• Title/Summary/Keyword: Anti-metastatic

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Structural Analysis of Anti-metastatic Polysaccharides Isolated from Opuntia humifusa (천년초에서 분리한 항전이 다당의 구조 분석)

  • Choi, Jung-Ho;Shin, Kwang-Soon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.2
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    • pp.214-222
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    • 2011
  • To examine the new practical utilization of mucilages in Opuntia humifusa, polysaccharides were isolated from O. humifusa and their anti-metastatic activity and structural analysis were carried out. In experimental lung metastasis of B16BL6 melanoma cells, prophylactically intravenous (i.v.) administration of the crude polysaccharide (CNC-0) from O. humifusa significantly inhibited lung metastasis in a dose-dependant manner. The main polysaccharide, CNC-Ia was purified to homogeneity from CNC-0 by two successive column chromatographies using DEAE-Sepharose FF and Sephadex G-100 and its structure was characterized. Molecular mass of CNC-Ia was estimated to be 700 kDa and it mainly consisted of arabinose, galactose and xylose in addition to two minor sugars such as rhamnose and fucose. Methylation analysis indicated that CNC-Ia comprised at least 18 different glycosyl linkages such as terminal Araf, 5-linked Araf, 4-linked Galp and terminal Xylp in addition to three characteristic linkages such as full branched Araf, 3,4,6-branched Galp and full branched Galp. To analyze the fine structure of CNC-Ia, it was sequentially digested by exo-${\alpha}$-L-arabinofuranosidase and endo-${\beta}$-1,4-D-galactanase. These analyses suggested that CNC-Ia belongs to be a highly branched Type I arabinogalactan which has a ($1{\rightarrow}4$)-${\beta}$-galactan backbone with arabinosyl oligosaccharide side chains.

Anti-Metastatic Activity of Juniperus chinensis Extract by Galectin-3 Inhibition (향나무 추출물의 Galectin-3 저해에 의한 암 전이 억제 효과)

  • Lee, Keyong Ho;Rhee, Ki-Hyeong
    • The Korean Journal of Food And Nutrition
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    • v.25 no.4
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    • pp.713-718
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    • 2012
  • The purpose of this study was to examine the anti-metastatic effect of Juniperus chinensis extract by inhibition of galectin-3 expression. For this study, we carried out the experiment of galectin-3 expression assay and in vivo metastasis mouse model bearing colon 26-M3.1 lung carcinoma, and also MMP-1, MMP-2 and MMP-9 inhibitory assays relating metastasis mechanism. J. chinensis extract significantly showed the inhibitory effect of basal expression and MNNG-induced expression of galectin-3 in colon 26-M3.1 lung carcinoma at the all tested doses (5, 50 and $500{\mu}g/m{\ell}$). In case of the inhibition of MMP-1, MMP-2 and MMP-9, the weak activity was showed at the doses of 50 and $500{\mu}g/m{\ell}$ and was not detected at the dose of $5{\mu}g/m{\ell}$. However, J. chinensis extract significantly showed the anti-metastatic activity on mouse mode bearing colon 26-M3.1 lung carcinoma. Therefore, this study strongly suggests that J. chinensis is a potent inhibitor of galectin-3 expression, and holds great promise for use in inhibiting metastasis induced by elevated expression of galectin-3.

Surgical Treatment of Metastatic Lung Cancer (전이성 폐암의 외과적 치료)

  • 조성래
    • Journal of Chest Surgery
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    • v.25 no.9
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    • pp.948-954
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    • 1992
  • In spite of recent progress in anticancer chemotherapy, the survival of patients with metastases to the lung treated nonsurgically has been extremely poor. So we adopted more aggressive surgical approaches for the treatment of patients with pulmonary metastases since 1985. We experienced 22 operations of metastatic lung cancer in 19 patients in the department of Thoracic & Cardiovascular Surgery in Kosin Medical College since 1985, so we reviewed the results of treatment retrospectively. The results were as follows: 1. The primary organs of metastatic lung cancer were 4 cases in each of the breast, uterus, and extremities, 3 cases in the rectum, 2 cases in the kidney, 1 case in each of the pelvis and liver, and the pathological findings were 13 cases in carcinoma and 6 cases in sarcoma. 2. The treatments for primary lesions were 15 cases of the operations with anticancer chemotherapy or radiation therapy, 2 cases of choriocarcinoma with anticancer chemotherapy only, 1 cases of uterine cervical carcinoma with chemo-radiation therapy, and 1 case of pelvic synovia sarcoma with intra-arterial anticancer chemotherapy. 3. Disease free intrerval were as follows: 7 cases were in 2 years to 4 years, 4 cases were in 1 year to 2 years, and 5 cases were beyond one year, of them one case was discovered primary lesion and metastatic lung tumor concomittently. 3 cases were above 4 years, of them one case of breast cancer were above 13 years especially. 4. The sites of metastatic lung cancer was 15 lesions in the right lung, and 9 lesions in the left lung, And the lobar sites were 10 lesions in the upper lobe, 2 lesions in the middle lobe, and 12 lesions in the lower lobe. 5. The operative methods of metastatic lung cancer were 7 case of partial resection of lung, 12 cases of pulmonary lobectomy, 1 case of pneumonectomy and 1 case of dissection of mediastinal lymph node. 6. The postoperative complications were 1 case of mild respiratory insufficency, 1 cases of pyothorax, and 1 case of urethral stricture. 7. Postoperative adjuvant therapy were as follows: No adjuvant therapy were 4 cases, anti-cancer chemotherapy were 8 cases, radiation therapy was 1 case, and combined with chemo k radiation therapy were 8 cases. 8. The results of long term follow-up were as follows: The 5 patients were died at 2 months, 22 months, 24 months, 32 months, and 49 months postoperatively, so mean survival period was 32 months postoperatively excluding one patient who was died at 2 months postoperatively. And 14 patients are aliving, of them 3 patients are living in recurred state, and the other 11 patients are living without any evidence of recurrence.

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Trastuzumab-based Retreatment after Lapatinib in Heavily Pretreated HER2 Positive Metastatic Breast Cancer: an Anatolian Society of Medical Oncology Study

  • Uncu, Dogan;Bayoglu, Ibrahim Vedat;Arslan, Ulku Yalcintas;Kucukoner, Mehmet;Artac, Mehmet;Koca, Dogan;Oguz, Arzu;Demirci, Umut;Arpaci, Erkan;Dogan, Mutlu;Kucukzeybek, Yuksel;Turker, Ibrahim;Isikdogan, Abdurrahman;Guler, Tunc;Zengin, Nurullah
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.4127-4131
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    • 2015
  • Background: For HER2 positive metastatic breast cancer (MBC), continuing anti-HER2 therapy beyond progression is associated with improved outcome. However retreatment with trastuzumab after lapatinib progression is controversial. We retrospectively analyzed the efficacy of trastuzumab-based chemotherapy in HER2+ metastatic breast cancer patients whose disease progressed after lapatinib. Materials and Methods: Between October 2010 and May 2013, 54 patients whose disease progressed after lapatinib were retreated with trastuzumab-based chemotherapy. Efficacy and toxicity results were evaluated retrospectively. Results: The median age of patients was 46 (range 27-67). Fourteen patients (26%) had metastases at the time of diagnosis. All of the patients had received trastuzumab in an adjuvant or metastatic setting, while 16 (30%) had received two lines of trastuzumab. All patients had received lapatinib plus capecitabine. The median chemotherapy line for the metastatic setting was 2 (range 1-7). Cranial metastases were identified in 27 (50%) patients. 53 patients received trastuzumab-based chemotherapy following lapatinib progression while one patient received trastuzumab monotherapy. Combination chemotherapy consisted of navelbin (n=33), taxane (n=10), gemcitabine (n=2), platinum (n=2) and platinum with taxane (n=6). The median treatment cycle was 5 (range 1-44). Among 49 patients assessed for response 2 (4%) showed CR, 12 (25%) PR, 11 (22%) SD and 24 (49%) disease progression. Asymptomatic cardiotoxicity was reported in 2 (4%) of the patients. At a median follow-up of 9 months (1-39), median progression-free survival was 5 months (95% CI 4.1-5.9) and median overall survival was 10 months (95% CI 6.9-13.0). PFS and OS were not affected by the absence/presence of cranial metastases. Conclusions: Retreatment with trastuzumab-based therapy after lapatinib progression showed efficacy in heavily treated MBC patients.

Aqueous Extract of Anticancer Drug CRUEL Herbomineral Formulation Capsules Exerts Anti-proliferative Effects in Renal Cell Carcinoma Cell Lines

  • Verma, Shiv Prakash;Sisoudiya, Saumya;Das, Parimal
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8419-8423
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    • 2016
  • Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of ${\approx}4mg/mL$ in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL.

Study on Antitumor Activity of Sobokchukeotang and Kamisobokchukeotang (소복축어탕과 가미소복축어탕이 항암활성에 미치는 영향)

  • 신원웅;최주선;길재호;김성훈
    • The Journal of Korean Medicine
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    • v.22 no.2
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    • pp.22-30
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    • 2001
  • This study was attempted to investigate the anti-tumor and anti-metastatic effects of Sobokchukeotang(SBCT) and Kamisobokchukeotang(KSBCT). Cytotoxicity against various cancer cell lines, anti-adhesion, pulmonary colonization, anti-angiogenesis, and T/C% were evaluated. SBCT and KSBCT exhibited no cytotoxicity against HT-1080, A549, SK-OV-3, B16-F10 and SK-Mel-2 cell lines. In inhibitory effect on DNA topoisomerase I, the $IC_{50S}$ were shown $250-500{\;}\mu\textrm{g}/ml$ of SBCT and $62.5-125{\;}\mu\textrm{g}/ml$ of KSBCT respectively. In the in vivo experiments, SBCT(135.98%) and KSBCT(151.92%) apparently increased the life span of mice bearing sarcoma-180. KSBCT significantly inhibited the adhesion of HT-1080 to complex extracellular matrix in a dose-dependent manner in contrast to SBCT. In pulmonary colonization assay by B16-F10, a number of colonies in the lungs were decreased more significantly in KSBCT group than those in SBCT group. In vitro neovascularization and CAM assay, angiogenesis was more significantly inhibited in KSBCT-treated group than in SBCT- treated group. Above results suggests that KSBCT is more effectively applied to prevention and treatment of cancer than SBCT.

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The Anti-tumor Effect of Polysaccharide from the Leaves of Panax Ginseng C.A. Meyer(MB40) in a Murine Squamous Cell Carcinoma Model (편평세포암 동물 모델에서 고려인삼잎-다당체(MB40)의 항암치료효과)

  • Joo, Eun-Jung;Choi, Jun;Chung, Eun-Jae;Hong, Seok-Jin;Cho, Jae-Gu;Baek, Seung-Kuk;Woo, Jeong-Soo;Jung, Kwang-Yoon;Kwon, Soon-Young
    • Korean Journal of Head & Neck Oncology
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    • v.25 no.1
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    • pp.3-7
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    • 2009
  • Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

Ginsenoside $Rh_1$$Rh_2$의 HT1080 세포 침윤억제 작용에 관한 연구

  • 박문택;차희재
    • Journal of Ginseng Research
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    • v.22 no.3
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    • pp.216-221
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    • 1998
  • We examined the anti-invasive activity of ginsenosides Rhl, Rha on the highly metastatic HT1080 human fibrosarcoma cell line. In vitro invasion assay showed ginsenoside Rhr reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber more than ginsenoside Rh1. Significant down-regulation of matrix metalloproteinase-9 (MMP-9) by ginsenosides Rh, and Rh2 was detected by Northern blot analysis. However, the expression of MMP-2 was not affected by Rh, and Rhr. The expression of tissue inhibitor of metalloproteinase-2 (TIMP-2) was increased by Rhl after 0.5, 1 or 3 day-treatment but reduced after 6 day-treatment. However, the expression of TIMP-2 was not changed by treatment with Rh2. Plasminogen activator inhibitor (PAI) and urokinase-type plasmlnogen activator (uPA) were not changed by treatment with Rh1 and Rh2 for 3 and 6 days. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but MMP-2 after treatments with ginsenosides Rhl and Rha. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of ginsenosides Rhl and Rhr in the HT1080 cells.

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Anti-metastatic Effects of Shiquandabutang on Human Fibrosarcoma cells, HT1080 (십전대보탕(十全大補湯)이 암전이(癌轉移) 억제(抑制)에 미치는 영향(影響))

  • Yoon, Jae-Ho;Choi, Seung-Hoon;Ahn, Kyoo-Seok
    • THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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    • v.4 no.1
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    • pp.131-146
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    • 1998
  • To examine the effect of Shiquandabutang on the metastasis of cancer, the following experiments were made. Before the main experiments, the cytotoxicity was measured by putting Shiquandabutang sample in HT1080. Then zymography was made to examine the change of gelatinolytic activity. And western blotting was carried out to examine the changes of Fos, Jun, Ets, the transcription factors of MMP-2, MMP-9, and Erk, JNK on signal transduction pathway to AP-1. Third, in vitro invasion assay with transwells coated by collagen and matrigel was carried out. From the results of the above the following conclusions were obtained. 1. The experimental result about cytotoxicity of Shiquandabutang against HT1080 was as below. The stained cell count after being treated by Shiquandabutang sample $400{\mu}g/ml$ for 24 hours was 0.9% of total cells, and the stained cell count by Shiquandabutang sample $100{\mu}g/ml$ was 1.5% of total cells. Both were near the level of control group which showed 0.6% stained. 2. The result of collagenase assay was as below. In Shiquandabutang sample $400{\mu}g/ml$, MMP-2 was reduced as compared with TPA control group, and the band of MMP-9 induced by TPA disappeared. In Shiquandabutang sample $800{\mu}g/ml$, both bands of MMP-2 and MMP-9 disappeared. 3. The results of western blots for Jun, Fos, Ets, Erk, JNK were as below. In Shiquandabutang sample $200{\mu}g/ml$, Ets was reduced, and Fos were increased. 4. The result of invasion assay was as below. The number of cells which migrated across transwell membrane in Shiquandabutang-treated group was less than that of +TPA control group. From the above results, it was concluded that Shiquandabutang might control the appearing and acting of collagenase not by the MMP-2, -9 promoter but by other way.

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