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BACKGROUND: Lung cancer, especially non-small cell lung cancer (NSCLC), poses a significant health challenge globally due to its high mortality. Afatinib, a second-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has shown superior efficacy over traditional chemotherapy in NSCLC treatment. However, issues like secondary resistance and adverse effects call for alternative therapies. HAD-B1, comprising 4 herbal medicines, has shown promise in lung cancer treatment in both preclinical and clinical settings. This study assesses the combination of HAD-B1 and Afatinib in advanced NSCLC patients to potentially improve outcomes by addressing the limitations of current EGFR-TKI therapies. METHOD: A randomized, open-label trial evaluated the efficacy and safety of HAD-B1 with Afatinib in 90 EGFR-mutation-positive NSCLC patients. Participants were divided into treatment and control groups, receiving Afatinib with or without HAD-B1. The study focused on the initial dose maintenance rate and disease control rate (DCR) of Afatinib, alongside secondary outcomes like survival rates and quality of life, under continuous safety monitoring. RESULTS: Among the 90 participants, no significant difference was found in initial dose maintenance (60.98% in the treatment group vs 52.50% in the control, P = .4414) or DCR (80.49% vs 90.00%, P = .2283). Secondary outcomes like PFS, TTP, and OS showed no notable differences. However, physical functioning significantly improved in the treatment group (P = .0475, PPS group). The control group experienced higher rates of adverse events of special interest and adverse drug reactions (P = .01), suggesting HAD-B1 with Afatinib might enhance physical function without increasing adverse effects. CONCLUSION: Combining HAD-B1 with Afatinib potentially improves quality of life and reduces adverse events in advanced NSCLC patients. Further research is necessary to confirm the long-term benefits of this combination therapy, aiming to advance NSCLC treatment outcomes. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) of the Republic of Korea, https://cris.nih.go.kr/ (ID: KCT0005414).
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Afatinib , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Calidad de Vida , Humanos , Afatinib/uso terapéutico , Afatinib/efectos adversos , Afatinib/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Femenino , Persona de Mediana Edad , Receptores ErbB/genética , Anciano , Adulto , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologíaRESUMEN
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.
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Antígenos CD , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Semaforinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Estudio de Asociación del Genoma Completo , TemperaturaRESUMEN
Atezolizumab (a PD-L1 inhibitor) has shown remarkable efficacy and tolerability in various cancer types. Despite its efficacy and safety, atezolizumab monotherapy has limitations, such as acquired resistance and adverse events. Bojungikki-tang (BJIKT) is an herbal decoction widely prescribed in Asian countries and used to treat cancer-related symptoms including fatigue, appetite loss, gastrointestinal disorders, and other side effects from cancer therapy. Due to its immunomodulatory effects, Bojungikki-tang has been investigated as a combined treatment with anticancer agents. We evaluated the potential drug-drug interaction (DDI) between Bojungikki-tang and the anti-PD-L1 antibody based on the Food and Drug Administration (FDA) guidelines. In the study, we conducted an in vivo drug-drug interaction study using a syngeneic mouse model of CMT-167 in C57BL/6. We then determined the antibody concentrations to evaluate the pharmacokinetic (PK) drug-drug interaction and measured variable biomarkers related to therapeutic efficacy and immune response. The pharmacodynamic (PD) drug-drug interaction study investigated changes in response between anti-PD-L1 antibody monotherapy and combination therapy. Using the pharmacokinetic and pharmacodynamic data, we conducted a statistical analysis to assess drug-drug interaction potential. In the presence of Bojungikki-tang, the pharmacokinetic characteristics of the anti-PD-L1 antibody were not changed. This study suggested that combination treatment with Bojungikki-tang and atezolizumab is a safe treatment option for non-small cell lung cancer. Clinical studies are warranted to confirm this finding.
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Cancer immunotherapy with immune checkpoint inhibitors (ICIs) is a major treatment option for several types of cancer, including non-small cell lung cancer (NSCLC). The proposed study aims to investigate the safety and efficacy of Bojungikki-tang (BJIKT) therapy (an herbal medicine) in patients with advanced NSCLC treated with ICIs. This multicenter, randomized, placebo-controlled pilot study will be performed at three academic hospitals. Thirty patients with advanced NSCLC, undergoing atezolizumab monotherapy as second- and subsequent-line treatment, will be recruited and randomly assigned to either BJIKT treatment (atezolizumab + BJIKT) or placebo (atezolizumab + placebo). The primary and secondary outcomes are the incidence of adverse events (AEs), including immune- related AEs (irAEs) and non-immune-related AEs (non-irAEs); and early termination rate, withdrawal period, symptom improvement of fatigue, and skeletal muscle loss, respectively. The exploratory outcomes are patient objective response rate and immune profile. This is an ongoing trial. Recruitment started on 25 March 2022 and is expected to be completed by 30 June 2023. This study will provide basic evidence for the safety profiles, including irAEs, of herbal medicine in patients with advanced NSCLC treated with ICIs.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Proyectos Piloto , Extractos Vegetales/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como AsuntoRESUMEN
Treatment strategies combining immune checkpoint inhibitors with sesquiterpene lactones have attracted much attention as a promising approach for cancer treatment. We systemically analyzed gene expression profiles of cells in response to two major sesquiterpene lactones, alantolactone and isoalantolactone, and determined whether the sesquiterpene lactone-rich fraction of Inula helenium L. (SFIH) enhances the antitumor effect of anti-PD-1 antibody in MC38 colorectal cancer-bearing mice. Gene expression and pathway analysis using RNA sequencing data were used to identify the SFIH-driven combined activity with anti-PD-1 antibody. The results showed that SFIH significantly enhanced the antitumor effect of anti-PD-1 antibody by reducing tumor growth and increasing the survival time of mice. Specifically, SFIH exhibited antitumor activity when combined with anti-PD-1 antibody, and the effects were further enhanced compared with monotherapy. An analysis of immune cells indicated that combination treatment with SFIH and anti-PD-1 antibody significantly increased the proportion of CD8+ T cells. Moreover, combination treatment enhanced antitumor immunity by decreasing the population of myeloid-derived suppressor cells and increasing the number of M1-like macrophages. Pathway enrichment analysis revealed that combination therapy activated immune-related pathways to a greater extent than monotherapy. In conclusion, our integrative analysis demonstrates that SFIH enhances the response of murine tumors to anti-PD-1 antibody. These findings provide insight into developing integrative therapeutics and molecular data for the use of natural products as an adjunct treatment for colorectal cancer.
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Plasma cell-free DNA (cfDNA) sequencing data have been widely studied for early diagnosis and treatment response or recurrence monitoring of cancers because of the non-invasive benefits. In cancer studies, whole exome sequencing (WES) is mostly used for discovering single nucleotide variants (SNVs), but it also has the potential to detect copy number alterations (CNAs) that are mostly discovered by whole genome sequencing or microarray. In clinical settings where the quantity of the acquired blood from the patients is limited and where various sequencing experiments are not possible, providing various types of mutation information such as CNAs and SNVs using only WES will be helpful in the treatment decision. Here, we questioned whether the plasma cfDNA WES data for patients with advanced non-small cell lung cancer (NSCLC) could be exploited for CNA detection. When the read count (RC) signals of the WES data were investigated, a similar fluctuation pattern was observed among the signals of different samples, and it can be a major challenge hindering CNA detection. When these RC patterns among cfDNA were suppressed by the method we proposed, the cancerous CNAs were more distinguishable in some samples with higher cfDNA quantity. Although the potential to detect CNAs using the plasma cfDNA WES data for NSCLC patients was studied here, further studies with other cancer types, with more samples, and with more sophisticated techniques for bias correction are required to confirm our observation. In conclusion, the detection performance for cancerous CNAs can be improved by controlling RC bias, but it depends on the quantity of cfDNA in plasma.
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Carcinoma de Pulmón de Células no Pequeñas , Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Secuenciación del Exoma , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Carcinoma de Pulmón de Células no Pequeñas/genética , Variaciones en el Número de Copia de ADN/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Ácidos Nucleicos Libres de Células/genética , Biomarcadores de Tumor/genéticaRESUMEN
Vaginal cancer is a rare and uncommon disease that is rarely discussed. Although vaginal cancer traditionally occurs in older postmenopausal women, the incidence of high-risk human papillomavirus (HPV)-induced cancers is increasing in younger women. Cervical cancer cells contain high-risk human papillomavirus (HPV) E6 and E7 proteins and inhibiting HPV gene expression leads the cells to stop proliferating and enter senescence. As E6, and E7 protein promoted the carcinogenesis mechanism, and here not only regulate the cellular degradation of P53, and pRb but also enhances the cell proliferation along with E6 protein targets the p53 for breakdown and subsequently promote the apoptotic cell death, and DNA repair inhibition, that is indispensable to the continue the lifecycle of the HPV. As a synchronous or metachronous tumor, vaginal cancer is frequently found in combination with cervical cancer. It is uncertain what causes invasive female vaginal organ cancer. HPV type 16 is the most often isolated HPV type in female vaginal organ cancers. Due to cancer's rarity, case studies have provided the majority of etiologic findings. Many findings demonstrate that ring pessaries, chronic vaginitis, sexual behavior, birth trauma, obesity, vaginal chemical exposure, and viruses are all risk factors. Because of insufficient understanding and disease findings, we are trying to find the disease's mechanism with the available data. We also address different risk factors, therapy at various stages, diagnosis, and management of vaginal cancer in this review.
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Immune checkpoint blockage targeting PD-L1 has led to breakthroughs in cancer treatment. Although anti-PD-L1-based immunotherapy has been approved as standard therapy in various cancer types, its therapeutic efficacy in most colorectal cancers (CRC) is still limited due to the low response to immunotherapy. Therefore, combining treatment with herbal medicines could be an alternative approach for treating CRC to overcome this limitation. Bojungikki-Tang (BJIKT), a herbal formula used in traditional Chinese medicine, clinically improves the quality of life for cancer patients and has been associated with antitumor and immune-modulating activities. However, the regulatory effect of BJIKT on the immune response in the tumor microenvironment remains largely uninvestigated. In this study, we verified the inhibitory effect of BJIKT on tumor growth and investigated the regulatory effect of combination therapy with BJIKT and anti-PD-L1 on antitumor immune responses in an MC38 CRC-bearing C57BL/6 mouse model. Immune profiling analysis by flow cytometry was used to characterize the exact cell types contributing to anticancer activities. Combination treatment with BJIKT and anti-PD-L1 therapy significantly suppressed tumor growth in MC38-bearing mice and increased the proportion of cytotoxic T lymphocytes and natural killer cells in tumor tissues. Furthermore, BJIKT suppressed the population of myeloid-derived suppressor cells, suggesting that this combination treatment effectively regulates the immunological function of T-cells by improving the tumor microenvironment. The herbal formula BJIKT can be a novel therapeutic option for improving anti-PD-L1-based immunotherapy in patients with CRC.
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New approaches to personalized medicine are made possible by the discovery of biomarkers [...].
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The overexpression of matrix metalloproteinase-9 (MMP-9) is associated with tumor development and angiogenesis, and hence, it has been considered an attractive drug target for anticancer therapy. To assist in drug design endeavors for MMP-9 targets, an in silico study was presented to investigate whether our compounds inhibit MMP-9 by binding to the catalytic domain, similar to their inhibitor or not. For that, in the initial stage, a deep-learning algorithm was used for the predictive modeling of the CHEMBL321 dataset of MMP-9 inhibitors. Several regression models were built and evaluated based on R2, MAE MSE, RMSE, and Loss. The best model was utilized to screen the drug bank database containing 9,102 compounds to seek novel compounds as MMP-9 inhibitors. Then top high score compounds were selected for molecular docking based on the comparison between the score of the reference molecule. Furthermore, molecules having the highest docking scores were selected, and interaction mechanisms with respect to S1 pocket and catalytic zinc ion of these compounds were also discussed. Those compounds, involving binding to the catalytic zinc ion and the S1 pocket of MMP-9, were considered preferentially for molecular dynamics studies (100 ns) and an MM-PBSA (last 30 ns) analysis. Based on the results, we proposed several novel compounds as potential candidates for MMP-9 inhibition and investigated their binding properties with MMP-9. The findings suggested that these compounds may be useful in the design and development of MMP-9 inhibitors in the future.
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This study was performed to provide information on classifying eye irritating chemicals using the BCOP assay. After the BCOP assay, bovine corneas were classified by IVIS presented in OECD test guideline 437, and three special staining methods (H&E, MT, and PAS) were performed for histopathological evaluation. Non-irritant chemicals (IVIS ≤ 3), showed intact structures. In the 3 < IVIS ≤ 55 group, epithelial cell edema was observed by H&E staining, and loose collagen bundles were confirmed by MT staining. In PAS staining, bleaching of the epithelium and reduced visibility of the basement membrane were observed. Severe irritant chemicals (IVIS > 55) showed large increases edema and nuclear condensation by H&E staining. Loose collagen bundles and vacuoles around keratocytes were also observed by MT staining. Bleaching of the epithelial layer, reduction in visibility, and thickness of the basement membrane were confirmed by PAS staining. Based on the stepwise histopathological analysis, we set the criteria and grades for histopathological evaluation and found that eye irritation was increased following the irritation degree of test chemicals. Further histopathological study will support and lead to improvements in the BCOP assay.
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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.
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Oncología Integrativa , Neoplasias , Humanos , Neoplasias/terapia , Calidad de Vida , República de Corea/epidemiología , Tasa de SupervivenciaRESUMEN
The cold-heat syndrome type (ZHENG) is one of the essential elements of syndrome differentiation in East Asian Medicine. This pilot study aimed to explore the characteristics of non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) based on the cold-heat syndrome type. Twenty NSCLC patients treated with ICI monotherapy were included in the study and completed the cold-heat syndrome differentiation questionnaire. Demographic and clinical characteristics of the included patients were obtained through electronic medical records. Additionally, blood samples of 10 patients were analyzed with cytokine level and immune profiling. Patients were divided into two groups of cold type (n = 9) and non-cold type (n = 11), according to the cold symptoms questionnaire's cutoff point. No significant difference between the two groups was observed in clinical response to ICIs (p=0.668). Progression-free survival (PFS) seemed to be longer in patients with non-cold type than cold type (p=0.332). In patients with adenocarcinoma, the non-cold type showed longer PFS than the cold type (p=0.036). Also, there were more patients with PD-L1 negative in the cold type compared to the non-cold type (p=0.050). In immune profiling, the proportion of effector memory CD8 T-cells was higher in patients with cold type than with non-cold type (p=0.015), and the proportion of terminal effector CD8 T-cells was lower in patients with cold type than with non-cold type (p=0.005). This pilot study has shown the potential for differences in prognosis and immune status between patients with cold and non-cold types. Hopefully, it provides essential information and insight into NSCLC patients' characteristics from the perspective of syndrome differentiation. Further large-scale observational studies and intervention studies are required.
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In order to overcome the limitations of single in vitro eye irritation tests, Integrated Approaches to Testing Assessment strategies have been suggested for evaluating eye irritation. This study developed two tiered approaches combining alternative test methods. They were designed in consideration of the solubility property of test chemicals and to use the RhCE tests at final steps. The tiered approach A is composed of the STE, BCOP, HET-CAM or RhCE tests, whereas the tiered approach B is designed to perform simultaneously two in vitro test methods at the first stage and the RhCE test at the final stage. The predictive capacity of the two tiered approaches was estimated using 47 chemicals. The accuracy, sensitivity, and specificity value of the tiered approach A were 95.7% (45/47), 100% (34/34), and 84.6% (11/13), respectively, whereas those of the tiered approach B were 95.7% (45/47), 97.1% (33/34), and 92.3% (12/13), respectively. The approach A and B were considered to be available methods for distinguishing test chemicals of Category 1 (all 73.3%) and No Category (84.6% and 92.3%), respectively. Especially, the approach B was considered as an efficient method as the Bottom-Up approach, because it predicted correctly test chemicals classified as No Category.
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Córnea/efectos de los fármacos , Epitelio/efectos de los fármacos , Irritantes/toxicidad , Pruebas de Toxicidad , Alternativas a las Pruebas en Animales , Animales , Bovinos , Embrión de Pollo , Membrana Corioalantoides/efectos de los fármacos , Opacidad de la Córnea/inducido químicamente , Humanos , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Anorexia is a common cause of malnutrition and is associated with negative effects on the quality of life (QOL) for patients with cancer. Management of appetite is the key to improving both the QOL and the prognosis for such patients. Yukgunja-tang (YGJT) is a traditional herbal medicine extensively prescribed in Korea as a remedy for various gastrointestinal syndromes. Currently, no standardized herbal medicine treatment exists for patients with cancer who are suffering from anorexia after surgery, chemotherapy, and/or radiotherapy. For that reason, this study aims to examine the efficacy and the safety of using YGJT to treat anorexia in such patients and to establish whether or not YGJT can be recommended as the primary therapy. METHODS: We will enroll 52 cancer patients diagnosed with anorexia. The enrolled participants will be randomly allocated to 2 groups: The control group will receive nutrition counseling, and the YGJT group will receive nutrition counseling and be administered YGJT at a dose of 3âg twice a day for 4 weeks (a total of 56 doses of 3.0âg per dose). The primary outcome of this study is the change in the score on the anorexia/cachexia subscale (A/CS) of the Functional Assessment of Anorexia/Cachexia Therapy (FAACT). The secondary outcomes are the changes in the FAACT score with the A/CS score excluded, the score on the Visual Analogue Scale (VAS) for appetite, the weight and the body mass index (BMI), and laboratory tests for compounds such as leptin, tumor necrosis factor-α (TNF-α), ghrelin, and IL-6. All variables related to the safety assessment, such as vital signs, electrocardiography results, laboratory test results (CBC, chemistry, urine test), and adverse events, will be documented on the case report form (CRF) at every visit. CONCLUSION: This study is the first randomized controlled trial to investigate the efficacy and the safety of using YGJT for treating patients with cancer-related anorexia in Korea. We designed this study based on previous research about YGJT. This study will serve as a pilot and provide data for planning further clinical trials on herbal medicine and cancer-related anorexia. TRIAL REGISTRATION: Clinical Research Information Service (CRIS), Republic of Korea, ID: KCT0002847. Registered retrospectively on 3 April 2018.
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Anorexia/tratamiento farmacológico , Anorexia/etiología , Caquexia/tratamiento farmacológico , Caquexia/etiología , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Apetito , Índice de Masa Corporal , Peso Corporal , Método Doble Ciego , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/efectos adversos , Femenino , Pruebas Hematológicas , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Calidad de Vida , República de Corea , Proyectos de Investigación , Adulto JovenRESUMEN
We investigated the antitumor effect of Cordyceps militaris extract (CME) on A549 cisplatin-resistant (CR) lung cancer cells. The proliferation of A549/CR cells was suppressed by CME. Apoptosis of the cells was induced by CME. The cell cycle arrest was observed in the sub-G1 phase in the cells treated with CME. Proteomic profile analysis showed that H-Ras was downregulated in CME-treated cells and it was confirmed by western blot analysis. Collectively, these data demonstrated that CME is an alternative treatment for the anticancer effect.
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Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cordyceps/química , Neoplasias Pulmonares/fisiopatología , Proteína Oncogénica p21(ras)/genética , Extractos Vegetales/farmacología , Células A549 , Apoptosis/efectos de los fármacos , Regulación hacia Abajo/efectos de los fármacos , Resistencia a Antineoplásicos , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteína Oncogénica p21(ras)/metabolismoRESUMEN
INTRODUCTION: Bu-Zhong-Yi-Qi-Tang (BZYQT) is an herbal drug that is widely used to treat various diseases, including gastrointestinal diseases, allergic rhinitis, and atopic dermatitis (AD) in East Asian countries. BZYQT has been shown to have anti-allergic, anti-inflammatory, and immunoregulatory properties in experimental studies, and there is substantial clinical evidence of its effect on AD. This review will systematically assess the evidence of BZYQT for the treatment of AD. METHODS/DESIGN: Eleven databases will be searched from their inception without language restriction. Randomized controlled trials that examined BZYQT or modified BZYQT for AD will be included. The selection of the studies, data abstraction, and validations will be performed independently by 2 researchers. The methodological qualities of the randomized controlled trials will be assessed using the Cochrane Collaboration tool for assessing the risk of bias. ETHICS AND DISSEMINATION: This systematic review will be published in a peer-reviewed journal and will also be disseminated electronically or in print. It will be useful to inform and guide healthcare practitioners. TRIAL REGISTER NUMBER: CRD42018105173.
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Dermatitis Atópica/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Asia Oriental/epidemiología , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/efectos de los fármacos , Ensayos Clínicos Controlados Aleatorios como Asunto , Rinitis Alérgica/tratamiento farmacológico , Resultado del TratamientoRESUMEN
OBJECTIVES: Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+. METHODS: An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains of Salmonella typhimurium and Escherichia coli (E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and an in vivo micronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety. RESULTS: According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on the in vitro genotoxicity tests, including the Ames test and the chromosome aberration test, or on the in vivo in mice bone marrow micronucleus test. CONCLUSION: On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.
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In this study, a method which is environmentally sound, time and energy efficient has been used for recovery of indium from used liquid crystal display (LCD) panels. In this method, indium tin oxide (ITO) glass was crushed to micron size particles in seconds via high energy ball milling (HEBM). The parameters affecting the amount of dissolved indium such as milling time, particle size, effect time of acid solution, amount of HCl in the acid solution were tried to be optimized. The results show that by crushing ITO glass to micron size particles by HEBM, it is possible to extract higher amount of indium at room temperature than that by conventional methods using only conventional shredding machines. In this study, 86% of indium which exists in raw materials was recovered about in a very short time.