• Molecules and Cells
• /
• 제28권1호
• /
• pp.37-42
• /
• 2009

Iron binding lactoferrin (Lf) is involved in the control of cell cycle progression. However, the molecular basis underlying the effects of Lf on cell cycle control, as well as its target genes, remains incompletely understood. In this study, we have demonstrated that a relatively low level of ironsaturated Lf, Lf($Fe^{3+}$), can stimulate S phase cell cycle entry, and requires Akt activation in MCF-7 cells. Lf($Fe^{3+}$) immediately induced Akt phosphorylation at Ser473, which subsequently induced the phosphorylation of two G1-checkpoint Cdk inhibitors, $p21^{Cip/WAF1}$ and $p27^{kip1}$. The Lf($Fe^{3+}$)-induced phosphorylation of Cdk inhibitors impaired their nuclear import behavior, thereby inducing cell cycle progression. However, the treatment of cells with a PI3K inhibitor, LY294002, almost completely blocked Lf($Fe^{3+}$)-stimulated cell cycle progression. LY294002 treatment abrogated Lf($Fe^{3+}$)-induced Akt activation, and prevented the cytoplasmic localization of $p27^{kip1}$. Higher levels of $p21^{Cip/WAF1}$ were also detected in the cytoplasmic sub-cellular compartment as a measure of cellular response to Lf($Fe^{3+}$). Consequently, the degree of phosphorylation of retinoblastoma protein was enhanced in response to Lf($Fe^{3+}$). Therefore, we conclude that Lf($Fe^{3+}$), as a potential antagonist of Cdk inhibitors, can facilitate the functions of E2F during progression to S phase via the Akt signaling pathway.

• Investigative Magnetic Resonance Imaging
• /
• 제23권4호
• /
• pp.351-360
• /
• 2019

Purpose: To investigate noninvasive biomarkers for predicting treatment response in patients with locally advanced HCC who underwent concurrent chemoradiotherapy (CCRTx). Materials and Methods: Thirty patients (55.5 ± 10.2 years old, M:F = 24:6) who underwent CCRTx due to advanced HCC were enrolled. Contrast-enhanced US (CEUS) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were obtained before and immediately after CCRTx. The third CEUS was obtained at one month after CCRTx was completed. Response was assessed at three months after CCRTx based on RECIST 1.1. Quantitative imaging biomarkers measured with CEUS and MRI were compared between groups. A cutoff value was calculated with ROC analysis. Overall survival (OS) was compared by the Breslow method. Results: Twenty-five patients were categorized into the non-progression group and five patients were categorized into the progression group. Peak enhancement of the first CEUS before CCRTx (PE1) was significantly lower in the non-progression group (median, 18.6%; IQR, 20.9%) than that in the progression group (median, 59.1%; IQR, 13.5%; P = 0.002). There was no significant difference in other quantitative biomarkers between the two groups. On ROC analysis, with a cutoff value of 42.6% in PE1, the non-progression group was diagnosed with a sensitivity of 90.9% and a specificity of 100%. OS was also significantly longer in patients with PE1 < 42.6% (P = 0.014). Conclusion: Early treatment response and OS could be predicted by PE on CEUS before CCRTx in patients with HCC.

• 대한소아치과학회지
• /
• 제25권1호
• /
• pp.62-75
• /
• 1998

The main purpose of this study was to compare the anticariogenecity of glass ionomer restorative material polymerized by argon laser versus visible light, The results from the present study can be summarized as follows; 1. Under the polarized light microscope, the specimens of laser-cured group showed the shallower lesion body than that of visible-light cured group, both in the stage of lesion initiation and progression. 2. Glass ionomer material cured by visible light showed shallower body of lesion than that of composite resin cured by argon laser at the stage of lesion progression(p<0.05). It was suggested fluoride released from the glass ionomer might have the additive anticariogenic effect. 3. Statistical difference between groups on depth of lesion body was evident after lesion progression (p<0.05). It was suggested that anticariogenic effect by argon laser was more effective at the stage of lesion progression than the lesion initiation. 4. The increment of lesion body during progression was highest in group IV (p<0.05). 5. Based upon the above-mentioned results of this study, it can be concluded that the advantage of anticariogenic effect and short curing time of argon laser in glass ionomer polymerization should be considered in children and adolescents whose caries activity is relatively higher.

• 대한교통학회지
• /
• 제21권3호
• /
• pp.71-83
• /
• 2003

교차로의 신호시간 계획이나 간선도로 축의 제어에 있어서 가장 대표적인 문제는 수시로 변화하는 교통상황이다. 또한 이러한 변화로 인해 정확한 교통 데이터를 얻기 힘들고, 그에 대한 분석 또한 어렵다. 따라서 본 논문에서는 이러한 불명확한 교통데이터를 이용하여 교차로 및 간선도로의 제어를 하기 위해, 인간의 사고와 유사한 추론이 가능하다고 판단되는 Fuzzy Logic을 적용함으로써 불명확한 상황에 대하여 수학적인 함수로 표현되지는 않지만 언어적인(Linguistic) 제어가 가능하도록 하여, 기존의 교통제어 방법보다 교통상황에 민감하게 대처할 수 있는 새로운 제어전략을 제시하였다. 본 연구는 "영상검지기를 이용한 실시간 교통신호 감응제어(김성호, 1996)"의 독립교차로의 신호 제어 부분을 기초로 하여 간선도로 상의 연속진행 제어에 대한 전략을 제안하고, 그 효과를 기존의 제어 방법에 의한 효과와 비교·분석하였다. 또한 각 제어 방법에 대한 분석을 위하여, 교통 시뮬레이션 소프트웨어인 TRAF-NETSIM을 이용하여 각각의 효과를 비교하였다.

• Experimental and Molecular Medicine
• /
• 제50권12호
• /
• pp.8.1-8.12
• /
• 2018

FAM46B is a member of the family with sequence similarity 46. Little is known about the expression and functional role (s) of FAM46B in prostate cancer (PC). In this study, the expression of FAM46B expression in The Cancer Genome Atlas, GSE55945, and an independent hospital database was measured by bioinformatics and real-time PCR analysis. After PC cells were transfected with siRNA or a recombinant vector in the absence or presence of a ${\beta}$-catenin signaling inhibitor (XAV-939), the expression levels of FAM46B, C-myc, Cyclin D1, and ${\beta}$-catenin were measured by western blot and realtime PCR. Cell cycle progression and cell proliferation were measured by flow cytometry and the CCK-8 assay. The effects of FAM46B on tumor growth and protein expression in nude mice with PC tumor xenografts were also measured. Our results showed that FAM46B was downregulated but that ${\beta}$-catenin was upregulated in patients with PC. FAM46B silencing promoted cell proliferation and cell cycle progression in PC, which were abrogated by XAV-939. Moreover, FAM46B overexpression inhibited PC cell cycle progression and cell proliferation in vitro and tumor growth in vivo. FAM46B silencing promoted ${\beta}$-catenin protein expression through the inhibition of ${\beta}$-catenin ubiquitination. Our data clearly show that FAM46B inhibits cell proliferation and cell cycle progression in PC through ubiquitination of ${\beta}$-catenin.

• Korean Journal of Ophthalmology
• /
• 제32권6호
• /
• pp.470-477
• /
• 2018

Purpose: To investigate the relationship between the progression of visual field (VF) loss and changes in lamina cribrosa depth (LCD) as determined by spectral-domain optical coherence tomography (SD-OCT) enhanced depth imaging in patients with primary open angle glaucoma (POAG). Methods: Data from 60 POAG patients (mean follow-up, $3.5{\pm}0.7$ years) were included in this retrospective study. The LCD was measured in the optic disc image using SD-OCT enhanced depth imaging scanning at each visit. Change in the LCD was considered to either 'increase' or 'decrease' when the differences between baseline and the latest two consecutive follow-up visits were greater than the corresponding reproducibility coefficient value ($23.08{\mu}m$, as determined in a preliminary reproducibility study). All participants were divided into three groups: increased LCD (ILCD), decreased LCD (DLCD), and no LCD change (NLCD). The Early Manifest Glaucoma Trial criteria were used to define VF deterioration. Kaplan-Meier survival analysis and Cox's proportional hazard models were performed to explore the relationship between VF progression and LCD change. Results: Of the 60 eyes examined, 35.0% (21 eyes), 28.3% (17 eyes), and 36.7% (22 eyes) were classified as the ILCD, DLCD, and NLCD groups, respectively. Kaplan-Meier survival analysis showed a greater cumulative probability of VF progression in the ILCD group than in the NLCD (p < 0.001) or DLCD groups (p = 0.018). Increased LCD was identified as the only risk factor for VF progression in the Cox proportional hazard models (hazard ratio, 1.008; 95% confidence interval, 1.000 to 1.015; p = 0.047). Conclusions: Increased LCD was associated with a greater possibility of VF progression. The quantitative measurement of LCD changes, determined by SD-OCT, is a potential biomarker for the prediction of VF deterioration in patients with POAG.

• Journal of Periodontal and Implant Science
• /
• 제49권2호
• /
• pp.60-75
• /
• 2019

The primary aim of this systematic review was to assess the evidence on periodontal disease progression after treatment in patients receiving supportive periodontal therapy (SPT) and to identify predictors of clinical attachment level (CAL) loss. A protocol was developed to answer the following focused question: In adult patients treated for periodontitis, what is the disease progression in terms of CAL loss after surgical or non-surgical treatment? Randomized controlled clinical trials, prospective cohort studies, and longitudinal observational human studies with a minimum of 5 years of follow-up after surgical or non-surgical treatment that reported CAL and probing depth changes were selected. Seventeen publications reporting data from 14 investigations were included. Data from 964 patients with a follow-up range of 5-15 years was evaluated. When the CAL at the latest follow-up was compared to the CAL after active periodontal therapy, 10 of the included studies reported an overall mean CAL loss of ${\leq}0.5mm$, 3 studies reported a mean CAL loss of 0.5-1 mm, and 4 studies reported a mean CAL loss of >1 mm. Based on 7 publications, the percentage of sites showing a CAL loss of ${\geq}2mm$ varied from 3% to 20%, and a high percentage of sites with CAL loss was associated with poor oral hygiene, smoking, and poor compliance with SPT. The outcomes after periodontal therapy remained stable over time. Disease progression occurred in a reduced number of sites and patients, mostly associated with poor oral hygiene, poor compliance with SPT, and smoking.

• Journal of Ginseng Research
• /
• 제43권2호
• /
• pp.312-318
• /
• 2019

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D. Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in $CD^{4+}$ T cell counts over $96{\pm}59months$ was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene. Results: $CD^{4+}$ T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment (p < 0.001). Of these, two subtype D-infected patients and 116 subtype B-infected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the $KRG-na{\ddot{i}}ve$ group irrespective of subtype (p < 0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype D-infected patients than in subtype B-infected patients (p < 0.01). KRG treatment had a greater effect on AD in subtype D-infected patients than in subtype B-infected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 $KRG-na{\ddot{i}}ve$ (p < 0.001) and all 163 (p < 0.01) patients infected with subtype D than subtype B. Conclusion: Subtype D infection is associated with a >2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.

• BMB Reports
• /
• 제52권4호
• /
• pp.277-282
• /
• 2019

Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the $HIF-1{\alpha}/BNIP3$ pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the $HIF-1{\alpha}/BNIP3$ pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA.

• BMB Reports
• /
• 제57권4호
• /
• pp.167-175
• /
• 2024

Cancer progression is driven by genetic mutations, environmental factors, and intricate interactions within the tumor microenvironment (TME). The TME comprises of diverse cell types, such as cancer cells, immune cells, stromal cells, and neuronal cells. These cells mutually influence each other through various factors, including cytokines, vascular perfusion, and matrix stiffness. In the initial or developmental stage of cancer, neurotrophic factors such as nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor are associated with poor prognosis of various cancers by communicating with cancer cells, immune cells, and peripheral nerves within the TME. Over the past decade, research has been conducted to prevent cancer growth by controlling the activation of neurotrophic factors within tumors, exhibiting a novel attemt in cancer treatment with promising results. More recently, research focusing on controlling cancer growth through regulation of the autonomic nervous system, including the sympathetic and parasympathetic nervous systems, has gained significant attention. Sympathetic signaling predominantly promotes tumor progression, while the role of parasympathetic signaling varies among different cancer types. Neurotransmitters released from these signalings can directly or indirectly affect tumor cells or immune cells within the TME. Additionally, sensory nerve significantly promotes cancer progression. In the advanced stage of cancer, cancer-associated cachexia occurs, characterized by tissue wasting and reduced quality of life. This process involves the pathways via brainstem growth and differentiation factor 15-glial cell line-derived neurotrophic factor receptor alpha-like signaling and hypothalamic proopiomelanocortin neurons. Our review highlights the critical role of neurotrophic factors as well as central nervous system on the progression of cancer, offering promising avenues for targeted therapeutic strategies.