• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.139-143
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• 2014

Although correlations between platelets and lung cancer has been recognized, effects on non-small cell lung cancer (NSCLC) metastasis remain to be determined in detail. In the present study, wound healing assays revealed a role of platelets in NSCLC cell migration. Thus the mean migration rate of lung adenocarcinoma A549 cells was significantly elevated after co-culture with platelets ($81.7{\pm}0.45%$ vs $41.0{\pm}3.50%$, P<0.01). Expression of GAPDH was examined by reverse transcription-polymerase chain reaction to study the effect of platelets on NSCLC cell proliferation. The result showed that the proliferation of A549 and SPC-A1 cells was not affected. Mouse models were established by transfusing A549 cells and SPC-A1 cells into mice lateral tail veins. We found tumor metastasis nodules in lungs to be increased significantly after co-transfusion with platelets (in A549, $4.33{\pm}0.33$ vs $0.33{\pm}0.33$, P=0.01; in SPC-A1, $2.67{\pm}0.33$ vs $0.00{\pm}0.00$, P=0.01). In addition, consecutive inoperable patients with newly diagnosed NSCLC (TNM stage III or IV) between January 2009 and December 2011 were retrospectively reviewed. Using the Kaplan-Meier method, NSCLC patients with a high platelet counts demonstrated a significantly shorter progression free survival compared with those with a low platelet count (> $200{\times}10^9/L$, 3 months versus ${\leq}200{\times}10^9/L$, 5 months, P=0.001). An elevated platelet count was also identified as an independent prognostic factor by Cox regression analysis for prgression free survival (adjusted hazard ratio: 1.69; 95% CI: 1.16, 2.46; P=0.006). This study suggested that platelets might contribute to the hematogenous metastatic process by promoting cancer cell migration, which eventually affects the prognosis of NSCLC.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4969-4976
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• 2014

Background: miR-152 is involved in the genesis and development of several malignancies. However, its role in HCC has not been fully clarified. The aim of this study was to investigate the clinicopathological significance of miR-152 and its effect on the malignant phenotype of HCC cells. Methods: miR-152 expression was detected using real-time quantitative RT-PCR in 89 pairs of HCC formalin-fixed paraffin-embedded and their adjacent tissues. Functionally, in vitro effects and mechanisms of action of miR-152 on proliferation, viability, caspase activity, apoptosis and motility were explored in HepG2, HepB3 and SNU449 cells, as assessed by spectrophotometry, fluorimetry, fluorescence microscopy, wound-healing and Western blotting, respectively. Results: miR-152 expression in HCC was downregulated remarkably compared to that in adjacent hepatic tissues. miR-152 levels in groups of advanced clinical stage, larger tumor size and positive HBV infection, were significantly lower than in other groups. A miR-152 mimic could suppress cell growth, inhibit cell motility and increase caspase activity and apoptosis in HCC cell lines. Furthermore, Western blotting showed that the miR-152 mimic downregulated Wnt-1, DNMT1, ERK1/2, AKT and TNFRS6B signaling. Intriguingly, inverse correlation of TNFRF6B and miR-152 expression was found in HCC and bioinformatics confirmed that TNFRF6B might be a target of miR-152. Conclusions: Underexpression of miR-152 plays a vital role in hepatocarcinogenesis and lack of miR-152 is related to the progression of HCC through deregulation of cell proliferation, motility and apoptosis. miR-152 may act as a tumor suppressor miRNA by also targeting TNFRSF6B and is therefore a potential candidate biomarker for HCC diagnosis, prognosis and molecular therapy.

• Advances in Traditional Medicine
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• v.1 no.1
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• pp.8-27
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• 2000

Components of extracellular matrix and the matrix-degrading enzymes are some of the key regulators of tumor metastasis and angiogenesis. Hyaluronic acid (HA), a matrix glycosaminoglycan, is known to promote tumor adhesion and migration, and its small fragments are angiogenic. Until now, we have compared levels of hyaluronidase, an enzyme that degrade HA, in normal adult prostate, benign prostate hyperplasia and prostate cancer tissues and in conditioned media from epithelial explant cultures, using a substrate (HA)-gel assay and ELISA-like assay (Kim et al., unpublished results). The present review described an overall characterization of hyaluronidases and its application to human diseases. The hyaluronidases are a family of enzymes that have, until recently, deed thorough explication. The substrate for these enzymes, hyaluronan, is becoming increasingly important, recognized now as a major participant in basic processes such as cell motility, wound healing, embryogenesis, and implicated in cancer progression. And in those lower life forms that torment human beings, hyaluronidase is associated with mechanisms of entry and spread, e.g. as a virulence factor for bacteria, for tissue dissection in gas gangrene, as a means of treponema spread in syphilis, and for penetration of skin and gut by nematode parasites. Hyaluronidase also comprises a component of the venom of a wide variety of organisms, including bees, wasps, hornets, spiders, scorpions, sh, snakes and lizards. Of particular interest is the homology between some of these venom hyaluronidases and the enzyme found in the plasma membrane of mammalian spermatozoa, attesting to the ancient nature of the conserved sequence, a 36% identity in a 300 amino acid stretch of the enzyme protein. Clearly, hyaluronidase is of biological interest, being involved in the pathophysiology of so many important' human disorders. Greater effort should be made in studying this family of enzymes that have, until recently, been overlooked. Also, oriental medical application of the hyaluronidase will be discussed with respect to inhibition and suppression of inflammation and malignacy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.5
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• pp.2291-2295
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• 2014

Although nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis and expression has been observed in some types of human cancer and stem cells, the molecular mechanisms involved in mediation of cell proliferation and cell cycling remains largely elusive. The aim of the present study was to evaluate NS as a potential target for gene therapy of human breast carcinoma by investigating NS gene expression and its effects on SKBR-3 cell proliferation and apoptosis. NS mRNA and protein were both found to be highly expressed in all detected cancer cell lines. The apoptotic rate of the pcDNA3.1-NS-Silencer group ($12.1-15.4{\pm}3.8%$) was significantly higher than those of pcDNA3.1-NS ($7.2-12.0{\pm}1.7%$) and non-transfection groups ($4.1-6.5{\pm}1.8%$, P<0.01). MTT assays showed the knockdown of NS expression reduced the proliferation rate of SKBR-3 cells significantly. Matrigel invasion and wound healing assays indicated that the number of invading cells was significantly decreased in the pcDNA3.1-NS-siRNA group (P<0.01), but there were no significant difference between non-transfected and over-expression groups (P>0.05). Moreover, RNAi-mediated NS down-regulation induced SKBR-3 cell G1 phase arrest, inhibited cell proliferation, and promoted p53 pathway-mediated cell apoptosis in SKBR-3 cells. NS might thus be an important regulator in the G2/M check point of cell cycle, blocking SKBR-3 cell progression through the G1/S phase. On the whole, these results suggest NS might be a tumor suppressor and important therapeutic target in human cancers.

• Journal of Periodontal and Implant Science
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• v.23 no.3
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• pp.359-373
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• 1993

The ultimate objective of periodontal therapy is not only stopping the progression of periodontal disease, but also promoting the regeneration of lost periodontal tissue. Guided Tissue Regeneration, which is based on the principle that the goal of periodontal regeneration can be achieved by preventing apical migration of gingival epithelium and blocking cells originating from connective tissue, has been developed and used as a clinical procedure, and although it has shown excellent results in connective tissue healing, there have not been many studies showing its effect on the regeneration of alveolar bone loss due to periodontal disease. The objectives of this study are to investigate the result of 12 months-long treatment following guided tissue regeneration using expanded polytetrafluoroehylene membrane, and to observe the presence of regenerated alveolar bone. Forty-one teeth from 28 patients with clinical diagnosis of periodontitis has been selected. In fifteen of those interproximal intrabony defects, only flap operation had been carried out, and designated as the control group. Twenty-six intrabony defects received e-PTFE membrane following flap operation, and designated as the experimental group. Eleven teeth whose membrane had been exposed were excluded from the experiment. Various measurements including probing depth, loss of attachment, probing bone level and gingival recession have been recorded at 6th month and 12th month, and the significance of the changes has been analyzed. The results are as follows: 1. Probing depth at 6th and 12th month has shown a significant decrease in both groups (p<0.01), but significantly higher decrease was found in the experimental group compared to the control at the month(p<0.05). 2. Loss of attachment at 6th and 12th month has shown a significant decrease in both groups, but significantly higher decrease was found in the experimental group compared to the control (p<0.05). 3. Probing bone level at 6th and 12th month has shown a insignificant decrease in the control group and significant decrease in the experimental group (p<0.01). Significantly higher decrease in probing bone level was found in the experimental group (p<0.05). 4. Gingival recession at 6th and 12th month has shown a statistically significant increase (p<0.05), and the control group showed higher increase compared to the experimental group although no statistical significance was found. As these results have shown, the use of e-PTFE membrane in intrabony pockets results in marked decrease in the loss of attachment and probing bone level. This seems to indicate that e-PTFE membrane may play a role in alveolar bone regeneration in intrabony defects.

• Journal of Life Science
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• v.22 no.12
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• pp.1600-1607
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• 2012

The matrix metalloproteinase (MMP) family plays essential roles in physiological processes such as embryonic development, angiogenesis, wound healing, and tissue homeostasis as a consequence of MMPr capacity for breaking down many types of extracellular matrix proteins. Imbalanced regulation of MMP expression can also lead to pathological conditions such as tumor progression. We recently reported that the Drosophila Mmp1 gene is highly expressed in the digestive tract and is required for the maintenance of intestinal homeostasis such as by restriction of uncontrolled intestinal stem cell proliferation. However, the regulatory mechanisms of MMP gene expression in the intestine remain unclear. In this study, we determined that the expression of Mmp1 is regulated by the homeodomain transcription factor Caudal. Experiments using the targeted expression of Caudal under the regulation of Gal4-UAS system indicated that endogenous Caudal is required for the Mmp1 gene expression in the adult Drosophila intestine and that exogenous Caudal induces Mmp1 expression. Transient transfection experiments indicated that Caudal can activate the promoter activity of Mmp1 and that several putative Caudal binding sites in the 5'-flanking region of the Mmp1 gene may be critical to the upregulation by Caudal. Our data suggest that Mmp1 is one of the target genes of Caudal in physiological normal condition and in tumorigenesis.

• Journal of Korean Ophthalmic Optics Society
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• v.13 no.4
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• pp.161-169
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• 2008

Purpose: To better understand the corneal regeneration after alkali burn regarding the initial clinical progression and the therapy, we investigated the changes of the multi factors following chemical injury in cornea. Methods: This study was performed to observation on the healing process of alkali burned cornea in aspect of immunohistochemistry by immunofluorescence or H-E staining and TUNEL assay. Results: The results showed that although a healing process occurred after alkali burn, apoptosis of epithelial, stromal and endothelial cells in the cornea was continuously observed. Neovascularization and expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) from limbus and from injured cornea, respectively, were observed after 3 days of alkali burn. Formation of collagen III in corneal stroma and increased expression of chondroitin sulfate are coincident with expression of ${\alpha}$-SMA and transforming growth factor-${\beta}$ (TGF-${\beta}$). Conclusions: These data suggest that medical treatment within 3 days of alkali burn will be effective to inhibit neovascularization and formation of collagen III and chondroitin sulfate. This study extends our immumohistochemical understanding of healing process in alkali burned cornea, and the results get in this study will be cornerstones in the development of therapeutic agent for accelerating renewal of chemical damaged cornea.

• Clean Technology
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• v.29 no.2
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• pp.135-144
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• 2023

Pseudomonas aeruginosa and Staphylococcus aureus are the two most frequently encountered pathogens responsible for chronic wound infections, often coexisting in such cases. These infections exhibit heightened virulence compared to single infections, leading to unfavorable patient outcomes. The interaction among microorganisms within polymicrobial infections has been shown to exacerbate disease progression. Polymicrobial infections, prevalent in various contexts such as the respiratory tract, wounds, and diabetic foot, typically involve diverse microorganisms, with Pseudomonas aeruginosa and Staphylococcus aureus being the most commonly identified pathogens. This study aimed to compare the growth patterns of bacteria under a concentration gradient of toxic chemicals, focusing on a Gram-negative strain of Pseudomonas aeruginosa and a Gram-positive strain of Staphylococcus aureus. The minimum inhibitory concentration (MIC), which signifies the concentration at which bacterial growth is inhibited, was determined by performing broth microdilution and assessing the bacteria's growth curves. The growth curves of both Pseudomonas aeruginosa and Staphylococcus aureus were confirmed, and the exponential growth phases were applied to calculate the doubling times of bacteria. The MIC value for each toxic chemical was determined through broth microdilution. These results allowed for the identification of disparities in growth rates between Gram-positive and Gram-negative bacteria, as well as differences in resistance to individual toxic substances. We expect that this approach has a strong potential for further development towards the innovative treatment of bacteria-associated infections.

• 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 Korean Journal of Pharmacology
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• v.7 no.1
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• pp.53-65
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• 1971

It is well known that diabetes mellitus is associated with metabolic derangements, such as hyper-glycemia, ketosis, glycosuria, and also widespread alterations in the blood vessels, kidneys, eyes, peripheral nerves and heart. It is also recognized that healing of skin wound is delayed in diabetics. In bone, according to Aegerter, osteopenia develops in diabetes mellitus and it is chiefly ascribed to overutilization of protein. Shim claims that total blood flow to the entire skeletal system is approximately 4 to 8 percent of resting cardiac output and blood supply to the skeletal system would be decreased on account of secondary arteriosclerotic changes in the diabetics. An adequate blood supply is an essential factor in the healing process of fracture, and disturbed blood flow, either local or systemic, will invariably delay union of the fragments or the fragments from being fused. As the author has encountered several cases of diabetics in whom healing of fracture was delayed or incomplete, this experimental study was undertaken to elucidate the effects of hyperglycemia and diabetes mellitus on the healing process of fracture. In this experiment adult albino rabbits, weighing about 2 kg. were used and divided into 6 groups. The femur of each animal was fractured surgically, and then the healing process of fracture was periodically checked by radiography at an interval of one week for a period of 6 weeks. Thereafter, all the rabbits were killed to obtain tissue preparation of the femur. The experimental groups were as follows; 1) Control group: Six rabbits sustained a surgical fracture to the femur, without being given any other treatment or drug. 2) Alloxan-treated group: For inducing diabetes, alloxan was given intravenously to 17 rabbits in various dose as follows; to 7 of them 40 mg/kg, to 6 rabbits 80 mg/kg and to 4 rabbits 120 mg/kg of body weight, respectively. 3) Insulin-treated group: Protamine-zinc insulin was injected subcutaneously to each of 6 rabbits in a daily dose of 1 unit per kilogram of body weight. 4) Group treated with insulin after alloxan: Four rabbits were given 80 mg of alloxan once and than 1 unit of insulin per kilogram of body weight daily. Another 5 rabbits were injected 1 unit of insulin per kg of body weight daily following administration of alloxan in a dose of 120 mg/kg. 5) Homotransplantation group: Following intravenous injection of alloxan in a dose of 120 mg/kg, 10 rabbits underwent homotransplantation of a short bone segment to the femur. Five of them were subsequently given 1 unit/kg of insulin daily. 6) Sugar-treated group: six rabbits were fed $15{\sim}20$ gm of sugar daily throughout the period of experiment. The results obtained are summarized as follows; 1. Blood sugar level and damage to the pancreatic islet increased proportionately when alloxan was given to the rabbits in various doses. No appreciable change could be observed in the islets when the blood sugar level was altered by either oral administration of sugar or subcutaneous injection of insulin. 2. Comparing with the control group, healing of fracture was delayed in the alloxan-treated group, while callus formation and periosteal reaction were shown to be more prominent in this group and subsequently, the ultimate osseous tissue formed at the fracture site was significantly smaller in amount and less compact. These findings were more marked as the amount of alloxan increased. 3. Administration of insulin prevented the delay in healing process of fracture in the rabbits with alloxan-induced hyperglycemia. In this case, the course and progression of fracture healing were almost similar to those of control group. 4. Union between the host bone and the fragment transplanted from other rabbit of the same species was more delayed in the group treated with alloxan alone than in the group to which insulin was administered after development of alloxan-induced diabetes. In both groups periosteal new bone developed from the ends of the host bone, above and below the transplanted fragment, and directly fused with failure of periosteal callus to bridge the adjacent ends of the host bone and the transplanted fragment. 5. The healing process of fracture was not inhibited by alteration in blood sugar level when the blood sugar was abnormally increased by excessive sugar intake or lowered by administration of insulin alone. The healing of fracture in these groups progressed similarly as in the control group. In brief summary, it appears that the healing process of fracture would be definitely disturbed in diabetic state brought about by damage to the pancreatic islet. As such an inhibition could be overcome with insulin, it seems that insulin plays an important role in healing of fracture, but alteration in blood sugar level alone does not modify healing process of fracture to significant degree.