Comparative study of new autologous material, bone-cartilage composite graft, for ossiculoplasty with Polycel® and Titanium.

OBJECTIVE: Ossiculoplasty is a surgical procedure that recreates sound transmission of the middle ear in conductive hearing loss. Various materials have been used for ossicular reconstruction, but the most ideal material for ossiculoplasty remains controversial. The purpose of this study was to introduce a novel method of autologous ossiculoplasty, bone-cartilage composite graft (BCCG) and to compare its surgical results with different types of ossiculoplastic prostheses. STUDY DESIGN: A retrospective study was performed in a tertiary referral centre. METHODS: Data of 275 patients who received ossiculoplasty using the three different materials of BCCG, Polycel® and titanium were analysed according to type of ossiculoplasty: partial or total ossicular replacement prosthesis (PORP or TORP). Hearing results, complication rates and clinical parameters including age, sex, past history, preoperative diagnosis and surgery type were compared among different groups. RESULTS: Ossiculoplasty with BCCG showed satisfactory hearing outcomes and the lowest complication rate among the three different materials. In particular, its extrusion rate was 0%. CONCLUSION: We propose that the BCCG technique is a useful alternative method for ossiculoplasty, with proper patient selection.

Licoricidin, an isoflavonoid isolated from Glycyrrhiza uralensis Fisher, prevents UVA-induced photoaging of human dermal fibroblasts.

OBJECTIVE: Licoricidin is an isoflavonoid isolated from Glycyrrhiza uralensis Fisher. In this study, we investigated the effects of licoricidin on photoaging of UVA-irradiated human dermal fibroblasts (HDFs). METHODS: In vitro reactive oxygen species (ROS) scavenging activity, cellular protective effect and inhibition of elastase activity was determined by Fe3+ -EDTA/H2 O2 systems, photohaemolysis and elastase activity assay, respectively. Anti-oxidative capacity of the compound was evaluated by fluorescent ELISA and 2', 7'-dichlorofluorescin-diacetate (DCF-DA) assay. The expression of protein and phosphorylation was examined using Western blot. RESULTS: The ROS scavenging activity (OSC50 ) of licoricidin was 2.77 µM. It was 3.1-fold higher than that of L-ascorbic acid. Its protective effects were confirmed in a study of 1 O2 -induced cellular damage to human erythrocytes. The τ50 value of 10 µM of licoricidin was 71.0 min; this was markedly higher than that obtained with α-tocopherol (37.0 min). The elastase inhibitory activity of licoricidin (IC50 of 61.2 µM) was 2.1-fold more potent than that of oleanolic acid. Licoricidin markedly reduced the UVA-induced intracellular ROS in a concentration-dependent manner. Western blot revealed that licoricidin attenuated the UVA-dependent induction of MMP-1 protein. Mechanistically, this appeared to be due to licoricidin-dependent inhibition of mitogen-activated protein kinases (MAPK) phosphorylation, which resulted in decreased c-Jun activation and reduced c-Jun and c-Fos expression. CONCLUSION: Licoricidin blocks UVA-induced photoaging via ROS scavenging. This activity converges to limit the activity of MMP-1. These data suggest that licoricidin may be considered as an active ingredient in new topically applied anti-ageing formulations.

Blue Emitters Based on Aryl End-Capped Pyrene Groups for OLEDs.

We have synthesized four pyrene-derived blue emitting materials using Suzuki cross coupling reactions. All OLED devices using these materials as emitting materials showed efficient blue electroluminescence (EL). Particularly, a device using 1,1'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis-pyrene (1) showed best EL properties with the luminous efficiency of 4.32 cd/A, the power efficiency of 3.98 lm/W and the external quantum efficiency of 2.48% at 500 cd/m2.

Evaluation of anti-microbial activities of ZnO, citric acid and a mixture of both against Propionibacterium acnes.

OBJECTIVE: In this study, anti-microbial activities of ZnO of three different particle sizes of citric acid (CA) and of mixtures of ZnO and CA were confirmed against Propionibacterium acnes. METHODS: ZnO with the smallest particle size showed relatively high anti-microbial activity by disc diffusion assay and broth macrodilution assay. The mixtures of ZnO and CA also showed relatively high anti-microbial activity when the particle size of ZnO was the smallest. Furthermore, anti-microbial activities of ZnO, CA and the mixtures of ZnO and CA were compared through the checkerboard assay. RESULTS: The results indicated that a 1 : 1 ratio of ZnO and CA resulted in the highest anti-microbial activity. The substances were confirmed to have synergic anti-microbial effects. With the time-kill curve assay, the mixture of ZnO-containing CA reduced the surviving microbial content the most after 24 h. CONCLUSION: The results of our study suggest that ZnO may not only be an anti-microbial ingredient for the prevention of and treatment of acne. The results of our study suggest that ZnO may be an anti-microbial ingredient for the prevention of and treatment of acne when mixed with CA.

Photolysis of the organic UV filter, avobenzone, combined with octyl methoxycinnamate by nano-TiO2 composites.

A protection of the skin from harmful UV rays is important in preventing the skin damage and skin aging when exposed to sunlight. Titanium dioxide composites are used as a UV filter in sunscreen products combined with organic compounds such as butyl methoxydibenzoyl methane (avobenzone) and octyl methoxycinnamate (OMC) to improve the function of the sunscreen. In this study, the photolysis of avobenzone and OMC caused by the photocatalytic TiO2 nano composites (NCs) is investigated. Three different types of oil/water (O/W) sunscreen formulations containing avobenzone and OMC were prepared. Each formulation contained one of three different types of surface modified TiO2 NCs, which were WP-S (small sized hydrophilic TiO2NCs, ~10nm), OP-S (small sized hydrophobic TiO2NCs, ~15nm), and OP-L (large sized hydrophobic TiO2NCs, ~200nm). The physicochemical properties of the NCs were analyzed using biophysical tools. Addition of a different size of TiO2NCs into O/W sunscreen formulations significantly increased the photolysis of OMC. Effect of quercetin on degradation of avobenzone and OMC by the NCs was also studied for all three formulations. Although the OP-S NCs showed the lowest photocatalytic ability and the highest UV blocking capability, the NCs promoted the photolysis of OMC to the greatest extent. These results can be utilized to design more effective sunscreens, which could potentially ensure optimal photo-protection.

Physical characterization and in vitro skin permeation of solid lipid nanoparticles for transdermal delivery of quercetin.

OBJECTIVE: Quercetin, a phenolic compound isolated from plants, can act as an antioxidant to protect the skin from oxidative stress induced by ultraviolet rays. The aims of this work were (i) to compare the physical characterization of quercetin-loaded solid lipid nanoparticles (QSLNs) and (ii) to investigate the enhanced skin permeation of quercetin using QSLNs. METHODS: QSLNs were prepared with a certain amount lipid (palmitic acid) and the different ratio of surfactant (Tween(®) 80) by homogenization and ultrasonification method. RESULTS: QSLNs showed mono-dispersed particle size distribution in the ranges of 274.0-986.6 nm and zeta potential from -50.4 to -29.4 mV. Entrapment efficiency of QSLN was 15.2-46.2%, and their crystallinity index was low (0-18.2%). In vitro occlusion test showed QSLN-2 has the highest occlusive effect due to its smallest particle size (274.0 nm), and through these result, QSLN-2 was selected as the optimum formulation. Transmission electron microscopy (TEM) analysis further confirmed the uniform spherical shape of QSLN-2 particles. Field emission-scanning electron microscope (FE-SEM) analysis and histological observation of hairless rat skin showed that the lipid particles of QSLN-2 formed a fused lipid film and, subsequently, it hydrated the surface of the rat skin. Franz diffusion cell was used to measure in vitro skin permeation of quercetin dissolved in propylene glycol (QPG), QSLN-2 and QSLN-3. The results showed that QSLN-2 (33.5 µg cm(-2) , 21.9%) exhibited higher skin permeability than QPG (6.6 µg cm(-2) , 4.2%) and QSLN-3 (14.2 µg cm(-2) , 9.1%), which was visually confirmed by confocal laser scanning microscope (CLSM) image analysis as well. CONCLUSION: The results suggest that QSLN-2, prepared with a surfactant content of 2%, could be used as useful skin delivery system for transdermal delivery of hydrophobic antioxidants such as quercetin.

Preparation and characterization of W/O microemulsion for removal of oily make-up cosmetics.

OBJECTIVE: In the present study, W/O microemulsions (MEs) were prepared for efficient removal of oily make-up cosmetics and the detergency characteristics were studied. METHODS: The W/O MEs were prepared by mixing of a spontaneous emulsifier, cosurfactant and oil, and solubilizing the mixture during addition of water. The wettability and emulsifying activity were, respectively, evaluated by measuring contact angle and absorbance after preparing a total of 20 samples using three emulsifying systems and seven oils. RESULTS: Based on the results, a lower viscosity of the oil component is favourable for higher wettability, and the lower the viscosity of the emulsifying systems, the higher the wettability of the ME. Except in the case of oleic acid (OA), oils having high polarity showed significant emulsifying activity. The equation describing [detergency(ΔE)=98.1wettability(cosθ)+120.5EAI(emulsifyingactivityindex)-77.1] was derived from the detergency measurement results, and it was verified that the wettability contributed more significantly to the detergency than the emulsifying activity. CONCLUSION: These results suggest that the prepared W/O microemulsions can be utilized as cleaning agents for efficient removal of oily make-up cosmetics.

Enhanced skin delivery of liquiritigenin and liquiritin-loaded liposome-in-hydrogel complex system.

OBJECTIVE: To study the permeation of liquiritigenin (LQG) and liquiritin (LQ) as licorice flavonoids into the skin, we prepared ceramide liposome-in-cellulose hydrogel complex system. METHODS: Liposome-in-hydrogel complex systems were developed by incorporating ceramide liposomes into cellulose hydrogels by the swelling method. We evaluated their physical and chemical properties, encapsulation efficiency and skin permeability using Franz Diffusion Cell. It was visually seen by CLSM images analysis. RESULTS: The ceramide liposome, consisting of biocompatible lipid membranes, remained stable for over 3 weeks. Encapsulation efficiencies for liquiritigenin and liquiritin-loaded liposome-in-hydrogel were 69.39% and 64.71%, respectively. Liposome-in-hydrogel complex systems (LQG: 56.55%, LQ: 66.99%) had greater skin permeability than control (LQG: 4.92%, LQ: 5.30%) or a single liposome systems (LQG: 43.34%, LQ: 48.97%) and hydrogel systems (LQG: 38.21%, LQ: 55.07%). CONCLUSION: Liposome-in-hydrogel system can be a potential drug delivery system for topical delivery of antioxidants such as licorice flavonoids to construct antioxidative skin barrier.

α-Synuclein deficiency and efferent nerve degeneration in the mouse cochlea: a possible cause of early-onset presbycusis.

OBJECTIVES/HYPOTHESIS: Efferent nerves under the outer hair cells (OHCs) play a role in the protection of these cells from loud stimuli. Previously, we showed that cochlear α-synuclein expression is localized to efferent auditory synapses at the base of the OHCs. To prove our hypothesis that α-synuclein deficiency and efferent auditory deficit might be a cause of hearing loss, we compared the morphology of efferent nerve endings and α-synuclein expression within the cochleae of two mouse models of presbycusis. STUDY DESIGN: Comparative animal study of presbycusis. METHODS: The C57BL/6J(C57) mouse strain, a well-known model of early-onset hearing loss, and the CBA mouse strain, a model of relatively late-onset hearing loss, were examined. Auditory brainstem responses and distortion product otoacoustic emissions were recorded, and cochlear morphology with efferent nerve ending was compared. Western blotting was used to examine α-synuclein expression in the cochlea. RESULTS: Compared with CBA mice, C57 mice showed earlier onset high-frequency hearing loss and decreased function in OHCs, especially within high-frequency regions. C57 mice demonstrated more severe pathologic changes within the cochlea, particularly within the basal turn, than CBA mice of the same age. Weaker α-synuclein and synaptophysin expression in the efferent nerve endings and cochlear homogenates in C57 mice was observed. CONCLUSIONS: Our results support the hypothesis that efferent nerve degeneration, possibly due to differential α-synuclein expression, is a potential cause of early-onset presbycusis. Further studies at the cellular level are necessary to verify our results.

Clinical characteristics and audiological significance of spontaneous otoacoustic emissions in tinnitus patients with normal hearing.

OBJECTIVE: To define the clinical and audiological features of normal-hearing tinnitus patients with spontaneous otoacoustic emissions, and to evaluate the role of spontaneous otoacoustic emissions in tinnitus generation. MATERIALS AND METHODS: Thirty-two patients with spontaneous otoacoustic emissions were compared with 29 patients without spontaneous otoacoustic emissions, regarding clinical and audiological aspects. RESULTS: The mean age of the study group subjects was significantly lower, and they experienced the kindling effect less frequently than the control group. The mean tinnitus handicap inventory score of the study group was considerably higher than that of the controls, although the difference was not statistically significant. The study group had significantly quieter tinnitus, and higher transient evoked and distortion product otoacoustic emission responses, compared with the control group. CONCLUSIONS: Normal-hearing tinnitus patients with spontaneous otoacoustic emissions have different clinical and audiological characteristics, compared with those without spontaneous otoacoustic emissions. Appropriate evaluation and treatment should be considered at an early stage in these patients.

The need for public education on HPV and cervical cancer prevention in Asia. Opinions of experts at the AOGIN conference.

Asia accounts for more than half of all cases of cervical cancer registered globally and improving prevention is urgently needed. A range of tools and strategies is now available to effectively prevent this disease, including two new prophylactic HPV vaccines approved and recommended for adolescents and young women. However, without communication these tools may have little impact on disease burden. The conferences of the Asia Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists whose work is related to genital infections, particularly HPV, cervical dysplasia and neoplasia, as well as other anogenital cancers, with the aim of improving communication on prevention through human papillomavirus (HPV) vaccination and screening in Asian countries. The scope of this year's AOGIN conference was to extend education to include health workers, family doctors, paediatricians, governmental health agencies, and the general public through patients' testimonials that can reach out to women raising awareness of this silent disease. Community based initiatives and awareness campaigns were also reported, and can empower the people to engage in a dialog with local governments towards prioritization of cancer prevention programs, achieving more for the public than isolated actions. Parents and teachers are encouraged to communicate about these issues within families and schools. Evidence was discussed that males can participate in cervical cancer control as well, and prevention programs involving men should not be neglected as they may reduce genital disease burden in women. Opinion leaders proposed prevention measures to be considered for governmental decisions. While each country develops a locally appropriate policy for cervical cancer control there is a need to revise these programs regularly, as knowledge increases in response to public need, as well as to gather evidence about disease burden and the effectiveness of education and interventions. In conclusion, AOGIN is committed to improve communication with patients, health authorities, professional organizations and opinion leaders towards strengthening cervical cancer prevention in Asia, to achieve a timely steep reduction in this cancer.

Localization of synucleins in the mammalian cochlea.

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, alpha-, beta-, and gamma-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that beta-synuclein is the most abundantly expressed form, followed by gamma- and then alpha-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (alpha- and gamma-synuclein), spiral ganglion (beta-synuclein), inner spiral bundle (gamma-synuclein), and stria vascularis (alpha- > beta-synuclein). Developmentally, gamma-synuclein can be seen in the region of the outer hair cells by E19, while alpha- and beta-synuclein do not clearly appear there until approximately P10. Additional studies in a null-mutant gamma-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, gamma-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of gamma-synuclein remains to be determined.

The determination of sensation-dependent bladder emptying time in patients with complete spinal cord injury above T11.

STUDY DESIGN: Retrospective investigation using urodynamic studies and medical records. OBJECTIVE: To evaluate the safety of sensation-dependent bladder emptying in complete spinal cord injury (SCI) patients, based on the preservation of the desire to void. SETTING: Spinal Cord Injury Unit, Yonsei Rehabilitation Hospital, Seoul, Korea. METHODS: This study was performed retrospectively on 79 complete SCI patients with lesions above T11, who had preserved the desire to void during conventional urodynamic studies. Patients were classified according to detrusor compliance and maximal bladder capacity. The clinical and urodynamic characteristics of each group were analyzed. RESULTS: Forty-five (57.0%) patients were classified as group A and 34 (43.0%) patients were classified as group B. There were no significant differences in clinical features, such as voiding methods and the presence of autonomic dysreflexia between the two groups. Compared with group B, there were significantly more areflexic neurogenic bladder cases in group A (P<0.05). There were significantly higher maximal detrusor pressures in group B (P<0.05). There were significantly more cases with the preservation of the strong desire to void in group B (P<0.05). CONCLUSION: Not all patients with discomplete SCIs accepted the use of sensation-dependent bladder emptying. The safe use of sensation-dependent bladder emptying will be determined based on the results of urodynamic studies.

Protective effect of oxidative stress in HaCaT keratinocytes expressing E7 oncogene.

In a previous study, we established a stable cell line which constitutively expresses E7 in HaCaT human keratinocyte cell line and identified various relevant factors including oxygen modulators affected by the E7 oncogene. E7-expressing HaCaT cells (HaCaT/E7) appeared to be more resistant to H2O2-induced cell death. Here, we demonstrate how E7 oncogene would modulate oxidative stress-induced cell death. In addition, we verified the increased expression of catalase in the HaCaT/E7 by Western blot analysis. The results suggest that the E7 oncogene would induce higher resistance to ROS-induced cell injury in the E7-infected cells via the upregulation of catalase. To investigate these paradoxical effects of high concentrations of H2O2 (500 microM-1 mM), we examined their effects on receptor mediated apoptosis, cell death via the mitochondrial pathway and modulation of apoptosis related factors. Our results revealed that HaCaT keratinocytes infected with HPV 16 E7 oncogene modulated expressions of catalase, Bcl-xL, IL-18, Fas, Bad, and cytochrome c as well as NF-kappaB, resulting in the resistance to oxidative stress-induced cell death.

Standardization of anti-lethal toxin potency test of antivenoms prepared from two different Agkistrodon halys venoms

In Korea, antivenoms for the treatment of patients bitten by venomous snakes have been imported from Japan or China. Although there is cross-reactivity between these antibodies and venoms from snakes indigenous to Korea (e.g. Agkistrodon genus), protection is not optimal. Antivenoms specifically prepared to neutralize Korean snake venoms could be more effective, with fewer side effects. To this end, we established an infrastructure to develop national standards and created a standardized method to evaluate the efficacy of two horse-derived antivenoms using mouse lethal toxin test. Additionally, we determined the antivenoms neutralizing activity against lethal doses (LD50) of Agkistrodon halys (from Japan) and Jiangzhe Agkistrodon halys (from China) venoms. We also performed cross-neutralization tests using probit analysis on each pairing of venom and antivenom in order to check the possibility of using Jiangzhe A. halys venom as a substitute for A. halys venom, the current standard. Slope of A. halys venom with A. halys antivenom was 10.2 and that of A. halys venom with Jiangzhe A. halys antivenom was 9.6. However, Slope of Jiangzhe A. halys venom with A. halys antivenom was 4.7 while that of Jiangzhe A. halys venom with Jiangzhe A. halys antivenom was 11.5. Therefore, the significant difference in slope patterns suggests that Jiangzhe A. halys venom cannot be used as a substitute for the standard venom to test the anti-lethal toxin activity of antivenoms (p<0.05).(AU)

Effects of antibiotics and steroid on middle ear mucosa in rats with experimental acute otitis media.

The prevention of mucosal changes induced by experimental pneumococcal otitis media by means of antibiotics has been demonstrated previously. However, the effect of combined antibiotic and steroid therapy on the middle ear mucosa in acute otitis media (AOM) has not been determined. The right middle ears of 27 rats were inoculated with a log-phase type 3 Streptococcus pneumoniae, with the left ears serving as controls. Penicillin G was administered to nine rats and penicillin G and dexamethasone in combination were administered to nine rats after bacterial challenge; the remaining nine rats were not treated. Three animals from each group were sacrificed on Days 4, 7 and 14 after challenge. Tympanic membranes and middle ear mucosa were examined using otomicroscopy and light microscopy. Structural changes were diminished in both the antibiotic-treated and antibiotic + steroid-treated groups, compared with those in the untreated infected controls. The antibiotic + steroid-treated group showed the most marked decrease in structural change, especially in the mucosal metaplasia to the secretory epithelium. The results suggest that combination therapy with antibiotics and steroid in AOM is the most effective at reducing the treatment period and preventing persistent mucosal changes, which may decrease the risk of development of secretory otitis media as a sequela of AOM.

Different distribution of HLA class II alleles according to response to corticosteroid therapy in sudden sensorineural hearing loss.

OBJECTIVE: To investigate the association of HLA class II alleles with the susceptibility to sudden sensorineural hearing loss and with the results of corticosteroid treatment in the Korean population. DESIGN: HLA-DRB1, -DQA1, -DQB1, and -DPB1 genotyping by the sequence-specific oligonucleotide probes method in 41 patients with sudden sensorineural hearing loss and in 206 healthy control subjects. Initial hearing levels at the onset of hearing loss and final hearing levels after treatment were evaluated for the association with HLA class II alleles. SETTING: Tertiary care referral center, ambulatory and hospitalized care. SUBJECTS: Forty-one patients (24 men and 17 women; mean age, 49.2 years) were compared with 206 controls. Patients were divided into 2 groups according to their response to corticosteroid therapy (good response vs nonresponse). RESULTS: The frequencies of HLA-DRB1, -DQA1, -DQB1, and -DPB1 alleles were not significantly different between patients and controls (P>.05). When an association between the results of corticosteroid treatment and the frequency of HLA alleles was evaluated, the frequencies of HLA-DRB1*14 (relative risk [RR] = 3.5, P<.02), -DQA1*03 (RR = 4.2, P<.02), and -DQA1*05 (RR = 3.1, P<.03) were significantly increased, but HLA-DQA1*01 (RR = 0.2, P<.004) and -DQB1*06 (RR = 0.2, P<.009) were decreased in the group nonresponsive to corticosteroid therapy, compared with the controls. The distribution of HLA-DQA1*01 (P<.04), -DQB1*06 (P<.02), and -DQA1*03 (P<.003) was significantly different between the responsive and the nonresponsive groups. HLA-DQA1 allelic combination analysis showed that the frequencies of DQA1*03 and *05 had a high RR value in patients with sudden sensorineural hearing loss (RR = 4.1, P<.003) and in patients in the nonresponsive group (RR = 8.9, P<.001), compared with the controls. CONCLUSION: The presence of HLA class II alleles may be a useful genetic marker in forecasting a prognosis in Korean patients with sudden sensorineural hearing loss.

Down modulation of IL-18 expression by human papillomavirus type 16 E6 oncogene via binding to IL-18.

To understand modulation of a novel immune-related cytokine, interleukin-18, by human papillomavirus type (HPV) 16 oncogenes, HaCaT, normal keratinocyte cell line, and C-33A, HPV-negative cervical cancer cell line, were prepared to establish stable cell lines expressing E6, E6 mutant (E6m), E6E7, or E7 constitutively. Expressions of various HPV oncogene transcripts were identified by RT-PCR. Expression of HPV oncogene E6 was reversely correlated to the expression of interleukin-18, a novel pro-inflammatory cytokine. The expression of E6 in C-33A, independent of E6 splicing, resulted in decreased IL-18 expression and that of IL-18 was also significantly reduced in HaCaT cells expressing E6. The level of p53 was reduced in C-33A cells expressing E6 whereas not altered in HaCaT cells expressing E6, suggesting that E6 downregulated IL-18 expression via an independent pathway of p53 degradation in HaCaT cells which have a mutated p53 form. However, E7 did not affect IL-18 expression significantly in both C-33A and HaCaT cells. Cotransfection experiments showed that E6 oncogene did not inhibit the activities of IL-18 promoter P1 and P2, suggesting that E6 oncogene indirectly inhibited IL-18 expression. Taken together, E6, E6m and E6/E7 inhibited IL-18 expression with some variation, assuming that cells expressing E6 oncogene can evade immune surveillance by downregulating the expression of immune stimulating cytokine gene, IL-18, and inhibiting the cascade of downstream effects that follow activation of the IL-18 receptor.