• Asian Pacific Journal of Cancer Prevention
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• 제16권6호
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• pp.2313-2316
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• 2015

Objective: To investigate the correlation between extracellular matrix protein-1 (ECM1) and the growth, metastasis and angiogenesis of laryngeal carcinoma. Materials and Methods: Forty-five samples with laryngeal benign and malignant tumors confirmed by pathology in Laiwu City People's Hospital from March 2006 to March 2011 were collected, in which there were 29 cases with laryngeal carcinoma and 16 with benign tumors. The expression of ECM1 and factor VIII-related antigens in patients with laryngeal carcinoma and those with benign tumors was respectively detected using immunohistochemical method, and the correlation between ECM1 staining grade and microvessel density (MVD) was analyzed. Results: In laryngeal carcinoma tissue, ECM1 was mainly expressed in cytoplasm, less in cytomembrane or intercellular substance. With abundant expression in the tissue of laryngeal benign tumors (benign mesenchymoma and hemangioma), ECM1 was primarily expressed in the connective tissue, which was different from the expression in laryngeal carcinoma tissue. The proportion of positive ECM1 staining (++) in patients with laryngeal carcinoma was dramatically higher than those with benign tumors (p<0.05), and that of strongly-positive ECM1 staining (+++) slightly higher. The results of Spearman nonparametric correlation analysis revealed that ECM1 staining grade in laryngeal carcinoma tissue had a significantly-positive correlation with MVD (r=0.866, p=0.000). Conclusions: ECM1 expression in laryngeal carcinoma is closely associated with tumor cell growth, metastasis and angiogenesis, which can be considered as an effective predictor in the occurrence and postoperative recurrence of laryngeal carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6869-6874
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• 2013

Background: Vascular endothelial growth factor and matrix metalloproteinases are two important factors for angiogenesis associated with breast cancer growth and progression. The present study was aimed to examine the effects of tamoxifen and tranilast drugs singly or in combination on proliferation of breast cancer cells and also to evaluate VEGF and MMP-9 expression and VEGF secretion levels. Materials and Methods: Human breast cancer cell lines, MCF-7 and MDA-MB-231, were treated with tamoxifen and/or tranilast alone or in combination and percentage cell survival and proliferative activity were evaluated using LDH leakage and MTT assays. mRNA expression and protein levels were examined by real-time RT-PCR and ELISA assay, respectively. Results: LDH and MTT assays showed that the combined treatment of tamoxifen and tranilast resulted in a significant decrease in cell viability and cell proliferation compared with tamoxifen or tranilast treatment alone, with significant decrease in VEGF mRNA and protein levels. We also found that tamoxifen as a single agent rarely increased MMP-9 expression. A decrease in MMP-9 expression was seen after treatment with tranilast alone and in the combined treatment MMP-9 mRNA level was decreased. Conclusions: This combination treatment can able to inhibit growth, proliferation and angiogenesis of breast cancer cells.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제27권5호
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• pp.415-423
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• 2005

Distraction osteogenesis (DO) is frequently used technique in reconstruction of bony defects resulted from tumor resection, congenital deformity, and trauma in the maxillofacial region. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the exact changing of the surrounding tissues, such as nerve tissues, were still unclear. This study observed the histological changes and the expression of nerve growth factor (NGF) in the inferior alveolar nerve (IAN) after distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in eight mongrel dogs. Two animals were sacrificed at 7, 14, 28 and 56 days after completion of distraction, respectively. The distracted IAN and contralateral control nerve were harvested and processed for histological and innunohistochemical examinations. The signs of acute nerve injuries, such as demyelination and partial discontinuation of nerver fiber, were observed in the distracted IAN on 7 and 14 days after distraction. The initial remyelination and regeneration of distracted IAN were showed at 14 days after completion of distraction. At 56 days later, the histologic features of distracted IAN was similar to those of the normal control IAN. The expression of NGF was significantly increased in most distracted nerve tissues on 7, 14 and 28 days after distraction. On 56 days after distraction, the expression of NGF returned to the normal level. This study suggested that the acute IAN injury caused by mandibular distraction were mostly recovered during consolidation period. The NGF was seemed to be induced from Schwann cell and damaged nerve tissues, and it may have important roles in the initial healing of damaged nerves.

• Molecules and Cells
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• 제41권2호
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• pp.119-126
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• 2018

microRNA (miR)-612 shows anticancer activity in several types of cancers, yet its function in melanoma is still unclear. This study was undertaken to investigate the expression of miR-612 and its biological relevance in melanoma cell growth, invasion, and tumorigenesis. The expression and prognostic significance of miR-612 in melanoma were examined. The effects of miR-612 overexpression on cell proliferation, colony formation, tumorigenesis, and invasion were determined. Rescue experiments were conducted to identify the functional target gene(s) of miR-612. miR-612 was significantly downregulated in melanoma tissues compared to adjacent normal tissues. Low miR-612 expression was significantly associated with melanoma thickness, lymph node metastasis, and shorter overall, and disease-free survival of patients. Overexpression of miR-612 significantly decreased cell proliferation, colony formation, and invasion of SK-MEL-28 and A375 melanoma cells. In vivo tumorigenic studies confirmed that miR-612 overexpression retarded the growth of A375 xenograft tumors, which was coupled with a decline in the percentage of Ki-67-positive proliferating cells. Mechanistically, miR-612 targeted Espin in melanoma cells. Overexpression of Espin counteracted the suppressive effects of miR-612 on melanoma cell proliferation, invasion, and tumorigenesis. A significant inverse correlation (r = -0.376, P = 0.018) was observed between miR-612 and Espin protein expression in melanoma tissues. In addition, overexpression of miR-612 and knockdown of Espin significantly increased the sensitivity of melanoma cells to doxorubicin. Collectively, miR-612 suppresses the aggressive phenotype of melanoma cells through downregulation of Espin. Delivery of miR-612 may represent a novel therapeutic strategy against melanoma.

• BMB Reports
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• 제53권12호
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• pp.628-633
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• 2020

WNT11 is a member of the non-canonical Wnt family and plays a crucial role in tumor progression. However, the regulatory mechanisms underlying WNT11 expression are unclear. Tumor necrosis factor-alpha (TNFα) is a major inflammatory cytokine produced in the tumor microenvironment and contributes to processes associated with tumor progression, such as tumor invasion and metastasis. By using site-directed mutagenesis and introducing a serial deletion in the 5'-regulatory region of WNT11, we observed that TNFα activates the early growth response 1 (EGR1)-binding sequence (EBS) in the proximal region of WNT11 and that the transcription factor EGR1 is necessary for the TNFα-induced transcription of WNT11. EGR1 bound directly to the EBSs within the proximal 5'-regulatory region of WNT11 and ectopic expression of EGR1 stimulated WNT11 promoter activity, whereas the knockdown of EGR1 expression by RNA interference reduced TNFα-induced WNT11 expression in T47D breast cancer cells. We also observed that mitogen-activated protein kinases (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 kinase mediated TNFα-induced transcription of WNT11 via EGR1. Our results suggest that EGR1 directly targets WNT11 in response to TNFα stimulation in breast cancer cells.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4793-4799
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• 2012

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

• Clinical and Experimental Reproductive Medicine
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• 제48권4호
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• pp.303-310
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• 2021

Decorin (DCN) is a proteoglycan belonging to the small leucine-rich proteoglycan family. It is composed of a protein core containing leucine repeats with a glycosaminoglycan chain consisting of either chondroitin sulfate or dermatan sulfate. DCN is a structural component of connective tissues that can bind to type I collagen. It plays a role in the assembly of the extracellular matrix (ECM), and it is related to fibrillogenesis. It can interact with fibronectin, thrombospondin, complement component C1, transforming growth factor (TGF), and epidermal growth factor receptor. Normal DCN expression regulates a wide range of cellular processes, including proliferation, migration, apoptosis, and autophagy, through interactions with various molecules. However, its aberrant expression is associated with oocyte maturation, oocyte quality, and poor extravillous trophoblast invasion of the uterus, which underlies the occurrence of preeclampsia and intrauterine growth restriction. Spatiotemporal hormonal control of successful pregnancy should regulate the concentration and activity of specific proteins such as proteoglycan participating in the ECM remodeling of trophoblastic and uterine cells in fetal membranes and uterus. At the human feto-maternal interface, TGF-β and DCN play crucial roles in the regulation of trophoblast invasion of the uterus. This review summarizes the role of the proteoglycan DCN as an important and multifunctional molecule in the physiological regulation of oocyte maturation and trophoblast migration. This review also shows that recombinant DCN proteins might be useful for substantiating diverse functions in both animal and in vitro models of oogenesis and implantation.

• 한국미생물·생명공학회지
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• 제49권4호
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• pp.594-602
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• 2021

The NLRP3 (nucleotide-binding domain, leucine-rich repeat family pyrin domain containing 3) inflammasome plays an important role in the initiation of inflammatory responses, through the recognition of pathogen-associated molecular patterns and tumor progression, including tumor growth and metastasis. In this study, we examined the effects of defective NLRP3 on the growth, migration, and invasiveness of hepatocellular carcinoma (HCC) SK-Hep1 cell. First, HCC SK-Hep1 cells were transfected with human NLRP3 targeting LentiCRISPRv2 vector using the CRISPR-Cas9 system, and NLRP3 deficiency was confirmed by RT-qPCR and western blotting. NLRP3 deficient SK-Hep1 cells showed delayed cell growth and decreased protein expression of PI3K, p-AKT, and pNF-κB when compared to NLRP3 complete SK-Hep1 cells. In addition, NLRP3 deficiency arrested the cell cycle at G1 phase through an increase in p21 and a reduction in CDK6. NLRP3 deficient SK-Hep1 cells also showed significantly delayed cell migration, invasion, and wound healing. The expression of epithelial-mesenchymal transition signaling molecules, such as N-cadherin and MMP-9, was found to be dramatically decreased in NLRP3 deficient SK-Hep1 cells compared to NLRP3 complete SK-Hep1 cells.

• Asian Pacific Journal of Cancer Prevention
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• 제15권21호
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• pp.9217-9223
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• 2014

Background: Today, leukemia is one of the biggest problems worldwide. The Wilms' tumor gene (WT1) and the vascular endothelial growth factor (VEGF) gene are highly expressed in patients with various cancers. This study concerned the relationship between expression of WT1 and VEGF in patients with acute leukemia. Materials and Methods: We evaluated expression of WT1 mRNA and VEGF mRNA using real-time quantitative RT-PCR in the peripheral blood (PB) of 8 newly diagnosed AML and 4 newly diagnosed ALL patients, serially monitored for 2 months. A further 12 normal PB samples served as controls. Results: In the patient group, in comparison with the normal ranges, WT1 and VEGF gene expression was increased, the average values for the expression of these two genes being $0.2852{\pm}0.11$ and $0.2029{\pm}0.018$, respectively. While was no significant relevance between the two genes pre-treatment, a positive link between the two genes in 75% of patients with AML was noted during the procedure of chemotherapy, whereas in 75% of patients with ALL an antiparallel association was observed. Conclusions: Leukemia is associated with production of WT1, which may affect the expression of VEGF.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제28권5호
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• pp.445-453
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• 2006

Cyclosporine A (CsA) is a powerful immunosuppresive agent used to prevent graft rejection of organ and treat autoimmune disease. One of the major side effects associated with CsA treatment is the development of gingival overgrowth. The purpose of this study was to investigate the mRNA expression and association of the several growth factors in gingival overgrowth induced by CsA, respectively. Gingival fibroblasts were obtained from gingival tissues of healthy donor and the patients treated with CsA. The cultured gingival fibroblasts were incubated with increasing concentrations of CsA for 24 hours, and the expression of MMP-1, TIMP-1, $TGF-{\beta}_1$, p21 were determined by reverse transcription-polymerase chain reaction (RT-PCR). The expressions of MMP-1 was slightly increased according to the concentration of treated CsA, but there was no statistical significance. TIMP-1 showed the increased expression at the CsA concentration of 250 and 500 ng/ml and significantly decreased at the CsA concentration of 750ng/ml. $TGF-{\beta}_1$ showed the increased expression at the CsA concentration of 500 and 750 ng/ml. The expression of p21 was not changed significantly. We concluded that the gingival hyperplasia induced by CsA was more related with $TGF-{\beta}_1$ than MMP-1 or TIMP-1 on gingival collagen metabolism in patients treated with CsA.