Objectives : The purpose of this study was to investigate Acute$\cdot$Subacute Toxicity and Anti-cancer Effect of K-Herbal-acupuncture in mice and rats. Methods : Balb/c mice were injected intraperitoneally with K-herbal-acupuncture for $LD_{50}$ and acute toxicity test. Sprague-Dawley rats were injected intraperitoneally with K-herbal-acupuncture for subacute toxicity test. K-Herbal-acupuncture was injected on abdomen of mice with S-180 cancer cell line. Result : 1. $LD_{50}$ of K-Herbal-acupuncture was limited $4{\times}10^{-3}$ml/kg~$2{\times}10^{-3}$ml/kg by the test. 2. In acute toxicity test, all of mice were down to the moving reflex, but the weight of mice was increased in treatment group, compared with the normal group. (P<0.05) 3. In acute toxicity test of serum biochemical values of mice, glucose was increased in treatment II group, total cholesterol was increased both treatments.(P<0.05) 4. In subacute toxicity test, the clinical signs of toxication was down to the moving reflex, but it is not severe like acute toxicity test, and observed weight loss at the treatments. 5. In subacute toxicity test, liver weight was decreased compared with the normal group. (P<0.05) 6. In subacute toxicity test of complete blood count test (CBC) of rat, HCT was decreased in treatments, compared with the normal group.(P<0.05) 7. In subacute toxicity test of serum biochemical values of rat, uric acid and triglyceride were decreased, and glucose was increased in treatment groups compared with the control group. (P<0.05) 8. Median survival time was increased about $45\%$ in treatment groups compared with the control group.(P<0.05) 9. Natural killer cell activity was increased in B16F10 lung cancer model, but it was not in sarcoma-180 abdomen cancer. 10. In interleukin-2 productivity test, treatment groups didn't show significant change in lung cancer and abdomen cancer, compared with the normal group.(P<0.005) 11. In making an examination of metastatic cancer with the naked eye, melanoma metastasized in the Lung of C57BL/6 mice. The treated group showed more Melanoma than the control in the numbers and volume. Conclusion : According to the result, K-herbal-acupuncture need further study to know the function and effect in cancer.
Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.
In this study, we examined the immunostimulating characteristics of a hot water extract (RCW) and crude polysaccharides (RCP) of red cabbage. RCW and RCP did not show any cytotoxicity in B16BL6 cells and macrophages. Although the sugar compositions of RCW and RCP were similar, the uronic acid content of RCP was higher than that of RCW RCP significantly increased the production of various cytokines and NO, whereas RCW did not affect the production of cytokines and NO. In an ex vivo assay of natural killer (NK) cell activity, intravenous (i.v.) administration of RCP significantly augmented NK cytotoxicity against Yac-1 tumor cells at 3 days after RCP treatment. In an experimental lung metastasis model using B16BL6 melanoma cells, i.v. administration of RCP at a dose of $1,000{\mu}g$ per mouse significantly inhibited 47.3% of lung metastasis. These results suggest that crude polysaccharide isolated from red cabbage is a promising food ingredient for the prevention of tumor metastasis.
Kang, Shin Ae;Chun, Sung Sik;Kang, Shin Kwon;Chung, Young Chul;Cheon, Eun Woo;Cho, Sang Uk;Jung, Kyung Hwa;Ahn, Soon Cheol;Yu, Hak Sun
Journal of Life Science
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v.24
no.5
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pp.567-572
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2014
Extracts of Platycodon grandiflorum have been reported to show anti-inflammatory, antioxidant, anti-metastatic, and hepato-protective effects. This study was designed to evaluate T-cell activation and M1/M2 differential macrophage activation by extracts of P. grandiflorum or P. grandiflorum containing various medicinal herbs. Using real-time RT-PCR, we analyzed expression levels of c-fos, and CD40L (T-cell activation markers) in splenocytes and iNOS, Ym1, and ARG1 in RAW 246.7 cells after treatment of CC (hot water extract of P. grandiflorum), MAEK (hot water extract of P. grandiflorum [82%] and six different plants), and HWAL (hot water extract of P. grandiflorum [7%] and eight different plants. The results showed that MAEK significantly elevated the expression of T-cell activation markers of splenocytes, with the c-fos gene activated more than 10-fold and the CD40L gene activated more than 6-fold. Although CD40L was significantly increased by CC and HWAL, the increase was only about 2-fold. In addition, CC and HWAL did not significantly activate the expression of the c-fos gene. On the other hand, CC elevated the M1 activation marker iNOS, and HWAL elevated the M2 activation marker Ym1 and ARG1 gene expression. In conclusion, MAEK could be used as an immune stimulant because of its ability to activate T cells (elicited c-fos and CD40L gene expression), whereas HWAL could serve as an anti-inflammatory agent because of its differential activation of M2 macrophages.
Cell migration plays a fundamental role in cancer cell invasion and metastasis as well as in many physiological responses. Here, we screened four different sources of garlic - water extract of normal and black garlic, as well as dried normal and black garlic - for the identification of anti-invasive and anti-metastatic activity on cancer cells. Inhibition of cancer cell migration was observed in the hexane extract of dried-garlic. Inhibitory activity was further purified to near homogeneity by thin layer chromatography and named $\b{i}$nhibitor of $\b{c}$ancer $\b{m}$etastasis from garlic #27 (ICMG-27). ICMG-27 completely blocked insulin-like growth factor-1 (IGF-1)-induced OVCAR-3 cell migration at 6 ${\mu}g/ml$. ICMG-27 completely blocked IGF-1-induced OVCAR-3 and NIH-3T3 cell migration whereas IGF-1-induced mouse embryonic fibroblast (MEF) cell migration was not affected byICMG-27. ICMG-27 inhibited all the tested IGF-1-induced cancer cell migration such as OVCAR-3, SKOV-3, and MDA-MB-231 cells. Finally, ICMG-27 could inhibit IGF-1-, lysophosphatidic acid (LPA)-, sphingosine-1-phosphate (S1P)-, leukotriene B4 (LTB4)-, and angiotensin II (AngII)-induced OVCAR-3 cell migration. These results indicate that ICMG-27 inhibits cancer cell migration by blocking essential steps in many agonists-induced cancer cell migrations. Unveiling an anti-invasive mechanism of ICMG-27 on cancer cells will provide a basis for cancer therapy.
Purpose: This study was conducted to provide basic data for developing an effective strategy for cancer pain management by comparing the levels of barriers to pain management of metastatic or advanced cancer patient and their nurses. Methods: The subject of this study were 155 patients who were treated for metastatic or advanced cancer at one of three hospitals in Seoul from January 2004 to January 2005, and 153 nurses who take care of those patients. The levels of barriers to pain management were measured using a tool developed by Gunnarsdottir et al. (2002), 27 questions on a six point scale. The levels of stresses were measured using a tool modified from a stress response measurement reported by Goh Gyung-bong et al. (2000), 27 questions on a five point scale. The levels of barriers in cancer patients were analyzed using t-test and ANOVA, while the data obtained from patients and nurses were compared by t-test. Results: Higher levels of barriers to pain management were found in three groups: 'less than middle school,' 'not treated with anti-cancer chemotherapy,' and 'ECOG of 2.' The level (2.55) of barriers to pain management in the patient group was higher than that (1.76) of the nurse group. Both of the two groups had high levels of barriers in two variables: 'There is a danger of becoming addicted to pain medicine.' and 'Using pain medicine blocks your ability to know if you have any new pain.' There was not a significant difference in the levels of stresses between the two groups. Conclusion: It was found that, for effective cancer pain management practices, it would be necessary to provide cancer patients and their nurses with education and training about pain management and related barriers.
Purpose: To evaluate the outcomes and prognostic factors of postoperative radiotherapy (PORT) for patients with pathological stage III non-small-cell lung cancer (NSCLC) at a single institution. Materials and Methods: From 2000 to 2007, 88 patients diagnosed as having pathologic stage III NSCLC after curative resection were treated with PORT. There were 80 patients with pathologic stage IIIA and eight patients with pathologic stage IIIB in the AJCC 6th staging system. The majority of patients (n=83) had pathologic N2 disease, and 56 patients had single station mediastinal LN metastasis. PORT was administered using conventional technique (n=76) or three-dimensional conformal technique (n=12). The median radiation dose was 54 Gy (range, 30.6 to 63 Gy). Thirty-six patients received chemotherapy. Radiation pneumonitis was graded by the Radiation Therapy Oncology Group system, and other treatment-related toxicities were assessed by CTCAE v 3.0. Results: Median survival was 54 months (range, 26 to 77 months). The 5-year overall survival (OS) and disease free survival (DFS) rates were 45% and 38%, respectively. The number of metastatic lymph nodes was associated with overall survival (hazard ratio, 1.037; p-value=0.040). The 5-year locoregional recurrence free survival (LRFS) and distant metastasis free survival (DMFS) rates were 88% and 48%, respectively. Multiple stations of mediastinal lymph node metastasis was associated with decreased DFS and DMFS rates (p-value=0.0014 and 0.0044, respectively). Fifty-one relapses occurred at the following sites: 10 loco-regional, 41 distant metastasis. Grade 2 radiation pneumonitis was seen in three patients, and symptoms were well tolerated with anti-tussive medication. Grade 2 radiation esophagitis was seen in 11 patients. There were no grade 3 or more severe complications associated with PORT. Conclusion: Our retrospective data show that PORT for pathological stage III NSCLC is a safe and feasible treatment and could improve loco-regional control. The number of metastatic lymph nodes and stations of mediastinal lymph node metastasis were analyzed as prognostic factors. Furthermore, efforts are needed to reduce distant metastasis, which is a major failure pattern of advanced stage NSCLC.
Kim, Do-Hoon;Park, So-Jeong;Lee, Seung-Yeon;Yoon, Hyun-Seo;Park, Chung Mu
Korean Journal of Clinical Laboratory Science
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v.50
no.3
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pp.337-344
/
2018
Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.
Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.
Photodynamic therapy (PDT) is a great potential approach for the localized tumor removal with fewer metastatic potentials and side effects in treating the disease. In the treatment process, a photosensitizer (PS) that absorbs a light energy to generate reactive oxygen is essential. In general, a visible light is used as a light source of PDT, so that side effects from the light source are inevitable. For this reason, upconversion nanoparticles (UCNPs) using near-infrared (NIR) as an excitation source are attracting attention in the field of disease diagnosis and treatment. UCNPs have the low cytotoxicity and phototoxicity, and also advantages such as deep tissue penetration and low background autofluorescence. For PDT, UCNPs should be combined with a PS which absorbs the light energy from UCNPs and transfers it to the surrounding oxygen to produce reactive oxygen. In addition, the therapeutic efficacy can be improved by modifying nanoparticle surfaces, adding anti-cancer drugs, or combining with photothermal therapy (PTT). In this review, we summarize the recent research to improve the efficiency of PDT using UCNPs.
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