• Title/Summary/Keyword: matrix metalloproteinase-11

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Correlation between Microvascular Density and Matrix Metalloproteinase 11 Expression in Prostate Cancer Tissues: a Preliminary Study in Thailand

  • Kanharat, Nongnuch;Tuamsuk, Panya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6639-6643
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    • 2015
  • Background: Prostate cancer is a major concern of public health. Microvascular density (MVD) is one of the prognostic markers for various solid cancers. Matrix metalloproteinase 11 (MMP11) plays an important role in angiogenesis and changes in its expression level are known to be associated with tumor progression and clinical outcome. Aim: To investigate the relationship between MVD and MMP11 expression in prostatic adenocarcinoma tissues. Materials and Methods: The expression levels of MMP11 and MVD were analyzed immunohistochemically for 50 specimens of prostatic adenocarcinoma. Results: MMP11 was mainly expressed in stromal cells but rarely seen in epithelial cells. Mean MVD was $36/mm^2$, and it was correlated significantly only with bone metastases. MVD was also significantly correlated with MMP11 expression (r=0.29, p=0.044). Conclusions: MMP11 may alter the stromal microenvironment of prostate cancer to stimulate tumor angiogenesis.

High Expression of Matrix Metalloproteinase-11 indicates Poor Prognosis in Human Cholangiocarcinoma

  • Tongtawee, Taweesak;Kaewpitoon, Soraya J;Loyd, Ryan;Chanvitan, Supachai;Leelawat, Kawin;Praditpol, Niphol;Jujinda, Supathip;Kaewpitoon, Natthawut
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3697-3701
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    • 2015
  • Background: Cholangiocarcinoma (CHCA) is serious public health problem in Thailand, especially in the northeastern and northern regions. CHCA is known as one of the most aggressive malignant tumors associated with local invasion and a high rate of metastasis. A crucial step in the invasion process is the proteolytic degradation of the extracellular matrix (ECM) and basal membranes, for which several studies have shown a critical role played by matrix metalloproteinase-11 (MMP-11). Objective: This study aim to detect MMP-11 expression in CHCA specimens and any correlation with survival time. Materials and Methods: A retrospective analysis was conducted of 30 patients with CHCA in Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11. Relationships between clinicopathological data and MMP-11 expression in CHCA specimens were analyzed by the ${\chi}^2$ test or Fisher's exact test. The estimated survival and the survival differences were analyzed by the Kaplan-Meier method and the log-rank test, respectively. Results: MMP-11 expression was found in 15 specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4-338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant for the positive and negative MMP-11(p=0.022), but not well differentiated tumor and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388). Conclusions: The positive MMP-11 expression indicates poor prognosis in CHCA specimens.

Overexpression of Matrix Metalloproteinase 11 in Thai Prostatic Adenocarcinoma is Associated with Poor Survival

  • Nonsrijun, Nongnuch;Mitchai, Jumphol;Brown, Kamoltip;Leksomboon, Ratana;Tuamsuk, Panya
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.3331-3335
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    • 2013
  • Background: The incidence of prostate cancer, one of the most common cancers in elderly men, is increasing annually in Thailand. Matrix metalloproteinase 11 (MMP-11) is a member of the extracellular matrix metalloproteases which has been associated with human tumor progression and clinical outcome. Aim: To quantify MMP-11 expression in prostatic adenocarcinoma tissues and to determine whether its overexpression correlates with survival outcome, and to assess its potential as a new prognostic marker. Materials and Methods: Expression of MMP-11 was analyzed using immunohistochemistry in 103 Thai patients with prostatic adenocarcinoma. Overall survival was analyzed using Kaplan-Meier methods and Cox regression models. Results: Immunoreactivity of MMP-11 was seen in the stroma of prostatic adenocarcinoma tissue samples, high expression being significantly correlated with poor differentiation in Gleason grading, pathologic tumor stage 4 (pT4), and positive-bone metastasis (p<0.05), but not age and prostatic-specific antigen (PSA) level. Patients with high levels of MMP-11 expression demonstrated significantly shorter survival (p<0.001) when compared to those with low levels. Multivariate analysis showed that MMP-11 expression and pT stage were related with survival in prostatic adenocarcinoma [hazard ratio (HR)=0.448, 95% confidence interval (95%CI)=0.212-0.946, HR=0.333, 95%CI=0.15-0.74, respectively]. Conclusions: Expression of MMP-11 is significantly associated with survival in prostatic adenocarcinoma. High levels may potentially be used for prediction of a poor prognosis.

Inhibitory Effect of Gallic Aicd on TNF-α-induced matrix metalloproteinase-1 (MMP-1) in HaCaT Cells (HaCaT세포에서 TNF-α에 의해 유도되는 MMP-1에 대한 Gallic Aicd의 저해 효과)

  • Kim, Pom-Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.11
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    • pp.5778-5784
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    • 2013
  • In order to develop anti-wrinkle agent, we measured the anti-oxidative activity of gallic acid (GA) from Paeonia suffruticosa Andrews and investigated its cytotoxicity in HaCaT cells and then investigated its effect on tumor necrosis factor alpha (TNF-${\alpha}$)-induced matrix metalloproteinase-1 (MMP-1) mRNA, protein expressions and secretion in same cells. GA showed anti-oxidative activity with $IC_{50}$ of 30 ${\mu}g/mL$ and its activity was higher than that of butylated hydroxyanisol (BHA). GA showed weak cytotoxicity with high concentration (200 ${\mu}g/mL$) in HaCaT cells. MMP-1 mRNA, protein expression and secretion induced by tumor necrosis factor alpha (TNF-${\alpha}$) in HaCaT cells were significantly decreased by treatment of GA with dose-dependent manner(p<0.05). Therefore, our findings suggest that GA can be useful as an active ingredient for cosmeceuticals of anti-wrinkle effects.

Effect of Fucus evanescens Fucoidan on Expression of Matrix Metalloproteinase-1 Promoter, mRNA, Protein and Signal Pathway (Fucus evanescens fucoidan의 matrix metalloproteinase-1 promoter, mRNA, 단백질 발현과 신호전달경로에 미치는 효과)

  • Ku, Mi-Jeong;Jung, Ji-Won;Lee, Myeong-Sook;Cho, Byung-Kyu;Lee, Soon-Rye;Lee, Hye-Sook;Vischuk, Olesya S.;Zvyagintseva, Tatyana N.;Ermakova, Svetlana P.;Lee, Yong-Hwan
    • Journal of Life Science
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    • v.20 no.11
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    • pp.1603-1610
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    • 2010
  • Fucoidans are sulfated fucosylated polymers from the cell wall of brown algae. We assessed the effects of Fucus evanescens fucoidan on ultraviolet-B (UVB)-induced expression of matrix metalloproteinase-1 (MMP-1) protein, mRNA, and promoter, and the phosphorylation of mitogen-activated protein kinases in vitro using an immortalized human keratinocyte cell line. Pretreatment with 10 and $100\;{\mu}g/ml$ fucoidan significantly inhibited UVB-induced MMP-1 protein, mRNA and promoter activity, compared to UVB irradiation alone. Extracellular signal regulated kinase activation was markedly inhibited by treatment with fucoidan, though c-JUN N-terminal kinase activity and p38 activation were only marginally affected by fucoidan. F. evanescens fucoidan may be a potential therapeutic agent for the prevention and treatment of skin photoaging.

Expression of Matrix Metalloproteinase 2 and Tissue Inhibitor of Metalloproteinase 2 in Papillary Microcarcinoma of the Thyroid Gland are Not Related with Extrathyroid Invasion, Multifocality and Lymph Node Metastasis of the Tumor (갑상선 유두상미세암종에서 갑상선외 침윤, 다원성 및 경부전이에 대한 Matrix Metalloproteinase 2 및 Tissue Inhibitor of Matrix Metalloproteinase 2 발현의 의의 : 부정적 결과 보고)

  • Choi Seung-Ho;Nam Soon-Yuhl;Cho Kyung-Ja;Kim Sang-Yoon
    • Korean Journal of Head & Neck Oncology
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    • v.21 no.2
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    • pp.121-125
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    • 2005
  • Objectives: To investigate the role of MMP-2 and TIMP-2 in the invasion and metastasis of thyroid papillary microcarcinomas. Materials and Methods: We performed immunohistochemical study on MMP-2 and its tissue inhibitor (TIMP-2) using tissue microarrays containing 2 cores of 40 microPTC and 8 non-neoplastic thyroid tissue. The expression intensity was semiquantitatively scored as -, ${\pm}$, +1, +2, and +3. Results: Both MMP-2 and TIMP-2 expression was observed in all tumors(100%) and in 1 of 8 non-neoplastic tissue(12.5%), and the positive staining was restricted to the epithelial cells. In 17 and 23 tumors with or without extrathyroid invasion, respectively, 8(47%) and 10(43%) cases showed moderate to strong(+23) positivity for MMP-2. TIMP-2 expression was moderate to strong in 13 cases(76%) and 16 cases(70%) in each group. In multifocal and solitary tumors, 3 of 6(50%) and 11 of 21(52%) cases showed moderate to strong MMP-2 expression, and 5/6(83%) and 15/21(71%) showed moderate to strong TIMP-2 expression. Conclusion: There is no relationship between MMP-2 or TIMP-2 expression and extrathyroid invasion or tumor multifocality in papillary microcarcinoma of the thyroid gland.

Inhibitory Effect of Methanol Extract of Magnolia officinalis on Matrix Metalloproteinase-2

  • Lee, Dong-Yup;Kim, Cheorl-Ho;Kim, Dong-Soo
    • Preventive Nutrition and Food Science
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    • v.11 no.3
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    • pp.191-197
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    • 2006
  • Matrix metalloproteinase-2 (MMP-2) is a key enzyme involved in tumor invasiveness. The plant of Magnolia officinalis Rehd. et Wils. is often included as an ingredient in various herbal remedies recommended for cancer theraphies in Korea. Various extracts prepared from stems of M. officinalis were tested for cytotoxic activity on human hepatocellular carcinoma cell line, SK-Hep cells using the XTT assay method. Then, the inhibitory effect was examined on MMP-2 activity using gelatin zymography. Methanol (MeOH) extract of M. officinalis caused the strongest inhibition of the MMP-2 activity, as measured by gelatin zymography method for enzyme activity. $IC_{50}$ values of fractions on MMP-2 activity were in a range of $4.9{\sim}11.3\;{\mu}g/mL$. Among each fraction, butanol and ethylacetate (EtOAc) fractions showed the strong inhibitory activities ($IC_{50}=10.7\;and\;4.9\;{\mu}g/mL$, respectively). When the M. officinalis's constituents such as magnolol, honokiol, (-)-epigallocatechin gallate (EGCG) and ovovatol were examined for inhibitory effects on MMP-2 activity, EGCG showed strong inhibitory activity. However, MeOH extract of M. officinalis was dose-dependently inhibited to MMP-2 activity. The MeOH extract, hexane and EtOAc fractions $(IC_{50}\;of\;>200\;{\mu}g/mL)$ exhibited weak cytotoxicity activity, while butanol $(IC_{50}=80\;{\mu}g/mL)$ and chloroform fractions $(IC_{50}=90\;{\mu}g/mL)$ exhibited relatively strong cytotoxic activity. From these results, M. officinalis could be suitable for cancer treatment and chemopreventive drugs.

Effects of (-)-Epigallocatechin-3-gallate on Brain Infarction and the Activity Change of Matrix Metalloproteinase-9 Induced by Middle Cerebral Artery Occlusion in Mice

  • Qian, Yong-Ri;Kook, Ji-Hyun;Hwang, Shin-Ae;Kim, Do-Kyung;Kim, Jong-Keun
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.3
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    • pp.85-88
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    • 2007
  • Matrix metalloproteinases (MMPs) can degrade a wide range of extracellular matrix components. It has been reported that MMP-9 are activated after focal ischemia in experimental animals. (-)-Epigallocatechin-3-gallate (EGCG), a major constituent of green tea polyphenols, is a potent free radical scavenger and reduces the neuronal damage caused by oxygen free radicals. And it has been known that EGCG could reduce the infarction volume in focal brain ischemia and inhibit MMP-9 activity. To delineate the relationship between the anti-ischemic action and the MMP-9-inhibiting action of EGCG, we investigated the effect of EGCG on brain infarction and the activity of matrix metalloproteinase-9 induced by permanent middle cerebral artery occlusion (pMCAO) in ICR mice. EGCG (40 mg/kg, i.p. $15{\sim}30min$ prior to MCAO) significantly decreased infarction volume at 24 hr after MCAO. GM 6001 (50 mg/kg, i.p. $15{\sim}30min$ prior to MCAO), a MMP inhibitor, also significantly reduced infarction volume. In zymogram, MMP-9 activities began to increase at ipsilateral cortex at 2 hr after MCAO, and the increments of MMP-9 activities were attenuated by EGCG treatment. Western blot for MMP-9 also showed patterns similar to that of zymogram. These findings demonstrate that the anti-ischemic action of EGCG ire mouse focal cerebral ischemia involves its inhibitory effect on MMP-9.