• Title/Summary/Keyword: Cancer angiogenesis

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HDAC3 acts as a negative regulator of angiogenesis

  • Park, Deokbum;Park, Hyunmi;Kim, Youngmi;Kim, Hyuna;Jeoung, Dooil
    • BMB Reports
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    • v.47 no.4
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    • pp.227-232
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    • 2014
  • Histone deacetylase-3 (HDAC3) is involved in cellular proliferation, apoptosis and transcriptional repression. However, the role of HDAC3 in angiogenesis remains unknown. HDAC3 negatively regulated the expression of angiogenic factors, such as VEGF and plasminogen activator inhibitor-1 (PAI-1). HDAC3 showed binding to promoter sequences of PAI-1. HDAC3 activity was necessary for the expression regulation of PAI-1 by HDAC3. VEGF decreased the expression of HDAC3, and the down-regulation of HDAC3 enhanced endothelial cell tube formation. HDAC3 negatively regulated tumor-induced angiogenic potential. We show the novel role of HDAC3 as a negative regulator of angiogenesis.

Correlation Between Apoptosis and Intratumoral Microvessel Density in Non-Small Cell Lung Cancer. (비소세포 폐암에서 아포프토시스와 종양내 미세 혈관 밀도의 관계)

  • 장인석;김종우;김진국;한정호
    • Journal of Chest Surgery
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    • v.32 no.2
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    • pp.151-157
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    • 1999
  • Background: Increasing evidences from experimental studies indicate that apoptosis may be inversely related to angiogenesis in tumor progression. Material and Method: To explore how apoptosis correlates with tumor angiogenesis, we measured the apoptotic index(AI) using the terminal deoxynucleotidyl transferase method(Apop Tag In Situ Apoptosis Detection Kit, ONCOR) and the intratumoral microvessel density using the anti-CD31 monoclonal antibody in non-small cell lung cancer. Result: Statistical analysis revealed an inverse correlation between AIs and intratumoral microvessel densities in squamous cell lung carcinoma(Spearman rank correlation coefficient r=- 0.229, p=0.047). Conclusion: The results of this study demonstrated that the amount of apoptosis in squamous cell lung carcinoma may be influenced by the extent of neovascularization. This suggests that tumor angiogenesis may contribute to a reduction of apoptosis in tumor cells.

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2-Methoxy-1,4-naphthoquinone (MNQ) regulates cancer key genes of MAPK, PI3K, and NF-κB pathways in Raji cells

  • Wong, Teck Yew;Menaga, Subramaniam;Huang, Chi-Ying F.;Ho, Siong Hock Anthony;Gan, Seng Chiew;Lim, Yang Mooi
    • Genomics & Informatics
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    • v.20 no.1
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    • pp.7.1-7.13
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    • 2022
  • 2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

Effect of Grape Procyanidins on Tumor Angiogenesis in Liver Cancer Xenograft Models

  • Feng, Li-Li;Liu, Bing-Xia;Zhong, Jin-Yi;Sun, Li-Bin;Yu, Hong-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.737-741
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    • 2014
  • Background: In recent years a wide variety of flavonoids or polyphenolic substances have been reported to possess substantial anti-carcinogenic and antimutagenic activities. Grape proanthocyanidins (GPC) are considered as good examples for which there is evidence of potential roles as anti-carcinogenic agents. Methods: A xenograft model was established using H22 cells subcutaneously injected into mice and used to assess different concentrations of grape proanthocyanidins (GPC) and Endostar. Treatments were maintained for 10 days, then levels of vascular endothelial growth factor (VEGF) and microvessel density (MVD) were examined by immunohistochemistry, while VEGF mRNA was determined by real-time PCR in tumor tissue. Results: The expression of MVD and VEGF decreased gradually as the concentration of GPC increased.There was a significant positive correlation between MVD and VEGF. Conclusions: These results suggest that GPC restrains the growth of tumor, possibly by inhibiting tumour angiogenesis.

Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

  • Kuppala, Manohar Babu;Syed, Sunayana Begum;Bandaru, Srinivas;Varre, Sreedevi;Akka, Jyothy;Mundulru, Hema Prasad
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5353-5361
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    • 2012
  • Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

Effects of a Multikinase Inhibitor Motesanib (AMG 706) Alone and Combined with the Selective DuP-697 COX-2 Inhibitor on Colorectal Cancer Cells

  • Kaya, Tijen Temiz;Altun, Ahmet;Turgut, Nergiz Hacer;Ataseven, Hilmi;Koyluoglu, Gokhan
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1103-1110
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    • 2016
  • In the present study, we investigated the effects of motesanib (AMG 706), a multikinase inhibitor alone and in combination with DuP-697, an irreversible selective inhibitor of COX-2, on cell proliferation, angiogenesis, and apoptosis induction in a human colorectal cancer cell line (HT29). Real time cell analysis (RTCA, Xcelligence system) was used to determine the effects on colorectal cancer cell proliferation. Apoptosis was assessed with annexin V staining and angiogenesis was determined with chorioallantoic membrane model. We found that motesanib alone exerted antiproliferative, antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Combination with DUP-697 increased the antiproliferative, antiangiogenic and apoptotic effects. Results of this study indicate that motesanib may be a good choice in treatment of colorectal tumors. In addition, the increased effects of combination of motesanib with DuP-697 raise the possibility of using lower doses of these drugs and therefore avoid/minimize the dose-dependent side effects generally observed.

Inhibitory Effect of Chloroform Extract of Marine Algae Hizikia Fusifomis on Angiogenesis (Hizikia fusiformis 클로로포름 추출물의 in vitro 및 in vivo 혈관신생 억제 연구)

  • Myeong-Eun Jegal;Yu-Seon Han;Shi-Young Park;Ji-Hyeok Lee;Eui-Yeun Yi;Yung-Jin Kim
    • Journal of Life Science
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    • v.34 no.6
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    • pp.399-407
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    • 2024
  • Angiogenesis is the process by which new blood vessels form from existing blood vessels. This phenomenon occurs during growth, healing, and menstrual cycle changes. Angiogenesis is a complex and multifaceted process that is important for the continued growth of primary tumors, metastasis promotion, the support of metastatic tumors, and cancer progression. Impaired angiogenesis can lead to cancer, autoimmune diseases, rheumatoid arthritis, cardiovascular disease, and delayed wound healing. Currently, there are only a handful of effective antiangiogenic drugs. Recent studies have shown that natural marine products exhibit antiangiogenic effects. In a previous study, we reported that the hexane extract of H. fusiformis (HFH) could inhibit the development of new blood vessels both in vitro and in vivo. The aim of this study was to describe the inhibitory effect of chloroform extracts of H. fusiformis on angiogenesis. To investigate how chloroform extract prevents blood vessel growth, we examined its effects on HUVEC, including cell migration, invasion, and tube formation. In a mouse Matrigel plug assay, H. fusiformis chloroform extract (HFC) also inhibited angiogenesis in vivo. Certain proteins associated with blood vessel growth were reduced after HFC treatment. These proteins include vascular endothelial growth factor (VEGF), mitogen-activated protein kinase (MAPK)/extracellular signal transduction kinase, and serine/threonine kinase 1 (AKT). These studies have shown that the chloroform extract of H. fusiformis can inhibit blood vessel growth both in vitro and in vivo.

The Production of IFN-${\gamma}$ by 3LL/TNF-$\alpha$-Activated Macrophages Requires p38. JAK-2 Signalling and is Enhanced by New Protein Synthesis.

  • Park, Dae-Sup;Cho, Seong-Jun;Baeg, Hye-Kyoung;Baek, So-Young;Lee, Hyun-Ah;Pyo, Suhk-Neung
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.310.3-311
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    • 2002
  • Macrophages have been known to play an essential role in tumor angiogenesis and produce a number of growth stimulators and inhibitors. Thus macrophages appear to influence every stage of angiogenesis. In this report, TNF-$\alpha$ was able to induce the production of IFN-${\gamma}$ in cancer cell-contanted macrophage. TNF-${\gamma}$ alone released relatively little IFN-${\gamma}$ whereas live tumor cells (3LL) alone releasd IFN-${\gamma}$ markedly from macrophage. (omitted)

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Immunopreventive Effects against Murine H22 Hepatocellular Carcinoma in vivo by a DNA Vaccine Targeting a Gastrin-Releasing Peptide

  • Meko'o, Jean Louis Didier;Xing, Yun;Zhang, Huiyong;Lu, Yong;Wu, Jie;Cao, Rongyue
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.9039-9043
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    • 2014
  • There is a continuing need for innovative alternative therapies for liver cancer. DNA vaccines for hormone/growth factor immune deprivation represent a feasible and attractive approach for cancer treatment. We reported a preventive effect of a DNA vaccine based on six copies of the B cell epitope GRP18-27 with optimized adjuvants against H22 hepatocarcinoma. Vaccination with pCR3.1-VS-HSP65-TP-GRP6-M2 (vaccine) elicited much higher level of anti-GRP antibodies and proved efficacious in preventing growth of transplanted hepatocarcinoma cells. The tumor size and weight were significantly lower (p<0.05) in the vaccine subgroup than in the control pCR3.1-VS-TP-HSP65-TP-GRP6, pCR3.1-VS-TP-HSP65-TP-M2 or saline subgroups. In addition, significant reduction of tumor-induced angiogenesis associated with intradermal tumors of H22 cells was observed. These potent effects may open ways towards the development of new immunotherapeutic approaches in the treatment of liver cancer.

Inhibitory Effects of Citaowan on Metastatic Cancer Growth and Agiogenesis in an Orthotopic Model of Breast Cancer (생쥐의 동소이식 유방암에서 자도환(慈桃丸)의 in vivo 전이암 성장 억제 및 혈관신생 억제 효과)

  • Myung, Eu-Gene;Kang, Hee;Shim, Bum-Sang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1502-1506
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    • 2006
  • To investigate the inhibitory effects of Citaowan (CTW) on the growth and angiogenesis of breast cancer in vivo. Orthotopic breast cancer model was established by injection of MDA-MB-231 cells into mammary fat pad of nude mice. Seven weeks after injection, CTW was orally administered at dose of 50, 100 mg/mouse every day for 40 days. Body weight, tumor volume, tumor apoptosis, microvessel density and tumor proliferation were evaluated, after the mice were sacrificed. The body weight and tumor volume were not significantly changed in CTW group compared with the control group. Tumor apoptosis, proliferation and microvessel density were significantly reduced in CTW group (100 mg/mouse) compared with the control group. These data indicate that CTW has anti-angiogenic and proapoptotic effects on breast cancer.