Genome-wide Analysis Identified SEMA4D, Novel Candidate Gene for Temperature Sensitivity in Patients With Non-Small Cell Lung Cancer.

BACKGROUND: In the era of precision medicine, individual temperature sensitivity has been highlighted. This trait has traditionally been used for cold-heat pattern identification to understand the inherent physical characteristics, which are influenced by genetic factors, of an individual. However, genome-wide association studies (GWASs) on this trait are limited. METHODS: Using genotype data from 90 patients with advanced non-small cell lung cancer (NSCLC) and epidermal growth factor receptor mutations, we performed a GWAS to assess the association between single nucleotide polymorphisms (SNPs) and temperature sensitivity, such as cold and heat scores. The score of each participant was evaluated using self-administered questionnaires on common symptoms and a 15-item symptom-based cold-heat pattern identification questionnaire. RESULTS: The GWAS was adjusted for confounding factors, including age and sex, and significant associations were identified for cold and heat scores: SNP rs145814326, located on the intron of SORCS2 at chromosome 4p16.1, had a P-value of 1.86 × 10-7; and SNP rs79297667, located upstream from SEMA4D at chromosome 9q22.2, had a P-value of 8.97 × 10-8. We also found that the genetic variant regulates the expression level of SEMA4D in the main tissues, including the lungs and white blood cells, in NSCLC. CONCLUSIONS: SEMA4D was found to be significantly associated with temperature sensitivity in patients with NSCLC, suggesting an increased expression of SEMA4D in patients with higher heat scores. The potential role of temperature sensitivity as a prognostic or predictive marker of immune response in NSCLC should be further studied.

Comprehensive Evaluation of Traditional Herbal Medicine Combined With Adjuvant Chemotherapy on Post-Surgical Gastric Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Gastric cancer is a common cause of global mortality, with significant challenges during treatment due to side effects and complications. Traditional herbal medicine (THM) has emerged as a potential adjuvant therapy to enhance cancer treatment by reducing side effects and bolstering the immune response. This study conducted a meta-analysis to assess the efficacy and safety of THM as an adjuvant therapy in post-surgical gastric cancer patients. METHODS: PubMed, Cochrane Library, EMBASE, CNKI, CiNii, KMBASE, KISS, OASIS, RISS, and ScienceON databases were searched from inception through December, 2021. The outcomes considered in this analysis encompassed tumor response, quality of life (QoL), side effects, and tumor markers. Additionally, a frequency analysis of the most commonly used herbs in the included studies was conducted. A total of 36 randomized controlled trials (RCTs) were included, and data were extracted according to study design. The analysis compared groups receiving chemotherapy alone with those receiving both chemotherapy and THM treatment. RESULTS: The group receiving both chemotherapy and THM showed substantial improvement in tumor response compared to the chemotherapy-only control group (RR 1.25, 95% CI [1.09, 1.45]). QoL also significantly increased in the THM-treated group. Most drug adverse reactions displayed statistical significance, except for platelet reduction. Tumor markers CEA, CA19-9, and CA72-4 exhibited significant improvements, but CA125 did not. The 1, 2, and 3-year survival rates improved, with RR values of 1.08 (95% CI [1.02, 1.14]), 1.32 (95% CI [1.19, 1.47]), and 1.42 (95% CI [1.12, 1.79]) respectively. However, some publication bias was indicated. CONCLUSION: THM may offer potential benefits as a complementary approach to post-surgical anticancer therapy in gastric cancer patients. Improved tumor response, quality of life, and survival rates were reported. However, it is important to exercise caution due to the possibility of publication bias, and further research is needed to confirm these findings.Registration:PROSPERO CRD 42022354133.

Low-Molecular-Weight Fish Collagen Peptide (Valine-Glycine-Proline-Hydroxyproline-Glycine-Proline-Alanine-Glycine) Prevents Osteoarthritis Symptoms in Chondrocytes and Monoiodoacetate-Injected Rats.

The objective of this study was to investigate the effect of low-molecular-weight fish collagen (valine-glycine-proline-hydroxyproline-glycine-proline-alanine-glycine; LMWCP) on H2O2- or LPS-treated primary chondrocytes and monoiodoacetate (MIA)-induced osteoarthritis rat models. Our findings indicated that LMWCP treatment exhibited protective effects by preventing chondrocyte death and reducing matrix degradation in both H2O2-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. This was achieved by increasing the levels of aggrecan, collagen type I, collagen type II, TIMP-1, and TIMP-3, while simultaneously decreasing catabolic factors such as phosphorylation of Smad, MMP-3, and MMP-13. Additionally, LMWCP treatment effectively suppressed the activation of inflammation and apoptosis pathways in both LPS-treated primary chondrocytes and cartilage tissue from MIA-induced osteoarthritis rats. These results suggest that LMWCP supplementation ameliorates the progression of osteoarthritis through its direct impact on inflammation and apoptosis in chondrocytes.

Effect of Traditional Korean Medicine Oncotherapy on the Survival, Quality of Life, and Telomere Length: A Prospective Cohort Study.

A 4-year prospective cohort study on patients with lung, gastric, hepatic, colorectal, breast, uterine, and ovarian cancer was conducted at the East-West Cancer Center (EWCC) of Daejeon Korean Medicine Hospital in Daejeon, Korea. We divided patients into 2 groups based on how long they had been receiving TKM oncotherapy and compared event-free survival (EFS), telomere length change, and quality of life (QoL). The study collected data on 83 patients from October 2016 to June 2020 and discovered no statistical differences in EFS based on the duration of TKM oncotherapy. In the analysis of changes in QoL outcomes, there were no statistically significant group differences between the groups. After controlling for covariates that could affect telomere length, the long-term TKM oncotherapy group had a higher daily telomere attrition rate. The study of the relationship between telomere length and prognostic factors discovered that patients with advanced N stage at the time of diagnosis and who had previously received radiotherapy had shorter telomere length. When examining associations between SNP genotype and percentile score of telomere length, this study was able to confirm an association between telomere length and rs4387287. This study is significant because it is the first to assess the effects of TKM oncotherapy and investigate telomere length-related factors. To assess the effects of TKM oncotherapy on cancer patients' survival and QoL, a longer-term observational study with a larger sample size is required.

Immunostimulatory Activity of Syneilesis palmata Leaves through Macrophage Activation and Macrophage Autophagy in Mouse Macrophages, RAW264.7 Cells.

Syneilesis palmata (SP) is a traditional medicinal plant. SP has been reported to have anti-inflammatory, anticancer, and anti-human immunodeficiency virus (HIV) activities. However, there is currently no research available on the immunostimulatory activity of SP. Therefore, in this study, we report that S. palmata leaves (SPL) activate macrophages. Increased secretion of both immunostimulatory mediators and phagocytic activity was observed in SPL-treated RAW264.7 cells. However, this effect was reversed by the inhibition of TLR2/4. In addition, inhibition of p38 decreased the secretion of immunostimulatory mediators induced by SPL, and inhibition of TLR2/4 decreased the phosphorylation of p38 induced by SPL. SPL augmented p62/SQSTM1 and LC3-II expression. The increase in protein levels of p62/SQSTM1 and LC3-II induced by SPL was decreased by the inhibition of TLR2/4. The results obtained from this study suggest that SPL activates macrophages via TLR2/4-dependent p38 activation and induces autophagy in macrophages via TLR2/4 stimulation.

Comparison of the clinical effectiveness of treatments for aromatase inhibitor-induced arthralgia in breast cancer patients: A systematic review with network meta-analysis.

Aromatase inhibitor-induced arthralgia (AIA) contributes to poor adherence of aromatase inhibitor therapies in patients with breast cancer. A systematic review using network meta-analysis (NMA) was conducted to examine the clinical effectiveness of multiple therapies and rank probabilities for the management of AIA. Randomized controlled trials (RCTs) assessing treatments for AIA in postmenopausal women with stage 0-III hormone receptor-positive breast cancer were searched from inception to October 2021. The main NMA involved 1516 participants from 17 RCTs. Acupuncture was the highest ranked intervention to improve pain intensity followed by sham acupuncture, multicomponent herbal medicine, exercise, duloxetine, vitamin D, omega-3 fatty acids, physical therapy, testosterone, and inactive controls. Single natural products were inferior to controls. The current review provides new insights into the management of AIA in breast cancer survivors for increased survival and can be utilized to make evidence-based decisions regarding treatment.

SH-PRO extract alleviates benign prostatic hyperplasia via ROS-mediated activation of PARP/caspase 3 and inhibition of FOXO3a/AR/PSA signaling in vitro and in vivo.

To target benign prostatic hyperplasia (BPH) as a common urinary disease in old men, in the current study, the antiproliferative and apoptotic mechanism of SH-PRO, a mixture of Angelica gigas and Astragalus membranaceus (2:1), was evaluated in BPH-1 cells and rats with testosterone-induced BPH. Herein, SH-PRO significantly reduced the viability of BPH-1 cells and dihydrotestosterone (DHT)-treated RWPE-1 cells. Also, SH-PRO increased the sub-G1 population in BPH-1 cells and consistently attenuated the expression of pro-PARP, pro-caspase 3, Bcl2, FOXO3a, androgen receptor (AR), and prostate-specific antigen (PSA) in BPH-1 cells and DHT-treated RWPE-1 cells. Of note, SH-PRO generated reactive oxygen species (ROS) in BPH-1 cells, while ROS inhibitor N-acetyl-l-cysteine (NAC) disturbed the ability of SH-PRO to reduce the expression of pro-PARP, FOXO3a, catalase, SOD, and increase sub-G1 population in BPH-1 cells. Furthermore, oral treatment of SH-PRO significantly abrogated the weight of the prostate in testosterone-treated rats compared to BPH control with the reduced expression of AR, PSA, and DHT and lower plasma levels of DTH, bFGF, and EGF with no toxicity. Overall, these findings highlight the antiproliferative and apoptotic potential of SH-PRO via ROS-mediated activation of PARP and caspase 3 and inhibition of FOXO3a/AR/PSA signaling as a potent anti-BPH candidate.

Synergistic Effect of HAD-B1 and Afatinib Against Gefitinib Resistance of Non-Small Cell Lung Cancer.

In epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), acquired resistance to EGFR tyrosine kinase inhibitors (TKI) leads to disease progression. Strategies to overcome the resistance are required in treatment for advanced lung cancer. In this study, we investigated the therapeutic effect of afatinib and HangAmDan-B1 (HAD-B1) co-administration in gefitinib-resistant NSCLC using HCC827-GR, NSCLC cell line with gefitinib resistance, and the HCC827-GR cell implanted mouse model. HAD-B1 consists of 4 herbs, Panax notoginseng Radix, Cordyceps militaris, Panax ginseng C. A. Mey, and Boswellia carteri Birdwood, and has been reported to be effective in patients with advanced lung cancer in clinical practice. Our findings demonstrated that HAD-B1 combined with afatinib markedly inhibited cell proliferation and induced apoptosis compared to afatinib monotherapy and HAD-B1 monotherapy. Inhibition of HCC827-GR cell proliferation by HAD-B1 occurred through MET amplification and reduced phosphorylation, and the synergistic effect of afatinib and HAD-B1 induced cell cycle arrest and apoptosis in HCC827-GR cells via the downregulation of ERK and mTOR signaling pathways. In hematology and biochemistry tests, HAD-B1 alleviated the toxicity of tumor. In conclusion, HAD-B1 combined with afatinib would be a promising therapeutic strategy for NSCLC with EGFR-TKI resistance.

Immunostimulatory activity of Hovenia dulcis branches extracts through TLR4/JNK-dependent macrophage activation and TLR4-dependent macrophage autophagy in RAW264.7 cells.

Hovenia dulcis, one of the traditional medicinal plants, is currently being used as a functional ingredient for the development of health functional foods that protects the liver from alcohol damage in Korea. A variety of pharmacological effects of Hovenia dulcis have been reported so far, but studies on immune-enhancing activity are insufficient. Thus, in this study, we report that Hovenia dulcis branches (HDB) induce the activation of macrophages. HDB increased the production of immunostimulatory factors and phagocytosis in RAW264.7 cells. TLR4 inhibition blocked HDB-mediated production of immunostimulatory factors. In addition, the JNK inhibition reduced the HDB-mediated production of immunostimulatory factors, and the HDB-mediated JNK activation was blocked by the TLR4 inhibition. HDB increased the level of LC3-II and p62/SQSTM1. TLR4 inhibition blocked HDB-mediated increase in the level of LC3-II and p62/SQSTM1. These findings indicate that HDB may induce TLR4/JNK-dependent macrophage activation and TLR4-dependent macrophage autophagy.

Selective Immune Modulating Activities of Viscum album and Its Components; A Possibility of Therapeutics on Skin Rash Induced by EGFR Inhibitors.

Viscum album var. coloratum (Kom.) Ohwi is a traditional herbal medicine used in East Asia to treat hypertension, skeletal muscle disorders, and cancer. The inhibitory effects of Viscum album (VA) extract on chemokines and its therapeutic potential in erlotinib-induced skin rash were investigated in this study. ELISA was used to measure the levels of chemokines, MCP-1 and RANTES, which are thought to be mediators of erlotinib-induced skin rash in RAW264.7 cells. Western blot analysis was used to look into the activation of signaling pathways like AKT, MAPK, and EGF. In order to investigate the active compounds in VA extract, solvent fractionation and preparative HPLC were performed sequentially. VA extract significantly reduced the production of TNF-α, MCP-1, and RANTES but not IL-1. Furthermore, macrophage transmigration was inhibited without causing cell toxicity. VA extract had no effect on the phosphorylation of EGF receptors stimulated by EGF or suppressed by erlotinib in both A549, a non-small cell lung cancer cells, and Hacat, a human skin keratinocyte. The isolated viscumneoside III and viscumneoside V from VA extract significantly suppressed the expression of MCP-1, according to activity guided fractionation with organic solvent fractionation and preparative HPLC. These findings suggest that VA extract and its active compounds, viscumneoside III and viscumneoside V, regulate MCP-1 production and may have the potential to suppress erlotinib-induced skin toxicity by modulating macrophage activity without neutralizing anti-cancer efficacy.

The Current Status of Integrative Oncology in Korea.

Cancer is one of the leading causes of death worldwide, and Korea is no exception. Humanity has been fighting cancer for many years, and as a result, we now have effective treatments such as chemotherapy, radiation, and surgery. However, there are other issues that we are only now beginning to address, such as cancer patients' quality of life. Moreover, numerous studies show that addressing these issues holistically is critical for overall cancer treatment and survival rates. This paper describes how Korea is attempting to reduce cancer incidence and recurrence rates while also managing the quality of life of cancer patients. Integrative Oncology is the field that addresses these broad issues, and understanding the current state of integrative oncology in Korea is critical. The goal of this paper is to provide an overview of the current state of integrative oncology in Korea as well as to look ahead to future developments.

Acute and sub-chronic toxicological evaluation of the herbal product HAD-B1 in Beagle dogs.

HAD-B1 is a herbal formula originated from Korean Traditional Medicine that used to treat lung cancer patients. Herein we assessed acute and sub-chronic toxicity of HAD-B1 in beagle dogs. Acute study, 4 weeks dose rate finding (DRF) study and sub chronic toxicity study for 13 weeks were done by oral administration at doses of 0, 500, 1000, and 2000 mg/kg. Neither oral acute toxicity study nor DRF study showed any significant clinical signs, death, or weight changes. Based on that, a sub-chronic study for 13-weeks was performed. As a result, HAD-B1 caused a decrease of mean daily feed consumption in females, infiltration of intestinal inflammatory cells in both sexes, a significant decrease in total cholesterol (TCHO) in females, Kupffer cell hypertrophy/hyperplasia in the liver as well as dilation of the sinusoid. However, there were no significant toxic effects in the treated group compared to the control group. Therefore, the No Observed Adverse Effect Level (NOAEL) of the HAD-B1 is at least 2000 mg/kg/day when administrated orally for 13 consecutive weeks. These results demonstrate that HAD-B1 consumption is relatively non-toxic and safe for clinical usage.

Nonclinical Safety Pharmacology Study of the Herbal Product HAD-B1.

HAD-B1 is a Korean herbal formula designed to treat solid tumors, and through cell experiments, it has proven to have an anticancer effect. The current study aims to test the safety of HAD-B1. This experiment is under the regulation of ICH. In order to find if HAD-B1 has any effect on the CNS, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally administered to male and female rats once. To discover any effect on the respiratory system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male rats followed by measuring the respiratory rate, tidal volume, and minute respiratory volume. To assess the possibility of a delayed QT period as a result of the drug administration, hERG analysis was conducted at 0, 0.1, 0.3, and 1 µg/ml. To assess any effect on the cardiovascular system, 0, 500, 1000, and 2000 mg/kg/day of HAD-B1 were orally given to male beagle dogs once followed by temperature, blood pressure, ECG, and heart rate analyses. There were no clinically significant changes in both male and female rats on assessing any effects on the CNS. There were no clinically significant changes in male rats' respiratory assessment. There were no clinically significant changes in hERG analysis results. There were no clinically significant changes in the cardiovascular system of male beagle dogs. Our results demonstrate that HAD-B1 is a safe herbal formula that does not have a clinically significant effect on the CNS, respiratory, and cardiovascular systems.

Artichoke Extract Directly Suppresses Inflammation and Apoptosis in Hepatocytes During the Development of Non-Alcoholic Fatty Liver Disease.

We evaluated the effect of artichoke leaf extract (ALE) on the livers of mice with non-alcoholic fatty liver disease (NAFLD) induced by high-fat/high-fructose diet and H2O2-treated HepG2 cells, as well as the mechanism underlying its hepatoprotective effects. Supplementation with ALE suppressed the NAFLD-induced increases in serum lipids, bilirubin, gamma-glutamyl transferase, aspartate transaminase (AST), and alanine aminotransferase. In addition, we observed that supplementation with ALE attenuated the increases in antioxidant enzyme activity, mRNA levels of proinflammatory cytokines, and apoptosis signaling pathways caused by a high-fat/high-fructose diet. We found that ALE treatment suppressed inflammation and apoptosis caused by H2O2-induced oxidative stress in HepG2 cells. These findings suggest that ALE supplementation directly suppresses inflammation and apoptosis in hepatocytes during the development of NAFLD. Based on these results, we suggest that supplementation with ALE may be useful for preventing the progression of liver diseases, including hepatic steatosis and non-alcoholic steatohepatitis.

Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Evaluate the Efficacy and Safety of HAD-B1 for Dose-Finding in EGFR Mutation Positive and Locally Advanced or Metastatic NSCLC Subjects Who Need Afatinib Therapy.

Afatinib is a target anticancer drug of the second-generation EGFR TKI type, showing an advantage in treatment effect compared to conventional chemotherapy. However, patients on EGFR-TKI drugs also usually progress after 9 to 13 months according to secondary resistance. HAD-B1 is composed of drugs that are effective against lung cancer. This study is an exploratory study to evaluate the efficacy and safety between dosage groups by conducting a clinical trial in subjects requiring afatinib drug treatment in non-small cell lung cancer with EGFR mutation positive to determine the optimal dosage for HAD-B1 administration. At the final visit compared to before administration, each change in the disease control rate was measured according to the HAD-B1 doses of the test group 1 (972 mg), the test group 2 (1944 mg), and the control group. The efficacy and safety of HAD-B1 were compared and evaluated through sub-evaluation variables. As a result of the study, there was no statistically significant difference in the disease control rate at 12 weeks after dosing, but complete and partial remission were evaluated as 1 patient each in the test group 1, and none in the other groups. There was no statistically significant difference between groups in the sub-evaluation variable. In addition, there was no problem of safety from taking the test drug. However, the initially planned number of subjects was 66, but the number of enrolled subjects was only 14, which may limit the results of this study.

Acute and Subchronic Toxicological Evaluation of the Herbal Product HAD-B1 in Rats.

This study evaluates acute and subchronic toxicity of a Korean herbal formula HAD-B1 in rat to investigate whether HAD-B1 has potential toxicity to humans. First, the study to assess the acute oral toxicity at dose levels of 0, 500, 1000, and 2000 mg/kg body weight (BW) was performed in male and female SD rats (Crl: CD, specific pathogen-free) (n = 5/group). Based on the result of the acute oral study, 4 weeks' dose range finding study and 13 weeks' subchronic study were performed (dose range finding study, DRF; n = 5/group) and 13 weeks (subchronic study; n = 10/group) in male and female SD rats. The control group was administered with distilled water (DW). Clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematological/biochemical parameters, gross finding at necropsy, and histopathological examination were investigated and recorded. In the oral acute toxicity study of SD rats, no clinical signs, mortality, body weight changes, and gross findings were observed. Also, there were no treatment-related changes in the 4-week DRF study. Based on these results, a 13-week repeated-dose toxicity study (subchronic) in SD rats was performed. HAD-B1 showed temporal hypersalivation in clinical signs and an increased tendency in body weight at 2000 mg/kg BW. However, there were no treatment-related changes in mortality, food consumption, ophthalmology, urinalysis, hematology, biochemistry, gross finding at necropsy, organ weights, and histopathology in either sex of any group. Based on this toxicological evaluation of HAD-B1, we concluded that no target organ was determined, and the no observed adverse effect level (NOAEL) of HAD-B1 was determined to be > 2000 mg/kg B W. Therefore, we decided that consuming HAD-B1 is relatively nontoxic.

Electroacupuncture for post-thoracotomy pain: A systematic review and meta-analysis.

BACKGROUND: Thoracotomy is an invasive surgical procedure that produces intense postoperative pain. Electroacupuncture has been used to induce analgesia in various situations, including after surgery. The aim of the following systematic review and meta-analysis was to evaluate the effect of electroacupuncture on post-thoracotomy pain. METHODS: The studies for the systematic review were searched using the following 9 databases: PubMed, Cochrane Library, EMBASE, MEDLINE Complete, Google Scholar, China National Knowledge Infrastructure (CNKI), Korean Medical Database (KMBASE), Koreanstudies Information Service System (KISS), and OASIS, without language restriction. Randomized controlled trials (RCTs) that met the inclusion criteria were selected. The quality assessment was performed using the Cochrane risk-of-bias tool, and RevMan 5.3 was used for meta-analysis. The review protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42019142157. RESULTS: Eleven randomized controlled trials were included in the systematic review. The meta-analysis was performed for two outcome measures: pain score 24 hours after surgery and total dose of opioid analgesics. A subgroup analysis was performed according to the control group: sham acupuncture and conventional analgesia group. Pain score 24 hours after surgery of electroacupuncture group showed a standard mean difference of -0.98 (95% CI: -1.62 to -0.35) compared to sham acupuncture. The standard mean difference was -0.94 (95% CI: -1.33 to -0.55) compared to conventional analgesia. The total dose of opioid analgesics of electroacupuncture group showed a standard mean difference values of -0.95 (95% CI: -1.42 to -0.47) compared to sham acupuncture. The standard mean difference was -1.96 (95% CI: -2.82 to -1.10) compared to conventional analgesia. CONCLUSION: Current evidence suggests that electroacupuncture might provide useful pain relieving effect on post-thoracotomy patients. However, due to low quality and high heterogeneity of existing data, further rigorously designed studies should be performed to confirm the safety and efficacy.

Efficacy and Safety of Yukgunja-Tang for Patients with Cancer-related Anorexia: A Randomized, Controlled Trial, Pilot Study.

OBJECTIVE: The purpose of this study is both to estimate the efficacy and the safety of Yukgunja-tang (YGJT) and to establish evidence for the use of herbal medicines in the management of patients with cancer-related anorexia. METHODS: We enrolled 40 patients with cancer-related anorexia. The enrolled participants were randomly allocated to 2 groups: the control group (n = 20), which received nutrition counseling, and the treatment group (n = 20), which received nutrition counseling and was administered YGJT at twice a day for 4 weeks (a total of 56 times @ 3.0 g each time). The primary outcome of this study was the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes were the FAACT score with the ACS score excluded, the score on the Visual Analog Scale (VAS) for appetite, and the results on laboratory tests regarding appetite, such as leptin, tumor necrosis factors (TNF-α), interleukin-6 (IL-6), and ghrelin. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (complete blood cell count, chemistry, urine test), and adverse events, were documented on the case report form (CRF) at every visit. RESULT: The difference in the primary outcome, that is, the score on the anorexia/cachexia subscale (ACS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT), between the control and the treatment groups was statistically significant (P = .023) as was the difference in the FAACT scores with the ACS score excluded, a secondary outcome, between the 2 groups; however, no statistically significant differences were noted in the scores on the VAS or the levels of leptin, TNF-α, IL-6, and ghrelin. In addition, no significant differences in the numbers and the types of adverse events or in the results on the laboratory tests between the control and the treatment groups were recorded. CONCLUSION: These results obtained in this research confirmed the efficacy and the safety of using YGJT as a herb-medicine treatment option for patients with cancer-related anorexia.

A randomized, multi-center, open-label study to compare the safety and efficacy between afatinib monotherapy and combination therapy of afatinib and HAD-B1 for the locally advanced or metastatic NSCLC patients with EGFR mutations.

BACKGROUND: Afatinib is an epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) with proven efficacy for treating patients with advanced or metastatic non-small cell lung cancer (NSCLC). Unfortunately, responses are limited by acquired resistance. Because traditional Korean medicine may have synergistic effects when combined with chemotherapy or radiotherapy, the aim of our study is to elucidate the efficacy and safety of afatinib plus HangAmDan-B1 (HAD-B1) combination therapy in the treatment of patients with NSCLC, as well as EGFR mutations, who need afatinib therapy. METHODS/DESIGN: This study is a randomized, multi-center, open clinical trial. A total of 178 eligible subjects, recruited at 8 centers, are randomly assigned to take Afatinib (20-40 mg) ±â€ŠHAD-B1 (0.972 g/day) for 48 weeks. In the test group, HAD-B1 and afatinib will be used in combination. The primary outcome is a comparison of progression-free survival (PFS) between afatinib monotherapy and afatinib plus HAD-B1 combination therapy in patients with local advanced or metastatic (Stage IIIA, B, C/IV) NSCLC. Secondary outcomes are the overall survival rates, clinical responses, tumor size reductions, health-related qualities of life, and safety. DISCUSSION: The result of this clinical trial will provide evidence for the efficacy and safety of using HAD-B1 in the treatment of EGFR-positive patients with locally advanced or metastatic NSCLC who require afatinib therapy. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea (ID: KCT0005414), on September 23, 2020.

Clinical Evaluation of Acetaminophen-Galgeuntang Interaction Based on Population Approaches.

Galgeuntang (GGT), a traditional herbal medicine, is widely co-administered with acetaminophen (AAP) for treatment of the common cold, but this combination has not been the subject of investigation. Therefore, we investigated the herb-drug interaction between GGT and AAP by population pharmacokinetics (PKs) modeling and simulation studies. To quantify PK parameters and identify drug interactions, an open label, three-treatment, three-period, one-sequence (AAP alone, GGT alone, and AAP and GGT in combination) clinical trial involving 12 male healthy volunteers was conducted. Ephedrine (EPD), the only GGT component detected, was identified using a one-compartment model. The PKs of AAP were described well by a one-compartment model and exhibited two-phase absorption (rapid followed by slow) and first-order elimination. The model showed that EPD significantly influenced the PKs of AAP. The simulation results showed that at an AAP dose of 1000 mg × 4 times daily, the area under the concentration versus time curve of AAP increased by 16.4% in the presence of GGT compared to AAP only. In conclusion, the PKs of AAP were affected by co-administration of GGT. Therefore, when AAP is combined with GGT, adverse effects related to overdose of AAP could be induced possibly.