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The oral disintegrating film (ODF) has advantages over suspension and tablet. These include convenience of administration, patient compliance, and accurate dosing. We evaluated the bioequivalence between the ODF and the meloxicam suspension by using a crossover design with a 3-week washout period. Six healthy male beagle dogs were randomized to receive both formulations of meloxicam, 2 mg. Plasma meloxicam concentrations were measured at the same times. From the start until maximum concentration, the initial absorption of the ODF meloxicam formulation was more rapid (2.08 ± 1.56 hr) as compared to the suspension (3.33 ± 1.03 hr). Mean elimination half-lives were 28.77 ± 4.01 and 32.85 ± 9.79 hr for the ODF and the suspension, respectively. Bioequivalence of the ODF was confirmed, based on the relative ratios of geometric mean concentrations (and 90% confidence intervals within the range of 80%-125%) for a maximum concentration of 101.05% (88.59-115.25), for the area under the plasma concentration-time curve (AUC) to the last sampling time of 96.07% (87.06-115.25), and for AUC to infinity of 92.65% (86.76-98.94). The meloxicam ODF may be used as an alternative to suspension formulations in the treatment of inflammatory joint diseases and painful musculoskeletal disorders.

INTRODUCTION We assessed the characteristics of micro-enterprises (businesses with fewer than five workers) focusing on occupational safety and health (OSH) issues. METHODS We performed a secondary analysis of data from the Economically Active Population Supplementary Survey and the fourth Korean Working Conditions Survey of 2014. RESULTS Relative to larger businesses, micro-enterprises employ more women, temporary workers, and older workers (>55 years). In addition, more workers in micro-enterprises held "elementary occupations" (unskilled or under-skilled) or "sales and service jobs." Key sectors of such employment included the sectors of "wholesale and retail trade" and "hotel and restaurants." Furthermore, lower skilled workers in such micro-enterprises more frequently reported exposure to ergonomic risk factors and subsequent musculoskeletal disorders, and they also experienced a much higher fatality rate due to occupational injuries. CONCLUSION Our results indicate that Korean workers in micro-enterprises are more vulnerable to OSH problems than workers in larger businesses.

BACKGROUND Permanent jobs are in decline world-wide, and are being replaced with temporary, casual, part-time, and contract jobs. We investigated the characteristics and occupational safety and health (OSH) vulnerabilities of workers with nonstandard and standard employment. METHODS We used the Korean Working Conditions Survey of 2017 to compare working conditions and OSH vulnerabilities of workers with standard and nonstandard employment in five major job categories. RESULTS Workers with nonstandard employment were older, less educated, had lower monthly incomes, were employed in smaller businesses, worked fewer hours per week, had shorter work durations, and were more likely to report exposure to physical/chemical and ergonomic hazards, and musculoskeletal and mental symptoms. Among nonstandard workers, the rates of occupational hazards and work-related health problems depended on the type of work performed. In particular, nonstandard male workers who were unskilled manual workers, older, had less education, and earned low wages had a greater risk of working in unstable occupations, greater exposures to occupational hazards, and more musculoskeletal pain (back pain: odds ratio [OR], 2.4; upper extremity pain: OR, 2.1; and lower extremity pain: OR, 1.7) than those performing other types of work. CONCLUSION Male unskilled manual workers with nonstandard employment were most vulnerable to OSH problems. Our findings suggest the need for OSH programs that specifically target nonstandard workers especially those in manual unskilled occupations.

5,3'-Dihydroxy-6,7,4'-trimethoxyflavanone (DHTMF) is one of the constituents of Vitex rotundifolia, a medicinal herb that is used for the treatment of various disorders in China and Korea. In this study we evaluated the antitumor and antiangiogeneic activities of DHTMF. DHTMF significantly suppressed growth and induced apoptosis in lung carcinoma cells in a dose-dependent manner, as indicated by a decrease in Bcl-2 levels and increases in Bax and cleaved caspase-3 levels. In addition, DHTMF treatment significantly reduced the phosphorylation of Akt and mammalian target of rapamycin (mTOR), accompanied by reductions in the protein level of hypoxia-inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF), which are key angiogenic molecules in H522 lung cancer cells. Furthermore DHTMF inhibited VEGF-induced angiogenesis, as indicated by reduced expression of CD34, tube formation and migration in human umbilical vein endothelial cells (HUVECs), as well as reduced neovascularization in an in vivo mouse Matrigel plug assay. DHTMF also inhibited phosphorylation of Akt, mTOR, and p70S6K in HUVECs and lung cancer cells. Taken together, our finding indicated that DHTMF inhibits Akt/mTOR signaling and reduces the expression of HIF-1 α and VEGF in tumor cells, which in turns inhibits endothelial cell-mediated angiogenesis. These results suggest that DHTMF inhibits angiogenesis as well as induces apoptosis via the Akt/mTOR pathway and might elicit pharmacological effects that are useful for treatment of lung cancer.

Angiogenesis is the process of new vessel formation from pre-existing blood vasculature and is critical for continuous tumor growth. We previously reported that an ethanolic extract of Gleditsia sinensis thorns (EEGS) and its active constituent, cytochalasin H, have anti-angiogenic activity in vitro and in vivo via suppression of endothelial cell functions. In the present study, EEGS and cytochalasin H were observed to efficiently inhibit tumor growth in an in ovo xenograft model without significant toxicity. We repeatedly observed the anti-tumor and anti-metastatic effects of EEGS in representative animal models. These results suggest that EEGS and its active constituent, cytochalasin H, are potential candidates for the development of anti-angiogenic cancer drugs.

Background South Korea’s population is aging more rapidly than any other country. Aging of the productive population will lead to shortage of labor and the decreasing quality of the labor force in South Korea. South Korea needs health care strategies to support the establishment of work environments that are appropriate for elderly workers who have reduced physical capacity. This paper aims to identify occupations that are dominated by aged workers and assess the exposure to hazards and work-related health problems of aged workers in these occupations. Methods We identified the 20 occupations in South Korea that employ the most aged workers (at least 55 years-old), among all 149 occupations that are defined as minor categories (identified by three digits) by the Korean Standard Classification of Occupations (KSCO). Exposure to hazards and work-related health problems of individuals in these occupations were evaluated by analyzing the results of the fourth Working Conditions Survey of 2014. Results Among the 20 occupations that employ the most aged workers, ‘Elementary Occupations’, which the KSCO classifies as major category (9), had the largest proportion of aged workers. After this, there were five occupations of skilled manual workers and six occupations of skilled non-manual workers. Aged workers in elementary and skilled manual occupations reported frequent exposure to job-specific hazards, such as noise, vibrations, high and low temperatures, solvents, and chemicals. Relative to other workers, aged workers in the occupations reported more frequent exposure to ergonomic hazards, such as tiring or painful positions, carrying or moving heavy loads, and repetitive movements, and also reported more work-related musculoskeletal disorders and general fatigue. Injury due to accident was common in machinery-handling occupations. Conclusion Job-specific hazards should be reduced to prevent occupation-related disorders in elementary and skilled manual occupations that are dominated by aged workers.

Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.

Magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, has been reported to possess anticancer activity. Recent studies have also demonstrated that magnolol inhibits cell growth and induces the apoptosis of cancer cells. However, the effects of magnolol on vascular endothelial growth factor (VEGF)-induced angiogenesis in endothelial cells have not been studied. In the present study, we have used human umbilical vein endothelial cells (HUVECs) to investigate the antiangiogenic effect and molecular mechanism of magnolol. Magnolol inhibited the VEGF-induced proliferation, chemotactic motility and tube formation of HUVECs in vitro as well as the vessel sprouting of the aorta ex vivo. Furthermore, magnolol inhibited VEGF-induced Ras activation and subsequently suppressed extracellular signal-regulated kinase (ERK), phosphatidylinositol-3-kinase (PI3K)/Akt and p38, but not Src and focal adhesion kinase (FAK). Interestingly, the knockdown of Ras by short interfering RNA produced inhibitory effects that were similar to the effects of magnolol on VEGF-induced angiogenic signaling events, such as ERK and Akt/eNOS activation, and resulted in the inhibition of proliferation, migration, and vessel sprouting in HUVECs. In combination, these results demonstrate that magnolol is an inhibitor of angiogenesis and suggest that this compound could be a potential candidate in the treatment of angiogenesis-related diseases.

Background The transcription factor signal transducer and activator of transcription 3 (Stat3) is constitutively activated in many human cancers. It promotes tumor cell proliferation, inhibits apoptosis, induces angiogenesis and metastasis, and suppresses antitumor host immune responses. Therefore, Stat3 has emerged as a promising molecular target for cancer therapies. In this study, we evaluated the Stat3-suppressive activity of 38 herbal medicines traditionally used in Korea. Methods Medicinal herb extracts in 70% ethanol were screened for their ability to suppress Stat3 in the A549 human lung cancer cell line. A Stat3-responsive reporter assay system was used to detect intracellular Stat3 activity in extract-treated cells, and Western blot analyses were performed to measure the expression profiles of Stat3-regulated proteins. Results Fifty percent of the 38 extracts possessed at least mild Stat3-suppressive activities (i.e., activity less than 75% of the vehicle control). Ethanol extracts of Bupleurum falcatum L., Taraxacum officinale Weber, Solanum nigrum L., Ulmus macrocarpa Hance, Euonymus alatus Sieb., Artemisia capillaris Thunb., and Saururus chinensis (Lour.) Baill inhibited up to 75% of the vehicle control Stat3 activity level. A549 cells treated with these extracts also had reduced Bcl-xL, Survivin, c-Myc, and Mcl-1 expression. Conclusion Many medicinal herbs traditionally used in Korea contain Stat3 activity-suppressing substances. Because of the therapeutic impact of Stat3 inhibition, these results could be useful when developing novel cancer therapeutics from medicinal herbs.

This study was planned to analyze the effect of the types of employment on work-related injury experience. The types of employment may have influenced on working conditions including the exposure to risk factors. Korean Working Conditions Survey have collected the various working conditions as household survey with structured questionnaire. The probability of work-related injury of self-employed is more than that of regular worker. But there is no difference of probability of work-related injury experience between regular and irregular worker controlled by general characteristics and the exposure to risk factors. Authors have found that the type of employment have indirect effect on work-related injury experience via the exposure to risk factors. The result of this study may be heuristic one because of data limitation as cross sectional survey data. In future, well designed survey data can evaluate the effect of the type of employment on safety and health status.

Background Our previous genome-wide gene expression analysis revealed that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptors 4 (DR4) and 5 (DR5) are markedly upregulated by the ethanolic extract of D. sohia seeds (EEDS) in A549 TRAIL-refractory cancer cells. In the present study, we investigated whether the EEDS-mediated upregulation of TRAIL death receptors was associated with increased TRAIL-mediated toxicity in A549 cells in vitro. Methods Cell proliferation and viability were determined by an automatic cell counter. Gene silencing was performed by introducing small interfering RNA into cells. Expression changes of cellular proteins were determined by western blot analysis. Apoptotic cell death was monitored by western blot analysis. Analysis of variance followed by the post-hoc Dunnett’s test was used to compare the data. Results EEDS treatment increased both mRNA and protein levels of DR4 and DR5 in the TRAIL refractory A549 cells. Co-treatment of A549 cells with sub-lethal dose of EEDS and recombinant TRAIL increased the apoptotic cell death. Upregulation of DR5 by EEDS was mediated by an endoplasmic reticulum stress-induced transcription factor, CCAAT/enhancer-binding protein homologous protein (CHOP), and knockdown of CHOP expression inhibited EEDS-induced DR5 upregulation and abolished the EEDS-associated increase in TRAIL toxicity in A549 cells. Conclusions EEDS can sensitize A549 cells to TRAIL cytotoxicity by upregulation of TRAIL death receptors. Our findings suggested that EEDS is a good initial herbal source for the development of an anticancer supplement for anticancer therapeutics associated with TRAIL. Electronic supplementary material The online version of this article (doi:10.1186/s12906-016-1094-0) contains supplementary material, which is available to authorized users.

Background Oxaliplatin can induce peripheral neuropathy (OXIPN) as an adverse side effect in cancer patients. Until now, no effective preventive or therapeutic drug has been developed; therefore, the dose-limiting factor of OXIPN is still an obstacle in the use of oxaliplatin to treat cancer patients. In the present study, we report for the first time that the aqueous extract of Lithospermi radix (WLR) can attenuate the OXIPN in both in vitro and in vivo neuropathic models. Methods The protective effect of WLR on OXIPN was evaluated in vitro by quantifying nerve growth factor (NGF)-stimulated neurite outgrowth in PC12 cells treated with a combination of oxaliplatin and WLR. The neuroprotective potential of WLR was further confirmed by measuring the changes in nociceptive sensitivities to external mechanical stimuli in neuropathic animals induced by oxaliplatin. Histological and immunohistochemical studies were further done to examine the effect of WLR in mouse spinal cords and footpads. Results Oxaliplatin-induced neurotoxicity in NGF-stimulated PC12 cells. It could reduce the lengths and branching numbers of neuritis in NGF-stimulated PC12 cells. Co-treatment of WLR rescued the differentiated PC12 cells from the neurotoxicity of oxaliplatin. In a chronic OXIPN animal model, administration of oxaliplatin i.p. induced enhanced nociceptive sensitivity to mechanical stimuli (25.0 to 72.5 % of response rate) along with spinal activation of microglias and astrocytes and loss of intraepidermal nerve fibers in footpads, which is remarkably suppressed by oral administration of WLR (67.5 to 35 % of response rate at the end of experiment). Cytotoxicity of oxaliplatin determined in human cancer cells was not affected irrespective of the presence of WLR. Conclusions In conclusion, we demonstrated that WLR can attenuate OXIPN in both in vitro and in vivo experimental models, which may be in part attributed to its anti-inflammatory activity in the spinal cord and its neuroprotective potential in the peripheral nerve system without affecting the anti-tumor potential of oxaliplatin. Therefore, WLR could be considered as a good starting material to develop a novel therapeutic agent targeting OXIPN. However, further studies should be done to elucidate the underlying mechanism such as molecular targets and active constituent(s) in WLR with neuroprotective potential.

The original dataset supporting the findings in this study. (PPTX 477 kb)

The pharmacokinetics of a novel peroxisome proliferator-activated receptor-γ agonist, KR-62980, were characterized in vitro with respect to liver metabolic stability, cell permeability, and plasma protein binding and in vivo using Sprague-Dawley rats and ICR mice. The metabolic half-life of 0.1-10 μM KR-62980 was 11.5-15.2 min in rat liver microsomes and 25.8-28.8 min in human liver microsomes. KR-62980 showed high permeability across MDCK cell monolayers, with apparent permeability coefficients of 20.4 × 10(-6) to 30.8 × 10(-6) cm/sec. The plasma protein binding rate of KR-62980 was 89.4%, and most was bound to serum albumin. After intravenous administration of KR-62980 (2 mg/kg), the systemic clearance was 2.50 L/h/kg, and the volume of distribution at steady-state was 9.16 L/kg. The bioavailability after oral administration was approximately 60.9%. The dose-normalized AUC values were 0.50 ± 0.09, 0.41 ± 0.20, and 0.62 ± 0.08 h · μg/mL after oral administration of 2, 5, and 10 mg/kg KR-62980, respectively, showing no dose-dependency. The in vivo pharmacokinetic parameters in ICR mice were also dose independent. These data suggest that KR-62980 is not significantly dose dependent in rats or mice, although it may disappear rapidly from the systemic circulation via metabolism in the liver.

A sensitive liquid chromatography/tandem mass spectrometry (LC–MS/MS) method was developed for a novel dipeptidyl peptidase IV agonist (DDP-IV) agonist, KR-66223, in rat plasma. It involves liquid-liquid extraction (LLE) followed by HPLC separation and electrospray ionization tandem mass spectrometry. KR-66223 and imipramine (IS) was separated on Gemini-NX C18 column with mixture of acetonitrile–ammonium formate (10 mM) (90:10, v/v) as mobile phase. The ion transitions monitored were m / z 553.2 → 206.2 for KR-66223, m / z 281.3 → 86.1 for imipramine in multiple reaction monitoring (MRM) mode. The linear ranges of the assay were 0.003–10 μg/ml with a correlation coefficient ( R 2 ) greater than 0.99 and the lower limit of quantification was 3 ng/ml. The average recovery was 78.9% and 87.1% from rat plasma for KR-66223 and imipramine, respectively. The coefficients of variation of intra- and inter-assay were 3.9–14.4% and the relative error was 0.8–11.5%. The method was validated and successfully applied to the pharmacokinetic study of KR-66223 in rat.

Summary: A novel phosphodiesterase-4 inhibitor, 2-aryl-7(3',4'-dialkoxyphenyl)-pyrazolo[1,5-alpha] pyrimidine (PDE-310), has been synthesized for the treatment of respiratory diseases. We conducted in vitro and in vivo studies to characterize the pharmacokinetics of PDE-310. The high liver microsomal stability and low inhibitory potency against CYP isoforms of PDE-310 suggested a low first-pass effect and high bioavailability. PDE-310 exhibited high Caco-2 cell permeability in the absorptive direction (apparent permeability coefficients, ~ 20 × 10 − 6 cm/s), with higher transport in the secretory direction, giving efflux ratios of 3.9 and 2.6 at 5 and 10 μΜ, respectively. In addition, the high efflux ratio and improved absorption on treatment with efflux transporter inhibitors such as verapamil and MK-571 indicated the involvement of P-gp, BCRP and MRP2 in intestinal transport. PDE-310 bound strongly to human plasma proteins, whereas significantly more PDE-310 (27–34%) was free in rat plasma. Following intravenous administration, nonlinear elimination of PDE-310 was observed at the tested dose ranges (K m , 0.87 μg/mL; V max , 0.3 mg-h − 1. kg − 1 ). Following oral PDE-310 administration, dose-normalized AUC and T max increased significantly in a dose-dependent manner. PDE-310 exhibited high oral bioavailability (> 70%) and was distributed well to various tissues except brain and testis.

In the leak before break (LBB) concept, catastrophic pipe failure can be prevented if leak rate through a crack is more than the minimum detectable leak rate of a leak detection system before a crack grows to the critical crack size. Therefore accurate estimation of leak rate is important to evaluate the validity of LBB concept in pipe line design. Usually LOCA probability analysis is performed with constant crack morphology parameters. Since leak rate is affected by the crack morphology parameters, the LOCA probability may be affected by the parameters also. In this paper the effect of crack morphology parameters on LOCA probability was examined assuming the crack morphology parameters to be normally distributed random variables. A developed probabilistic fracture mechanics program, called P-PIE, was used in the analysis.

Angiogenesis, the process of new vessel formation from the pre-existing blood vasculature, is critical for continuous tumor growth and is considered to be a validated antitumor target. The results of our previous study demonstrate the anti-angiogenic potential of an extract of Gleditsia sinensis thorns, which has been traditionally used in Korean medicine to remedy diverse diseases, including tumors. In the present study, we attempted to identify the active anti-angiogenic constituents of the ethanol extract of G. sinensis thorns (EEGS). By virtue of in vitro activity-guided fractionation using human umbilical vein endothelial cells (HUVEC) primary endothelial cells, chromatographic separation, and NMR spectral analyses, we isolated and identified the potent active constituent, cytochalasin H, a biologically active secondary metabolite of fungi. This unexpected active constituent may have originated from the endophytic fungi, Chaetomium globosum, which naturally populate G. sinensis, the identity of which was determined by analysis of fungal community. Cytochalasin H isolated from the EEGS showed in vitro anti-angiogenic activities such as suppressed cell growth and mobility in HUVEC, and inhibited the pro-angiogenic protein-induced formation of new blood vessels in vivo. The anti-angiogenic effect of cytochalasin H was in part due to reduced expression of pro-angiogenic factor, such as endothelin-1. This is the first report regarding the isolation and identification of cytochalasin H, as an active anti-angiogenic constituent of G. sinensis thorns.

and emesis. In the present study, we investigated the antiobesity effects and antioxidant activity of KE-06. Methods: 3T3-L1 preadipocytes were differentiated into adipocytes with or without KE-06. After differentiation, we measured Oil Red O staining, glycerol-3-phosphate dehydrogenase (GPDH) activity and leptin production in 3T3-L1 adipocytes. In addition, we analyzed its effect on scavenging activities of 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (A BTS) and 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radicals in in vitro systems. Its effect on low-density lipoprotein (LD L) oxidation was assessed by measuring production of malondialdehyde (MDA). Results: KE-06 significantly inhibited lipid accumulation and triglyceride production, and mediated GPDH, a major enzyme in the process of adipogenesis. Consistent with this, KE-06 stimulation significantly decreased the amount of leptin in 3T3-L1 adipose cells. Furthermore, KE-06 enhanced the scavenging activities on ABTS and DPPH radicals. The generation of MDA during LDL oxidation was significantly reduced by KE-06 treatment. Conclusion:Overall, our findings suggest thatKE-06has the potential for anti-adipogenic activity and antioxidant properties. Contact: Sae-Rom Yoo, k2aori@kiom.re.kr

A novel peroxisome proliferator-activated receptor γ (PPARγ) agonist, KR-62980, was determined by liquid–liquid extraction with ethyl acetate and liquid chromatography–tandem mass spectrometry (LC/MS/MS) in rat plasma. In order to evaluate the pharmacokinetics of KR-62980, a reliable, selective and sensitive high-performance liquid chromatographic method with electrospray ionization tandem mass spectrometry was developed for the quantification of KR-62980 in rat plasma. KR-62980 and imipramine (IS) were separated on Hypersil GOLD C18 column with a mixture of acetonitrile–ammonium formate (10 mM) (80:20, v/v) as mobile phase. The ion transitions monitored were m/z 437.2 → 114.2 for KR-62980, m/z 281.3 → 86.1 for imipramine in multiple reaction monitoring (MRM) mode. The percent recoveries of KR-62980 and imipramine were 90.1 and 98.4% from rat plasma, respectively. The linear dynamic range extended from 0.01 to 10 μg/ml with a correlation coefficient (R2) greater than 0.99 and the lower limit of quantification was 0.01 μg/ml. The mean of intra- and inter-assay precisions was 2.1 and 9.3%. The method was validated and successfully applied to the pharmacokinetic study of KR-62980 in rat.

Purpose: To investigate the biological effect of IL-17/NFB immune inflammatory pathway on pathological damage in synovium tissue of Rheumatoid arthritis (RA) and study in regulation mechanism of Chinese herbal compound Tengmei decotion for IL-17/NFB signal pathway. Methods: To establish collagen II-induced rats arthritis(CIA)models. The successful models of SD rats were randomly divided intomodel group, positive group, and high-, medium-groupsofChinesemedicine, 6 rats in eachgroup. The normal control and model groups were given distilled water (10mlkg-1d) by gavage. The positive drug group was given leflunomide (1.87gkg-1d) by gavage. The high and medium dose Chinese medicine groups were given crude medicine of 31.8 gkg-1d and 15.9 gkg-1d by gavage. After twelve weeks of treatment intervention, all SD rats were executed, the blood and synovium tissue samples were kept for detecting IL-17, NF-KB P65 mRNA transcription and protein expression by RT-PCR, WESTEN BLOT and ELISA Analysis, and detecting inflammatory infiltration in synovium tissue by Histopathological analysis. Results: (1)Compared to the normal control group, levels of mRNA transcription and protein expression of IL-17 and NFB P65 were significantly up-regulated (P < 0.01) in the model group. Compared to the model group, levels of mRNA transcription and protein expression of IL-17 and NFB P65 were significantly down-regulated in the positive and Chinese medicine groups (P < 0.01).(2) Histopathological analysis displayed that mild hyperplasia of epithelial cells covering the articular cartilage synovium, joint cavity narrowing, and mild inflammatory lymphocytes infiltration in model group, with joint lesions improved in treatment groups. Conclusion: The molecular mechanisms of Chinese herbal Tengmei decotion in inhibiting immune inflammatory pathological damage in synovium of CIA rats models related to its effects on IL-17/NFB pathway. Contact: Yanan Wang, xingmiao2008@live.cn

Lung cancer is the most frequent malignancy and also one of the leading causes of mortality in both men and women worldwide. Despite current advances in diagnostics and medicines, the incidence of lung cancer is increasing and effective treatment is very challenging. These facts emphasize on the importance of both proper animal models and seeking anticancer materials from traditionally used herbal materials for developing therapy for lung cancer. Here we developed a murine orthotopic lung cancer model using A549 human lung cancer cell line orthotopically injected to the lung of immune-impaired Balb/c mice for measuring the anticancer effect of Traditional Korean medicinal herb, Descurainia sophia. Traditional use of D.Sophia includes relieving cough, chest pain, and many other symptoms which commonly accompanied with lung cancer. Our data showed oral administration of KIOM-CRC#5, an ethanol extract of Descurainia sophia, effectively attenuated the lung tumor growth in this animal model after 4 weeks of drug administration. This effect was even greater in the pretreatment group, which received 5 times/week KIOM-CRC#5 administration for 3 weeks prior to tumor cell injection. In vitro study revealed that Stat3 phosphorylation at Tyr 705 site was rapidly diminished in A549 cells treated with KIOM-CRC#5 as low as 5μg/ml and the expressions of downstream targets of Stat3 including c-Myc and cyclin D1 were also abolished. Additionally, Stat3 reporter assay showed marked reduction of transcriptional activity of Stat3 in KIOM-CRC#5 treated cells. In the present study, we developed a murine model of orthotopic lung tumor, which can be useful in the screening and testing the efficacy of therapeutic candidates from medicinal herbs, and tested the anticancer activity of ethanol extract of Descurainia Sophia (KIOM-CRC#5). Oral admistration of KIOM-CRC#5 attenuated orthotopic lung tumor growth possible through blocking the Stat3 signaling pathway, which is hyper-activated in many cancers including lung cancer. Considering that there was no adverse effect related with the oral administration of KIOM-CRC#5 in the tested animals and its effect on blocking tumor growth in vivo as well as potent cytotoxic effect on various cancer cell lines in vitro, KIOM-CRC#5 can be a good candidate for chemotherapeutic agent for lung cancer. Citation Format: Jinhee Kim, Jong-Shik Park, Myung-Gi Baek, Haejin Kim, You Jin Lee, Jun Lee, No Soo Kim, Ok-Sun Bang. Oral administration of ethanol extract of Descurainia sophia (KIOM-CRC#5) attenuates A549 xenograft lung cancer growth in murine orthotopic lung cancer model through blocking Stat3 signaling. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B49.

KIOM210091 is an ethanol extract of seeds from one of Brassicaceae plant which has been widely used to relieve cough, prevent asthma, and reduce edema as traditional medicine in Korea and China. However, little is known about its chemical property, biological activity, and the molecular mechanism. In our preliminary experiments, KIOM210091 showed potent cytotoxic effect on all of our 30 panels of different cancer cell lines originated from different tissue origins such as lung, kidney, intestine, prostate, uterine, and lymphocytes. It is previously unknown if KIOM210091 is effective against tumors when delivered as a dietary component, so we attempted to assess the anti-tumorigenic property of KIOM210091 in vivo xenograft tumor system. Here our date showed that KIOM210091 attenuated tumor growth in H460-injected Balb/c athymic nude mice. A group of mice (n=6) was treated with 250mg/kg/d of KIOM210091 ad lib for 5 days/week for 3 week-period. This group of mice showed inhibited xenografted H460 cell tumor growth which was comparable to those groups treated with chemotherapeutic agents, rapamycin and 5-fluorouracil. However, low dose (50mg/kg/d) treatment had little or no effect on inhibition of tumor growth. Additionally, there was no adverse effect of KIOM210091 treatment during 3 week period administration. Bioassy-guided fractionation revealed that the cytotoxic compound of KIOM210091 was found in ethyl acetate fraction and purification of single active compound is on the way. This fraction showed enhanced cytotoxic effects on tumor cells compared to the 80% ethanol extract. Our data also suggested that KIOM210091 as well as the active fraction had an effect on inhibiting the proliferative kinases and inducing apoptosis-related proteins. Our data demonstrated the anti-tumorigenic effect of orally administrated KIOM210091, as well as the signaling pathway modulation. This study implicates this relatively safe, natural compound as a potential therapeutic and chemopreventive agent for lung cancer. This research was supported by Korea Institute of Oriental Medicine Grant #K11062. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B172.

Background Despite current advances in diagnostics and medicines, the incidence of lung cancer is increasing and effective treatment is very challenging. Traditional herbal formulae as well as many herbal plant extracts have been recognized as attractive sources for novel multi-targeted therapy of cancer with minimal side effects. Methods The ethanol extract of Kilkyung-baeksan (EE-KKBS) and its component herbs were tested for their ability to inhibit cancer growth in several lung cancer cell lines. The effects of EE-KKBS and ethanol extract of Croton tiglium Linne seed (EE-CT) on cell cycle progression were measured by flow cytometric analysis using propidium iodide staining. Western blot analyses were performed to measure the expression profiles of proteins regulating cell cycle checkpoints. Results EE-KKBS inhibited the growth of lung cancer cells after 24–72hours treatment. Lung cancer cells treated with either EE-KKBS or EE-CT showed strong G0/G1 cell cycle arrest. The expressions of p21 and p27, two key regulators of G1 cell cycle checkpoint, were significantly upregulated upon treatment with EE-KKBS and EE-CT. Conclusion EE-KKBS exerted its cytostatic activity through regulating G1 cell cycle checkpoint in lung cancer cells, and this activity is mainly mediated by one of its component herbs, seeds of Croton tiglium . Collectively, our data suggest that EE-KKBS could be a novel candidate for adjuvant therapy for lung cancer.