Ha-Young Lee

Is Diffusion-Weighted MRI Useful for Differentiation of Small Non-Necrotic Cervical Lymph Nodes in Patients with Head and Neck Malignancies?

Objective To evaluate the usefulness of measuring the apparent diffusion coefficient (ADC) in diffusion-weighted magnetic resonance imaging to distinguish benign from small, non-necrotic metastatic cervical lymph nodes in patients with head and neck cancers. Materials and Methods Twenty-six consecutive patients with head and neck cancer underwent diffusion-weighted imaging (b value, 0 and 800 s/mm2) preoperatively between January 2009 and December 2010. Two readers independently measured the ADC values of each cervical lymph node with a minimum-axial diameter of ≥ 5 mm but < 11 mm using manually drawn regions of interest. Necrotic lymph nodes were excluded. Mean ADC values were compared between benign and metastatic lymph nodes after correlating the pathology. Results A total of 116 lymph nodes (91 benign and 25 metastatic) from 25 patients were included. Metastatic lymph nodes (mean ± standard deviation [SD], 7.4 ± 1.6 mm) were larger than benign lymph nodes (mean ± SD, 6.6 ± 1.4 mm) (p = 0.018). Mean ADC values for reader 1 were 1.17 ± 0.31 × 10-3 mm2/s for benign and 1.25 ± 0.76 × 10-3 mm2/s for metastatic lymph nodes. Mean ADC values for reader 2 were 1.21 ± 0.46 × 10-3 mm2/s for benign and 1.14 ± 0.34 × 10-3 mm2/s for metastatic lymph nodes. Mean ADC values between benign and metastatic lymph nodes were not significantly different (p = 0.594 for reader 1, 0.463 for reader 2). Conclusion Measuring mean ADC does not allow differentiating benign from metastatic cervical lymph nodes in patients with head and neck cancer and non-necrotic, small lymph nodes.

Abstract B04: Early detection of ovarian cancer recurrence using p53-mutated circulating tumor DNA as non-invasive biomarkers.

Objectives: Epithelial ovarian cancer is the most lethal gynecologic cancer and it has a very high recurrence rate. Early detection of recurrence is very important as well as good treatment; however, the accuracy of CA-125 is approximately 50%. Circulating cell-free DNA (cfDNA) carrying tumor-specific somatic alterations, as called circulating tumor DNA (ctDNA), can be isolated from human body fluids. Recently, ctDNA is emerging as a new generation of non-invasive cancer biomarker Moreover ctDNA could be a more sensitive and specific biomarker than CA-125 in epithelial ovarian cancer. According to The Cancer Genome Atlas (TCGA) data, 95% of high-grade serous ovarian cancer (HGS-OC) has mutations in the p53 gene. This study is to investigate that p53-mutated ctDNA could be a biomarker for the early detection of recurrence comparing to CA-125 in HGS-OC. Procedures: We enrolled 85 patients with suspected ovarian cancer from July 2013 to June 2015 and 51 patients were epithelial ovarian cancer. We monitored the level of p53-mutated ctDNA compared with CA-125 in 25 of 38 patients (66%) with HGS-OC who were receiving surgery and continuing chemotherapy treatment. We used targeted-p53 whole exon sequencing to detect somatic genomic alterations from cancer tissue and used droplet digital polymerase chain reaction (ddPCR) to verify ctDNA in serially collected plasma samples. Results: We evaluated ctDNA levels as a monitoring method of the response to chemotherapy and tumor progression. We detected p53 mutations in 38 of 51 women (76%) by whole exon sequencing in cancer tissue and somatic genomic alteration of p53 showed in various sites. Ten of twenty-five (40%) patients who were monitored by ctDNA showed increasing levels of p53-mutated ctDNA during or after scheduled chemotherapy. Even though the ctDNA levels of these 10 patients were increased, the levels of CA-125 were still remained in normal range (under 35 Unit/mL). Especially, 3 patients, the disease progression was observed by imaging method after a few months after the increasing ctDNA. Conclusions: In conclusion, these data suggest that sequential monitoring of p53-mutated ctDNA may have potential as a sensitive and specific biomarker for early detection of recurrence in HGS-OC Citation Format: Ha-Young Lee, Shin-Wha Lee, Geum-Hee Na, Sang-Eun Lee, Dong-Woo Kang, Yong-Man Kim. Early detection of ovarian cancer recurrence using p53-mutated circulating tumor DNA as non-invasive biomarkers. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr B04.

Abstract 1191: Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAnnBackground: Endometrial cancer is the most common malignancy of the female reproductive tract and the third most common cause of death from womens cancer. Risk factors of endometrial cancer include high levels of estrogen, obesity, diabetes mellitus, breast cancer, long term use of tamoxifen, late menopause, high blood pressure, and increasing age. Although the exact mechanisms in endometrial carcinogenesis due to chronic exposure are unclear, it is though that the pro-proliferative and DNA-damaging effects of estrogen and its metabolites, related with and insufficient counterbalance by progesterone, promote the hyper-proliferation and transformation of cells. Selective progesterone receptor modulator (SPRM) is an agent that acts on the progesterone receptor. Ulipristal acetate (UA) is one of SPRM and other SPRM, such as Mifepristone, showed inhibitory effect on various endometrial cancer cell lines. UA has been available as an emergency contraception and a treatment for uterine leiomyoma. The effect of UA on leiomyoma is decreasing neovascularization, proliferation, and viability.nnObjective: This study was undertaken to investigate antitumor effect of UA and to explore the effect of combination treatment with chemotherapy drug in endometrial cancer.nnMethod: Inhibitory concentration (IC), proliferation assay, and migration assay were performed using Ishikawa, HEC-1-A, HEC-1-B, and/or patient-derived primary cancer cells (PCC). Different concentration of UA were treated in endometrial cancer cell lines and PCCs for the each assay. The CellTiter-Glo assay were performed to investigate IC50 in cell lines and PCCs. Crystal violet staining and wound healing assay were performed to examine cell proliferation and migration.nnResults: UA inhibited cell viability of endometrial cancer cell lines and PCCs at high concentration, most abviously 10uM in dose-dependent manner. In combination treatment assay with paclitaxel, UA showed synergistic anti-tumor effect with low-dose of paclitaxel on cell lines and PCCs.nnConclusions: We showed that combination treatment of UA and paclitaxel effectively than single treatment by low dosage. In summary, we are actively exploring new effective applicable drugs for endometrial cancer, and our data suggest that UA may have therapeutic value with chemo-combination treatment of patients with endometrial cancer.nnCitation Format: Ha-Young Lee, A Ra Ko, Dong-Woo Kang, Yu-Seon Kim, Su-Min Kim, Tae-Wook Kang, Shin-Wha Lee, Yong-Man Kim. Anti-tumor effect of selective progesterone receptor modulator (ulipristal acetate) on endometrial cancer cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1191.

The expression and function of toll-like receptors (TLRs) in ovarian cancer cell lines.

Meeting abstractsnnThis study is to investigate which Toll Like Receptors (TLRs) are expressed on human ovarian cancer cell lines and to evaluate the effect of TLR expression on the growth of ovarian cancer cells.nnFour human ovarian epithelial carcinoma cell lines SKOV3 (clear), OVCAR3 (serous

Abstract 5132: Evaluation of multi-marker in tissue-derived cancer cells from patients with epithelial ovarian carcinoma

Objective: The objective of this study is to refine a simple, rapid and reproducible method for the isolation and characterization of epithelial ovarian cancer (EOC) cells from ovarian tumor tissues and to evaluate the intracellular expression of CK-7, CA-125, HE4 and FOLR-1 in primary ovarian cancer cells. Methods: Fourteen patients diagnosed with papillary serous adenocarcinoma of ovary were selected in ASAN Medical Center. Isolation of tumor EOC cells involves the mechanical disruption of the tumor tissue and placed directly into culture with very little manipulation. Primary ovarian cancer cells were monitored after initial plating and every day for following 15 days. Confocal laser scanning microscopy was used for the imaging of intracellular immunofluorescence of CK-7, CA-125, HE4 and FOLR-1. Results: Two days after plating primary ovarian cancer cells began to adhere to the plate by the presence of small adherent clusters. The primary ovarian cancer cells became a confluent monolayer and displayed the typical epithelial cobblestone morphology. The mean duration of passage was 8.5 days, it was revealed variously in the primary ovarian cancer cells. Immunofluorescent detection of CK-7 expression in EOC cells demonstrates the epithelial origin, however their expression was not constant. CA-125, HE-4 and FOLR-1 were expressed by all tissue-derived EOC cells. The expression pattern of CA-125, HE-4 and FOLR-1 was different in each patient and that was not correlated with the serum level of CA-125. Conclusions: The isolation and characterization of tissue-derived cancer cells from patients with EOC using the expression of CK-7, CA-125, HE4 and FOLR-1 were reasonable method. This result could provide clinically relevant models suitable for investigation of the ex vivo biological characteristics of ovarian cancers. Citation Format: Shin-Wha Lee, Sang-Eun Lee, Ha-Young Lee, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam. Evaluation of multi-marker in tissue-derived cancer cells from patients with epithelial ovarian carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5132. doi:10.1158/1538-7445.AM2015-5132

Abstract 333: Evaluation of the mixed solution of sodium hyaluronate and hydroxyethylstarch on gynecologic cancer cell line

Effect of hyaluronic acid and hydroethyl starch mixture in ovarian cancer cell Objective: Post-operative tissue adhesion is a very serious problem in patients with ovarian cancer. This study is to investigate the role of hyaluronic acid and hydroethyl starch mixture against the tissue adhesion through in vitro experimentations with ovarian cancer cell lines. Methods: We used different concentrations of hyaluronic acid and hydroethyl starch (HA/HES) mixture in SKOV3 cell lines. We performed the adhesion and proliferation inhibition assay in different method, mixing and spreading cells. For the migration inhibition assay, we evaluated the effect according to the concentration of HA/HES mixture. The wound-healing assay was performed after artificial injury and physical barrier of 100% HA/HES mixture was evaluated. Results: In adhesion and proliferation inhibition assay, the viable adherent cells were decreased according to the concentration of HA/HES mixture. The confluence increased over time, except for 100% HA/HES mixture. This result was more obvious in spreading method. The wound recovery was slow in high concentration of HA/HES mixture in the migration inhibition assay and wound-healing assay. The physical barrier of 100% HA/HES mixture inhibited the cell growth until 48 hours. Conclusion: The proliferation and recovery inhibition of SKOV3 cell lines using HA/HES mixture was confirmed and the inhibitory effect appeared to be in proportion of the concentration of HA/HES mixture. This growth inhibition effect of HA/HES mixture will be useful clinically in patients with ovarian cancer Citation Format: Ha-Young Lee, Hyun-Jung Cho, Shin-Wha Lee, Sang-Eun Lee, Dae-Yeon Kim, Jong-Hyeok Kim, Yong-Man Kim, Young-Tak Kim, Joo-Hyun Nam. Evaluation of the mixed solution of sodium hyaluronate and hydroxyethylstarch on gynecologic cancer cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 333. doi:10.1158/1538-7445.AM2015-333

Abstract 3073: Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods

Objective: The quantitative and qualitative analysis of circulating tumor cells (CTCs) aids in diagnosis of disease, prognosis, disease recurrence, and therapeutic response in several cancers. However, detection and isolation of CTCs from the blood circulation is a difficult task because of their scarcity and the lack of reliable markers to identify these cells. Especially, in epithelial ovarian cancer, there is a little reported data for CTCs and their CTCs has been defined to the EpCAM+ cells, even though EpCAM+ cells are just a few in ovarian cancer. The aim of this study is to investigate the effective principles and methods to detect and isolate CTCs through novel markers in ovarian cancer. Methods: CTC analysis was performed in the spiking test to find cancer cells in the human serum mixed with WBCs. Four cell lines including OVCAR3, SKOV3, SNU8 and SNU251 were used and primary cancer cells from 4 patients were analyzed. Cancer cells were isolated on the basis of cell size by filtration through CytoGen capture device, followed by identification according to validated immunocytochemistry based on the expression of DAPI, CD45, EpCAM, CK, CA-125 and HE4. Results: We obtained cancer cells more than 90% based on the cell size by filtration. Immunocytochemistry confirmed the epithelial origin through the expression of CK and EpCAM in cancer cell lines. The rate of expression was 35-99 % for CK and 1-99 % for EpCAM. A small number of cancer cell lines expressed CD45 that is the marker of WBC. The expression of CA-125 and HE4 showed their ovarian origin. The rate of expression was 7-98 % for CA-125 and 40-99 % for HE4 in cancer cell lines. Primary cancer cells were detected most effectively as the method of combination with 4 markers, including DAPI, CD45, EpCAM and HE4. Conclusion: Our findings provide the first evidence for effective methods to detect and isolate CTCs in ovarian cancer. Combination of DAPI, CD45, EpCAM and HE4 could be a useful marker to support CTCs research in epithelial ovarian cancer. Citation Format: Shin-Wha Lee, Ha-Young Lee, Jin-Young Mo, Byung Chul Kim, Eun Hye Kim, Yong-Man Kim. Detection and isolation of circulating tumor cells in ovarian cancer: Principles and methods. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3073. doi:10.1158/1538-7445.AM2014-3073