Jae-Sung Kim

Rush University Medical Center, Chicago, Illinois, United States

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Publications (101)252.19 Total impact

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    ABSTRACT: To compare the dosimetric effects of Acuros XB (AXB) and Anisotropic Analytical Algorithm (AAA) on volumetric modulated arc therapy (VMAT) planning for postoperative prostate cancer patients irradiated using an endorectal balloon (ERB). We measured central axis doses with film in a phantom containing an air cavity, and compared measurements with calculations of the AAA and AXB. For clinical study, 10 patients who had undergone whole pelvic radiotherapy (WPRT) followed by prostatic bed-only radiotherapy (PBRT) using VMAT were enrolled. An ERB was used for PBRT but not for WPRT. To compare dosimetric parameters, the cumulative dose-volume histograms, mean, maximum, and minimum doses were measured for the planning target volume. Homogeneity of plans were confirmed using V95%, V107% (VX%, percentage volumes receiving at least X% of prescribed doses) and conformity indices (homogeneity index [HI], conformity index [CI], and conformation number [CN]). We compared volumes of the organ-at-risk receiving 10% to 100% (10-tier at 10% interval) of prescribed doses (V10% - V100%). In the phantom study, the AAA showed larger disagreement with the measurements, and overestimated the dose in the air cavity, comparing with the AXB. For WPRT planning, the AAA predicted a lower maximum dose and V107% than the AXB. For PBRT planning, the AAA estimated a higher minimum dose, lower maximum dose, and smaller V107%, and larger V95% than the AXB. Regarding the conformity indices, the AAA was estimated to be more homogenous than the AXB for PBRT planning (HI, 0.088 vs. 0.120, p = 0.005; CI, 1.052 vs. 1.038, p = 0.022; and CN, 0.920 vs. 0.900, p = 0.007) but not for WPRT planning. Among V10% to V100% of the rectum, the PBRT exhibited significant discrepancies in V30%, V40%, V70%, V80%, and V90%; while the WPRT did in V20% and V30%. The phantom study demonstrated that the AXB calculates more accurately in the air cavity than the AAA. In the clinical setting, the AXB exhibited different dosimetric distributions in the VMAT plans for PBRT containing an ERB. The AXB should be considered for prostate cancer patients irradiated with an ERB for better applying of heterogeneous condition.
    Radiation Oncology 12/2015; 10(1). DOI:10.1186/s13014-015-0346-3 · 2.36 Impact Factor
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    ABSTRACT: We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays and in vivo brain tumor model. The effect of PP2 on radiosensitivity of U251 and T98G cells was investigated using clonogenic assays. The expression of E-cadherin, MMP2, EphA2, and VEGF was measured by Western blotting and an accumulation of γH2AX foci 6 h after radiotherapy was measured after PP2 treatment. The effect of PP2 on migration, invasion, and vasculogenic mimicry formation (VMF) of U251 cells was evaluated. In an orthotopical brain tumor model with U251 cells, PP2 was injected intraperitoneally with or without oral TMZ before, during and after whole brain radiotherapy. Bioluminescence images were taken to visualize in vivo tumors and immunohistochemical staining of VEGF, CD31, EphA2, and HIF1a was performed. PP2 increased radiosensitivity of U251 and T98G cells without decreasing survival of normal human astrocytes. Chemoradiotherapy with PP2 and TMZ resulted in increased accumulation of γH2AX foci. PP2 induced overexpression of E-cadherin and suppression of MMP2, VEGF, and EphA2. PP2 also compromised invasion, migration, and VMF of U251 cells. In brain tumors, chemoradiotherapy with PP2 and TMZ decreased tumor volume best, but not statistically significantly compared with chemoradiotherapy with TMZ. The expression of VEGF and CD31 was suppressed in PP2-treated tumors. s PP2 enhances radiosensitivity of malignant glioma cells and suppresses invasion and migration of U251 cells. Chemoradiotherapy with PP2 and TMZ resulted in non-significant tumor volume decrease.
    Cancer Research and Treatment 06/2015; DOI:10.4143/crt.2014.320 · 2.98 Impact Factor
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    ABSTRACT: To compare the impact of postoperative chemoradiotherapy (CRT) versus adjuvant chemotherapy alone on recurrence and survival in patients with stage II and III upper rectal cancer undergoing curative resection. From our institutional database, 190 patients who underwent primary curative resection between 2003 and 2010 for stage II or III upper rectal cancer were identified. None of the patients received preoperative CRT. Of these, 136 patients received postoperative chemotherapy alone (the CTx group) and 54 patients received postoperative CRT (the CRT group). The CRT group had poorer prognostic features (pT4, pN2, poor differentiation, or involved resection margin) compared with the CTx group. To reduce the impact of treatment selection bias on treatment outcomes, propensity score-matching analysis was used. The matched cohort consisted of 50 CRT and 50 CTx patients with a median follow-up period of 76 and 63 months, respectively. In the matched cohort, CRT resulted in an improved 5-year local control (98.0% vs. 85.2%, p = 0.024) and overall survival rate (89.9% vs. 69.8%, p = 0.021) compared with CTx. In the subgroup analysis to identify subpopulations of patients that benefit most from receiving CRT, local recurrence did not occur in patients who did not have poor prognostic features regardless of the receipt of CRT. For patients with any poor prognostic features, CRT resulted in an improved 5-year local control compared with CTx (96.4% vs. 70.7%, p = 0.013). After adjusting for clinicopathologic factors by propensity score-matching, postoperative CRT was associated with improved local control and overall survival in stage II and III upper rectal cancer. Our results suggest that surgery followed by chemotherapy alone is acceptable for patients who did not have poor prognostic features, while additional radiotherapy should be given for patients who have any poor prognostic features.
    PLoS ONE 04/2015; 10(4):e0123657. DOI:10.1371/journal.pone.0123657 · 3.53 Impact Factor
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    ABSTRACT: The purpose of this study was to elucidate the molecular mechanisms of microRNA-203 (miR-203) as a tumor suppressor in KB human oral cancer cells. MicroRNA microarray results showed that the expression of miR-203 was significantly down-regulated in KB cells compared with normal human oral keratinocytes. The viability of KB cells was decreased by miR-203 in the time- and dose-dependent manners. In addition, over-expressed miR-203 not only increased the nuclear condensation but also significantly increased the apoptotic population of KB cells. These results indicated that the over-expression of miR-203 induced apoptosis of KB cells. Furthermore, the target gene array analyses revealed that the expression of Yes-1, a member of the Src family kinases (SFKs), was significantly down-regulated by miR-203 in KB cells. Moreover, both the mRNA and protein levels of Yes-1 were strongly reduced in KB cells transfected with miR-203. Therefore, these results indicated that Yes-1 is predicted to be a potential target gene of miR-203. Through a luciferase activity assay, miR-203 was confirmed to directly targets the Yes-1 3' untranslated region (UTR) to suppress gene expression. Therefore, our findings indicate that miR-203 induces the apoptosis of KB cells by directly targeting Yes-1, suggesting its application in anti-cancer therapeutics. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.
    Journal of Bioscience and Bioengineering 04/2015; DOI:10.1016/j.jbiosc.2015.02.002 · 1.79 Impact Factor
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    ABSTRACT: We report generation and characterization of pain-related behavior in a minimally-invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer. After hyperalgesia was established, pathological changes in lumbar FJs and alterations of intervertebral foramen size were assessed by histological and imaging analyses. To investigate treatment options for lumber FJ osteoarthritis-induced pain, animals with established hyperalgesia were administered with analgesic drugs, such as morphine, a selective COX-2 inhibitor, a non-steroidal anti-inflammatory drug (NSAID) (ketorolac), or pregabalin. Effects were assessed by behavioral pain responses. One week after percutaneous puncture-induced injury of the lumbar FJs, ipsilateral primary pressure hyperalgesia developed and was maintained for at least 12 weeks without foraminal stenosis. Animals showed decreased spontaneous activity, but no secondary hyperalgesia in the hind paws. Histopathological and microfocus X-ray computed tomography analyses demonstrated that the percutaneous puncture injury resulted in osteoarthritis-like structural changes in the FJs cartilage and subchondral bone. Pressure hyperalgesia was completely reversed by morphine. The administration of celecoxib produced moderate pain reduction with no statistical significance while the administration of ketorolac and pregabalin produced no analgesic effect on FJ osteoarthritis-induced back pain. Our animal model of non-open percutanous puncture-induced injury of the lumbar FJs in rats shows similar characteristics of low back pain produced by human facet arthropathy. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Journal of Cellular Physiology 04/2015; DOI:10.1002/jcp.25015 · 3.87 Impact Factor
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    ABSTRACT: To test by immunohistochemical (IHC) staining whether carbonic anhydrase (CA) 9 and 12 have an effect on sentinel lymph node (SLN) metastasis in early breast cancer and to find clinicopathologic factors associated with SLN metastasis. Between June 2003 and June 2011, medical records of 470 patients diagnosed with breast cancer with pT1-2, pN0-2 and M0 were reviewed. Of these 470, 314 patients who underwent SLN biopsy ± axillary dissection were subjects of this study. Using tissue microarray, IHC staining for CA9 and CA12 was performed. Clinicopathologic factors such as patient age, tumour size, lymphatic invasion, hormone receptor status, and the Ki-67 labelling index were analysed together. The mean age of all patients was 51.7 years. The mean number of harvested SLN was 3.62, and 212 (67.5%) patients had negative SLN. Lymphatic invasion, the Ki-67 labelling index of primary tumours, and CA9 staining of stromal cells, were independent risk factors for SLN metastasis in the multivariate analysis. In 33 patients (10.5%) without the three risk factors, no patient had SLN metastasis. In 80 patients without lymphatic invasion of primary tumours or CA9 staining of stromal cells, only four patients (5%) had positive SLN. CA9 staining of stromal cells is an independent risk factor for SLN metastasis as well as lymphatic invasion and a low-Ki-67 labelling index of primary tumours in patients with early breast cancer. IHC staining of primary tumours for CA12 was not associated with SLN metastasis.
    Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.243 · 2.98 Impact Factor
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    ABSTRACT: In the present study, we examined the anticancer properties of berberine in KB oral cancer cells with a specific focus on its cellular mechanism. Berberine did not affect the cell viability of the primary human normal oral keratinocytes that were used as a control. However, the viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner. Furthermore, in KB cells, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation. In addition, caspase-3 and -7 activation, and an increase in apoptosis were observed. Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL. In turn, this upregulation triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, pro-apoptotic factors such as Bax, Bad and Apaf-1 were also significantly upregulated by berberine. Anti-apoptotic factors such as Bcl-2 and Bcl-xL were downregulated. Z-VAD-FMK, a cell-permeable pan-caspase inhibitor, suppressed the activation of caspase-3 and PARP. These results clearly indicate that berberine-induced cell death of KB oral cancer cells was mediated by both extrinsic death receptor-dependent and intrinsic mitochondrial-dependent apoptotic signaling pathways. In addition, berberine-induced upregulation of FasL was shown to be mediated by the p38 MAPK signaling pathway. We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK. In summary, berberine has the potential to be used as a chemotherapeutic agent, with limited side-effects, for the management of oral cancer.
    Oncology Reports 01/2015; 33(4). DOI:10.3892/or.2015.3768 · 2.19 Impact Factor
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    ABSTRACT: The neurotrophin-inducible gene VGF plays an important role in the maintenance of organismal energy balance and in the mediation of hippocampal synaptic activity. The regulatory mechanism of VGF transcription is not fully understood. The neuron-restrictive silencer factor (NRSF) binds with the neuron-restrictive silencer element (NRSE), thereby suppressing the transcription of NRSE-containing genes. In this study, we show that the NRSE sequence of the VGF gene critically regulates the repression of VGF expression in NMB cells. Sequence analysis also establishes the presence of two putative NRSEs (NRSE-1 and NRSE-2) in the promoter region of the VGF gene. In reporter gene experiments, a more than eight-fold increase in the promoter activity was observed when both NRSE-1 and NRSE-2 were deleted. Deletion of NRSE-2 alone did not affect the promoter activity, thus indicating that NRSE-1 could be solely responsible for the repression of VGF gene expression. Mutations in the NRSE-1 sequence increased promoter activity. However, no change in activity was observed when NRSE-1 was coexpressed with dominant-negative NRSF, thereby suggesting that endogenous NRSF interacts with NRSE-1. Binding of NRSF to NRSE in a sequence-specific manner was confirmed with chromatin immunoprecipitation assays, respectively. Furthermore, the overexpressed NRSF in PC12 cells significantly suppressed the VGF gene expression by interacting with the NRSE located in the VGF promoter region. Our results indicate that NRSF plays an important role as a repressor of VGF gene regulation in NMB cells through a mechanism that is dependent on VGF-NRSE.
    Neuroreport 01/2015; 26(3). DOI:10.1097/WNR.0000000000000316 · 1.64 Impact Factor
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    ABSTRACT: We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. In xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma.
    Food and Chemical Toxicology 01/2015; 77. DOI:10.1016/j.fct.2014.12.013 · 2.61 Impact Factor
  • Tissue Engineering Part A 12/2014; 20(23-24):3322-3331. DOI:10.1089/ten.tea.2013.0717 · 4.70 Impact Factor
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    ABSTRACT: Because miR-146a expression in articular chondrocytes is associated with osteoarthritis (OA), we assessed whether miR-146a is linked to cartilage degeneration in the spine. Monolayer cultures of nucleus pulposus (NP) cells from the intervertebral discs (IVD) of bovine tails were transfected with a miR-146a mimic. To provoke inflammatory responses and catabolic extracellular matrix (ECM) degradation, cells were co-treated with interleukin-1 (IL-1). Transfection of miR-146a decreases IL-1 induced mRNA levels of inflammatory genes and catabolic proteases in NP cells based on quantitative real-time reverse transcriptase PCR (qRT-PCR) analysis. Similarly, miR146a suppresses IL-1 induced protein levels of matrix metalloproteinases and aggrecanases as revealed by immunoblotting. Disc segments from wild type (WT) and miR-146a knockout (KO) mice were cultured ex vivo in the presence or absence of IL-1 for 3days. Histological and immuno-histochemical (IHC) analyses of disc organ cultures revealed that IL-1 mediates changes in proteoglycan (PG) content and in-situ levels of catabolic proteins (MMP-13 and ADAMTS-5) in the nucleus pulposus of the disc. However, these IL-1 effects are more pronounced in miR-146a KO discs compared to WT discs. For example, absence of miR-146a increases the percentage of MMP-13 and ADAMTS-5 positive cells after treatment with IL-1. Thus, miR-146a appears to protect against IL-1 induced IVD degeneration and inflammation. Stimulation of endogenous miR-146a expression or exogenous delivery of miRNA-146a are viable therapeutic strategies that may decelerate disc degeneration and regain a normal homeostatic balance in extracellular matrix production and turn-over.
    Gene 10/2014; 555(2). DOI:10.1016/j.gene.2014.10.024 · 2.08 Impact Factor
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    ABSTRACT: IntroductionA significant proportion of patients undergoing salvage radiotherapy (RT) for biochemical recurrence (BCR) following radical prostatectomy (RP) may again experience BCR after salvage RT. Thus, we evaluated the clinical significances of different parameters on the biochemical outcome of RT in salvage setting.MethodsWe reviewed the records of 212 patients who underwent salvage RT between November 2003 and December 2012 for BCR following primary RP. BCR-free survivals after salvage RT were estimated using the Kaplan–Meier method. Cox proportional hazard regression models were used to evaluate the impacts of clinicopathologic parameters on BCR following salvage RT.ResultsThe overall median follow-up duration was 63.5 months. The BCR-free survival rate after salvage RT was 58.2% at 5 years. Multivariate analysis showed that a pre-RT prostate-specific antigen (PSA) level of ≤0.5 ng/mL, a pre-RT PSA doubling time (PSADT) of >4.5 months, concomitant androgen deprivation therapy (ADT) with salvage RT, and a positive surgical margin were independent predictors of favorable biochemical outcomes after salvage RT (hazard ratios [HR] = 3.012, 1.132, 2.000, and 1.805, respectively, p = less than 0.001, 0.013, 0.005, and 0.036, respectively). In the early (pre-RT PSA ≤0.5 ng/mL) salvage RT setting, concomitant ADT administration was also shown to be significantly associated with higher risk of BCR-free survival following salvage RT (HR = 2.611, p = 0.038).ConclusionLower pre-RT PSA value, longer PSADT before salvage RT, concomitant ADT administration, and a positive surgical margin were significant predictors of favorable biochemical outcomes following salvage RT performed for BCR after primary RP.
    PLoS ONE 07/2014; 9(7):e103574. DOI:10.1371/journal.pone.0103574 · 3.53 Impact Factor
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    ABSTRACT: PurposeThe aim of this study was to examine the clinical implications of a pathologically complete response after neoadjuvant chemoradiotherapy (CRT) followed by local excision for patients with cT2 rectal cancer who refused radical surgery.Materials and MethodsSeventeen patients with cT2 primary rectal cancer within 6 cm from the anal verge who received neoadjuvant CRT and local excision because of patient refusal of radical surgery or poor performance status were included. Two patients had clinical involvement of a regional lymph node. Preoperative radiotherapy was delivered to the whole pelvis at a dose of 44 to 50.4 Gy in 22 to 28 fractions. All patients underwent transanal excision and eight patients (47%) received postoperative chemotherapy.ResultsTen patients (59%) achieved ypT0. At a median follow-up period of 75 months (range, 22 to 126 months), four (24%) patients developed recurrence (two locoregional and two distant). The 5-year disease-free survival of all patients was 82%, and was higher in patients with ypT0 (90%) than in patients with ypT1-2 (69%, p=0.1643). Decreased disease-free survival was also observed in patients receiving capecitabine compared with 5-fluorouracil (54% vs. 100%, p=0.0298).ConclusionLocal excision could be a feasible alternative to radical surgery in patients with ypT0 after neoadjuvant CRT for cT2 distal rectal cancer without further radical surgery.
    Cancer Research and Treatment 07/2014; 46(3):243-249. DOI:10.4143/crt.2014.46.3.243 · 2.98 Impact Factor
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    ABSTRACT: PurposeTo find the applicability of adjuvant radiotherapy for extrahepatic bile duct cancer (EBDC), we analyzed the pattern of failure and evaluate prognostic factors of locoregional failure after curative resection without adjuvant treatment.Materials and MethodsIn 97 patients with resected EBDC, the location of tumor was classified as proximal (n = 26) and distal (n = 71), using the junction of the cystic duct and common hepatic duct as the dividing point. Locoregional failure sites were categorized as follows: the hepatoduodenal ligament and tumor bed, the celiac artery and superior mesenteric artery, and other sites.ResultsThe median follow-up time was 29 months for surviving patients. Three-year locoregional progression-free survival, progression-free survival, and overall survival rates were 50%, 42%, and 52%, respectively. Regarding initial failures, 79% and 81% were locoregional failures in proximal and distal EBDC patients, respectively. The most common site was the hepatoduodenal ligament and tumor bed. In the multivariate analysis, perineural invasion was associated with poor locoregional progression-free survival (p = 0.023) and progression-free survival (p = 0.012); and elevated postoperative CA19-9 (≥37 U/mL) did with poor locoregional progression-free survival (p = 0.002), progression-free survival (p < 0.001) and overall survival (p < 0.001).ConclusionBoth proximal and distal EBDC showed remarkable proportion of locoregional failure. Perineural invasion and elevated postoperative CA19-9 were risk factors of locoregional failure. In these patients with high risk of locoregional failure, adjuvant radiotherapy could be considered to improve locoregional control.
    06/2014; 32(2):63-9. DOI:10.3857/roj.2014.32.2.63
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    ABSTRACT: The aim of this study was to compare the dosimetric performance and to evaluate the pretreatment quality assurance (QA) of a portal dosimetry and a commercial two-dimensional (2-D) array system. In the characteristics comparison study, the measured values for the dose linearity, dose rate response, reproducibility, and field size dependence for 6-MV photon beams were analyzed for both detector systems. To perform the qualitative evaluations of the 10 IMRT and the 10 VMAT plans, we used the Gamma index for quantifying the agreement between calculations and measurements. The performance estimates for both systems show that overall, minimal differences in the dosimetric characteristics exist between the Electron portal imaging device (EPID) and 2-D array system. In the qualitative analysis for pretreatment quality assurance, the EPID and 2-D array system yield similar passing rate results for the majority of clinical Intensity-modulated radiation therapy (IMRT) and Volumetric-modulated arc therapy (VMAT) cases. These results were satisfactory for IMRT and VMAT fields and were within the acceptable criteria of γ%≤1, γavg<0.5. The EPDI and the 2-D array systems showed comparable dosimetric results. In this study, the results revealed both systems to be suitable for patient-specific QA measurements for IMRT and VMAT. We conclude that, depending on the status of clinic, both systems can be used interchangeably for routine pretreatment QA.
    Journal- Korean Physical Society 04/2014; 64(8):1207-1212. DOI:10.3938/jkps.64.1207 · 0.43 Impact Factor
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    ABSTRACT: Pre-operative chemoradiotherapy (CRT) is the standard treatment in clinical stage T3/4 or node positive rectal cancer. However, there are no established biomarkers that can predict the pathological response and clinical outcome to CRT. Immunohistochemical staining was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 112 patients who received 5-FU based pre-operative CRT and surgery. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1alpha and ALDH1 were assessed and correlated with tumor regression grades and disease free survival. Of the 112 patients (M/F 74/38, median age: 62), 20 (17.9%) patients achieved pathologic complete remission (pCR). In analyzing the associations between marker expressions and tumor regression grades, high p21 expression at the pretreatment biopsy was significantly associated with non-pCR (p = 0.022) and poor disease free survival (median DFS - low vs high p21: 75.8 vs 58.1 months, p = 0.002). In the multivariate analysis, high p21 expression level at the pre-treatment biopsy was significantly associated with poor DFS (p = 0.001, HR 6.14; 95% CI 2.03, 18.55). High CD166 expression level at the pretreatment biopsy was also associated with poor DFS (p = 0.003; HR 5.61; 95% CI 1.81, 17.35). These show high p21 and CD166 expression at the pretreatment biopsy were associated with tumor regression and poor prognosis in patients treated with 5-FU based CRT. Larger, prospective and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to CRT.
    BMC Cancer 04/2014; 14(1):241. DOI:10.1186/1471-2407-14-241 · 3.32 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs) regulate cell differentiation by inhibiting mRNA translation or by inducing its degradation. However, the role of miRNAs in odontogenic differentiation is largely unknown. In this present study, we observed that the expression of miR-663 increased significantly during differentiation of MDPC-23 cells to odontoblasts. Furthermore, up-regulation of miR-663 expression promoted odontogenic differentiation and accelerated mineralization without proliferation in MDPC-23 cells. In addition, target gene prediction for miR-663 revealed that the mRNA of the adenomatous polyposis coli (APC) gene, which is associated with the Wnt/β-catenin signaling pathway, has a miR-663 binding site in its 3'-untranslated region (3'-UTR). Furthermore, APC expressional was suppressed significantly by miR-663, and this down-regulation of APC expression triggered activation of Wnt/β-catenin signaling through accumulation of β-catenin in the nucleus. Taken together, these findings suggest that miR-663 promotes differentiation of MDPC-23 cells to odontoblasts by targeting APC-mediated activation of Wnt/β-catenin signaling. Therefore, miR-663 can be considered a critical regulator of odontoblast differentiation and can be utilized for developing miRNA-based therapeutic agents.
    Biochemical and Biophysical Research Communications 04/2014; 446(4). DOI:10.1016/j.bbrc.2014.03.027 · 2.28 Impact Factor
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    ABSTRACT: Although lateral pelvic node dissection (LPND) is recommended for rectal cancer with clinically metastatic lateral pelvic lymph nodes (LPNs), LPNs may respond to neoadjuvant chemoradiotherapy (nCRT). Our aim was to determine the optimal indication for LPND after nCRT for mid/low rectal cancer. Of 2,263 patients with clinical stage II/III mid/low rectal cancer who were managed at three tertiary referral hospitals, 66 patients underwent curative surgery including LPND after nCRT were included in this study. Risk factors for LPN metastasis were retrospectively analyzed and oncologic outcomes determined according to LPN response to nCRT. Persistent LPNs greater than 5 mm on post-nCRT magnetic resonance imaging were significantly associated with residual tumor metastasis, unlike responsive LPN after nCRT (short-axis diameter ≤5 mm) (pathologically, 61.1 % [22 of 36] vs. 0 % [0 of 30], P < 0.001). Multivariable analysis revealed post-nCRT LPN size as a significant and independent risk factor for LPN metastasis (odds ratio 2.390; 95 % confidence interval 1.104-4.069). Over a median follow-up of 39.3 months, the recurrence rate was lower in patients with responsive nodes than in patients with persistent nodes (20 % [6 of 30] vs. 47.2 % [17 of 36], P = 0.012). The 5-year overall survival and 5-year disease-free survival rates were lower in patients with persistent LPN than in patients with responsive LPN (44.6 % vs. 77.1 %, P = 0.034; 33.7 % vs. 72.5 %, P = 0.011, respectively). In mid/low rectal cancer with clinically metastatic LPNs, the decision to perform LPND should be based on the LPN response to nCRT.
    Annals of Surgical Oncology 03/2014; 21(7). DOI:10.1245/s10434-014-3559-z · 3.94 Impact Factor
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    ABSTRACT: The aim of the present study was to investigate and compare the effects of diferuloylmethane (curcumin) and diphenyldifluoroketone (EF-24) on cell growth and apoptosis induction in human osteogenic sarcoma cells. This was examined by MTT assay, nuclear DAPI staining, caspase-activation assay, flow cytometry analysis and immunoblotting in Saos2 human osteogenic sarcoma cells. Curcumin and EF-24 inhibited the growth of Saos2 cells in a dose-dependent manner. The apparent potency of EF-24 was more than 3-fold higher that of curcumin. Treatment with curcumin or EF-24 resulted in nuclear condensation and fragmentation in the cells. The caspase-3/-7 activities were detected in living cells treated with curcumin or EF-24. Flow cytometry showed that the rate of apoptosis was increased by curcumin and EF-24 compared to the control. Curcumin and EF-24 promoted the proteolytic cleavages of procaspase-3/-7/-8/-9 with increases in the amount of cleaved caspase-3/-7/-8/-9. The curcumin- or EF-24-induced apoptosis in the Saos2 cells was mediated by the expression of Fas and activation of caspase-8, caspase-3 and poly(ADP-ribose) polymerase. Immunoblotting revealed the Bid and Bcl-2 proteins to be downregulated, and truncated-Bid, Bax and p53 proteins to be upregulated by curcumin and EF-24. Curcumin and EF-24 increased the Bax/Bcl-2 ratio significantly. These results suggest that the curcumin and EF-24 inhibit cell proliferation and induce apoptotic cell death in Saos2 human osteogenic sarcoma cells via both the mitochondria-mediated intrinsic pathway and the death receptor-mediated extrinsic pathway, and may have potential properties for anti-osteosarcoma drug discovery.
    Oncology Reports 03/2014; 31(5). DOI:10.3892/or.2014.3066 · 2.19 Impact Factor
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    ABSTRACT: Compared to most normal cells that express L-type amino acid transporter 2, L-type amino acid transporter 1 is highly expressed in cancer cells and presumed to support their elevated growth and proliferation. This study examined JPH203, a potent and selective L-type amino acid transporter 1 inhibitor, and its ability to suppress YD-38 human oral cancer cell growth. The YD-38 cells express L-type amino acid transporter 1 with its associating protein 4F2 heavy chain, but not L-type amino acid transporter 2. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, completely inhibited l-leucine uptake in YD-38 cells. As expected, the intrinsic affinity of JPH203 to inhibit l-leucine uptake was far more efficient than BCH. Likewise, JPH203 and BCH inhibited YD-38 cell growth, with JPH203 being superior to BCH. JPH203 up-regulated the population of apoptotic YD-38 cells through the activation of apoptotic factors, including caspases and PARP. These results suggest that the inhibition of L-type amino acid transporter 1 activity via JPH203, which may act as a potential novel anti-oral-cancer agent, leads to apoptosis by inducing the intracellular depletion of the neutral amino acids essential for cancer cell growth in YD-38 human oral cancer cells.
    Journal of Pharmacological Sciences 02/2014; 124(2). DOI:10.1254/jphs.13154FP · 2.11 Impact Factor

Publication Stats

979 Citations
252.19 Total Impact Points

Institutions

  • 2009–2015
    • Rush University Medical Center
      • • Department of Biochemistry
      • • Section of Rheumatology
      Chicago, Illinois, United States
  • 2008–2015
    • Seoul National University Bundang Hospital
      • Department of Radiation Oncology
      Sŏul, Seoul, South Korea
  • 2006–2015
    • Seoul National University
      • Department of Radiation Oncology
      Sŏul, Seoul, South Korea
  • 2005–2015
    • Chosun University
      • • Oral Biology Research Institute
      • • Department of Biotechnology
      Gwangju, Gwangju, South Korea
  • 2014
    • Seoul National University Hospital
      • Department of Radiation Oncology
      Sŏul, Seoul, South Korea
  • 2013
    • Konkuk University Medical Center
      • Department of Radiation Oncology
      Changnyeong, South Gyeongsang, South Korea
  • 2001–2011
    • Kepco
      Sŏul, Seoul, South Korea
  • 2010
    • University of Illinois at Chicago
      • Department of Bioengineering
      Chicago, Illinois, United States
  • 1999–2009
    • Korea Hydro and Nuclear Power - Central Research Institute
      Sŏul, Seoul, South Korea
  • 2002
    • Chungnam National University
      • College of Medicine
      Sŏngnam, Gyeonggi Province, South Korea