• BMB Reports
• /
• v.45 no.11
• /
• pp.595-603
• /
• 2012

Human Ly-6/uPAR molecules are a superfamily composed of two subfamilies; one is the membrane bound proteins with a GPI-anchor and the other are secreted proteins without the GPI-anchor. Ly-6/uPAR molecules have remarkable amino acid homology through a distinctive 8-10 cysteine-rich domain that is associated predominantly with O-linked glycans. These molecules are encoded by multiple tightly linked genes located on Chr. 8q23, and have a conserved genomic organization. Ly-6/uPAR molecules have an interesting expression pattern during hematopoiesis and on specific tumors indicating that Ly-6/uPAR molecules are associated with development of the immune system and carcinogenesis. Thus, Ly-6/uPAR molecules are useful antigens for diagnostic and therapeutic targets. This review summarizes our understanding of human Ly-6/uPAR molecules with regard to molecular structure as well as what is known about their function in normal and malignant tissues and suggest Ly-6/uPAR molecules as target antigens for cancer immunotherapy.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.6
• /
• pp.2887-2889
• /
• 2012

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

• Journal of Gastric Cancer
• /
• v.4 no.4
• /
• pp.207-212
• /
• 2004

Purpose: Invasion and metastasis in solid tumors require the action of tumor-associated proteases. The serine protease urokinase-type plasminogen (uPA) and receptor (uPAR) appear to have a major function in these processes. Expression of the uPAR is elevated in breast and colon carcinomas, and this is often associated with invasiveness and poor prognosis. The purpose of this study was to determine whether the expression of the uPAR gene correlates with clinico-pathological parameters in human gastric carcinomas. Materials and Methods: We examined the expression of uPAR mRNA by using northern blot analysis and RT-PCR in 35 gastric carcinomas and the surrounding normal mucosa. Macroscopic and histopathological tumor findings and survival rates were obtained from the patient records and from endoscopic, surgical, and pathological reports. Results: The expression of uPAR and was higher in most neoplasms than in the corresponding normal mucosal tissue. uPAR mRNA expression in tumors correlated well with lymph-node metastasis (P<0.02) and tumor stage (P<0.01). The survival rate of patients with tumors displaying high uPAR expression levels was significantly lower (P<0.04) than that of patients without uPAR expression, but IL-8 showed only the tendency of survival difference. Conclusion: These results suggest that uPAR may be an important prognostic factor in human gastric carcinomas.

• Clinical and Experimental Reproductive Medicine
• /
• v.33 no.4
• /
• pp.229-236
• /
• 2006

Objective: We investigated the expression of uPA and uPAR in eutopic endometrium of advanced stage endometriosis and control patients. Methods: The 33 endometriosis patients and 32 controls were enrolled. Endometrial samples were obtained from 65 premenopausal women aged 29-44 years, undergoing laparoscopic surgery or hysterectomy for non-malignant lesions. Sufficient samples were collected from 33 patients with endometriosis stage Ill and IV and 32 controls without endometriosis confirmed by laparoscopic surgery. The mRNA expression of uPA and uPAR from eutopic endometrium were analyzed by RT-QC PCR. Results: The mRNAs of uPA and uPAR were expressed in eutopic endometrium from endometriosis and normal controls throughout the menstrual cycle. Uterine endometrium from women with endometriosis expresses significantly (p<0.05) higher levels of u-PA mRNA than endometrium from normal women without endometriosis in the proliferative phase. There were no significant differences in expression of uPAR in eutopic endometrium between controls and endometriosis patients. Conclusion: These results suggest that eutopic endometrium from endometriosis patients may be more invasive and prone to peritoneal implantation because of greater u-PA mRNA expression than endometrium from women without endometriosis. Thus, increased proteolytic activity may be one etiology for the invasive properties of the endometrium resulting in the development of endometriosis.

• Journal of applied mathematics & informatics
• /
• v.27 no.3_4
• /
• pp.955-961
• /
• 2009

In this paper, we establish some characterizations which is satisfied by the independence of the upper record values from the Pareto distribution. We prove that $X\;{\in}\;PAR(1,\;{\beta})$, $\beta$ > 0, if and only if $\frac{X_{U(n)}}{X_{U(m)}}$ and $X_{U(m)}$, $1\;{\le}\;m\;<\;n$ are independent. We show that $X\;{\in}\;PAR(1,\;{\beta})$, $\beta$ > 0 if and only if $\frac{X_{U(n)}+X_{U{(n+1)}}}{X_{U(n)}}$ and $X_{U(n)}$, $n\;{\ge}\;1$ are independent. And we characterize that $X\;{\in}\;PAR(1,\;{\beta})$, $\beta$ > 0, if and only if $\frac{X_{U(n)}}{X_{U(n)}+X_{U{(n+1)}}}$ and $X_{U(n)}$, $n\;{\ge}\;1$ are independent.

• Molecules and Cells
• /
• v.38 no.2
• /
• pp.156-162
• /
• 2015

Urokinase plasminogen activator (uPA) and urokinase plasminogen activator receptor (uPAR) play a major role in the infiltrative growth of glioblastoma. Downregulatoion of the uPA and uPAR has been reported to inhibit the growth glioblastoma. Here, we demonstrate that tristetraprolin (TTP) inhibits the growth of U87MG human glioma cells through downregulation of uPA and uPAR. Our results show that expression level of TTP is inversely correlated with those of uPA and uPAR in human glioma cells and tissues. TTP binds to the AU-rich elements within the 3' untranslated regions of uPA and uPAR and overexpression of TTP decreased the expression of uPA and uPAR through enhancing the degradation of their mRNAs. In addition, overexpression of TTP inhibited the growth and invasion of U87MG cells. Our findings implicate that TTP can be used as a promising therapeutic target to treat human glioma.

• Journal of the Chungcheong Mathematical Society
• /
• v.20 no.1
• /
• pp.51-57
• /
• 2007

In this paper, we establish characterizations of the Pareto distribution by the independence of record values. We prove that $X{\in}PAR(1,{\beta})$ for ${\beta}$ > 0, if and only if $\frac{X_{U(n)}}{X_{U(n)}-X_{U(n+1)}}$ and $X_{U(n)}$ are independent for $n{\geq}1$. And we show that $X{\in}PAR(1,{\beta})$ for ${\beta}$ > 0, if and only if $\frac{X_{U(n)}-X_{U(n+1)}}{X_{U(n)}}$ and $X_{U(n)}$ are independent for $n{\geq}1$.

• Korean Journal of Clinical Laboratory Science
• /
• v.48 no.2
• /
• pp.74-81
• /
• 2016

Ureaplasma species can normally colonize in the bodies of healthy individuals. Their colonization is associated with various diseases including non-gonococcal urethritis, chorioamnionitis, neonatal meningitis, and prematurity. In 2012, the sum of the resistant and intermediate resistant rates of Ureaplasma spp. to ofloxacin and ciprofloxacin was 66.08% and 92.69%, respectively. DNA point mutations in the genes encoding DNA gyrase (topoisomerase II) and topoisomerase IV are commonly responsible for fluoroquinolone resistance. Each enzyme is composed of two subunits encoded by gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV. In the current study, these genes were sequenced in order to determine the role of amino acid substitutions in Ureaplasma spp. clinical isolates. From December 2012 to May 2013, we examined mutation patterns of the quinolone resistance-determining region (QRDR) in Ureaplasma spp. DNA sequences in the QRDR region of Ureaplasma clinical isolates were compared with those of reference strains including U. urealyticum serovar 8 (ATCC 27618) and U. parvum serovar 3 (ATCC 27815). Mutations were detected in all ofloxacin- and ciprofloxacin-resistant isolates, however no mutations were detected in drug-susceptible isolates. Most of the mutations related to fluoroquinolone resistance occurred in the parC gene, causing amino acid substitutions. Newly found amino acid substitutions in this study were Asn481Ser in GyrB; Phe149Leu, Asp150Met, Asp151Ile, and Ser152Val in ParC; and Pro446Ser and Arg448Lys in ParE. Continuous monitoring and accumulation of mutation data in fluoroquinolone-resistant Ureaplasma clinical isolates are essential to determining the tendency and to understanding the mechanisms underlying antimicrobial resistance.

• Molecules and Cells
• /
• v.40 no.10
• /
• pp.761-772
• /
• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• Journal of Microbiology and Biotechnology
• /
• v.23 no.9
• /
• pp.1197-1205
• /
• 2013

Urokinase (uPA) and its receptor (uPAR) play an important role in tumor growth and metastasis. Targeting the excessive activation of this system as well as the proliferation of the tumor vascular endothelial cell would be expected to prevent tumor neovasculature and halt the tumor development. In this regard, the amino-terminal fragment (ATF) of urokinase has been confirmed as effective to inhibit the proliferation, migration, and invasiveness of cancer cells via interrupting the interaction of uPA and uPAR. Previous studies indicated that ATF expressed in Escherichia coli was mainly contained in inclusion bodies and also lacked posttranslational modifications. In this study, the biologically active and soluble ATF was cloned and expressed in Pichia pastoris. The recombinant protein was purified to be homogenous and confirmed to be biologically active. The yield of the active ATF was about 30 mg/l of the P. pastoris culture medium. The recombinant ATF (rATF) could efficiently inhibit angiogenesis, endothelial cell migration, and tumor cell invasion in vitro. Furthermore, it could inhibit in vivo xenograft tumor growth and prolong the survival of tumor-bearing mice significantly by competing with uPA for binding to cell surfaces. Therefore, P. pastoris is a highly efficient and cost-effective expression system for large-scale production of biologically active rATFs for potential therapeutic application.