating the transcription of p53 gene as well as increasing the stability of p53 protein. It turned out that CLL extract repressed the transcription of HBx gene by suppressing HBV enhancer I and X promoter through p53 protein. In addition, CLL extract did not have any cytotoxic effects on liver cells. CONCLUSION These data showed that CLL extract represses HBV replication through enhancing the level of p53 protein. CLL extract can be used as a safe and specific drug for patients with liver diseases caused by HBV infection.

Bojungikki-Tang for Cancer-Related Fatigue: A Pilot Randomized Clinical Trial

BACKGROUND Bojungikki-tang (Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese) is a widely used herbal prescription in traditional medicine in China, Japan, and Korea. The aim of this study was to investigate the effectiveness of Bojungikki-tang for cancer-related fatigue. METHODS A total of 40 patients with cancer-related fatigue were randomized into an experimental or a waiting list control group. Patients in the experimental group were treated with Bojungikki-tang (TJ-41) and patients in the waiting list group remained without any intervention for 2 weeks. RESULTS The experimental group showed statistically significant improvements in fatigue level assessed by the Visual Analogue Scale of Global Fatigue (VAS-F) measuring the severity of fatigue (experimental vs control: -1.1 ± 2.1 vs 0.1 ± 0.9, P < .05) and results of Functional Assessment of Cancer Therapy-General (FACT-G), Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and Trial Outcome Index-Fatigue (TOI-F) also showed significant improvements (FACT-G, 3.7 ± 9.9 vs -2.4 ± 9.5, P < .05; FACT-F,F, 8.0 ± 13.6 vs -2.2 ± 14.1, P < .05; TOI-F, 6.5 ± 9.2 vs -0.5 ± 10.9, P < .05). CONCLUSIONS The results of this study indicate that Bojungikki-tang may have beneficial effects on cancer-related fatigue and quality of lives in cancer patients. More rigorous trials are needed to confirm the efficacy of Bojungikki-tang.Background: Bojungikki-tang (Bu-Zhong-Yi-Qi-Tang in Chinese or Hochu-ekki-to in Japanese) is a widely used herbal prescription in traditional medicine in China, Japan, and Korea. The aim of this study was to investigate the effectiveness of Bojungikki-tang for cancer-related fatigue. Methods: A total of 40 patients with cancer-related fatigue were randomized into an experimental or a waiting list control group. Patients in the experimental group were treated with Bojungikki-tang (TJ-41) and patients in the waiting list group remained without any intervention for 2 weeks. Results: The experimental group showed statistically significant improvements in fatigue level assessed by the Visual Analogue Scale of Global Fatigue (VAS-F) measuring the severity of fatigue (experimental vs control: -1.1 ± 2.1 vs 0.1 ± 0.9, P < .05) and results of Functional Assessment of Cancer Therapy–General (FACT-G), Functional Assessment of Cancer Therapy–Fatigue (FACT-F), and Trial Outcome Index–Fatigue (TOI-F) also showed significant improvements (FACT-G, 3.7 ± 9.9 vs -2.4 ± 9.5, P < .05; FACT-F, 8.0 ± 13.6 vs -2.2 ± 14.1, P < .05; TOI-F, 6.5 ± 9.2 vs -0.5 ± 10.9, P < .05). Conclusions: The results of this study indicate that Bojungikki-tang may have beneficial effects on cancer-related fatigue and quality of lives in cancer patients. More rigorous trials are needed to confirm the efficacy of Bojungikki-tang.

Rhus verniciflua Stokes prevents cisplatin-induced cytotoxicity and reactive oxygen species production in MDCK-I renal cells and intact mice.

Cisplatin-induced oxidative stress can cause liver and kidney damage, thus limiting therapeutic efficacy. Thus, in the present study, since Rhus verniciflua Stokes (RVS) containing flavonoids has antioxidant effects, we investigated whether it can protect cisplatin-induced toxicity in vitro and in vivo, The in vitro effects of RVS on the cell viability and reactive oxygen species (ROS) production were investigated using cisplatin-treated Madin-Darby Canine kidney (MDCK)-I renal cells. Its in vivo effects were also studied in BALB/c mice inoculated with CT-26 colon adenocarcinoma cells and treated with cisplatin with or without RVS. Liver and renal functions were assessed together with indices of tissue oxidation. RVS prevented cisplatin-induced cytotoxicity and ROS release against MDCK-I cells. RVS alone exerted modest antitumor activity against CT-26 cells. When used concurrently with cisplatin, RVS prevented the increases in serum blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and NO, while reducing liver and kidney tissue MDA content, and increasing catalase, glutathione (GSH), and superoxide dismutase (SOD) activities. Moreover, the antitumor efficacy of cisplatin was not altered by concurrent administration of RVS. These findings demonstrate that RVS prevents cisplatin-induced toxicity in vitro and in vivo via an antioxidant activity without hurting its antitumor effectiveness, suggesting that RVS can be usefully applied to the neoplastic patients as a combined chemopreventive agent with cisplatin.

Cancer Prevention and Therapy Integrating Traditional Korean Medicine Into Modern Cancer Care

In spite of billions of dollars spent on cancer research each year, overall cancer incidence and cancer survival has not changed significantly in the last half century. Instead, the recent projection from the World Health Organization suggests that global cancer incidence and death is expected to double within the next decade. This requires an “out of the box” thinking approach. While traditional medicine used for thousands of years is safe and affordable, its efficacy and mechanism of action are not fully reported. Demonstrating that traditional medicine is efficacious and how it works can provide a “bed to bench” and “bench to bed” back approach toward prevention and treatment of cancer. This current review is an attempt to describe the contributions of traditional Korean medicine (TKM) to modern medicine and, in particular, cancer treatment. TKM suggests that cancer is an outcome of an imbalance of body, mind, and spirit; thus, it requires a multimodal treatment approach that involves lifestyle modification, herbal prescription, acupuncture, moxibustion, traditional exercise, and meditation to restore the balance. Old wisdoms in combination with modern science can find a new way to deal with the “emperor of all maladies.”

Efficacy and Safety of Moxibustion for Relieving Pain in Patients With Metastatic Cancer: A Pilot, Randomized, Single-Blind, Sham-Controlled Trial

Background. Moxibustion has been traditionally used to manage pain related to chronic diseases, including cancer. This study aims to investigate the efficacy and safety of moxibustion for relieving cancer pain in patients with metastatic cancer. Methods. A total of 16 patients were randomly divided into a true moxibustion (TM) group or a sham moxibustion (SM) group. In both groups, moxibustion was applied for 10 minutes, once daily for 7 consecutive days. In the SM group, the moxa cone was removed earlier than in the TM group, so as not to deliver heat stimulation completely into the skin. The changes of pain severity using the Brief Pain Inventory (BPI) and quality of life measured by the Functional Assessment of Cancer Therapy–General (FACT-G) were observed. A blinding credibility test was done to validate the sham moxibustion procedure. Results. The total BPI score significantly decreased in the TM group compared with the SM group (TM vs SM: −0.97 ± 1.05 vs 0.35 ± 0.60, P = .025). The 2 subsets of BPI, pain intensity score and pain interference score, also significantly decreased in the TM group (TM vs SM: intensity, −0.82 ± 0.93 vs 0.46 ± 0.87, P = .020; interference, −1.12 ± 1.31 vs 0.24 ± 0.61, P = .047). Even after adjusting for the values of opioid consumption, these results remained significant. FACT-G did not significantly improve in the TM group. The blinding to sham moxibustion was credible and no serious adverse events occurred. Conclusion. We suggest that moxibustion could be a safe and potential modality for cancer-related pain in patients with metastatic cancer. With the limitation of small sample size, a larger and long-term follow-up study is necessary to determine more definitely the efficacy of moxibustion.

The Efficacy and Safety of Jaungo, a Traditional Medicinal Ointment, in Preventing Radiation Dermatitis in Patients with Breast Cancer: A Prospective, Single-Blinded, Randomized Pilot Study.

Purpose. This study was performed to evaluate the efficacy and safety of Jaungo in preventing radiation dermatitis in patients with breast cancer. Methods. Thirty patients were prospectively enrolled and randomly assigned to receive Jaungo or general supportive skin care. Radiation dermatitis and pain were examined at daily intervals from the start of radiotherapy until 4 weeks after its completion. The primary endpoint of this study was the incidence of radiation dermatitis. The secondary endpoints were time to onset of radiation dermatitis, duration of radiation dermatitis, and maximum pain score. Results. Jaungo reduced the incidence of grade ≥2 (46.7% versus 78.6%) and grade 3 radiation dermatitis (20.0% versus 50.0%) in comparison with general supportive skin care. Jaungo also delayed the onset of grade 2 dermatitis (35 days versus 30 days). In terms of time to onset of grade 3 dermatitis, duration of dermatitis, and maximum pain score, Jaungo showed results comparable to those achieved with general supportive skin care. No patients experienced adverse effects caused by Jaungo administration. Conclusions. Jaungo minimized radiation dermatitis in patients with breast cancer without causing adverse effects. Further randomized studies with a larger sample size are required to assess clinical use of Jaungo.

Efficacy and Safety of the Traditional Herbal Medicine, Gamiguibi-tang, in Patients With Cancer-Related Sleep Disturbance: A Prospective, Randomized, Wait-List-Controlled, Pilot Study.

Background: Sleep disturbance is the second most bothersome symptom in patients with cancer, and it can significantly impair their quality of life. The aim of this study was to investigate the efficacy and safety of the traditional herbal medicine Gamiguibi-tang (GGBT) in patients with cancer-related sleep disturbance. Methods: We conducted a prospective, randomized, wait-list-controlled, open-label pilot clinical trial on cancer-related sleep disturbance. Patients with cancer experiencing poor sleep quality with a Pittsburgh Sleep Quality Index of at least 6 were randomly assigned to the GGBT and wait-list groups to receive GGBT and conventional care, respectively, for 2 weeks. The primary endpoint was the Insomnia Severity Index (ISI) score. Fatigue, depression, and cognitive impairment were assessed as the secondary endpoints by using the Brief Fatigue Inventory (BFI), Beck Depression Inventory (BDI), and Montreal Cognitive Assessment (MoCA). Results: Thirty participants who met the eligibility criteria were enrolled. Sleep disturbance assessed using the ISI improved significantly more in the GGBT group than in the wait-list group (−5.5 ± 4.4 vs 0.1 ± 1.1, P < .001). Fatigue level determined using the BFI also improved significantly more in the GGBT group than in the wait-list group (−0.8 ± 0.8 vs 0.0 ± 0.3, P = .002). The BDI and MoCA scores showed no significant changes. Adverse events were reported in two patients in the GGBT group and consisted of mild dyspepsia and mild edema. Conclusion: GGBT may be a potential treatment option for cancer-related sleep disturbance. Further research is needed to investigate the efficacy and safety of GGBT.

A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in cancer patients. The aim of this review was to assess the effectiveness of herbal medicine in preventing and treating CIPN. Methods Randomised controlled trials were included in this review. Extracting and assessing the data independently, two authors searched 13 databases. Results Twenty-eight trials involving 2174 patients met the inclusion criteria. Although there were some exceptions, the methodological quality was typically low. Seventeen trials reported the incidence rate of CIPN assessed by various tools and 14 showed a significant difference regarding the decrease of the incidence rate between the two groups. For clinical improvement, 12 trials reported it using various tools and 10 showed a significant difference between two groups. Two cases of adverse events occurred in one trial; the other nine trials reported no adverse events. Conclusions We found that herbal medicines in combination with and/or without other therapies potentially have preventive or therapeutic effects on CIPN. However, conclusions cannot be drawn because of the generally low quality of the methodology, the clinical heterogeneity, and the small sample size for each single herbal medicine. Trials that are more rigorous and report sufficient methodological data are needed.

Anti-tumor Activities of Onbaekwon on Various Cancer Cells

Anti-tumor Activities of Onbaekwon on Various Cancer Cells Jee Young Lee, Hye Kyung Oh, Han Sung Ryu, Nam Jae Kim, Won-Yong Jung, Hyun-A Oh, Hyuck Jai Choi, Seong Woo Yoon, Bong-Ha Ryu 1 Department of Korean Internal Medicine, Kyung Hee University Hospital at Gangdong 2 East-West Medical Research Institute, Kyung Hee University Medical Center 3 Department of Korean Internal Medicine, Kyung Hee University Medical Center Received 15 November 2015, revised 19 December 2015, accepted 20 December 2015 Objective : The objective of this study was to investigate the experimental efficacy of anti-tumor activity of the complexed herbal formula, Onbaekwon (OBW), which was derived from the literature of Traditional Korean Medicine, Dongeuibogam. Methods : Nine Cancer cell lines, LoVo, MCF-7, HepG2, AGS, A549, NCI-H69, HL-60, Sarcoma 180, LL/2, were prepared and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2yl)-2,5-dephenyl tetrazolium bromide (MTT) assay. Four of them, NCI-H69, HL-60, Sarcoma 180, and LL/2, showed strong cytotoxic activities and they were additionally undergone flow cytometry to find out their effects on apoptosis. ICR male mice were implanted with Sarcoma 180 intraperitoneally and divided into 8 species for each group. Control group was treated with normal saline, positive control group was treated with cyclophosphamide 8mg/kg, and experimental group was treated with OBW 1 g/kg. Results : Among 9 cancer cell lines, NCI-H69, HL-60, Sarcoma 180, and LL/2, expressed less than 0.10 mg/ml of IC50 under 0.1~1mg/ml of OBW. NCI-H69, HL-60, Sarcoma 180, and LL/2, showed dose-dependent efficacy of apoptosis. When Sarcoma 180 cancer cell was implanted in ICR male mice and treated with the OBW, they prolonged the median overall survival for 0.8 days, from 17.5 to 18.3. 14 대한암한의학회지 2015;20(2):13-21 이지영.오혜경.류한성.김남재.정원용.오현아.최혁재.윤성우.류봉하 Conclusion : OBW showed strong cytotoxicity to some cancer cells, which are NCI-H69, HL-60, Sarcoma 180, and LL/2, and its apoptotic activity was dose-dependent. OBW prolonged the median survival of mice implanted with Sarcoma 180. Further researches would be expected to support the efficacy of OBW.

Elevated Serum Vitamin B12 Levels as a Prognostic Factor for Survival Time in Metastatic Cancer Patients: A Retrospective Study

ABSTRACT Background: Serum vitamin B12 levels have been proposed as one of the survival prediction factors, although no survival analysis in metastatic cancer patients has been conducted yet. This study examined whether serum vitamin B12 levels could be a prognostic factor in metastatic cancer patients. Methods: Data from a retrospective chart review were used to perform Kaplan-Meier and multivariate analyses of the Cox proportional hazards. Subgroup analysis was performed on patients without a liver lesion (hepatocellular carcinoma or liver metastasis). Results: A total of 523 patients were included. The median survival time was 1.8 months (mo) in the high B12 group (>911 pg/mL) and 5.1 mo in the normal B12 group (211–911 pg/mL) (p < 0.001). In patients without a liver lesion, the median survival times were 2.1 and 6.1 mo in the high and normal B12 groups, respectively (p < 0.001). Multivariate analysis revealed that serum vitamin B12 level was an independent prognostic factor for overall survival (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.34–1.96, p < 0.001). Conclusion: Serum vitamin B12 level can be used to predict survival time in metastatic cancer patients. Further large-scale cohort studies are required to confirm these findings.