Eun Kyoung Lee

Ectopic expression of neutrophil gelatinase-associated lipocalin suppresses the invasion and liver metastasis of colon cancer cells.

Neutrophil gelatinase‐associated lipocalin (NGAL), also known as lipocalin 2, is a 25‐kDa lipocalin initially purified from neutrophil granules. It is thought to play a role in regulating cellular growth since its expression is highly upregulated in a variety of proliferative cells such as cancer cells. However, experimental evidence showing a clear causal relationship between NGAL expression and the proliferation of tumor cells is lacking. Here, we found NGAL expression in highly and poorly metastatic colon cancer cell lines of the same genetic origin correlated inversely with the metastatic potential of these cells, which suggests NGAL participates in the metastatic process. To explore the role NGAL plays in tumor growth and metastasis, the KM12SM human colon cancer cell line, which is highly metastatic while showing decreased NGAL expression, was genetically manipulated to overexpress NGAL. The effects of this on tumor growth and liver metastasis were then analyzed using experimental animal models established by injecting BALB/c nude mice with tumor cells subcutaneously or intrasplenically. Ectopic expression of NGAL in the colon cancer cells had little effect on the growth and viability of the tumor cells both in vitro and in vivo. However, NGAL expression not only suppressed the ability of the colon carcinoma cells to invade Matrigel in vitro, it also substantially inhibited liver metastasis in an experimental animal model. Collectively, these results indicate that NGAL may be a candidate metastasis suppressor in colon cancer cells.

Inhibition of the proliferation and invasion of hepatocellular carcinoma cells by lipocalin 2 through blockade of JNK and PI3K/Akt signaling.

Lipocalin 2 (Lcn2) has been reported to induce cellular proliferation based on its expression in a variety of proliferative cells. Consistent with these findings, the present study demonstrates a significant increase in Lcn2 levels in human hepatocellular carcinoma (HCC) tissues compared with non-tumor liver tissues. However, the role of Lcn2 in hepatocarcinogenesis is far from clear. To investigate the effects of Lcn2 expression on hepatocarcinogenesis, Chang liver and SK-Hep1 HCC cell lines were genetically manipulated to express Lcn2, and the effects on the proliferation and invasion of HCC cells were analyzed. Ectopic expression of Lcn2 in HCC cells significantly inhibited the growth of HCC cells in vitro and in vivo, reduced the invasive potential of cells, and inhibited the expression of matrix metalloproteinase 2 (MMP-2). Lcn2 may exert its function partly through the inhibition of the c-Jun N-terminal kinase (JNK) and phospha-tidyl inositol 3-kinase (PI3K)/Akt signaling pathways in HCC cells. The selective inhibition of these pathways using pharmacological inhibitors significantly inhibited proliferation, invasion and MMP-2 expression, whereas Lcn2 expression suppressed the JNK and PI3K/Akt pathways. Collectively, these results clearly indicate that Lcn2 may play a protective role against the progression of HCCs by suppressing cell proliferation and invasion. The clinical significance of the present findings should be evaluated further.

Prediction of Response to Concurrent Chemoradiotherapy with Temozolomide in Glioblastoma: Application of Immediate Post-Operative Dynamic Susceptibility Contrast and Diffusion-Weighted MR Imaging.

Objective To determine whether histogram values of the normalized apparent diffusion coefficient (nADC) and normalized cerebral blood volume (nCBV) maps obtained in contrast-enhancing lesions detected on immediate post-operative MR imaging can be used to predict the patient response to concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ). Materials and Methods Twenty-four patients with GBM who had shown measurable contrast enhancement on immediate post-operative MR imaging and had subsequently undergone CCRT with TMZ were retrospectively analyzed. The corresponding histogram parameters of nCBV and nADC maps for measurable contrast-enhancing lesions were calculated. Patient groups with progression (n = 11) and non-progression (n = 13) at one year after the operation were identified, and the histogram parameters were compared between the two groups. Receiver operating characteristic (ROC) analysis was used to determine the best cutoff value for predicting progression. Progression-free survival (PFS) was determined with the Kaplan-Meier method and the log-rank test. Results The 99th percentile of the cumulative nCBV histogram (nCBV C99) on immediate post-operative MR imaging was a significant predictor of one-year progression (p = 0.033). ROC analysis showed that the best cutoff value for predicting progression after CCRT was 5.537 (sensitivity and specificity were 72.7% and 76.9%, respectively). The patients with an nCBV C99 of < 5.537 had a significantly longer PFS than those with an nCBV C99 of ≥ 5.537 (p = 0.026). Conclusion The nCBV C99 from the cumulative histogram analysis of the nCBV from immediate post-operative MR imaging may be feasible for predicting glioblastoma response to CCRT with TMZ.

Long-term results of fluocinolone acetonide intravitreal implant in Behçet intractable posterior uveitis

OBJECTIVEnTo evaluate the long-term efficacy and safety of the fluocinolone acetonide intravitreal implant in patients with Behçet disease with intractable noninfectious posterior uveitis.nnnDESIGNnConsecutive retrospective analysis.nnnPARTICIPANTSnEight eyes from 7 patients with Behçet uveitis who did not respond successfully to conventional treatment with topical and systemic steroids and/or systemic steroid-sparing agents were studied.nnnMETHODSnWe performed a chart review of patients who were treated with a 0.59-mg fluocinolone acetonide intravitreal implant at a single centre from September 2007 through June 2009. Snellen visual acuity, control of inflammation, and the development of complications such as infection or uncontrollable intraocular pressure (IOP) elevation were evaluated.nnnRESULTSnMean age at implant placement was 35.3 (range 17-42) years. Mean follow-up duration was 47.8 (range 39.5-57.6) months. Postoperative visual acuity improved by more than 3 lines in 6 eyes (75%). Five patients were able to discontinue all systemic medications. Six eyes (75%) exhibited postoperative IOP spikes of more than 30 mm Hg. Five patients required glaucoma shunting surgery postoperatively for IOP control. The single phakic eye developed a visually significant posterior subcapsular lens opacification that required cataract extraction. There was 1 case of postoperative cytomegalovirus endothelitis. Infection was controlled with oral valganciclovir and topical antibiotic medication, and the patient did not require implant removal.nnnCONCLUSIONSnThe fluocinolone implant is effective in the control of intractable inflammation in Behçet uveitis. Elevation of IOP remains a major potential complication, and the possibility of infection should be considered.

In vivo efficacy of recombinant leukotactin-1 against cyclophosphamide

Leukotactin-1 (Lkn-1), a human CC chemokine, has been demonstrated to induce chemotaxis of neutrophils, monocytes, eosinophils and lymphocytes and has been shown to suppress colony formation of hematopoietic stem and progenitor cells (HSPC)in vitro andin vivo. The temporal suppression of HSPC by chemokines could potentially be applicable for various indications, such as the protection of HSPC from the several anti-proliferating chemotherapeutics in cancer treatments. In order to evaluate the protective effects on myeloid progenitor cells, the recombinant Lkn-1 was produced byPichia pastoris and tested with cyclophosphamide, cytotoxic chemotherapeutics. The pretreatment of Lkn-1 increased the number of HSPC in bone marrow as well as the potency of resulting progenitor cells after the treatment of cyclophosphamide. After the first cycle of cyclophosphamide treatment these protections of HSPC correlated with the increased number of white blood cells and neutrophils in the peripheral blood. In lethal conditions created by the repeated aministration of cyclophosphamide, the treatment of Lkn-1 enhanced the survival of mice, suggesting the potential use of Lkn-1 as the protective agent for HSPC from various cytotoxic insults.

Effect of tumor volume on the enhancement pattern of parathyroid adenoma on parathyroid four-dimensional CT

IntroductionThe purpose of this study is to assess the effect of tumor volume on the enhancement pattern of parathyroid adenoma (PTA) on four-dimensional computed tomography (4D-CT).MethodsWe analyzed the enhancement patterns of PTA on four-phase 4D-CT in 44 patients. Dependency of the changes of Hounsfield unit values (ΔHU) on the tumor volumes and clinical characteristics was evaluated using linear regression analyses. In addition, an unpaired t test was used to compare ΔHU of PTAs between PTA volume ≥1xa0cm3 and <1xa0cm3, thyroid gland, and lymph node.ResultsPTA volume based on CT was the strongest factor on the ΔHUPre to Arterial and ΔHUArterial to Venous and ΔHUArterial to Delayed (R2u2009=u20090.34, 0.25, and 0.32, respectively, Pu2009<u20090.001 for both). PTA ≥1xa0cm3 had statistically significant greater enhancement between the unenhanced phase and the arterial phase than PTA <1xa0cm3 (mean valuesu2009±u2009standard deviations (SDs) of ΔHUPre to Arterial, 102.7u2009±u200933.7 and 57.5u2009±u200928.8, respectively, Pu2009<u20090.001). PTA ≥1xa0cm3 showed an early washout pattern on the venous phase, whereas PTA <1xa0cm3 showed a progressive enhancement pattern on the venous phase (mean valuesu2009±u2009SDs of ΔHUArterial to Venous, −13.2u2009±u200931.6 and 14.4u2009±u200932.7, respectively; Pu2009=u20090.009).ConclusionThe enhancement pattern of PTA on 4D-CT is variable with respect to PTA volume based on CT. Therefore, the enhancement pattern of PTA on 4D-CT requires careful interpretation concerning the tumor volume, especially in cases of PTA <1xa0cm3.