• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.13
• /
• pp.5389-5393
• /
• 2014

Background: A clinical pathway (CP) can standardize and improve perioperative care for a number of interventions. In hepatic surgery, however, pertinent evidence is very limited. This study was conducted to implement a CP for hepatocellular carcinoma (HCC) patients undergoing hepatectomy, and to evaluate its effects on hospital costs, length of hospital stay (LOHS) and early clinical outcomes. Materials and Methods: Medical records for HCC patients undergoing hepatectomy were retrospectively reviewed before implementation of a CP (the non-CP group) from March 2012 to August 2012. This information was compared with the data collected prospectively from patients after implementation of the CP (the CP group) between September 2012 and April 2013. Hospital costs, LOHS and early clinical outcomes were evaluated and compared between groups. Results: There were no significant differences in terms of patient clinical characteristics between the two groups. For clinical outcome measures, no significant differences were found in postoperative complications, mortality and readmission rate. The hospital costs were significantly reduced from 24,844 RMB in the non-CP group to 19,761 RMB in the CP group (p<0.01). In addition, patients of the CP group also had shorter LOHS compared with the non-CP group (8.3 versus 12.3 days, p<0.001). Conclusions: The CP proved to be an effective approach to minimize hospital costs and LOHS with hepatectomy for HCC without compromising patient care.

• International Journal of Oral Biology
• /
• v.34 no.2
• /
• pp.53-59
• /
• 2009

Periodontal ligament (PDL) tissue is a connective tissue that is interposed between the roots of the teeth and the inner wall of the alveolar bone socket. PDL is always exposed to physiologic mechanical force such as masticatory force and PDL cells play important roles during orthodontic tooth movement by synthesizing and secreting different mediators involved in bone remodeling. The Wnt/${\beta}$-catenin signaling pathway was recently shown to play a significant role in the control of bone formation. In the present study, we applied cyclic tensile stress of 20% elongation to cultured human PDL cells and assessed its impact after six days upon components of the Wnt/${\beta}$-catenin signaling pathway. RTPCR analysis showed that Wnt1a, Wnt3a, Wnt10b and the Wnt receptor LRP5 were down-regulated, whereas the Wnt inhibitor DKK1 was up-regulated in response to these stress conditions. In contrast, little change was detected in the mRNA expression of Wnt5a, Wnt7b, Fz1, and LRP6. By western blotting we found decreased expression of the ${\beta}$-catenin and p-GSK-3${\beta}$ proteins. Our results thus show that mechanical stress suppresses the canonical Wnt/${\beta}$-catenin signaling pathway in PDL cells.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.38 no.2
• /
• pp.101-109
• /
• 2012

Objectives: The inactivation of the tumor suppressor gene $p16^{INK4a}$ plays an important role in the development of malignant tumors, including oral squamous cell carcinoma. The p16 gene is involved in the p16/cyclin-dependent kinase/retinoblastoma (Rb) gene pathway of cell cycle control. The p16 protein is considered a negative regulator of this pathway. The p16 gene encodes an inhibitor of cyclin-dependent kinases 4 and 6 which regulate the phosphorylation of the retinoblastoma gene and G1 to S phase transition in the cell cycle. However, the p16 gene can lose its functionality through point mutations, loss of heterozygosity or methylation of its promoter region. Materials and Methods: In this study, the authors analyzed the correlation between various clinicopathological findings- patient age, gender and smoking, disease recurrence, tumor size, stage, and differentiation- and p16 protein expression or p16 promoter hypermethylation in 59 cases of head and neck squamous cell carcinoma. Results: The results revealed p16 protein expression and p16 promoter hypermethylation in 28 cases (47.5%) and 21 cases (35.6%), respectively, of head and neck squamous cell carcinoma. However, neither p16 protein expression nor p16 promoter hypermethylation had any statistical influence on clinicopathological findings or survival rate. Conclusion: This data, and a review of the literature, suggest that p16 promoter hypermethylation cannot yet be used as an independent prognostic factor influencing carcinogenesis, but must be considered as an important factor along with other genetic alterations affecting the pRb pathway.

• Korean Journal of Veterinary Research
• /
• v.54 no.1
• /
• pp.21-26
• /
• 2014

Although benfotiamine has various beneficial anti-diabetic effects, the detailed mechanisms underlying the impact of this compound on the insulin signaling pathway are still unclear. In the present study, we evaluated the effects of benfotiamine on the hepatic insulin signaling pathway in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which are a type 2 diabetes mellitus model. OLETF rats treated with benfotiamine showed decreased body weight gain and reduced adipose tissue weight. In addition, blood glucose levels were lower in OLETF rats treated with benfotiamine. Following treatment with benfotiamine, the levels of Akt phosphorylation (S473/T308) in the OLETF groups increased significantly compared to the OLETF control group so that they were almost identical to the levels observed in the control group. Moreover, benfotiamine restored the phosphorylation levels of both glycogen synthase kinase (GSK)-$3{\alpha}/{\beta}$ (S21, S9) and glycogen synthase (GS; S641) in OLETF rats to nearly the same levels observed in the control group. Overall, these results suggest that benfotiamine can potentially attenuate type 2 diabetes mellitus in OLETF rats by restoring insulin sensitivity through upregulation of Akt phosphorylation and activation of two downstream signaling molecules, GSK-$3{\alpha}/{\beta}$ and GS, thereby reducing blood glucose levels through glycogen synthesis.

• Journal of Ginseng Research
• /
• v.44 no.1
• /
• pp.96-104
• /
• 2020

Objectives: Oleanolic acid, a minor element of ginsenosides, and its derivatives have been shown to have cytotoxicity against some tumor cells. The impact of cytotoxic effect of oleanolic acid 3-acetate on ovarian cancer SKOV3 cells and endometrial cancer HEC-1A cells were examined both in vivo and in vitro to explore the underlying mechanisms. Methods: Cytotoxic effects of oleanolic acid 3-acetate were assessed by cell viability, phosphatidylserine exposure on the cell surface, mitochondrial release of cytochrome C, nuclear translocation of apoptosis-inducing factor, depolarization of mitochondrial transmembrane potential (∆Ψ_m), and generation of reactive oxygen species (ROS). In vivo inhibition of tumor growth was also assessed with xenografts in immunocompromised mice. Results: Oleanolic acid 3-acetate exhibited potent cytotoxicity toward SKOV3 and HEC-1A cells by decreasing cell viability in a concentration-dependent manner. Importantly, oleanolic acid 3-acetate effectively suppressed the growth of SKOV3 cell tumor xenografts in immunocompromised mice. Furthermore, oleanolic acid 3-acetate induced apoptotic cell death as revealed by loss of ∆Ψ_m, release of cytochrome c, and nuclear translocation of apoptosis-inducing factor with a concomitant activation of many proapoptotic cellular components including poly(ADP-ribose) polymerase, Bcl-2, and caspases-8, caspase-3, and caspase-7. Oleanolic acid 3-acetate, however, caused a decrease in ROS production, suggesting the involvement of an ROS-independent pathway in oleanolic acid 3-acetate-induced apoptosis in SKOV3 and HEC-1A cells. Conclusion: These findings support the notion that oleanolic acid 3-acetate could be used as a potent anticancer supplementary agent against ovarian and endometrial cancer. Oleanolic acid 3-acetate exerts its proapoptotic effects through a rather unique molecular mechanism that involves an unconventional ROS-independent but mitochondria-mediated pathway.

• Genomics & Informatics
• /
• v.20 no.2
• /
• pp.20.1-20.13
• /
• 2022

Recent studies have focused on the early detection of ovarian cancer (OC) using tumor materials by liquid biopsy. The mechanisms of microRNAs (miRNAs) to impact OC and signaling pathways are still unknown. This study aims to reliably perform functional analysis of previously validated circulating miRNAs' target genes by using pathfindR. Also, overall survival and pathological stage analyses were evaluated with miRNAs' target genes which are common in the The Cancer Genome Atlas and GTEx datasets. Our previous studies have validated three downregulated miRNAs (hsa-miR-885-5p, hsa-miR-1909-5p, and hsa-let7d-3p) having a diagnostic value in OC patients' sera, with high-throughput techniques. The predicted target genes of these miRNAs were retrieved from the miRDB database (v6.0). Active-subnetwork-oriented Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted by pathfindR using the target genes. Enrichment of KEGG pathways assessed by the analysis of pathfindR indicated that 24 pathways were related to the target genes. Ubiquitin-mediated proteolysis, spliceosome and Notch signaling pathway were the top three pathways with the lowest p-values (p < 0.001). Ninety-three common genes were found to be differentially expressed (p < 0.05) in the datasets. No significant genes were found to be significant in the analysis of overall survival analyses, but 24 genes were found to be significant with pathological stages analysis (p < 0.05). The findings of our study provide in-silico evidence that validated circulating miRNAs' target genes and enriched pathways are related to OC and have potential roles in theranostics applications. Further experimental investigations are required to validate our results which will ultimately provide a new perspective for translational applications in OC management.

• International Journal of Stem Cells
• /
• v.16 no.3
• /
• pp.315-325
• /
• 2023

Background and Objectives: Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its heterogeneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. Methods and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. Conclusions: Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.

• Journal of the Korean Society of Environmental Restoration Technology
• /
• v.21 no.1
• /
• pp.145-155
• /
• 2018

Problems and improvement plan in ecological pathways created by Environmental Impact Assessment(EIA) were found based on 504 expost environmental impact survey reports submitted to the National Institute of Ecology in 2016. A total of five improvement plans have been proposed. First, the concept and composition principle of ecological pathways should be unified. Second, Guidelines for consultation on the EIA should be provided for each stage to be applied on-site. Third, if ecological pathway is constructed differently than the consultation, the punishment clauses should be applied to prevent formal composition of ecological pathways. Fourth, We need to prepare measures to strengthen basic research for the installation of ecological pathways. Fifth, We need to strengthen the expost inspection function to compensate for the poorly created of ecological pathways. It is believed that the problems of ecological pathways created by consultation on environmental impact assessment could be corrected in the future. And it is deemed possible to systematically manage ecological pathways.

• Progress in Medical Physics
• /
• v.28 no.4
• /
• pp.144-148
• /
• 2017

When a high density metallic implant is placed in the path of the proton beam, spatial heterogeneity can be caused due to artifacts in three dimensional (3D) computed tomography (CT) scans. These artifacts result in range uncertainty in dose calculation in treatment planning system (TPS). And this uncertainty may cause significant underdosing to the target volume or overdosing to normal tissue beyond the target. In clinical cases, metal implants must be placed in the beam path in order to preserve organ at risk (OARs) and increase target coverage for tumors. So we should introduce Ti-mesh. In this paper, we measured the lateral dose profile for proton beam using an EBT3 film to confirm dosimetric impact of Ti-mesh when the Ti-mesh plate was placed in the proton beam pathway. The effect of Ti-mesh on the proton beam was investigated by comparing the lateral dose profile calculated from TPS with the film-measured value under the same conditions.

• Journal of Environmental Impact Assessment
• /
• v.18 no.6
• /
• pp.359-366
• /
• 2009

CCS (Carbon Capture and Storage) is considered as the most promising interim solution to deal with the greenhouse gas such as $CO_2$ responsible for global warming. Even though carefully chosen geologic formations are known to contain stored gas for a long time period, there are potential risks of leakage. Up to now, applicable risk assessment procedures for the leakage of $CO_2$ are not available. This study presents a basis for risk analysis applicable to a complex geologic storage system. It starts with the classification of potential leakage pathways. Receptors and the leakage effect on them are identified and quantified. Then, a fault tree is constructed, which yields the minimum cut set (i.e., the most vulnerable leakage pathway) and quantifies the probability of the leakage risk through the cut set. The methodology will provide a tool for risk assessment in a CCS project. The outcomes of the assessment will not only ensure the safety of the CCS system but also offer a reliable and efficient monitoring plan.