Experimental Evidence for the Anti-Metastatic Action of Ginsenoside Rg3: A Systematic Review.

Cancer metastasis is the leading cause of death in cancer patients. Due to the limitations of conventional cancer treatment, such as chemotherapy, there is a need for novel therapeutics to prevent metastasis. Ginsenoside Rg3, a major active component of Panax ginseng C.A. Meyer, inhibits tumor growth and has the potential to prevent tumor metastasis. Herein, we systematically reviewed the anti-metastatic effects of Rg3 from experimental studies. We searched for articles in three research databases, MEDLINE (PubMed), EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) through March 2022. In total, 14 studies (eight animal and six in vitro) provide data on the anti-metastatic effects of Rg3 and the relevant mechanisms. The major anti-metastatic mechanisms of Rg3 involve cancer stemness, epithelial mesenchymal transition (EMT) behavior, and angiogenesis. Taken together, Rg3 would be one of the herbal resources in anti-metastatic drug developments through further well-designed investigations and clinical studies. Our review provides valuable reference data for Rg3-derived studies targeting tumor metastasis.

Integrative cancer treatment may have a survival benefit in patients with lung cancer: A retrospective cohort study from an integrative cancer center in Korea.

Integrative oncology is being increasingly adopted in mainstream cancer care to strengthen anticancer effects and to control cancer-related symptoms.The objective of this study is to identify the characteristics of patients with lung cancer treated at an integrative cancer center in Korea and to determine the effects of integrative cancer treatment (ICT) on survival outcome in traditional Korean medicine (TKM).We reviewed medical records for lung cancer patients who visited a single integrative clinical setting, East-West Cancer Center, between January 2014 and December 2015. We classified the patients into groups according to their ICT and whether or not they underwent anticancer traditional Korean Medicine treatment with a multiherbal formula containing Panax notoginseng Radix, Cordyceps militaris, P ginseng C.A.Mey., and Boswellia carterii BIRDWOOD (HangAmDan-B), with a herbal formula containing Rhus verniciflua Stoke, or with cultivated wild ginseng pharmacopuncture. A descriptive analysis of the characteristics and a survival analysis using the Kaplan-Meier curves with log rank test and a Cox proportional hazard model were performed.A total of 91 patients were included, and the majority had advanced-stage cancer. Of those patients, 45.1% were in the mono-TKM group and 39.6% were integrative group. Patients with advanced stage had significantly higher mortality than patients with early stage (crude hazard ratio [HR]: 4.41, 95% confidence interval [CI]: 1.56-12.5; adjusted HR: 6.31, 95% CI: 1.24-32.1). In the unadjusted model, for patients in the integrative group, the mortality rate was reduced by 50% compared to mono-TKM group with statistical significance. After adjusting confounders, the mortality rate of integrative group was reduced by 6% compared to mono-TKM group, suggesting positive effect on survival probability of integrative group.The results suggest that integration of TKM and conventional cancer treatment may have survival benefits in patients with lung cancer. Even though this study has limitations including heterogeneity between treatment groups, the study results suggest that ICT has positive effect on survival probability. To clarify the impacts of ICT for lung cancer and other cancers on survival outcome, further prospective study with a rigorous study design is required in multiclinical setting.

Corrigendum to "Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial".

[This corrects the article DOI: 10.1155/2017/8780325.].

Effects of HAD-B1 on the proliferation of A549 cisplatin-resistant lung cancer cells.

The present study investigated the toxicity of HangAmDan-B1 (HAD-B1) on A549-Cisplatin resistant (A549CR) cells. HAD­B1 inhibited the growth of A549CR cells in a concentration­dependent manner; HAD­B1 was more effective at inhibiting A549CR cell viability compared with vehicle­treated cells. The reduction in viability may be due to S­phase cell cycle arrest and the induction of apoptosis in HAD­B1­treated cells. Cell cycle protein profile analysis of HAD­B1­treated A549CR cells using an InnoPharmaScreen (IPS) ProteoChip­based antibody microarray chip indicated downregulation of signal transducer and activator of transcription 3. The activities of caspase­3, ­8 and ­9 were significantly increased in HAD­B1­treated cells when compared with the vehicle­treated control group. Furthermore, the HAD­B1­treated group exhibited similarly increased caspase levels when compared with the Afatinib­treated group. Taken together, these observations suggest that HAD­B1 may be a promising candidate for further research into the therapeutic management of cisplatin-resistant lung cancer.

Correlation Between Natural Killer Cell Activity and Systemic Inflammatory Markers for Heterogeneous Cancer Patients Treated With Wheel Balance Cancer Therapy.

BACKGROUND AND OBJECTIVE: Natural killer (NK) cells are known to have an effect on the prevention of tumorigenesis for the initial cancer, as well as the metastatic cancer. For the past several years, the relationship between cancer and inflammation has been actively studied in preclinical and clinical settings, but there are no reports on alterations in and correlation for NK cell activity (NKA) and systemic inflammatory markers. Accordingly, this study aimed to measure correlation between NKA and the levels of other systemic inflammatory markers in patients with gastric, breast, and pancreatic cancer who received Wheel Balance Cancer Therapy (WBCT). METHODS: Forty-two electronic charts of patients with gastric, breast, and pancreatic cancer treated with WBCT from February 1, 2015 to September 30, 2015, were reviewed retrospectively. These charts were statistically analyzed, looking for alterations of and correlation for NKA and the expressions of systemic inflammatory markers. RESULTS: Patients with a NKA of under 300 pg/mL at admission showed significantly higher erythrocyte sedimentation rate (ESR) and neutrophil-to-lymphocyte ratio (NLR) values and decreasing NLR values due to WBCT than patients with an NKA greater than 300 pg/mL. As a result of the correlation analysis between NKA and the levels of the systemic inflammatory markers, NKA showed significant negative correlation with NLR, ESR, and fibrinogen values. CONCLUSIONS: Negative correlation was identified between NKA and NLR, NKA and ESR, and NKA and fibrinogen in patients with heterogeneous cancer patients.

Inhibition of lung cancer growth by HangAmDan-B is mediated by macrophage activation to M1 subtype.

Re-education of tumor-associated macrophages (TAMs) toward antitumor effectors may be a promising therapeutic strategy for the successful treatment of cancer. HangAmDan-B (HAD-B), a herbal formula, has been used for stimulating immune function and activation of vital energy to cancer patients in traditional Korean Medicine. Previous studies have reported the anti-angiogenic and anti-metastatic effects of HAD-B; however, evidence on the immunomodulatory action of HAD-B was not demonstrated. In the present study, immunocompetent mice were used to demonstrate the suppression of the in vivo growth of allograft Lewis lung carcinoma (LLC) cells, by HAD-B. In addition, HAD-B inhibited the in vitro growth of LLC cells by driving macrophages toward M1 polarization, but not through direct inhibition of tumor cell growth. Furthermore, culture media transfer of HAD-B-treated macrophages induced apoptosis of LLC cells. Results of the present study suggest that the antitumor effect of HAD-B may be explained by stimulating the antitumor function of macrophages. Considering the importance of re-educating TAMs in the regulation of the tumor microenvironment, the present study may confer another option for anti-cancer therapeutic strategy, using herbal medicines such as HAD-B.

Modified Panax ginseng extract regulates autophagy by AMPK signaling in A549 human lung cancer cells.

Panax ginseng has been used worldwide as a traditional medicine for the treatment of cancer and other diseases. The antiproliferative activity of ginseng has been increased after enzymatic processing of ginseng saponin, which may result in the accumulation of minor saponins, such as Rh2, Rg3, compound K and protopanaxatriol type (PPT) in modified regular ginseng extract (MRGX). In the present study, the anticancer activity and the associated mechanisms of MRGX were investigated using A549 human lung cancer cells. To elucidate the mechanisms underlying the effects of MRGX, we performed a microarray analysis of gene expression in the A549 cells. Molecular mechanisms that were associated with the anticancer activity of MRGX were studied, with a special focus on the autophagy-related multiple signaling pathways in lung cancer cells. Microarray analyses elucidated autophagy-related genes affected by MRGX. Administration of MRGX at 100 µg/ml induced punctate cytoplasmic expression of LC3, Beclin-1 and ATG5 and increased expression of endogenous LC3-II whereas 50 µg/ml did not inhibit the proliferation of A549 cells. Compared to the control cells, in cells treated with MRGX at 100 µg/ml, the level of p-Akt was increased, while that of mTOR-4EBP1 was decreased. Downregulation of mTOR and 4EBP1 in the MRGX-treated cells was found not to be a p-Ulk (S757)-dependent pathway, but a p-Ulk (S317)-dependent autophagic pathway, using AMPK. These data suggest that MRGX regulates AMPK and induces autophagy in lung cancer cells.

Traditional Oriental Herbal Medicine and Natural Killer Cells for Cancer Patients: A Systematic Review and Meta-analysis.

Traditional oriental herbal medicine (HM) is used by cancer patients to improve immunity. Natural killer (NK) cells are associated with development and progression of tumor and survival of cancer patients. This literature review examined randomized controlled trials (RCTs) in four electronic databases until October 2015 to evaluate the effects of oral HM on NK cells in cancer patients. Data were pooled and computed in a meta-analysis. The methodological quality was assessed according to the Cochrane risk of bias tool. Sixteen RCTs involving 1326 cancer patients were identified. Combination of HM and conventional treatment was associated with significantly higher level of NK cells compared with conventional cancer treatments (standardized mean difference, 1.218; 95% confidence interval 0.719-1.717; p < 0.001). Eight RCTs reported statistically significant improvements in the proportions or activity of NK cells in patient groups who received both HM and conventional treatment compared with patients who received conventional treatment alone, while eight RCTs reported no statistically significant differences between the two groups. Studies (n = 16) included in this review had insufficient quality of evidence with unclear (n = 1) and high (n = 15) values of the risk of bias. Although traditional oriental HM may have the positive effects on preserving the level of NK cells in cancer patients receiving conventional treatments, current evidence is inconclusive because of lack of high-quality evidence. Copyright © 2017 John Wiley & Sons, Ltd.

A Feasibility Study of Moxibustion for Treating Anorexia and Improving Quality of Life in Patients With Metastatic Cancer: A Randomized Sham-Controlled Trial.

OBJECTIVE: The aim of this study was to determine the feasibility, acceptability, and safety of using moxibustion for treating anorexia and improving quality of life in patients with metastatic cancer. METHODS: We conducted a randomized sham-controlled trial of moxibustion. Sixteen patients with metastatic cancer were recruited from Daejeon, South Korea. The patients were randomly placed into a true or a sham moxibustion group and received 10 true or sham moxibustion treatments administered to the abdomen (CV12, CV8, CV4) and legs (ST36) over a 2-week period. Outcome measures included interest in participating in the trial, identification of successful recruitment strategies, the appropriateness of eligibility criteria, and compliance with the treatment plan (ie, attendance at treatment sessions). Clinical outcomes included results of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), answers on the European Organization for Research and Treatment of Cancer 30-item core quality of life (EORTC QLQ-C30) questionnaires, scores on the visual analogue scale (VAS), and the results from blood tests and a safety evaluation. RESULTS: Moxibustion was an acceptable intervention in patients with metastatic cancer. Compliance with the treatment protocol was high, with 11 patients completing all 10 treatments. No serious adverse events related to moxibustion occurred, but 4 patients in the true moxibustion group reported mild rubefaction, which disappeared in a few hours. CONCLUSION: This study suggests that moxibustion may be safely used to treat anorexia and improve quality of life in patients with metastatic cancer. However, further research is needed to confirm this result.

Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Anorexia occurs in about half of cancer patients and is associated with high mortality rate. However, safe and long-term use of anorexia treatment is still an unmet need. Objective: The purpose of the present study was to examine the feasibility of Sipjeondaebo-tang (Juzen-taiho-to, Shi-Quan-Da-Bu-Tang) for cancer-related anorexia. Methods: A total of 32 participants with cancer anorexia were randomized to either Sipjeondaebo-tang group or placebo group. Participants were given 3 g of Sipjeondaebo-tang or placebo 3 times a day for 4 weeks. The primary outcome was a change in the Anorexia/Cachexia Subscale of Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes included Visual Analogue Scale (VAS) of anorexia, FAACT scale, and laboratory tests. Results: Anorexia and quality of life measured by FAACT and VAS were improved after 4 weeks of Sipjeondaebo-tang treatment. However, there was no significant difference between changes of Sipjeondaebo-tang group and placebo group. Conclusions: In the present study, [corrected] Sipjeondaebo-tang did not show a significant effect on anorexia [corrected]in patients with cancer. Further large-scale studies which compensate for the limitations of this study are needed to assess [corrected] the efficacy. Trial Registration: This trial is registered with ClinicalTrials.gov NCT02468141.

Allergen-Removed Rhus verniciflua Extract Induces Ovarian Cancer Cell Death via JNK Activation.

Nuclear factor-[Formula: see text]B (NF-[Formula: see text]B)/Rel transcription factors are best known for their central roles in promoting cell survival in cancer. NF-[Formula: see text]B antagonizes tumor necrosis factor (TNF)-[Formula: see text]-induced apoptosis through a process involving attenuation of the c-Jun-N-terminal kinase (JNK). However, the role of JNK activation in apoptosis induced by negative regulation of NF-[Formula: see text]B is not completely understood. We found that allergen-removed Rhus verniciflua Stokes (aRVS) extract-mediated NF-[Formula: see text]B inhibition induces apoptosis in SKOV-3 ovarian cancer cells via the serial activation of caspases and SKOV-3 cells are most specifically suppressed by aRVS. Here, we show that in addition to activating caspases, aRVS extract negatively modulates the TNF-[Formula: see text]-mediated I[Formula: see text]B/NF-[Formula: see text]B pathway to promote JNK activation, which results in apoptosis. When the cytokine TNF-[Formula: see text] binds to the TNF receptor, I[Formula: see text]B dissociates from NF-[Formula: see text]B. As a result, the active NF-[Formula: see text]B translocates to the nucleus. aRVS extract (0.5[Formula: see text]mg/ml) clearly prevented NF-[Formula: see text]B from mobilizing to the nucleus, resulting in the upregulation of JNK phosphorylation. This subsequently increased Bax activation, leading to marked aRVS-induced apoptosis, whereas the JNK inhibitor SP600125 in aRVS extract treated SKOV-3 cells strongly inhibited Bax. Bax subfamily proteins induced apoptosis through caspase-3. Thus, these results indicate that aRVS extract contains components that inhibit NF-[Formula: see text]B signaling to upregulate JNK activation in ovarian cancer cells and support the potential of aRVS as a therapeutic agent for ovarian cancer.

Growth inhibitory and apoptosis-inducing effects of allergen-free Rhus verniciflua Stokes extract on A549 human lung cancer cells.

Evidence suggests that Rhus verniciflua Stokes (RVS) or its extract has the potential to be used for the treatment of inflammatory and neoplastic diseases. However, direct use of RVS or its extract as a herbal medicine has been limited due to the presence of urushiol, an allergenic toxin. In the present study, we prepared an extract of the allergen­removed RVS (aRVS) based on a traditional method and investigated its inhibitory effect on the growth of various types of human cancer cells, including lung (A549), breast (MCF-7) and prostate (DU-145) cancer cell lines. Notably, among the cell lines tested, treatment with the aRVS extract strongly inhibited proliferation of the A549 cells at a 0.5 mg/ml concentration for 24 h that was not cytotoxic to normal human dermal fibroblasts. Furthermore, aRVS extract treatment largely reduced the survival and induced apoptosis of the A549 cells. At the mechanistic levels, treatment with the aRVS extract led to the downregulation of Bcl-2 and Mcl-1 proteins, the activation of caspase-9/-3 proteins, an increase in cytosolic cytochrome c levels, the upregulation of Bax protein, an increase in phosphorylated p53 protein but a decrease in phosphorylated S6 protein in the A549 cells. Importantly, treatment with z-VAD­fmk, a pan-caspase inhibitor attenuated aRVS extract-induced apoptosis in the A549 cells. These results demonstrate firstly that aRVS extract has growth inhibitory and apoptosis-inducing effects on A549 human lung cancer cells through modulation of the expression levels and/or activities of caspases, Bcl-2, Mcl-1, Bax, p53 and S6.

Modified Panax ginseng Extract Inhibits uPAR-Mediated α[Formula: see text]ß1-Integrin Signaling by Modulating Caveolin-1 to Induce Early Apoptosis in Lung Cancer Cells.

Urokinase receptor (uPAR) is enhanced in many human cancer cells and is frequently an indicator of poor prognosis. Activation of [Formula: see text]1-integrin requires caveolin-1 and is regulated by uPAR. However, the underlying molecular mechanism responsible for the interaction between uPAR and [Formula: see text]1-integrin remains obscure. We found that modified regular Panax ginseng extract (MRGX) had a negative modulating effect on the uPAR/[Formula: see text]1-integrin interaction, disrupted the uPAR/integrin interaction by modulating caveoline-1, and caused early apoptosis in cancer cells. Additionally, we found that siRNA-mediated caveoline-1 downregulation inhibited uPAR-mediated [Formula: see text]1-integrin signaling, whereas caveoline-1 up-regulation stimulated the signaling, which suppressed p53 expression, thereby indicating negative crosstalk exists between the integrin [Formula: see text]1 and the p53 pathways. Thus, these findings identify a novel mechanism whereby the inhibition of [Formula: see text]1 integrin and the activation of p53 modulate the expression of the anti-apoptotic proteins that are crucially involved in inducing apoptosis in A549 lung cancer cells. Furthermore, MRGX causes changes in the expressions of members of the Bcl-2 family (Bax and Bcl-2) in a pro-apoptotic manner. In addition, MGRX-mediated inhibition of [Formula: see text]1 integrin attenuates ERK phosphorylation (p-ERK), which up-regulates caspase-8 and Bax. Therefore, ERK may affect mitochondria through a negative regulation of caspase-8 and Bax. Taken together, these findings reveal that MRGX is involved in uPAR-[Formula: see text]1-integrin signaling by modulating caveolin-1 signaling to induce early apoptosis in A549 lung-cancer cells and strongly indicate that MRGX might be useful as a herbal medicine and may lead to the development of new herbal medicine that would suppress the growth of lung-cancer cells.

Survival Analysis of Advanced Non-Small Cell Lung Cancer Patients Treated by Using Wheel Balance Cancer Therapy.

Objective To investigate the clinical effect and the overall survival (OS) rate of patients with advanced non-small cell lung cancer (NSCLC) who have undergone Wheel Balance Cancer Therapy (WBCT). Methods The cases of 33 patients with advanced NSCLC who were treated with WBCT at the East West Cancer Center (EWCC) between October 4, 2004, and October 3, 2013, without undergoing concurrent conventional treatment were analyzed. The Kaplan-Meier method was used to estimate the OS of the cases, and the median OS was calculated according to age, Eastern Cooperative Oncology Group Performance Status (ECOG PS), conventional-treatment history, WBCT treatment duration, and histological tumor type. Results The median OS of all patients was 31.1 (95% confidence interval [CI] = 3.5-58.7) months; the OS rates were 63.6% and 24.2% at years 1 and 2, respectively. The median OS rates of patients under and over 65 years were 45.2 (95% CI = 13.5-76.9) and 19.5 (95% CI = 7.1-31.8) months, respectively (P = .189). The median OS rates of patients who received WBCT for >14 days but <28 days and those who received WBCT for ≥28 days were 16.2 (95% CI = 13.3-19.2) and 45.2 (95% CI = 14.4-76.0) months, respectively (P = .437). The median OS rates of patients who had undergone prior conventional treatment and those who had not were 45.2 (95% CI = 9.1-81.3) and 3.9 (95% CI = unable to calculate) months, respectively (P = .000). The median OS rates of patients with squamous cell carcinoma (SCC) and non-SCC lung cancer were 5.6 (95% CI = unable to calculate) and 45.2 (95% CI = 9.1-81.3) months, respectively (P = .262). The median OS rate of patients with ECOG PS ≥3 was 14.3 (95% CI = 8.8-19.8) months; that of patients ECOG PS <3 could not be calculated. However, the mean OS rates of patients with ECOG PS <3 and with ECOG PS ≥3 were 85.7 (95% CI = 58.4-113.0) and 12.7 (95% CI = 8.5-16.9) months, respectively (P = .000). No severe adverse events were encountered. Conclusions Our study indicates that WBCT might be effective to prolong the length of survival for patients with advanced NSCLC who have previously undergone conventional treatment and have an ECOG PS <3.

Cancer-related Fatigue in Patients with Advanced Cancer Treated with Autonomic Nerve Pharmacopuncture.

The purpose of this study was to observe the effects of autonomic nerve pharmacopuncture (ANP) treatment on cancer-related fatigue (CRF) in patients with advanced cancer. This observational case study was conducted at the East West Cancer Center of Daejeon University's Dunsan Korean Medical Hospital. Two patients were observed. One patient was diagnosed with left thymic cancer metastatic to the left pleura. The other patient had terminal-stage cervical cancer with iliac bone and lumbar 5 metastases. We injected mountain ginseng pharmacopuncture (MGP) into acupoints alongside the spine (Hua-Tuo-Jia-Ji-Xue, EX B2). We examined the patients for CRF using the Korean version of the Revised Piper Fatigue Scale (RPFS-K), which is a self-assessment tool. The scores on the RPFS-K for both patients tended to decrease during the treatment. Laboratory findings, including hematological changes, were also checked. Liver and renal function tests showed that the treatment was safe. Although further large-population studies are necessary, this case study suggests that ANP has a favorable effect on CRF in patients with advanced cancer.

Effect of acupuncture for radioactive-iodine-induced anorexia in thyroid cancer patients: a randomized, double-blinded, sham-controlled pilot study.

OBJECTIVE: The aim of this study is to evaluate the efficacy and safety of acupuncture for radioactive iodine (RAI)-induced anorexia in thyroid cancer patients. METHODS: Fourteen thyroid cancer patients with RAI-induced anorexia were randomized to a true acupuncture or sham acupuncture group. Both groups were given 6 true or sham acupuncture treatments in 2 weeks. Outcome measures included the change of the Functional Assessment of Anorexia and Cachexia Treatment (FAACT; Anorexia/Cachexia Subscale [ACS], Functional Assessment of Cancer Therapy-General [FACT-G]), Visual Analogue Scale (VAS), weight, body mass index (BMI), ACTH, and cortisol levels. RESULTS: The mean FAACT ACS scores of the true and sham acupuncture groups increased from baseline to exit in intention-to-treat (ITT) and per protocol (PP) analyses; the true acupuncture group showed higher increase but with no statistical significance. Between groups, from baseline to the last treatment, statistically significant differences were found in ITT analysis of the Table of Index (TOI) score (P = .034) and in PP analysis of the TOI (P = .016), FACT-G (P = .045), FAACT (P = .037) scores. There was no significant difference in VAS, weight, BMI, ACTH, and cortisol level changes between groups. CONCLUSION: Although the current study is based on a small sample of participants, our findings support the safety and potential use of acupuncture for RAI-induced anorexia and quality of life in thyroid cancer patients.

An enzymatically fortified ginseng extract inhibits proliferation and induces apoptosis of KATO3 human gastric cancer cells via modulation of Bax, mTOR, PKB and IκBα.

Accumulative evidence suggests ginseng extract and/or its major components, ginsenosides and compound K, a metabolized ginseng saponin, have anti-cancer effects. In the present study, the effects of a ginseng butanolic extract (GBX) and an enzymatically fortified ginseng extract (FGX), with enriched ginsenosides and compound K, on the growth of KATO3 human gastric cancer cells were investigated using a cell viability assay. While treatment with GBX at 31.25-125 mg/ml for 24 h did not affect the proliferation of KATO3 cells, FGX under the same conditions inhibited cell proliferation in a concentration-dependent manner. Furthermore, Annexin V/PI-staining and flow cytometric analysis demonstrated that the population of apoptotic KATO3 cells was increased following treatment with FGX, which was greater than in the GBX-treated cells, suggesting that FGX had a stronger apoptotic effect than GBX. To investigate the underlying mechanism of the cytostatic and cytotoxic effects of the ginseng extracts, apoptosis-associated proteins were assessed using western blot analysis. The data revealed higher expression levels of B-cell lymphoma 2-associated X protein (Bax), lower expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα) and reduced phosphorylation of mammalian target of rapamycin (mTOR) and protein kinase B (PKB) in the FGX-treated KATO3 cells than in the GBX-treated cells. Collectively, these results demonstrated for the first time, to the best of our knowledge, that FGX had stronger anti-proliferative and pro-apoptotic effects on KATO3 cells than GBX. The anti-proliferative and/or pro-apoptotic effects of FGX appeared to be mediated via the upregulation of Bax, IκBα proteolysis (activation of nuclear factor-κB) and the blocking of mTOR and PKB signals.

Target genes involved in antiproliferative effect of modified ginseng extracts in lung cancer A549 cells.

Lung cancer is the most common cancer and the leading cause of cancer-related deaths. Panax ginseng has long been used to treat cancer and other diseases worldwide. Most of the pharmacological actions of ginseng are attributed to a variety of ginsenosides, which are often metabolized by intestinal bacteria into more effective forms. In this study, we found that the antiproliferative activity of ginseng was increased after enzymatic processing of ginseng saponin (50% inhibitory concentration, >70 µg/ml). To elucidate the mechanism by which modified ginseng extract (MGX) induced cell death in human lung cancer cells, the gene expression profiles of A549 cells regulated by MGX were assayed using Agilent PrimeView Human Gene Expression Arrays. The expression of 17 genes involved in the regulation of cell signaling, cell metabolism, transport, and cytoskeleton-regulation was up-regulated, whereas the expression of 16 genes implicated in invasion and metastasis and cellular metabolism was down-regulated in MGX-treated A549 cells. Moreover, nuclear staining with 4',6-diamidino-2-phenylindole revealed that MGX clearly caused nuclear condensation and fragmentation which are observed in apoptosis cell. These results elucidate crucial anticancer mechanisms of MGX and provide potential new targets for the assessment of anticancer activity of MGX.

Cancer pain control for advanced cancer patients by using autonomic nerve pharmacopuncture.

OBJECTIVES: The purpose of this study is to report a case series of advanced cancer patients whose cancer pain was relieved by using autonomic nerve pharmacopuncture (ANP) treatment. ANP is a subcutaneous injection therapy of mountain ginseng pharmacopuncture (MGP) along the acupoints on the spine (Hua-Tuo-Jia-Ji-Xue; 0.5 cun lateral to the lower border of the spinous processes of vertebrae) to enhance the immune system and to balance autonomic nerve function. METHODS: Patients with three different types of cancer (gastric cancer, lung cancer, colon cancer with distant metastases) with cancer pain were treated with ANP. 1 mL of MGP was injected into the bilateral Hua-Tuo-Jia-Ji-Xue on the T1-L5 sites (total 12 ─ 20 mL injection) of each patient's dorsum by using the principle of symptom differentiation. During ANP treatment, the visual analogue scale (VAS) for pain was used to assess their levels of cancer pain; also, the dosage and the frequency of analgesic use were measured. RESULTS: The cancer pain levels of all three patients improved with treatment using ANP. The VAS scores of the three patients decreased as the treatment progressed. The dosage and the frequency of analgesics also gradually decreased during the treatment period. Significantly, no related adverse events were found. CONCLUSION: ANP has shown benefit in controlling cancer pain for the three different types of cancer investigated in this study and in reducing the dosage and the frequency of analgesics. ANP is expected to be beneficial for reducing cancer pain and, thus, to be a promising new treatment for cancer pain.

Bee venom pharmacopuncture: an effective treatment for complex regional pain syndrome.

OBJECTIVES: Treating complex regional pain syndrome (CRPS) is difficult because it still does not have a recommended therapy. A 29-year-old man was diagnosed with CRPS after surgery on his 4(th) and 5(th) left toes 7 years ago. Though he had undergone diverse pain treatment, the symptoms persisted, so he visited Dunsan Korean Medicine Hospital of Daejeon University. This case report presents results on the effect of bee venom pharmacopuncture in treating patient with CRPS. METHODS: Bee venom pharmacopuncture (BVP), 0.15 to 0.4 mL dosage, was administered at GB43. The treatment was applied each week for a total 14 times. The symptoms were evaluated using a numeric rating scale (NRS) and the dosage of pain medicine. RESULTS: On the first visit, he was taking an anticonvulsant, a trycyclic antidepressant, and an analgesic. On the NRS the worst pain in the toes received a score of 8. He also complained of severe pain and hypersensitivity when the 4(th) and the 5(th) toes were touched just slightly. Other complaint included dyspepsia, rash, and depression. After treatment, on the NRS, the score for toe pain was 0, and he no longer needed to take pain medication. During the 4-months follow-up period, he has remained without pain; neither have additional symptoms appeared nor adverse events occurred. CONCLUSION: BVP may have potential benefits for treating patients with CRPS.