• Korean Journal of Head & Neck Oncology
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• v.14 no.2
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• pp.191-198
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• 1998

Objectives: We performed an immunohistochemical study to examine the place of neovascularization in the tumorigenic process of follicular thyroid carcinoma and to determine whether tumor angiogenic activity in follicular carcinoma plays a role in tumor aggression. Materials & Methods: We studied 63 follicular thyroid carcinomas and compared with 22 follicular adenomas. The areas of capsular invasion, vascular invasion and cellular atypism of the tumor were confimed on H & E stains. The paraffin embedded tissues were stained by the use of monoclonal antibodies against Ag CD34. Microvesseles were counted in the area of highest vascular density at 200 times magnification. The microvessel densities(MVD) were analized in relation to histologic type and location of the tumors. Results: There were 59 minimal invasive types and 4 widely invasive types of carcinoma. In the histologic specimens of carcinomas, capsular invasion was identified in all the cases, vascular invasion in 46 and cellular atypism in 24. Mean values of the MVDs of the minimal invasive carcinomas, the widely invasive carcinomas and the adenomas were $263.8{\pm}69.2,\;256.l{\pm}49.3\;and\;241.5{\pm}159.4$, respectively and there was no significant difference between each group. In follicular carcinomas, there was a regional difference of the MVDs. The areas of tumor showing cellular atypism and adjacent to or penetrating the capsule, in which represents the tumorigenic process of carcinoma, had a higher rate of vascularization, than other areas of the tumor(p<0.05). However, these features were not noted in the follicular adenomas. Conclusion: Although there was no significant difference of the MVD between follicular carcinomas and adenomas, there was a regional difference of the MVD within the carcinomas and the values were significantly higher in the more malignant areas, as indicated by cellular atypism and capsular invasion. Therefore, tumor angiogenic activity measured by MVD may play a role in tumor aggression in follicular thyroid carcinoma.

• Journal of Microbiology and Biotechnology
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• v.11 no.4
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• pp.656-662
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• 2001

Angiogenesis is known as a crucial process in the growth and spreading of tumor cells. Accordingly, the effective inhibition of this process would appear to be a promising way to cure angiogenesis-related diseases, including cancer. This study demonstrates that acalycixenolide E (AX-E) from the marine organism Acalycigorgia inermis exhibits a potent anti-angiogenic activity both in vitro and in vivo. AX-E inhibits the bFGF-induced proliferation of HUVECs in a dose dependent manner, along with the bFGF-induced migration, invasion, and tube formation of HUVECs. Moreover, AX-E potently inhibits the in vivo neovascularization of the chorioallantoic membranes (CAMs) of growing chick embryos. interestingly, AX-E suppresses the expression of metalloproteases 2 and 9, yet shows no effect on their activities. The novel chemical structure and potent anti-angiogenic activity of AX-E will be of great value in elucidating the molecular mechanism of angiogenesis as well as in the development of a novel anti-angiogenic drug.

• 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.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.456-465
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• 2023

Cervical tumors represent a prevalent form of cancer affecting women worldwide; current treatment options involve surgery, radiotherapy, and chemotherapy. Angiogenesis, the process of new blood vessel formation, is a crucial factor in cervical tumor growth. The molecular mechanisms underlying the effects of the liver kinase B1 (LKB1/STK11) tumor suppressor protein on tumor angiogenesis have not been elucidated. Therefore, we investigated the role of LKB1 in cervical tumor angiogenesis both in vitro and in vivo in this study. Our results demonstrated that LKB1 inhibited cervical tumor angiogenesis by suppressing the expression of angiogenesis-related factors such as vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1α. LKB1 directly affected both carcinoma and vascular endothelial cells, resulting in a significant reduction in tumor growth and angiogenesis. Furthermore, LKB1 was found to bind to VEGF receptor 2 (VEGFR-2) and target the VEGFR-2-mediated protein kinase B/mechanistic target of rapamycin signaling pathway in endothelial cells, thereby reducing cervical tumor growth and angiogenesis. Our study provides new insights into the molecular mechanisms underlying the anti-tumor and anti-angiogenic effects of LKB1 in cervical cancer. These findings will help develop new therapeutic strategies for cervical cancer.

• BMB Reports
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• v.40 no.3
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• pp.439-443
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• 2007

Tumor growth and metastasis are dependent on angiogenesis, and endothelial cell invasion and migration are apparent means of regulating tumor progression. We report here that saxatilin, a snake venom-derived disintegrin, suppresses the angiogenesis-inducing properties of NCI-H460 human lung cancer cells. Culture supernatants of NCI-H460 cells are able to induce human umbilical vascular endothelial cell (HUVEC) invasion and tube formation. However, treatment of the cancer cells with saxatilin resulted in reduced angiogenic activity of the culture supernatant. This suppressed angiogenic property was found to be associated with the level of vascular endothelial growth factor (VEGF) in the culture supernatant. Further experimental evidence indicated that saxatilin inhibits VEGF production in NCI-H460 cells by affecting hypoxia induced factor-1$\alpha$ (HIF-1$\alpha$) expression via the Akt pathway.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.532-537
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• 1993

Angiogenesis refers to the formation of new capillary blood vessels, or neovascularization occurring under various physical conditions, such as development of the embryo, formation of corpus luteum, wound healing and pathological conditions including tumor growth and metastases, hemangiomas, diabetic retinopathy, rheumatoid arthritis. There are many evidences that angiogenesis is important for the progressive growth of solid tumors and also permits the shedding of metastatic tumors from the primary site. Thus, treatment of angiogenesis inhibitors might be a novel strategy for tumor growth inhibition. Normal vascular endothelial cells are in a state of differentiation and angiogenic endothelial cells migrate and proliferate, and they subsequently differentiate into vessel-forming quiescent phenotype cells, Therfore, it was speculated that a modifier of cell differentiation could also affect angiogenesis. In order to identify new antiangiogenic factors, the research was conducted to estimate the inhibitory activities of cell differentiation agents by means of chick embryo chorioallantoic membrane(CAM) assay. Hence, we have established the CAM assay for the screening of antiangiogenic agents. Using the CAM assay, we found that ursolic acid, a tumor cell differentiation-inducing agent, showed a markedly inhibitory effect on chick embryonic angiogenesis.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.164.1-164.1
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• 2003

Wm was isolated from Cynanchum wilfordii (Asclepiadaceae) as a mixture form of polypregnane glycosides that included wilfoside K1N and wilfoside C1N. In the present study, we investigated the anti-angiogenic effect of wilfoside glycosides using in vivo and in vitro assay systems. We first demonstrated that concentrated conditioned media obtained from Wm-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of Wm-untreated concentrated conditioned media, suggesting that Wm may have an inhibitory effect on tumor-induced angiogenesis. (omitted)

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3909-3919
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• 2013

The aim of the present investigation was to evaluate the effect of A ferruginea extract on Dalton's lymphoma ascites (DLA) induced tumours in BALB/c mice. Experimental animals received A ferruginea extract (10 mg/kg.b.wt) intraperitoneally for 14 consecutive days after DLA tumor challenge. Treatment with extract significantly increased the life span, total white blood cell (WBC) count and haemoglobin (Hb) content and decreased the level of serum aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (${\gamma}$-GT) and nitric oxide (NO) in DLA bearing ascites tumor models. In addition, administration of extract significantly decreased the tumour volume and body weight in a DLA bearing solid tumor model. The levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), interleukin-6 (IL-6) and granulocyte monocyte-colony stimulating factor (GM-CSF), as well as pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were elevated in solid tumour controls, but significantly reduced by A ferruginea administration. On the other hand, the extract stimulated the production of interleukin-2 (IL-2) and interferon-gamma (IFN-${\gamma}$) in animals with DLA induced solid tumours. Increase in $CD4^+$ T-cell population suggested strong immunostimulant activity for this extract. GC/MS and LC/MS analysis showed quinone, quinoline, imidazolidine, pyrrolidine, cyclopentenone, thiazole, pyrazole, catechin and coumarin derivatives as major compounds present in the A ferruginea methanolic extract. Thus, the outcome of the present study suggests that A ferruginea extract has immunomodulatory and tumor inhibitory activities and has the potential to be developed as a natural anticancer agent.

• BMB Reports
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• v.34 no.3
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• pp.206-211
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• 2001

Endostatin, a proteolytic fragment of collagen XVIII, is a potent inhibitor of angiogenesis and the growth of several primary tumors. However, the opinions on the activity of endostatin derivatives deleted N- or C- terminal are still controversial. In this regard, we produced mouse endostatin and its derivatives in the prokaryotic system, and studied their anti-tumor activity. The [$^3H$]-thymidine incorporation assay demonstrated that N-terminal deleted mouse endostatin, and a C- and N-terminal deleted mutant, effectively inhibited the proliferation of human umbilical vein endothelial cells (HUVECs). The biological activity of endostatin was also shown by its in vivo anti-angiogenic ability on the chorioallantoic membrane (CAM) of a chick embryo. Treatment of $200\;{\mu}g$ of mouse endostatin, or N-terminal deleted mouse endostatin, inhibited capillary formation of CAM 45 to 71%, which is comparative to a 80% effect of positive control, $1\;{\mu}g$ of retinoic acid. An in vivo mouse tumor growth assay showed that N-terminal deleted mouse endostatin, and the N-/C-terminal deleted mutant, significantly repressed the growth of B16F10 melanoma cells in mice as did the full-length mouse endostatin. According to these results, N-and N-/C-terminal deleted mouse endostatins are the potent inhibitors of tumor growth and angiogenesis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.3
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• pp.499-506
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• 2002

Two of the essential processes required for metastasis are neoangiogenesis and tumor cell invasion of basement membranes (BM) and extracellular matrix (ECM). Recently, data showed that herbs removing blood stasis has an anti-angiogenic effects. Tonifying vital Qi and eliminating pathogenic factor was a basic modality in Oriental oncology. In this study, we investigated several Qi and Blood tonics for potent angiogenic inhibitors. Methanol extracts of samples inhibited the proliferation of ECV-304 at the concentration of 100 ㎍/㎖. Zizyphi Fructus, Glycyrrhizae Radix, Angelicae Gigantis Radix decreased the gelatinolytic activity of MMP-9 from ECV-3Q4, at the concentration of 100 ㎍/㎖ in gelatin zymography. In in vitro invasion assay, herbs inhibited the invasion activity of ECV-304 by 53% of control (Ginseng Radix), 39% (Zizyphi Fructus), 36% (Angelicae Gigantis Radix), 25% (Glycyrrhizae Radix). Ginseng Radix inhibited the capillary-like tube formation of ECV-304 at the concentration of 160 ㎍/㎖, Angelicae Gigantis Radix and Paeoniae Radix Alba inhibited at the concentration of 320 ㎍/㎖. These results indicated that Ginseng Radix, Glycyrrhizae Radix, and Angelicae Gigantis Radix could be considered as potent angiogenic inhibitiors.