Sanghun Lee

Rhus verniciflua Stokes against Advanced Cancer: A Perspective from the Korean Integrative Cancer Center

Active anticancer molecules have been searched from natural products; many drugs were developed from either natural products or their derivatives following the conventional pharmaceutical paradigm of drug discovery. However, the advances in the knowledge of cancer biology have led to personalized medicine using molecular-targeted agents which create new paradigm. Clinical benefit is dependent on individual biomarker and overall survival is prolonged through cytostatic rather than cytotoxic effects to cancer cell. Therefore, a different approach is needed from the single lead compound screening model based on cytotoxicity. In our experience, the Rhus verniciflua stoke (RVS) extract traditionally used for cancer treatment is beneficial to some advanced cancer patients though it is herbal extract not single compound, and low cytotoxic in vitro. The standardized RVS extracts action mechanisms as well as clinical outcomes are reviewed here. We hope that these preliminary results would stimulate different investigation in natural products from conventional chemicals.

Impact of Standardized Rhus verniciflua Stokes Extract as Complementary Therapy on Metastatic Colorectal Cancer: A Korean Single-Center Experience

Background. To investigate the clinical feasibility of the standardized Rhus verniciflua Stokes (RVS) extract for the metastatic colorectal cancer (mCRC), experimentally proven to have anticancer activities. Patients and Methods. From July 2006 to November 2007, patients with conventional chemotherapy refractory mCRC were checked. After fulfilling inclusion/exclusion criteria, 36 patients were eligible for the final analysis. Overall survival and adverse events of patients treated with RVS in the aftercare period were determined. Results. On October 21, 2008, a total of 26 patients died while the remaining 10 patients were alive with evidence of disease. The median RVS administration period was 2.7 months (95% confidence interval, 1.9-3.5). The median overall survival for the entire population was 10.9 months (95% confidence interval, 5.6-16.1) and 1-year survival rate was 44.4%, which is compatible with external controls. By survival analysis using Cox proportional hazards model, the performance status and the prior chemotherapy regimen number significantly affected overall survival. Adverse reactions to the RVS treatment were mostly mild and self-limiting. Conclusion. Complementary treatment with the standardized RVS extract might be beneficial for patients with mCRC, since it positively affected overall survival without significant side effects. This study suggests that RVS could be a natural anticancer agent candidate for the treatment of colorectal adenocarcinoma.

Shrinkage of gastric cancer in an elderly patient who received Rhus verniciflua Stokes extract.

BACKGROUND Many studies have suggested that the flavonoids from Rhus verniciflua Stokes (RVS) are anticancer agents, but a few clinical studies have reported on this topic. PATIENT AND METHOD We present here the case of a female patient (82 years old) with an adenocarcinoma of the stomach that was first diagnosed via an abdomen computed tomography (CT) scan and endoscopic biopsy. Any conventional therapy such as surgical resection was not performed because of her advanced age. She wanted to receive alternative care, and so she was exclusively treated with standardized RVS extract. COURSE OF THERAPY AND RESULTS: Daily therapy with 900 mg of orally administered RVS extract was initiated on September 25, 2006. Five (5) months later, the gastroscopy and abdomen CT scan showed a marked decrease in the polypoid mass at the mid body and a slight decrease in the flat elevated lesion at the prepyloric antrum, as compared to tumor sizes on the first gastroscopy and abdomen CT scan. She is alive and doing well at the present time (April 2009). CONCLUSIONS We suggest that RVS extract could be a candidate for a natural agent that induces selective apoptosis and inhibits cell growth in gastric adenocarcinoma.

Efficacy and Safety of Standardized Allergen-Removed Rhus verniciflua Stokes Extract in Patients with Advanced or Metastatic Pancreatic Cancer: A Korean Single-Center Experience

Background: Pancreatic cancer has the worst prognosis because of poor response to conventional therapy. We investigated the clinical feasibility of the standardized allergen-removed Rhus verniciflua Stokes (aRVS) extract as a potential therapeutic agent for advanced or metastatic pancreatic cancer. Patients and Methods: From July 2006 to June 2010, patients with advanced or metastatic pancreatic adenocarcinoma were checked in our institution. After applying inclusion/exclusion criteria, 42 patients were eligible for the final analysis. Overall survival, clinical benefit and adverse events of these patients treated with aRVS in the aftercare period were determined. Results: In May 2011, 39 patients had died and the remaining 3 patients were alive with evidence of disease. The mean RVS administration period was 3.86 months (95% confidence interval 2.52–5.20). The median overall survival for the entire population was 7.87 months (95% confidence interval 5.14–10.59), and the 1-year survival rate was 26.2%, which is compatible with external controls. Using univariate and multivariate analyses, aRVS treatment including performance status and prognostic index significantly affected overall survival. A clinical benefit response was also shown by aRVS treatment which was not dependent on concurrent chemotherapy. Adverse reactions to aRVS treatment were mostly mild and self-limiting. Conclusions: The standardized aRVS extract might be beneficial for patients with advanced or metastatic pancreatic cancer since it positively affected overall survival and clinical symptoms without significant adverse effects.

The Role of Heart Rate Variability in Advanced Non-Small-Cell Lung Cancer Patients.

Aim Several recent studies have suggested that assessing heart rate variability (HRV) is an easy method for obtaining prognostic information on cancer patients; however, these studies had limitations such as uncontrolled confounders and small numbers in a heterogeneous group. The intention of our study was to explore and validate the role of HRV variables in patients with advanced non-small-cell lung cancer (NSCLC). Method A total of 167 patients who were eligible for HRV testing were consecutively enrolled from a regional hospital in South Korea. Demographic and clinical variables, including the Eastern Cooperative Oncology Group (ECOG) performance status grade, NSCLC stage, therapeutic intervention, and other data were also recorded. The effects of time-domain and frequency-domain indices of HRV were compared with other clinical factors to determine overall survival. Results Among the HRV parameters, standard deviation of all normal-to-normal intervals (SDNN) significantly predicted poor survival by univariate analysis. However, multivariate analysis revealed that it was not an independent prognosticator for survival in NSCLC patients, as the HRV parameters significantly correlated with the ECOG performance status grade. Conclusion HRV variables should be used to monitor advanced NSCLC patients’ general well-being and ability to perform the activities of daily living rather than to predict their overall survival.

Impact of Standardized Allergen-Removed Rhus verniciflua Stokes Extract on Advanced Adenocarcinoma of the Ampulla of Vater: A Case Series

Background. Adenocarcinoma of the ampulla of Vater (AAV) is a rare malignancy that has a better prognosis than other periampullary cancers. However, the standard treatment for patients with relapsed or metastatic AAV has not been established. We investigated the clinical feasibility of standardized allergen-removed Rhus verniciflua stokes (aRVS) extract for advanced or metastatic AAV. Patients and Methods. From July 2006 to April 2011, we retrospectively reviewed all patients with advanced AAV treated with aRVS extract alone. After applying inclusion/exclusion criteria, 12 patients were eligible for the final analysis. We assessed the progression-free survival (PFS) and overall survival (OS) of these patients during the follow-up period. Results. The median aRVS administration period was 147.0 days (range: 72–601 days). The best tumor responses according to Response Evaluation Criteria in Solid Tumors were as follows: two with complete response, two with stable disease, and eight with progressive disease. The median OS was 15.1 months (range: 4.9–25.1 months), and the median PFS was 3.0 months (range: 1.6–11.4 months). Adverse reactions to the aRVS treatment were mostly mild and self-limiting. Conclusions. Prolonged survival was observed in patients with advanced AAV under the treatment of standardized aRVS extract without significant adverse effects.

Inhibition of Human Cytochrome P450 Enzymes by Allergen Removed Rhus verniciflua Stoke Standardized Extract and Constituents

Objective. Potential interactions between herbal extracts and the cytochrome P450 (CYP) system lead to serious adverse events or decreased drug efficacy. Rhus verniciflua stoke (RVS) and its constituents have been reported to have various pharmacological properties. We evaluated the inhibitory potential of RVS and its constituents on the major CYP isoforms. Methods. The effects of allergen removed RVS (aRVS) standardized extract and major components, fustin and fisetin isolated from aRVS, were evaluated on CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 isoenzyme activity by a luminescent CYP recombinant human enzyme assay. Results. The aRVS extract showed relative potent inhibitory effects on the CYP2C9 (IC50, <0.001 μg/mL), CYP2C19 (IC50, 9.68 μg/mL), and CYP1A2 (IC50, 10.0 μg/mL). However, it showed weak inhibition on CYP3A4 and CYP2D6. Fustin showed moderate inhibitory effects on the CYP2C19 (IC50, 64.3 μg/mL) and weak inhibition of the other CYP isoforms similar to aRVS. Fisetin showed potent inhibitory effects on CYP2C9, CYP2C19, and CYP1A2. Fisetin showed moderate inhibition of CYP2D6 and weak inhibition of CYP3A4. Conclusions. These results indicate that aRVS, a clinically available herbal medicine, could contribute to herb-drug interactions when orally coadministered with drugs metabolized by CYP2C9, CYP2C19, and CYP1A2.