• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.4071-4075
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• 2015

Background: Retinoblastoma protein-interacting zinc finger gene 1(RIZ1) functions as a tumor suppressor. Hypermethylation-mediated RIZ1 silencing has been reported in several cancers, but not in renal cell carcinoma (RCC) yet. Materials and Methods: We examined the RIZ1 expression and methylation in a panel of RCC cell lines and 50 primary tumors using semiquantitative/quantitative polymerase chain reaction (PCR), methylation specific PCR, and bisulfite sequencing genomic. We also explored the relationship between methylation status of RIZ1 and clinicopathological features in RCC patients. Results: RIZ1 expression was down-regulated or lost in OS-RC-2, 769-P, Caki-1, 786-O and A498 RCC cell lines. Restored expression of RIZ1 was detected after addition of 5-aza-2'-deoxycytidine with/without trichostatin A, suggesting that DNA methylation directly mediates its silencing. The RIZ1 expression was significantly reduced in RCCs compared to adjacent non-malignant renal samples (P<0.001). Aberrant methylation was detected in 15 of 50 (30%) RCCs and in 2 of 28 (7%) adjacent non-malignant renal samples (P=0.02). No statistically significant correlation between methylated and unmethylated cases with regard to age, gender, pathological stage and grade was observed. Conclusions: RIZ1 expression is down-regulated in human RCC, and this down-regulation is associated with methylation. RIZ1 methylation may play a role in renal carcinogenesis.

• Journal of Ginseng Research
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• v.35 no.4
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• pp.462-470
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• 2011

Myeloid-derived suppressor cells (MDSCs) actively suppress immune cells and have been considered as an impediment to successful cancer immunotherapy. Many approaches have been made to overcome such immunosuppressive factors and to exert effective anti-tumor effects, but the possibility of using medicinal plants for this purpose has been overlooked. Korean red ginseng (KRG) is widely known to possess a variety of pharmacological properties, including immunoboosting and anti-tumor activities. However, little has been done to assess the anti-tumor activity of KRG on MDSCs. Therefore, we examined the effects of KRG on MDSCs in tumor-bearing mice and evaluated immunostimulatory and anti-tumor activities of KRG through MDSC modulation. The data show that intraperitoneal administration of KRG compromises MDSC function and induces T cell proliferation and the secretion of IL-2 and IFN-${\gamma}$, while it does not exhibit direct cytotoxicity on tumor cells and reduced MDSC accumulation. MDSCs isolated from KRG-treated mice also express significantly lower levels of inducible nitric oxide synthase and IL-10 accompanied by a decrease in nitric oxide production compared with control. Taken together, the present study demonstrates that KRG enhances T cell function by inhibiting the immunosuppressive activity of MDSCs and suggests that although KRG alone does not exhibit direct anti-tumor effects, the use of KRG together with conventional chemo- or immunotherapy may provide better outcomes to cancer patients through MDSC modulation.

• Environmental Mutagens and Carcinogens
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• v.25 no.3
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• pp.118-123
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• 2005

Nicotine has been implicated as a potential factor in the pathogenesis of human lung cancer, however its mechanism of action in the development of lung cancer remains largely unknown. To explore the role of nicotine in the development of lung cancer, we first investigated the effects of nicotine on the expression of tumor associated genes by treating Sprague-Dawley rats with nicotine (10 mg/kg) by gavage once daily for 10 days. We determined the expression of proteins and mRNAs of the ras, raf, myc, jun, fos oncogenes and p53, Rb tumor suppressor genes by Western and Northern blotting, respectively. We did not detect any changes on the levels of proteins and mRNAs of these tumor associated genes in the lung of Sprague-Dawley rats from 3 days to 12 weeks after the last treatment of nicotine, indicating that nicotine appears to have no effect on expression of these oncogenes and tumor suppressor genes at an early stage in multistage chemical carcinogenesis. In a second experiment, we investigated the possibility that 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) could be formed endogenously by treating with nicotine and sodium nitrite. We treated groups of Fischer 344 rats with nicotine ($60{\mu}mol/kg$) and sodium nitrite ($180{\mu}mol/kg$), nicotine, sodium nitrite and NNK (120 nmol/kg) alone by gavage once daily for 7 days, respectively and determined the 8-hydroxydeoxyguanosine (8-OHdG), as an indicator of NNK formation, in the lungs of rats 24 hours and 48 hours after the last treatment by HPLC/ECD method. We detect increased level of 8-OHdG in the lungs of rats treated with NNK, but in the case of nicotine plus sodium nitrite, nicotine and sodium nitrite alone we could not detected any changes of 8-OHdG, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4329-4333
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• 2015

Background: To investigate the change of frequency and immuno-inhibitory function of myeloid-derived suppressor cells (MDSCs) after treatment of cisplatin (DDP) in A375 human melanoma model. Materials and Methods: BALB/c nude mice were inoculated with A375 cells to establish the human melanoma model and randomly divided into control group given normal saline (NS) and experimental group treated with DDP (5 mg/kg). The percentages of MDSCs in the tumor tissue and peripheral blood after DDP treatment were detected by flow cytometry. The proliferation and interferon-${\gamma}$ (IFN-${\gamma}$) secretion of T cells co-cultured with MDSCs were analyzed through carboxyfluorescein succinimidyl ester (CFSE) labeling assay and enzyme-linked immunospot (ELISPOT) assay, respectively. Results: In A375 human melanoma model, DDP treatment could significantly decrease the percentage of MDSCs in the tumor tissue, but exerted no effect on the level of MDSCs in peripheral blood. Moreover, DDP treatment could attenuate the immuno-inhibitory function of MDSCs. T cells co-cultured with DDP-treated MDSCs could dramatically elevate the proliferation and production of INF-${\gamma}$. Conclusions: DDP can decrease the frequency and attenuate immuno-inhibitory function of MDSCs in A375 melanoma model, suggesting a potential strategy to augment the efficacy of combined immunotherapy.

• BMB Reports
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• v.39 no.6
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• pp.649-655
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• 2006

The NSAID activated gene (NAG-1), a member of the TGF-$\beta$ superfamily, is involved in tumor progression and development. The over-expression of NAG-1 in cancer cells results in growth arrest and increase in apoptosis, suggesting that NAG-1 has anti-tumorigenic activity. This conclusion is further supported by results of experiments with transgenic mice that ubiquitously express human NAG-1. These transgenic mice are resistant to the development of intestinal tumors following treatment with azoxymethane or by introduction of a mutant APC gene. In contrast, other data suggest a pro-tumorigenic role for NAG-1, for example, high expression of NAG-1 is frequently observed in tumors. NAG-1 may be like other members of the TGF-$\beta$ superfamily, acting as a tumor suppressor in the early stages, but acting pro-tumorigenic at the later stages of tumor progression. The expression of NAG-1 can be increased by treatment with drugs and chemicals documented to prevent tumor formation and development. Most notable is the increase in NAG-1 expression by the inhibitors of cyclooxygenases that prevent human colorectal cancer development. The regulation of NAG-1 is complex, but these agents act through either p53 or EGR-1 related pathways. In addition, an increase in NAG-1 is observed in inhibition of the AKT/GSK-$3{\beta}$ pathway, suggesting NAG-1 alters cell survival. Thus, NAG-1 expression is regulated by tumor suppressor pathways and appears to modulate tumor progression.

• The Journal of Korean Institute of Communications and Information Sciences
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• v.28 no.1C
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• pp.81-89
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• 2003

For improving the performance of noise suppression in tactical communication environments, an enhanced MELP vocoder is suggested, in which an acoustic noise suppressor is integrated into the front end of the MELP algorithm, and an FEC code into the channel side of the MELP algorithm. The acoustic noise suppressor is the modified IS-127 EVRC noise suppressor which is adapted for the MELP vocoder. As for FEC, the turbo code, which consists of rate-113 encoding and BCJR-MAP decoding algorithm, is utilized. In acoustic noise environments, the lower the SNR becomes, the more the effects of noise suppression is increased. Moreover, The suggested system has greater noise suppression effects in stationary noise than in non-stationary noise, and shows its superiority by 0.24 in MOS test to the original MELP vocoder. When the interleave size is one MELP frame, BER 10-6 is accomplished at channel bit SNR 4.2 ㏈. The iteration of decoding at 3 times is suboptimal in its complexity vs. performance. Synthetic quality is realized as more than MOS 2.5 at channel bit SNR 2 ㏈ in subjective voice quality test, when the interleave size is one MELP frame and the iteration of decoding is more than 3 times.

• Molecules and Cells
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• v.37 no.9
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• pp.664-671
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• 2014

MiR-217 can function as an oncogene or a tumour suppressor gene depending on cell type. However, the function of miR-217 in lung cancer remains unclear to date. This study aims to evaluate the function of miR-217 in lung cancer and investigate its effect on the sensitivity of lung cancer cells to cisplatin. The expression of miR-217 was detected in 100 patients by real-time PCR. The effects of miR-217 overexpression on the proliferation, apoptosis, migration and invasion of SPC-A-1 and A549 cells were investigated. The target gene of miR-217 was predicted by Targetscan online software, screened by dual luciferase reporter gene assay and demonstrated by Western blot. Finally, the effects of miR-217 up-regulation on the sensitivity of A549 cells to cisplatin were determined. The expression of miR-217 was significantly lower in lung cancer tissues than in noncancerous tissues (p < 0.001). The overexpression of miR-217 significantly inhibited the proliferation, migration and invasion as well as promoted the apoptosis of lung cancer cells by targeting KRAS. The up-regulation of miR-217 enhanced the sensitivity of SPC-A-1 and A549 cells to cisplatin. In conclusion, miR-217 suppresses tumour development in lung cancer by targeting KRAS and enhances cell sensitivity to cisplatin. Our results encourage researchers to use cisplatin in combination with miR-217 to treat lung cancer. This regime might lead to low-dose cisplatin application and cisplatin side-effect reduction.

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

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.8
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• pp.1176-1182
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• 2018

Objective: Progesterone receptor (PGR) and AT-rich interactive domain 1A (ARID1A) have important roles in the establishment and maintenance of pregnancy in the uterus. In present studies, we examined the expression of mitochondrial tumor suppressor 1 (MTUS1) in the murine uterus during early pregnancy as well as in response to ovarian steroid hormone treatment. Methods: We performed quantitative reverse transcription polymerase chain reaction and immunohistochemistry analysis to investigate the regulation of MTUS1 by ARID1A and determined expression patterns of MTUS1 in the uterus during early pregnancy. Results: The expression of MTUS1 was detected on day 0.5 of gestation (GD 0.5) and then gradually increased until GD 3.5 in the luminal and glandular epithelium. However, the expression of MTUS1 was significantly reduced in the uterine epithelial cells of $Pgr^{cre/+}Arid1a^{f/f}$ and Pgr knockout (PRKO) mice at GD 3.5. Furthermore, MTUS1 expression was remarkably induced after P4 treatment in the luminal and glandular epithelium of the wild-type mice. However, the induction of MTUS1 expression was not detected in uteri of $Pgr^{cre/+}Arid1a^{f/f}$ or PRKO mice treated with P4. Conclusion: These results suggest that MTUS1 is a novel target gene by ARID1A and PGR in the uterine epithelial cells.

• Proceedings of the Botanical Society of Korea Conference
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• 1998.07a
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• pp.10-18
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• 1998

For improvement of plants in disease resistance, it is most important to elucidate the mechanism to perceive and respond to the signal molecules of invaders. A model system with pea and its pathogen, Mycosphaerella pinodes, showed that the fungal elicitor induced defense responses in all plant species tested but that the suppressor of the fungus blocked or delayed the expression of defense responses and induced accessibility only in the host plant. In the world, many researchers believe that the pathogens` signals are recognized only on the receptors in the plasma membranes. Though we found that the ATPase and polyphosphoinositide metabolism in isolated plasma membranes responded to these fungal signals, we failed to detect specific actions of the suppressor in vitro on these plasma membrane functions. Recently, we found that ATPase (NTPases) and superoxide generating system in isolated cell wall were regulated by these fungal signals even in vitro, especially, by the suppressor in a strictly species-specific manner and also that the cell wall alone prepared an original defense system. The effects of both fungal signals on the isolated cell wall functions in vitro coincide perfectly with those on defense responses in vivo. In this treatise, we discuss the key role of the cell wall, which is plant-specific and the most exterior organelle, in determining host-parasite specificity and molecular target for improvement of plants.