• Title/Summary/Keyword: anti-tumor growth

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Concomitant EGFR Inhibitors Combined with Radiation for Treatment of Non-small Cell Lung Carcinoma

  • Zheng, De-Jie;Yu, Guo-Hua;Gao, Jian-Feng;Gu, Jun-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4485-4494
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    • 2013
  • Epidermal growth factor receptor (EGFR) is considered to be one of the key driver genes in non-small cell lung cancer (NSCLC). Several clinical trials have shown great promise of EGFR tyrosine kinase inhibitors (TKIs) in the first-line treatment of NSCLC. Many advances have been made in the understanding of EGFR signal transduction network and the interaction between EGFR and tumor microenvironment in mediating cancer survival and development. The concomitant targeted therapy and radiation is a new strategy in the treatment of NSCLC. A number of preclinical studies have demonstrated synergistic anti-tumor activity in the combination of EGFR inhibitors and radiotherapy in vitro and in vivo. In the present review, we discuss the rationale of the combination of EGFR inhibitors and radiotherapy in the treatment of NSCLC.

Pharmacological Effects of Proteoglycans Extracted from Fruiting Bodies of Fomitella fraxinea (장수버섯 자실체의 열탕추출액으로부터 분리한 단백다당체의 약리적 효과)

  • Yoon, Sang-Hong;Lim, Jae-Hyeon;Kim, Yang-Seop;Kim, Chang-Han;Jo, Joon-Hyeong;Hwang, Young-Soo
    • The Korean Journal of Mycology
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    • v.26 no.4 s.87
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    • pp.511-518
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    • 1998
  • Anti-complementary assay for immuno-stimulating polysaccharide screening, human tumor colony-forming assay for discovering anti-tumor drugs, and toxic assay against mouse were performed to examine pharmacological activities of polysaccharides extracted from fruiting bodies of Jang-soo mushroom (Fomitella fraxinea). Hot water $(100^{\circ}C,\;FF-I)$, 1% ammonium oxalate solution $(80^{\circ}C,\;FF-II)$, and 5% sodium hydroxide solution $(80^{\circ}C,\;FF-III)$ were used for extraction of three polysaccharides from fruiting bodies of it. Anti-complementary activity of FF-I was more effective than the others. FF-I was further fractionated into three groups of polysaccharide by DEAE-Sephadex A25 column chromatography (FF-NP, FF-AP1, and FF-AP2). FF-AP1 showed not only the highest anti-complementary activity but also the growth-inhibitory activity against Snu-I (human stomach cancer cell) among 9 kinds of human tumor cell lines. But FF-AP2 exhibited its activity against Hep-2(larynx cancer) and KB(mouth epidermal cancer) cell lines at $500\;{\mu}g/ml$ although its anti-complementary activity was lower than it of FF-AP1. When FF-I was orally administrated to mice with dosage of 5000 mg/kg, no remarkable changes were observed in viewpoint of tissue-pathology.

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Inhibitory Effects of Bee Venom on Growth of A549 Lung Cancer Cells via Induction of Death Receptors

  • Jang, Dong Min;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.30 no.1
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    • pp.57-70
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    • 2013
  • This study was to investigated the effects of the bee venom on inhibition of cell growth via upregulation of death receptor expression in the A549 human lung cancer cells. Bee venom(1-5 ${\mu}g$/ml) inhibited the growth of A549 lung cancer cells by the induction of apoptotic cell death in a dose dependent manner. Consistent with apoptotic cell death, expression of TNFR1, Fas, death receptors(DR) 3, 4 and 6 was increased in the cells. Expression of DR downstream pro-apoptotic proteins including caspase-3, -9 and Bax was concomitantly increased, but the expression of Bcl-2, NF-${\kappa}B$ were inhibited by treatment with bee venom in A549 cells. Moreover, deletion of DR3, DR4 by small interfering RNA significantly reversed bee venom-induced cell growth inhibitory effect, whereas Apo3L strengthened anti-proliferative effect of bee venom through enhancement of DR3 expression. These results suggest that bee venom should exert anti-tumor effect through induction of apoptotic cell death in lung cancer cells via enhancement of death receptor expression, and that bee venom could be a promising agent for preventing and treating lung cancer.

The anti-tumor effect of combined treatment with arsenic trioxide and interferone-α on transplanted murine Lewis lung carcinoma

  • Seo, Deug-Log;Yang, Je-Hoon;Won, Chung-Kil;Kim, Myeong-Ok;Lee, Jong-Hwan;Kwark, Soo-Dong;Koh, Phil-Ok
    • Korean Journal of Veterinary Research
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    • v.45 no.1
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    • pp.17-23
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    • 2005
  • In the present study, we expected the anti-tumor effect by combined treatment of arsenic trioxide and interferon (IFN)-${\alpha}$ on murine Lewis lung carcinoma (LL2) cells through in vivo study. As a experimental model, LL2 cells ($1{\times}10^{6}$/mouse) were injected subcutaneously into the back region of mice. When the tumor volume reached $100mm^3$, mice were treated with 1 mg/kg arsenic trioxide, 50000 IU IFN-${\alpha}$, or arsenic trioxide and IFN-${\alpha}$. The development of tumor cells was significantly inhibited by combined treatment with arsenic trioxide and IFN-${\alpha}$. In arsenic trioxide and IFN-${\alpha}$ treated group, apoptotic index was reached a peak valve at 48 hr after the treatment and it was restored to approximately the control level at 8 days. Also, positive signals of Bax and Bad were increased at 48 to 96 hr and decreased at 8 day. Whereas, positive cells of Bcl-2 were steadily decreased at 12 to 48 hr and restored to the background level at 8 days. Our data showed that immunoreactivity of Bcl-2 was decreased at 12 to 48 hr, while positive signals of Bax and Bad were increased in accordance with apoptotic index at these times. In conclusion, our results suggest that the combined treatment with arsenic trioxide and IFN-${\alpha}$ significantly inhibited the growth of LL2 tumor cells and induced apoptosis through the up and down-regulation of Bcl-2 gene family.

In Vivo Toxicity and Anti-Tumor Activity of Korean Mistletoe Extracts (한국산 겨우살이 추출물의 in vivo 독성 및 항종양 효과)

  • Yoon, Taek-Joon;Park, Sung-Min;Yang, Seung-Hoon;Jung, Hoe-Yune;Lee, An-Na;Yoo, Yung-Choon;Kang, Tae-Bong;Kim, Jong-Bae
    • Korean Journal of Pharmacognosy
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    • v.40 no.3
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    • pp.205-212
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    • 2009
  • Antitumor activity of Korean mistletoe extract (KM-110) and European commercial mistletoe preparation (Helixor) was investigated. KM-110 showed the cytotoxic effect that it is high for various tumor cell lines and normal splenocytes in comparison with Helixor. Administration of two mistletoe extracts ($100{\mu}g$) to mice did not show any significant changes on the level of glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvate transaminase (GTP), blood creatinine (CRE) and blood urea nitrogen (BUN) in sera. The culture supernatant of macrophages stimulated with KM-110 inhibited effectively tumor growth whereas Helixor had little effect. Administration of KM-110 or Helixor resulted in a effective inhibition of lung metastasis after the i.v. inoculation of colon 26-M3.1 lung carcinoma, B16-BL6 melanoma and L5178Y-ML25 lymphomas. In all cases, the mice treated with KM-110 showed more effective anti-tumor metastatic activity than the mice of Helixor. These results suggest that Korean mistletoe extracts, KM-110 might be used as an alternative methods having antitumor activity like European mistletoe preparation, Helixor.

The Effects of Bee Venom Therapy on Melanoma of C57BL Mouse (봉독약침(蜂毒藥鍼)이 C57BL mouse의 흑색종(黑色腫)에 미치는 영향)

  • Oh, Gi-Nam;Lee, Jae-Dong;Park, Dong-seok
    • Journal of Acupuncture Research
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    • v.19 no.2
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    • pp.78-91
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    • 2002
  • Objective : This study was designed to investigate the anti-cancer effects of bee venom on melanoma in C57BL mice. Materials and Methods : For the induction of melanoma, C57BL mice were treated by DMBA(7, 12-dimethylbenz[a]anthracene). Each group of C57BL mouse was treated with DMBA $50{\mu}g$, $75{\mu}g$, $100{\mu}g$ respectively once a week for 15 weeks. Tumor generation in each group of 10 mice was observed. Cumulative curves were showed in the density and frequency of skin tumor generation. To know the effects of pre-treatment of bee venom on tumor generation by DMBA treatment(frequency of tumor generation), Each group of C57BL mouse was pretreated and treated with bee venom $5{\mu}{\ell}$, $25{\mu}{\ell}$, $50{\mu}{\ell}$ respectively once a week for 3 weeks, whereafter each mouse was treated with DMBA $100{\mu}g$ once a week for 15 weeks. Results and Conclusion (1) There was chemotherapeutic effect, but not chemopreventive effect. (2) Cpp32 activity was increased by $50{\mu}{\ell}$ bee venom treatment. (3) Bee venom treatment inhibited expression of cell-cycle regulating, growth-promoting genes such as c-Jun, c-Fos, and Cyclin Dl, and increased tumor suppressors p53 and p21/Wafl. (4) Bee venom treatment activated expression of a representative apoptosis-inducing gene Bax.

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Study on the Anti-angiogenic Therapy to Cancer disease with Oriental medicine (혈관신생억제를 통한 종양치료의 한의학적 고찰)

  • Song, Kee-Cheol;Choi, Byung-Ryel;Lee, Yong-Yeon;Seo, Sang-Hoon;Yoo, Hwa-Seung;Cho, Jung-Hyo;Lee, Yeon-Weol;Son, Chang-Gyu;Cho, Chong-Kwan;Choi, Woo-Jin
    • The Journal of Internal Korean Medicine
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    • v.22 no.4
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    • pp.639-645
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    • 2001
  • Angiogenesis is a fundamental process in reproduction and wound healing. Under these condition, neovascularization is tightly regulated. Unregulated angiogenesis may lead to several angiogenic diseases, and is thought to be indispensible for solid tumor growth and metastsis. The construction of new vascular network is a multistep cascade involving basement membrane degradation, endothelial cell proliferation, endothelial cell migration, and tube formation. Newly reported anti-angiogenic agents in oriental medical field have targeted both specific and multistep stages in the angiogenic process. From recent approach in oriental medical field with several herb medicines including activating blood flow and removing blood stasis medicine(活血化瘀藥), it may be possible in the future to develope specific anti-angiogenic agents that offer a less toxic potential therapy for cancer and angiogenic disease.

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Innate Immunity Activation and Anti-Inflammation Effects of Evodia Rutaecarpine Water Extract (오수유 물 추출물의 선천 면역 활성과 염증 억제 효과)

  • Jeong, So-Mi;Lee, Jin-Moo;Lee, Chang-Hoon;Hwang, Deok-Sang;Jang, Jun-Bock
    • The Journal of Korean Obstetrics and Gynecology
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    • v.34 no.2
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    • pp.1-15
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    • 2021
  • Objectives: This study was designed to examine immuno-modulatory effects of Evodia Rutaecarpine by activating innate immune system and inhibiting inflammation. Methods: First, Cell cytotoxicity was examined with 4T1 breast carcinoma and TG-induced macrophage. To investigate activating innate immune system of Evodiamine Rutacarpine Extract (ERE) on macrophage, we tested tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). In addition, TNF-α and nitric oxide (NO) induced by lipopolysaccharide (LPS) were measured after treating with ERE to observe innate immune modulating effect of ERE on RAW 264.7 cell. Also, mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) were examined by western blot analysis. Results: In cytotoxicity analysis, ERE significantly affected tumor cell growth above specific concentration. Also, ERE significantly affected macrophage growth above specific concetration. As compared with the control group, the production of TNF-α, IL-12 and IL-6 were increased in TG-induced macrophage. As compared with the control group, TNF-α and IL-6 were significantly up-regulated in RAW 264.7 cell. The expression of TNF-α and NO induced by LPS after treating ERE was significantly decreased compared with control group. In addition, We observed ERE inhibited the phosphorylation levels of p-extracellular signal-regulated kinase (p-ERK), p-Jun N-terminal kinase (p-JNK), and p-p38 in western blotting by treating ERE on RAW 264.7 cell. Conclusions: ERE seems to have considerable impact on the anti-cancer effect by activation of innate immune system and inflammation control.

Anti-Helicobacter pylori, Cytotoxic, and Anti-inflammatory Activities of White Ginseng Extract

  • Jee, Hee-Sook;Chang, Kyung-Hoon;Moon, Sun-Hee;Park, Se-Ho;Paik, Hyun-Dong
    • Food Science and Biotechnology
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    • v.17 no.5
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    • pp.1106-1109
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    • 2008
  • The anti-Helicobacter pylori activity, cytotoxicity, and anti-inflammatory activity of white ginseng extract (WGE) were investigated in vitro in this study. The antimicrobial effects of WGE toward H. pylori strains 52 J99, SSI, and 51 were tested using the disk diffusion method. Among these H. pylori strains, H. pylori 52 was the most sensitive, having the largest inhibition zone (19 mm), followed by J99, SSI, and 51. The zone of inhibition due to WGE increased significantly with increasing dosage. The cytotoxicity of WGE toward the human cancer cell lines A-549 (human lung carcinoma), HEC-1-B (human endometrial adenocarcinoma), HeLa (human uterin adenocarcinoma), and SW-156 (human kidney carcinoma) was measured using the 3-(4,5-dimethylthizol-2-yl)-2,5-diphenylate-tetrazolium bromide (MTT) assay. WGE exhibited an inhibitory effect on cell growth at 2.0 mg/mL for all tumor cell lines. An analysis of anti-inflammatory activity using the RAW 264.7 cell line showed that the inhibition of nitric oxide (NO) production increased as the WGE content increased. These results demonstrate the potential of WGE to be used as a health-promoting substance.

Peripheral Blood Immune Cell-based Biomarkers in Anti-PD-1/PD-L1 Therapy

  • Kyung Hwan Kim;Chang Gon Kim;Eui-Cheol Shin
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.8.1-8.15
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    • 2020
  • Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.